Next Article in Journal
A General Synthesis of Cross-Conjugated Enynones through Pd Catalyzed Sonogashira Coupling with Triazine Esters
Next Article in Special Issue
Bridged 1,2,4-Trioxolanes: SnCl4—Catalyzed Synthesis and an In Vitro Study against S. mansoni
Previous Article in Journal
Fe-Incorporated Nickel-Based Bimetallic Metal–Organic Frameworks for Enhanced Electrochemical Oxygen Evolution
Previous Article in Special Issue
Organocatalytic Asymmetric Peroxidation of γ,δ-Unsaturated β-Keto Esters—A Novel Route to Chiral Cycloperoxides
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 28
Issue 11
10.3390/molecules28114367
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

The Corey-Seebach Reagent in the 21st Century: A Review

by
Muhammad Haroon
1,
Ameer Fawad Zahoor
1,*,
Sajjad Ahmad
2,
Asim Mansha
1,
Muhammad Irfan
3,
Aqsa Mushtaq
1,
Rabia Akhtar
1,4,
Ali Irfan
1,
Katarzyna Kotwica-Mojzych
5 and
Mariusz Mojzych
6,*
1
Medicinal Chemistry Research Lab, Department of Chemistry, Government College University Faisalabad, Faisalabad 38000, Pakistan
2
Department of Chemistry, University of Engineering and Technology Lahore, Faisalabad Campus, Faisalabad 38000, Pakistan
3
Department of Pharmaceutics, Government College University Faisalabad, Faisalabad 38000, Pakistan
4
Department of Chemistry, Superior University, Faisalabad 38000, Pakistan
5
Laboratory of Experimental Cytology, Medical University of Lublin, Radziwiłłowska 11, 20-080 Lublin, Poland
6
Department of Chemistry, Siedlce University of Natural Sciences and Humanities, 3-Go Maja 54, 08-110 Siedlce, Poland
*
Authors to whom correspondence should be addressed.
Molecules 2023, 28(11), 4367; https://doi.org/10.3390/molecules28114367
Submission received: 11 April 2023 / Revised: 22 May 2023 / Accepted: 22 May 2023 / Published: 26 May 2023
(This article belongs to the Special Issue Recent Advances in Organic Synthesis Related to Natural Compounds)
Browse Figures
Review Reports Versions Notes

Abstract

:
The Corey-Seebach reagent plays an important role in organic synthesis because of its broad synthetic applications. The Corey-Seebach reagent is formed by the reaction of an aldehyde or a ketone with 1,3-propane-dithiol under acidic conditions, followed by deprotonation with n-butyllithium. A large variety of natural products (alkaloids, terpenoids, and polyketides) can be accessed successfully by utilizing this reagent. This review article focuses on the recent contributions (post-2006) of the Corey-Seebach reagent towards the total synthesis of natural products such as alkaloids (lycoplanine A, diterpenoid alkaloids, etc.), terpenoids (bisnorditerpene, totarol, etc.), polyketide (ambruticin J, biakamides, etc.), and heterocycles such as rodocaine and substituted pyridines, as well and their applications towards important organic synthesis.

Graphical Abstract

1. Introduction

Elias James Corey is an American chemist well-known for his contribution to the development of methodology and theory of organic synthesis, especially retrosynthetic analysis. He was awarded a Nobel Prize in 1990 for the development of retrosynthetic analysis. His research cooperation with other famous organic chemists has resulted in various name reactions, based on his name, in organic chemistry [1]. One of his famous reactions is the Corey-Seebach reaction which was a combined work of Corey and Dieter Seebach (a German chemist). The Corey-Seebach reagent is formed by the reaction of an aldehyde or a ketone with 1,3-propane-dithiol in the presence of acidic conditions (Lewis acid). Corey-Seebach is a nucleophilic moiety and has widespread applications in various organic transformations. This reaction was first published in 1965, which reported the synthesis of dicarbonyl derivative from 1,3-dithiane [2]. This acyl anion intermediate easily provides access to α-hydroxy ketones [3,4,5,6] by reacting with a range of electrophiles, including carbonyl compounds (Figure 1) [7].
In order to regenerate the carbonyl group that was initially masked when dithiane was utilized as an acyl anion equivalent, it must be hydrolyzed at some point during synthesis. Deprotection has frequently been challenging to accomplish, especially for complicated and sensitive compounds, and as a result, numerous processes have been adopted. The use of traditional methods such as metal salts (mercury(II) chloride [8]) for the deprotection of 1,3-dithiane requires toxic reagents that are generally harmful to the environment. However, there are some facile and efficient methods available in the literature, i.e., 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) deprotection [9] and the use of iodine catalyst/H2O2 [10] which are more environment friendly.
In a typical 1,3-dithiane addition process, 1,3-dithiane is combined with an equimolar quantity of a strong base, such as n-butyllithium, and the resultant 2-lithio-1,3-dithiane should serve as an appropriate nucleophile. According to a different procedure described by Andersen et al. [11] the 1,3-dithiane equivalent, 2-trimethylsilyl-1,3-dithiane (TMS-dithiane), could be activated by a stoichiometric quantity of tetrabutylammonium fluoride (TBAF), resulting in the matching carbanion. Corey et al. claim that various cesium salt mixtures that include cesium fluoride may be used as heterogeneous desilylating reagents. There are just a few cases when TMS-dithiane has been activated catalytically, and most of these reactions involve the use of fluoride reagents in equimolar amounts [12].
The Corey-Seebach umpolung technique has been extensively utilized to manufacture a wide variety of natural products such as Swinholide A [13] (1, a marine natural product, derived from sponge Theonella swinhoei, which shows antitumor and antifungal activity), pironetin [14,15,16] (2, derived from Streptomyces fermentation broths, which exhibits plant growth regulating action) (Figure 2), ciguatoxin 1B [17] (3, one of the main toxins responsible for ciguatera fish poisoning (Figure 3), discovered from moray eel Gymnothorax javanicus), and maytansine [18,19] (4, shows antitumor activity) (Figure 4). Many synthetic [20] compounds, such as photolabile safety benzoin linkers [21] and bis-3,4-dihydroisoquinolium salts [22], have also been attained using the Corey-Seebach reagent. Earlier, Foubelo et al. published a review article in 2003 concerning the use of 1,3-dithianes in the synthesis of natural products [23]. Until now, the Corey-Seebach reagent has found valuable applications in organic synthesis. Our review article focuses on the utilization of Corey-Seebach reagent in the synthesis of noteworthy natural and synthetic organic compounds reported post-2006.

2. Literature Review

2.1. Alkaloid-Based Natural Products Synthesis

2.1.1. Lycoplanine A Alkaloids

Lycopodium alkaloids are known to play an effective role in the medication of Alzheimer’s disease [24,25,26]. Over 300 lycopodium alkaloids have so far been isolated, and a number of total syntheses of these alkaloids have been published [27,28,29]. In 2017, Zhao and co-workers [30] first isolated lycoplanine A, a lycopodium alkaloid with the γ-lactone ring. According to biological investigations, lycoplanine alkaloid is a strong inhibitor of the calcium channel (Cav3.1 T-type) with an IC50 value of 6.06 μM. In 2021, Gao et al. [31] reported the synthesis of lycoplanine A isomer by utilizing the Corey-Seebach reagent. To achieve this task, the C=C bond was introduced by using 1,4-dithiane 5 and crotonaldehyde (E/Z > 98%) to afford alcohol 6 in an 88% yield, followed by oxidation to provide the product 7 with an 80% yield. Compound 7 was then treated with Nysted reagent for the introduction of the second C=C, followed by the introduction of fragment A to afford compound 8 by using the Mitsunobu reaction. After a few steps, compound 9 was formed, which upon reaction with Crabtree’s catalyst provided a tetrasubstituted C=C bond product 10 with excellent stereo and regioselectivities. After deprotection of the Boc group, compound 10 was immediately exposed to AcOH, initiating a cascade reaction that produced the stereo-specific cyclized product 11 with a 35% yield. The deprotection of the thioketal group was achieved by using PIFA to afford lycoplanine A 12 isomer with an 83% yield (Scheme 1).

2.1.2. Diterpenoid Alkaloids

Diterpenoid alkaloids have been the focus of study by scientists all over the globe because of their fascinating bioactivities and complicated structures [32]. These biologically active compounds were extracted from Delphinium and Aconitum species that belong to the Ranunculaceae family [33]. In 2017, Min Zhu et al. [34] reported the synthesis of hetidine-type C20-diterpenoid alkaloids by utilizing the Corey-Seebach reagent as a key step. For this purpose, 2-lithio-1,3-dithiane species 14 were reacted with iodide 13, followed by the deprotection of methoxymethyl to afford olefinic phenol 15 with an 80% yield. In the next step, compound 15 was treated with PhI(OAc)2, followed by the addition of Sml2 to obtain compound 16, which could then be transformed into the desired hetidine-type diterpenoid alkaloid 17 after a series of reactions (Scheme 2).

2.2. Terpenoids-Based Natural Products Synthesis

2.2.1. Bisnorditerpene

Diterpenoids are important natural products that display a wide range of chemical diversity and are useful both in medicine and industry. A large number of known diterpenoid compounds are isolated from plants and fungi, and investigations into these species have provided an understanding of their production [35]. In 2010, Pessoa et al. [36] first isolated a bisnorditerpene from Croton regelianus var. matosii. This herb is utilized in traditional medicine in the Northeastern state of “Caatinga”. In 2016, Xu et al. [37] designed a new strategy for the synthesis of bisnorditerpene by utilizing the Corey-Seebach reagent. To achieve this, an aldehyde 18 was allowed to react with 1,3-propane-dithiol 19 to furnish dithiane 20, which upon lithiation with epoxide [38] 21 by using the Corey-Seebach reaction afforded precursor 22 followed by the addition of Lewis acid to obtain tricyclic alcohol 23 with a 55% yield. In the next step, secondary alcohol 24 was obtained by desulfurization of 23 with Raney-Ni, followed by the oxidation of 24 with Dess-Martin periodinane (DMP) to afford ketone 25 with a 95% yield. The final process involved the demethylation of ketone 25 with BBr3 along with the addition of Phl(OAc)2 in CH3CN to generate bisnorditerpene 26 (Scheme 3).

2.2.2. Totarol Synthesis

Totarol belongs to diterpenes that are found in the sap of podocarpus totara, a New Zealand native conifer [39]. The antimicrobial properties [40,41,42,43] of the secondary metabolites in this sap are well known. The wood of this tree displays resistance against rot. Toothpaste and acne medications are just a couple of consumer goods that can contain totarol as an antibacterial ingredient. In 2010, Kim et al. [44] synthesized totarol by utilizing the Corey-Seebach approach as an important key step. The goal of their research was to synthesize totarol diterpenes as a part of a larger research project to determine the mechanism by which tiny molecules could inactivate FtsZ. In order to achieve this, benzonitrile 27 was treated with i-PrMgCl to produce compound 28, followed by the reduction and thioacetal formation to obtain product 29. In the next step, alkene 30 was synthesized through lithiation of 29 with fragment B followed by alkylation, respectively. Treatment of compound 30 with AD-mix-β afforded regio-isomeric diol 31 with 90–95% enantiomeric excess, and after a few steps, totarolone 32 was formed with a 33% yield. Totarolone 32 was transformed into the desired totarol 33 through the Wolff-Kishner reduction (Scheme 4).

2.3. Polyketide Based Natural Products

2.3.1. Ambruticin J Synthesis

A significant class of polyketide-based natural compounds known as ambruticin was initially isolated from the bacterium Sorangium cellulosum in 1977. They display high biological advantages such as strong antifungal action [45,46,47,48,49,50]. The mechanistic studies of these compounds suggested that ambruticins target Hik1 kinase [51,52] by interacting with fungal osmoregulation. The influence of ambruticin VS3 on soil myxobacteria has recently been studied, and results showed that they are beneficial for the environment by preventing the emergence of antagonistic myxobacterial species. In 2021, Trentadue et al. [53] reported the total synthesis of ambruticin J by utilizing the Corey-Seebach reagent as a key step. For this purpose, dithiane 34 (synthesized from propargyl alcohol) was reacted with epoxide 35 by using the Corey-Seebach reaction to afford compound 36 with a 70% yield, and after a few steps, vinyl iodide 37 was formed. In the following stage, vinyl iodide 37 reacted with pinacol boronic ester 38 through Suzuki coupling, followed by oxidation using Dess–Martin periodinane (DMP) to afford aldehyde 39. The aldehyde 39 was further treated with fragment C via Julia-Kocienski olefination to afford E-olefin 40, and after a few steps, the desired ambruticin J 41 was formed (Scheme 5).

2.3.2. Biakamides

Biakamides are naturally occurring polyketides with significant biological activity [54,55]. In 2017, Kotoku et al. [56] first isolated biakamides from a marine sponge Petrosaspongia sp. The purpose of this research project was to isolate marine-based anti-cancer drugs. To achieve this, marine-based biakamides were isolated, and the total synthesis of these drugs has also been described by using the Corey-Seebach reaction in one of their key steps. The synthesis was initiated by using substituted penta-diol 42, which was converted into corresponding Weinreb amide 43, followed by reduction with DIBAL to obtain compound 44. Aldehyde 44 was treated with 1,3-propane dithiol in the presence of iodine to afford 1,3-dithiane 45. Compound 45 was then allowed to react with alkyl iodide 46 in the presence of n-BuLi by using the Corey-Seebach reaction followed by TBAF addition and subsequent tetrapropylammonium perruthenate (TPAP) oxidation to furnish aldehyde 47. After a few steps, N-methyle-neamide 48 was synthesized from secondary amine 49, followed by the deprotection of 1,3-dithiane to provide compound 50. The chloromethylene moiety was introduced in the presence of (chloromethyl)triphenyl-phosphonium chloride with E/Z 3:2 by using the Wittig reaction, which resulted in compound 51. In the last step, TFA was used for the deprotection of the amine, followed by a condensation reaction with E-3-methoxy-2-butenoic acid 52 to afford (4R, 6S)-biakamides 53 and 54 (Scheme 6). The antiproliferative activity of biakamides 53 and 54 was also examined against PANC-1 cell culture (glucose deficient conditions), which provided an IC50 value of 0.5 μM.

2.4. Photoinitiators

2.4.1. Bisacyldigermanes

The synthesis of improved photoinitiator molecules for free radical polymerization has been a challenging task. So far, a large number of photoinitiators, such as acyl-phosphine oxides, have been successfully synthesized [57]. Among all types, germanium-based photoinitiators are of great importance due to their non-toxic behavior and excellent bleaching properties [58]. In 2022, Wiesner et al. [59] synthesized bisacyldigermanes 59 by utilizing the Corey-Seebach reaction. The purpose of this synthesis was to introduce double germanium content in order to achieve a higher polymerization rate. For this purpose, 1,2-dichloro-1,1,2,2-tetraethyldi-germane 56 was synthesized over four steps from diethyl dichloro germane 55, followed by lithiation with thioketals 57a–e to afford germane derivatives 58a–e. In the last step, compounds 58a–e were deprotected and oxidized using boron trifluoride etherate and (diacetoxyiodo)benzene (PIDA) to obtain bisacyldigermanes 59a–e in good yields (Scheme 7).

2.4.2. Benzoylgermanium Derivatives

Germanium-based photoinitiators have attained great importance due to their high radical polymerization capacity [60,61]. In 2009, Moszner et al. [62] synthesized benzoyl germanium derivatives using the Corey-Seebach reaction. These benzoyl germanium derivatives are used in dental cements and composites. In the first step, aromatic 1,3-dithianes 59 were reacted with n-BuLi by using the Corey-Seebach reaction, followed by the reaction with dichlorogermanium compound 60 to afford compound 61a–f. In the last step, compound 61 was dithioketolized in the presence of BF3·OEt2 and Phl(OAc)2 or in the presence of excess iodine and CaCO3 in THF to provide PIs 62a–f (Scheme 8).

2.4.3. Photoinduced Sensitization

The dithiane-based adducts have been found to be suitable candidates for photoinduced fragmentation [63]. The cleavage of dithiane has been studied by physical approaches such as kinetic isotopic effect [64], Hammett substituent effect, and laser flash photolysis studies [65]. In 2006, Gustafson et al. [66] synthesized benzophenone adducts by utilizing the Corey-Seebach reaction. They also studied computational mechanisms for photoinduced cleavage of dithiane-based benzophenone. For this purpose, the dithianes 63a–e were reacted with benzophenone 64 through the Corey-Seebach reaction to furnish dithiane-based benzophenone adducts 65a–e, followed by photoinduced fragmentation in a temperature range of −40 °C–40 °C (Scheme 9).

2.4.4. Photoinduced Bis-Addition

The Corey-Seebach methodology, which is built on lithiodithiane reactions with various electrophiles, particularly carbonyl compounds, has taken a leading position among many of the traditional modern synthetic chemistry strategies [67]. One of its variants, the methyl dithiane addition with benzoyl chloride or alkyl benzoates, provides access to tertiary alcohols with two dithiane moieties [68]. Valiulin et al. [69] reported a synthesis of dithiane adducts by using the Corey-Seebach reaction. The methodology involved the reaction of alkyl dithiane methyl benzoate or benzoyl chloride to afford the target molecule. It was observed that the dithiane adduct 67 was only formed when methyl-containing benzoyl dithiane 66 was used. The acetophenone tethered thio-ortho ester 68 was formed when the R group with the higher substitution was used (Scheme 10).

2.5. Bisbibenzyl Analogue

Riccardin C Synthesis

Bisbibenzyls are important natural products that are found in the bryophytes, such as liverworts [70,71,72]. Among these, riccardin C has gained great importance due to its effectiveness against cardiovascular diseases. Riccardin C also shows antifungal [73], anti-bacterial, and cytotoxic activity [74]. In 2016, Almalki et al. [75] purposed the total synthesis of riccardin C by using the Corey-Seebach macrocyclization strategy. For this purpose, compound 70 was synthesized from catechol 69 over a few steps, followed by the reaction of compounds 70 and 71 via Suzuki-Miyaura coupling to obtain compound 72. Further, compounds 73 and 74 were reacted to form biaryl ethers 75, followed by coupling with aldehydes 75 and alcohol 72 to afford compound 76. Compound 76 was transformed into 77 by the Heck reaction followed by the reduction of alkene using diimide. Next, SOCl2 or MsCl was used to convert the alcohol into chloride 78. In the last step, dithiane was deprotonated by using n-BuLi at 78 °C and the Corey-Seebach reaction to afford macrocycle 79, followed by the deprotection of benzyl ether and dithiane to achieve riccardin C 80 (Scheme 11).

2.6. Biocompatible Polyesters

Benzoin-Derived Diol Linker

The synthesis of photodegradable biocompatible polymers has created a serious problem due to their slow degradation and unwanted by-products. Such restrictions may be overcome by using dithiane-protected benzoin derivatives [76,77]. In 2018, Englert et al. [78] synthesized diol benzoin derivatives that act as active monomers for the polymerization process. The main focus of this study was to synthesize micro and nanoparticles that may release compounds on demand within predetermined time frames when “opened” by UV radiation. For this purpose, a diol precursor 82 was synthesized from 3-hydroxybenzaldehyde 81 in three steps by using the Corey-Seebach reaction. In the next step, product 82 was activated to obtain compound 83 or by the reaction of butyryl chloride with compound 82 to afford product 84 prior to activation. In the last step, the polymerization of compound 83 was done with adipoyl dichloride to attain polyester 85 through polycondensation (Scheme 12).

2.7. Tetraphenylcyclopentadienones

Tetraphenylcyclopentadienones are very important diene substrates that have been widely used in different product syntheses such as photochromic benzoyranes quinonoid intermediates and graphene intermediates [79,80]. In 2017, L. Prati et al. [81] synthesized new 1,3-diarylphencyclones by utilizing the well-known Corey-Seebach reaction. The purpose of this research was to present a stereodynamic and conformational study of 1,3-diaryl-phenylclones to obtain stable atropisomers. For this purpose, 1,3-dithiane 86 was allowed to react with benzyl derivatives by using a double Corey-Seebach reaction followed by the deprotection with NaHCO3/I2 to obtain 1,3-diarylketones 87. In the next step, compound 88 was reacted with 1,3-diarylketones 87 to afford 1,3-diaryl-phencyclones 89a–e (Scheme 13). Among all the synthesized compounds, 89d and 89e were found to exhibit exceptionally stable atropisomers (racemization energy > 35 kcal/mol).

2.8. Scleropentaside A

Scleropentasides are a prime class of natural products that have been extracted from the twigs, leaves, and stems of dendrotrophe frutescens and scleropyrum pentadrum [82], respectively. Both plants exhibit a variety of uses in traditional Asian medicine, including skin treatments, rheumatic pain relief, etc. This innovative class of natural compounds has an unrivaled anomeric-β-glycosidic motif and a furan ring [83]. One of the most iconic members of this class is scleropentaside A, which displays a radical scavenging activity. Boehlich et al. [84] reported an exclusive and general method for the preparation of acyl-glycosides by utilizing the Corey-Seebach reaction. This methodology has been exclusively used for the short synthesis of scleropentaside A. For this purpose, a silane-protected carbohydrate 90 was reacted with furfural dithiane 91 to obtain product 92, which upon deprotection, afforded sceropentaside A 93 with a good yield (Scheme 14).

2.9. Steroids

2.9.1. Withanolide A

One of the most potent components in the methanolic extracts of ashwagandha is withanolide A, which was isolated from the roots of Withania somnifera [85]. It has been shown to have strong pharmacological properties with regard to neurite regeneration, axonal outgrowth, and repair of damaged synapses in mice [86,87,88,89]. The synthesis of withanolide A has been presented with various synthetic problems. In 2013, Liffert et al. [90] reported a new method for the synthesis of withanolide A by using the Corey-Seebach reaction in one of their key steps. For this purpose, the pregnenolone 94 was protected with TBS, followed by lithiation with dithiane to obtain 95 by using the Corey-Seebach reaction. In the next step, the deprotection of dithiane was achieved by using (N-Chlorosuccinimide) NCS in the presence of dichloromethane (DCM) followed by MOM protection of the OH group to afford aldehyde 96. Aldehyde 96 was treated with vinylogous enolate and LiHMDS in the presence of DMPU and THF, which resulted in the synthesis of unsaturated lactone 97 with an 87% yield and excellent stereoselectivity (dr 93:7). After a few steps, unsaturated enone 98 was formed, which upon treatment with H2O2 (Triton B), hydrazine, and PDC afforded withanolide A 99 in a 30% yield (Scheme 15).

2.9.2. Cholanic Acid Derivatives

Cholanic acid is one of the important intermediates for many reactions. It was extracted from a sea pen by Djerassi et al. [91,92]. In 2007, Shingate et al. [93] reported the stereoselective method for the synthesis of 20-epi cholanic acid derivatives from dehydropregnenolone acetate by using the Corey-Seebach reaction in one of their key steps. The synthesis of cholanic acid was initiated from the chemo-selective catalytic hydrogenation of 16-dehydropregnenolone acetate 100, followed by hydrolysis to obtain compound 101. After a few steps, compound 102 was formed, which was further reacted with 1,3-dithiane using the Corey-Seebach reaction to afford compound 103 and side product 104 with a 77% and 4% yield, respectively. In the next step, compound 103 was treated with SOCl2 and pyridine in the presence of DCM to obtain ketene 105 with an 84% yield, which provided iso-methyl ether 106 after a few steps. In the last step, the deprotection of compound 106 was carried out to afford 20-epi cholanic acid derivative 107 (Scheme 16).

2.10. Rodocaine

Rodocaine is an important chemical that is used in ophthalmic anesthesia [94,95,96]. There are a number of methods that have been developed for the synthesis of this molecule. In 2017, Meyer et al. [97] developed a new method for the enantioselective synthesis of rodocaine through enantioselective hydroazidation by utilizing the Corey-Seebach reaction in one of their key steps. For this purpose, compound 108 was converted into cyclopentene 109 through Malaprade glycol, thioacetalization, and the Corey-Seebach reaction, respectively. Compound 109 was then subjected to enantioselective hydroazidation in the presence of (–)-IpcBH2 to afford trans azide 110 with a 61% yield (er 75:25), followed by desulfurization and Boc protection to furnish compound 111. In the last step, compound 111 was alkylated with iodide 112 to afford the impure rodocaine with a 68% yield (er 74:26), which was precipitated with H2O/MeOH to obtain pure enantiomeric rodocaine 113 with a 15% yield (Scheme 17).

2.11. D-Glucosamine Trimethylene Derivatives

The extension of the carbohydrate chain by using the Corey-Seebach method (dithiane chemistry) is well known [98]. A number of D-glucosamine-based trimethylene derivatives have been synthesized, but these approaches have some limitations regarding the tolerance of leaving groups. In 2006, Chen et al. [99] utilized trimethylene acyl-d-glucosamine to synthesize α-imidate dithiane. To achieve this, compound 114 was treated with n-BuLi to produce stabilized imidate-carba dianion 115, followed by the addition of D2O to afford compound 116. The iodination of compound 114 was also performed to check the reactivity, and two different products, 117 and 118, were obtained in different conditions. The carbon atom extended carbohydrate 119 was formed by the reaction of compound 114 with n-BuLi, followed by the reaction with DMF, ethyl chloroformate, and methyl chloroformate. Compound 114 was also treated with cyclohexanone or cyclopentanone to yield compounds 120 and 121. In addition to this, compound 114 was also reacted with substituted d-ribofuranose-3-ulose 122 to afford compound 123 with an average yield (up-to 28%) (Scheme 18).

2.12. (−)-Calystegine B3

As effective and selective glycosidase inhibitors, carbasugars and azasugars are among the most appealing compounds in the world of N-carbohydrates [100]. The majority of the compounds contain five- or six-membered fused-ring structures. Most of them are employed as chemotherapeutic agents to treat viral infections and diabetes. The calystegine compounds belong to the Solanaceae family [101,102], and their analogs have been created since they are thought to be pioneer compounds for novel bioactive drugs. Chen et al. [103] synthesized (−)-calystegine B3 from D-glucosamine-based trimethylene dithioacetal by virtue of the Corey-Seebach reaction. Their methodology involved the synthesis of compounds 124 and 125 from D-glucosamine followed by epoxidation to acquire diastereoisomers 126a, b and 127, respectively. The anionic cyclization of compounds 126a, b was performed using the Corey-Seebach reaction to afford carba-analogs 128a, b (ca. 1.5:11, 83%). Similarly, compound 127 cyclized through the Corey-Seebach methodology to obtain carba-analogs 129 and 130 (ca. 2.4:1, 78%). In addition, compound 130 was transformed into ketone 131 in a few steps, followed by Pd-C [104] addition in the presence of THF and O-Bn deprotection to yield the title compound (−)-calystegine B3 132 (Scheme 19).

2.13. Substituted Pyridines

The nitrogen-containing aromatic heterocycles are essential components in pharmaceutical and natural products [105]. Substituted pyridines are extremely evident among them. For three decades, the synthesis of pyridine has gained a lot of attention of from the scientific community [106]. Despite the fact that there are numerous chemical ways to generate such heteroaromatics, there is still a great deal of interest in finding new approaches that would provide quick and precise exposure [107]. Chen et al. [108] developed an efficient method for the synthesis of substituted pyridines by utilizing the Corey-Seebach reaction. The methodology involved the reaction of dithiane 133 with α,β-unsaturated ketones or aldehydes 134 to obtain a series of trisubstituted alkenes 135 in good to excellent yields (62% minimum and 96% maximum). These trisubstituted alkenes 135 underwent Ti-mediated coupling with substituted aldehydes 136 to furnish substituted pyridines 137 with average to good yields (33–82%) (Scheme 20). The role of alkene geometry in this reaction was also explored, and it was observed that the geometry of alkenes did not play any crucial role in the synthesis of pyridines.

3. Conclusions

This review article provides a thorough analysis of the synthesis of natural and synthetic compounds which involve the Corey-Seebach reaction as a major step in their synthetic methodologies. The Corey-Seebach reagent is of particular importance in organic synthesis owing to its ability to generate valuable chemical derivatives from basic, easily accessible starting materials. We, therefore, come to the conclusion that Corey-Seebach reagent serves as a synthetic equivalent as well as a protective group for the carbonyl functionality and has extensively been employed in the synthesis of natural products such as lycoplanine A, bisnorditerpene, totarol, ambruticin J, biakamides, as well as synthetic molecules (Bisacyldigermanes, photoinitiators, benzoin-derived diol linkers, substituted pyridines). With the fact that the Corey-Seebach reaction has been the subject of extensive investigation, we anticipate that this analysis will spur synthetic scientists to develop fresh approaches and innovative theories in this area.

Author Contributions

Conceptualization, A.F.Z.; resources, A.F.Z. and A.I.; data curation, A.I. and S.A.; writing—original draft preparation, M.H.; writing—review and editing, A.F.Z., A.M. (Aqsa Mushtaq), M.I., A.M. (Asim Mansha), S.A., A.I., R.A., K.K.-M. and M.M.; supervision, A.F.Z. and M.M.; project administration, A.F.Z. and M.M.; funding acquisition, A.I., K.K.-M., and M.M. All authors have read and agreed to the published version of the manuscript.

Funding

The research was partly financed by research projects: Siedlce University of Natural Sciences and Humanities (UPH/WNSP/ICH/zadaniebadawcze/143/23/B), Medical University of Lublin (DS 730).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

All data is contained in the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Not Applicable.

References

  1. Corey, E.J. The logic of chemical synthesis: Multistep synthesis of complex carbogenic molecules (nobel lecture). Angew. Chem. Int. Ed. 1991, 30, 455–465. [Google Scholar] [CrossRef]
  2. Corey, E.J.; Seebach, D. Carbanions of 1,f Dithianes. Reagents for C -C Bond Formation by Nucleophilic Displacement and Carbonyl Addition. Angew. Chem. Int. Ed. 1965, 4, 1075–1077. [Google Scholar] [CrossRef]
  3. Seebach, D.; Corey, E.J. Generation and synthetic applications of 2-lithio-1,3-dithianes. JOC 1975, 40, 231–237. [Google Scholar] [CrossRef]
  4. Seebach, D.; Kolb, M. Zur Umpolung der Carbonylreaktivität; Deprotonierung von Ketenthioacetalen zu 1, 1-dithiosubstituierten Allyl-und Pentadienyllithiumverbindungen sowie deren Reaktionen mit Elektrophilen. Justus Liebigs Ann. Der Chem. 1977, 1977, 811–829. [Google Scholar] [CrossRef]
  5. Grobel, B.T.; Seebach, D. Umpolung of the reactivity of carbonyl compounds through sulfur-containing reagents. Synthesis 1977, 1977, 357–402. [Google Scholar] [CrossRef]
  6. Seebach, D. Methods of reactivity umpolung. Angew. Chem. Int. Ed. 1979, 18, 239–258. [Google Scholar] [CrossRef]
  7. Donabauer, K.; Murugesan, K.; Rozman, U.; Crespi, S.; König, B. Photocatalytic Reductive Radical-Polar Crossover for a Base-Free Corey–Seebach Reaction. Chem. Eur. J. 2022, 26, 12945–12950. [Google Scholar] [CrossRef]
  8. Corey, E.J.; Ericson, B.W.J. Oxidative hydrolysis of 1,3-dithiane derivatives to carbonyl compounds using N-halosuccinimide reagents. Org. Chem. 1971, 36, 3553–3560. [Google Scholar] [CrossRef]
  9. Tanemura, K.; Dohya, H.; Imamura, M.; Suzuki, T.; Horaguchi, T. Deprotection of 1,3-dithianes by 2, 3-dichloro-5, 6-dicyano-p-benzoquinone (DDQ). Chem. Lett. 1994, 23, 965–968. [Google Scholar] [CrossRef]
  10. Ganguly, N.C.; Barik, S.K. A facile mild deprotection protocol for 1,3-dithianes and 1,3-dithiolanes with 30% hydrogen peroxide and iodine catalyst in aqueous micellar system. Synthesis 2009, 2009, 1393–1399. [Google Scholar] [CrossRef]
  11. Andersen, N.H.; McCrae, D.A.; Grotjahn, D.B.; Gabhe, S.Y.; Theodore, L.J.; Ippolito, R.M.; Sarkar, T.K. The use of metalloids (-SiMe3,-SnR3) as protected carbanions: Selective activation and new cyclization processes. Tetrahedron 1981, 37, 4069–4079. [Google Scholar] [CrossRef]
  12. Porter, Q.N.; Utley, J.H. Electrochemical removal of 1,3-dithian protecting groups. J. Chem. Soc. Chem. Commun. 1978, 6, 255–256. [Google Scholar] [CrossRef]
  13. Carmely, S.; Kashman, Y. Structure of swinholide-A, a new macrolide from the marine sponge Theonella swinhoei. Tetrahedron Lett. 1985, 26, 511–514. [Google Scholar] [CrossRef]
  14. Kobayashi, S.; Tsuchiya, K.; Harada, T.; Nishide, M.; Kurokawa, T.; Nakagawa, T.; Kobayashi, K. Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958 I. Taxonomy, production, isolation and preliminary characterization. J. Antibiot. 1994, 47, 697–702. [Google Scholar] [CrossRef] [PubMed]
  15. Sahar, A.; Khan, Z.A.; Ahmad, M.; Zahoor, A.F.; Mansha, A.; Iqbal, A. Synthesis and antioxidant potential of some biscoumarin derivatives. Trop. J. Pharm. Res. 2017, 16, 203–210. [Google Scholar] [CrossRef]
  16. Kobayashi, S.; Tsuchiya, K.; Kurokawa, T.; Nakagawa, T.; Shimada, N.; Iitaka, Y. Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958 II. Structural elucidation. J. Antibiot 1994, 47, 703–707. [Google Scholar] [CrossRef]
  17. Scheuer, P.J.; Takahashi, W.; Tsutsumi, J.; Yoshida, T. Ciguatoxin: Isolation and chemical nature. Science 1967, 155, 1267–1268. [Google Scholar] [CrossRef]
  18. Corey, E.J.; Weigel, L.O.; Floyd, D.; Bock, M.G. Total synthesis of (+-)-N-methylmaysenine. J. Am. Chem. Soc. 1978, 100, 2916–2918. [Google Scholar] [CrossRef]
  19. Corey, E.J.; Weigel, L.O.; Chamberlin, A.R.; Lipshutz, B. Total synthesis of (−)-N-methylmaysenine. J. Am. Chem. Soc. 1980, 102, 1439–1441. [Google Scholar] [CrossRef]
  20. Michida, M.; Mukaiyama, T. Lewis Base Catalyzed 1,3-Dithiane Addition to Carbonyl and Imino Compounds Using 2-Trimethylsilyl-1,3-dithiane. Chem. Asian J. 2008, 3, 1592–1600. [Google Scholar] [CrossRef]
  21. Lee, H.B.; Balasubramanian, S. Studies on a dithiane-protected benzoin photolabile safety catch linker for solid-phase synthesis. J. Org. Chem. 1999, 64, 3454–3460. [Google Scholar] [CrossRef] [PubMed]
  22. Dewar, G.H.; Marshall, I.G.; Patel, S.S.; Waigh, R.D. Chemodegradable neuromuscular blocking agents-I: Bis 3, 4-dihydroisoquinolinium salts. Pharm. Sci. Commun. 1993, 4, 3–14. [Google Scholar]
  23. Yus, M.; Nájera, C.; Foubelo, F. The role of 1,3-dithianes in natural product synthesis. Tetrahedron 2003, 59, 6147–6212. [Google Scholar] [CrossRef]
  24. Liu, J.S.; Zhu, Y.L.; Yu, C.M.; Zhou, Y.Z.; Han, Y.Y.; Wu, F.W.; Qi, B.F. The str uctures of huperzine A and B, two new alkaloids exhibiting marked anticholinesterase activity. Can. J. Chem. 1986, 64, 837–839. [Google Scholar] [CrossRef]
  25. Hirasawa, Y.; Morita, H.; Shiro, M.; Kobayashi, J.I. Sieboldine A, a Novel Tetracyclic Alkaloid from Lycopodium s ieboldii, Inhibiting Acetylcholinesterase. Org. Lett. 2003, 5, 3991–3993. [Google Scholar] [CrossRef] [PubMed]
  26. He, J.; Chen, X.Q.; Li, M.M.; Zhao, Y.; Xu, G.; Cheng, X.; Zhao, Q.S. Lycojapodine A, a novel alkaloid from Lycopodium japonicum. Org. Lett. 2009, 11, 1397–1400. [Google Scholar] [CrossRef]
  27. Aver, W.A.; Trifonov, L.S. Lycopodium alkaloids. Alkaloids Chem. Pharmacol. 1994, 45, 233–266. [Google Scholar] [CrossRef]
  28. Heathcock, C.H.; Smith, K.M.; Blumenkopf, T.A. Total synthesis of (+-)-fawcettimine (Burnell’s base A). J. Am. Chem. Soc. 1986, 108, 5022–5024. [Google Scholar] [CrossRef]
  29. Linghu, X.; Kennedy-Smith, J.J.; Toste, F.D. Total synthesis of (+)-fawcettimine. Angew. Chem. 2007, 119, 7815–7817. [Google Scholar] [CrossRef]
  30. Zhang, Z.J.; Nian, Y.; Zhu, Q.F.; Li, X.N.; Su, J.; Wu, X.D.; Zhao, Q.S. Lycoplanine A, a C16N Lycopodium alkaloid with a 6/9/5 tricyclic skeleton from Lycopodium complanatum. Org. Lett. 2017, 19, 4668–4671. [Google Scholar] [CrossRef]
  31. Gao, W.; Wang, X.; Yao, L.; Tang, B.; Mu, G.; Shi, T.; Wang, Z. Synthesis of an isomer of lycoplanine A via cascade cyclization to construct the spiro-N, O-acetal moiety. Org. Biomol. Chem. 2021, 19, 1748–1751. [Google Scholar] [CrossRef] [PubMed]
  32. Wang, F.P.; Chen, Q.H.; Liu, X.Y. Diterpenoid alkaloids. Nat. Prod. Rep. 2010, 27, 529–570. [Google Scholar] [CrossRef] [PubMed]
  33. Wang, F.P.; Chen, Q.H.; Liang, X.T. The C18-diterpenoid alkaloids. Alkaloids Chem. Biol. 2009, 67, 1–78. [Google Scholar] [CrossRef] [PubMed]
  34. Zhu, M.; Li, X.; Song, X.; Wang, Z.; Liu, X.; Song, H.; Qin, Y. Studies towards Bioinspired Synthesis of Hetidine-Type C20-Diterpenoid Alkaloids. Chin. J. Chem. 2017, 35, 991–1000. [Google Scholar] [CrossRef]
  35. Hanson, J.R.; Nichols, T.; Mukhrish, Y.; Bagley, M.C. Diterpenoids of Terrestrial Origin. Nat. Prod. Rep. 2019, 36, 1499–1512. [Google Scholar] [CrossRef]
  36. Torres, M.C.M.; Braz-Filho, R.; Silveira, E.R.; Diniz, J.C.; Viana, F.A.; Pessoa, O.D.L. Terpenoids from Croton regelianus. Helv. Chim. Acta 2010, 93, 375–381. [Google Scholar] [CrossRef]
  37. Xu, S.; Zhang, M.; Zhang, W.; Xie, X.; She, X. Concise Total Synthesis of the Bisnorditerpene (+)-(5β, 8α, 10α)-8-hydroxy-13-methylpodocarpa-9 (11), 13-diene-3, 12-dione. Asian J. Org. Chem. 2016, 5, 986–990. [Google Scholar] [CrossRef]
  38. Ahmad, S.; Zahoor, A.F.; Naqvi, S.A.R.; Akash, M. Recent trends in ring opening of epoxides with sulfur nucleophiles. Mol. Divers. 2018, 22, 191–205. [Google Scholar] [CrossRef]
  39. Bendall, J.G.; Cambie, R.C. Totarol: A non-conventional diterpenoid. Aust. J. Chem. 1995, 48, 883–917. [Google Scholar] [CrossRef]
  40. Muroi, H.; Kubo, I. Bactericidal effects of anacardic acid and totarol on methicillin-resistant Staphylococcus aureus (MRSA). Biosci. Biotechnol. Biochem. 1994, 58, 1925–1926. [Google Scholar] [CrossRef]
  41. Muroi, H.; Kubo, I. Antibacterial activity of anacardic acid and totarol, alone and in combination with methicillin, against methicillinresistant Staphylococcus aureus. J. Appl. Bacteriol. 1996, 80, 387–394. [Google Scholar] [CrossRef] [PubMed]
  42. Oike, S.; Muroi, H.; Kubo, I. Mode of antibacterial action of totarol, a diterpene from Podocarpus nagi. Planta Med. 1996, 62, 122–125. [Google Scholar] [CrossRef]
  43. Constantine, G.H.; Karchesy, J.J.; Franzblau, S.G.; LaFleur, L.E. (+)− Totarol from Chamaecyparis nootkatensis and activity against Mycobacterium tuberculosis. Fitoterapia 2001, 72, 572–574. [Google Scholar] [CrossRef] [PubMed]
  44. Kim, M.B.; Shaw, J.T. Synthesis of antimicrobial natural products targeting FtsZ:(+)-totarol and related totarane diterpenes. Org. Lett. 2010, 12, 3324–3327. [Google Scholar] [CrossRef] [PubMed]
  45. Hahn, F.; Guth, F.M. The ambruticins and jerangolids–chemistry, biology and chemoenzymatic synthesis of potent antifungal drug candidates. Nat. Prod. Rep. 2020, 37, 1300–1315. [Google Scholar] [CrossRef]
  46. Shubitz, L.F.; Galgiani, J.N.; Tian, Z.Q.; Zhong, Z.; Timmermans, P.; Katz, L. Efficacy of ambruticin analogs in a murine model of coccidioidomycosis. Antimicrob. Agents Chemother. 2006, 50, 3467–3469. [Google Scholar] [CrossRef]
  47. Connor, D.T.; Greenough, R.C.; Von Strandtmann, M. W-7783, a unique antifungal antibiotic. J. Org. Chem. 1977, 42, 3664–3669. [Google Scholar] [CrossRef]
  48. Just, G.; Potvin, P. Synthesis of ring A of ambruticin and proof of its absolute stereochemistry. Can. J. Chem. 1980, 58, 2173–2177. [Google Scholar] [CrossRef]
  49. Zahoor, A.F.; Yousaf, M.; Siddique, R.; Ahmad, S.; Naqvi, S.A.R.; Rizvi, S.M.A. Synthetic strategies toward the synthesis of enoxacin-, levofloxacin-, and gatifloxacin-based compounds: A review. Synth. Commun. 2017, 47, 1021–1039. [Google Scholar] [CrossRef]
  50. Michelet, V.; Genet, J.P. An overview of synthetic and biological studies of ambruticin and analogues. Curr. Org. Chem. 2005, 9, 405–418. [Google Scholar] [CrossRef]
  51. Dongo, A.; Bataille-Simoneau, N.; Campion, C.; Guillemette, T.; Hamon, B.; Iacomi-Vasilescu, B.; Simoneau, P. The group III two-component histidine kinase of filamentous fungi is involved in the fungicidal activity of the bacterial polyketide ambruticin. AEM 2009, 75, 127–134. [Google Scholar] [CrossRef] [PubMed]
  52. Vetcher, L.; Menzella, H.G.; Kudo, T.; Motoyama, T.; Katz, L. The antifungal polyketide ambruticin targets the HOG pathway. Antimicrob. Agents Chemother. 2007, 51, 3734–3736. [Google Scholar] [CrossRef] [PubMed]
  53. Trentadue, K.; Chang, C.F.; Nalin, A.; Taylor, R.E. Enantioselective Total Synthesis of the Putative Biosynthetic Intermediate Ambruticin J. Chem. Eur. J. 2021, 27, 11126–11131. [Google Scholar] [CrossRef]
  54. Vaupel, P.; Kallinowski, F.; Okunieff, P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: A review. Cancer Res. 1989, 49, 6449–6465. [Google Scholar] [PubMed]
  55. Rohwer, N.; Cramer, T. Hypoxia-mediated drug resistance: Novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist. Updates 2011, 14, 191–201. [Google Scholar] [CrossRef]
  56. Kotoku, N.; Ishida, R.; Matsumoto, H.; Arai, M.; Toda, K.; Setiawan, A.; Kobayashi, M. Biakamides A–D, unique polyketides from a marine sponge, act as selective growth inhibitors of tumor cells adapted to nutrient starvation. J. Org. Chem. 2017, 82, 1705–1718. [Google Scholar] [CrossRef]
  57. Benedikt, S.; Wang, J.; Markovic, M.; Moszner, N.; Dietliker, K.; Ovsianikov, A.; Liska, R. Highly efficient water-soluble visible light photoinitiators. J. Polym Sci. A Polym. Chem. 2016, 54, 473–479. [Google Scholar] [CrossRef]
  58. Wiesner, T.; Haas, M. Do germanium-based photoinitiators have the potential to replace the well-established acylphosphine oxides? Dalton Trans. 2021, 50, 12392–12398. [Google Scholar] [CrossRef]
  59. Wiesner, T.; Glotz, G.; Wunnicke, O.; Bleger, D.; Knezevic, I.; Torvisco, A.; Haas, M. The Road to Bisacyldigermanes: A New Compound Class Suitable as Visible Light Photoinitiators. Chem. Photo. Chem. 2022, 6, e202200107. [Google Scholar] [CrossRef]
  60. Stansbury, J.W. Curing dental resins and composites by photopolymerization. J. Esthet. Restor. Dent. 2000, 12, 300–308. [Google Scholar] [CrossRef]
  61. Ullrich, G.; Ganster, B.; Salz, U.; Moszner, N.; Liska, R. Photoinitiators with functional groups. IX. Hydrophilicbisacylphosphine oxides for acidic aqueous formulations. J. Polym. Sci. A Polym. Chem. 2006, 44, 1686–1700. [Google Scholar] [CrossRef]
  62. Moszner, N.; Zeuner, F.; Lamparth, I.; Fischer, U.K. Benzoylgermanium derivatives as novel visible-light photoinitiators for dental composites. Macromol. Mater. Eng. 2009, 294, 877–886. [Google Scholar] [CrossRef]
  63. Gravel, D.; Farmer, L.; Denis, R.C.; Schultz, E. Photoinduced rearrangement of carbocyclic 2-phenylthio-1,3-diols to deoxysugars. Tetrahedron Lett. 1994, 35, 8981–8984. [Google Scholar] [CrossRef]
  64. McHale, W.A.; Kutateladze, A.G. An Efficient Photo-SET-Induced Cleavage of Dithiane− Carbonyl Adducts and Its Relevance to the Development of Photoremovable Protecting Groups for Ketones and Aldehydes. J. Org. Chem. 1998, 63, 9924–9931. [Google Scholar] [CrossRef]
  65. Vath, P.; Falvey, D.E.; Barnhurst, L.A.; Kutateladze, A.G. Photoinduced CC bond cleavage in dithiane-carbonyl adducts: A laser flash photolysis study. J. Org. Chem. 2001, 66, 2887–2890. [Google Scholar] [CrossRef]
  66. Gustafson, T.P.; Kurchan, A.N.; Kutateladze, A.G. Externally sensitized mesolytic fragmentations in dithiane–ketone adducts. Tetrahedron 2006, 62, 6574–6580. [Google Scholar] [CrossRef]
  67. Kita, Y.; Sekihachi, J.; Hayashi, Y.; Da, Y.Z.; Yamamoto, M.; Akai, S. An efficient synthesis of. alpha.-silylacetates having various types of functional groups in the molecules. J. Org. Chem. 1990, 55, 1108–1112. [Google Scholar] [CrossRef]
  68. Li, Z.; Kutateladze, A.G. Anomalous C− C Bond Cleavage in Sulfur-Centered Cation Radicals Containing a Vicinal Hydroxy Group. J. Org. Chem. 2003, 68, 8236–8239. [Google Scholar] [CrossRef] [PubMed]
  69. Valiulin, R.A.; Kottani, R.; Kutateladze, A.G. When ethyl is infinitely different from methyl: Double addition of lithiated dithianes to aromatic carboxylates revisited. J. Org. Chem. 2006, 71, 5047–5049. [Google Scholar] [CrossRef]
  70. Asakawa, Y. Chemosystematics of the Hepaticae. Phytochemistry 2004, 65, 623–669. [Google Scholar] [CrossRef]
  71. Zinsmeister, H.D.; Becker, H.; Eicher, T. Bryophytes, a source of biologically active, naturally occurring material? Angewandte Chemie Int. Ed. 1991, 30, 130–147. [Google Scholar] [CrossRef]
  72. Harrowven, D.C.; Kostiuk, S.L. Macrocylic bisbibenzyl natural products and their chemical synthesis. Nat. Prod. Rep. 2012, 29, 223–242. [Google Scholar] [CrossRef] [PubMed]
  73. Xie, C.F.; Qu, J.B.; Wu, X.Z.; Liu, N.; Ji, M.; Lou, H.X. Antifungal macrocyclic bis (bibenzyls) from the Chinese liverwort Ptagiochasm intermedlum L. Nat. Prod. Res. 2010, 24, 515–520. [Google Scholar] [CrossRef]
  74. Fujii, K.; Morita, D.; Onoda, K.; Kuroda, T.; Miyachi, H. Minimum structural requirements for cell membrane leakage-mediatedanti-MRSA activity of macrocyclic bis (bibenzyl). Bioorg. Med. Chem. Lett. 2016, 26, 2324–2327. [Google Scholar] [CrossRef] [PubMed]
  75. Almalki, F.A.; Harrowven, D.C. A Corey–Seebach Macrocyclisation Strategy for the Synthesis of Riccardin C and an Unnaural Macrocyclic Bis (bibenzyl) Analogue. Eur. JOC. 2016, 2016, 5738–5746. [Google Scholar] [CrossRef]
  76. Peach, J.M.; Pratt, A.J.; Snaith, J.S. Photolabile benzoin and furoin esters of a biologically active peptide. Tetrahedron 1995, 51, 10013–10024. [Google Scholar] [CrossRef]
  77. Patchornik, A.; Amit, B.W.R.B.; Woodward, R.B. Photosensitive protecting groups. J. Am. Chem. Soc. 1970, 92, 6333–6335. [Google Scholar] [CrossRef]
  78. Englert, C.; Nischang, I.; Bader, C.; Borchers, P.; Alex, J.; Pröhl, M.; Schubert, U.S. Photocontrolled release of chemicals from nano-and microparticle containers. Angew. Chem. Int. Ed. 2018, 57, 2479–2482. [Google Scholar] [CrossRef]
  79. Wang, H.; Liang, Y.; Xie, H.; Lu, H.; Zhao, S.; Feng, S. Unexpected SiMe 3 effect on color-tunable and fluorescent probes of dendritic polyphenyl naphthalimides with aggregation-induced emission enhancement. J. Mater. Chem. C 2016, 4, 745–750. [Google Scholar] [CrossRef]
  80. Mandal, S.; Parida, K.N.; Samanta, S.; Moorthy, J.N. Influence of (2,3,4,5,6-pentamethyl/phenyl) phenyl scaffold: Stereoelectronic control of the persistence of o-quinonoid reactive intermediates of photochromic chromenes. J. Org. Chem. 2011, 76, 7406–7414. [Google Scholar] [CrossRef]
  81. Prati, L.; Mancinelli, M.; Ciogli, A.; Mazzanti, A. Tetrasubstituted cyclopentadienones as suitable enantiopure ligands with axial chirality. Org. Biomol. Chem. 2017, 15, 8720–8728. [Google Scholar] [CrossRef] [PubMed]
  82. Disadee, W.; Mahidol, C.; Sahakitpichan, P.; Sitthimonchai, S.; Ruchirawat, S.; Kanchanapoom, T. Unprecedented furan-2-carbonyl C-glycosides and phenolic diglycosides from Scleropyrum pentandrum. Phytochemistry 2012, 74, 115–122. [Google Scholar] [CrossRef] [PubMed]
  83. Faiz, S.; Zahoor, A.F.; Ajmal, M.; Kamal, S.; Ahmad, S.; Abdelgawad, A.M.; Elnaggar, M.E. Design, synthesis, antimicrobial evaluation, and laccase catalysis effect of novel benzofuran–oxadiazole and benzofuran–triazole hybrids. J. Heterocycl. Chem. 2019, 56, 2839–2852. [Google Scholar] [CrossRef]
  84. Boehlich, G.J.; Schützenmeister, N. β-Selective C-Glycosylation and its Application in the Synthesis of Scleropentaside A. Angew. Chem. Int. Ed. 2019, 58, 5110–5113. [Google Scholar] [CrossRef] [PubMed]
  85. Subramanian, S.S.; Sethi, P.D.; Glotter, E.; Kirson, I.; Lavie, D. 5, 20α (R)-dihydroxy-6α, 7α-epoxy-1-oxo-(5α) witha-2, 24-dienolide, a new steroidal lactone from Withania coagulans. Phytochemistry 1971, 10, 685–688. [Google Scholar] [CrossRef]
  86. Jain, S.; Shukla, S.D.; Sharma, K.; Bhatnagar, M. Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions of female albino rat. Phytother. Res. 2001, 15, 544–548. [Google Scholar] [CrossRef]
  87. Kuboyama, T.; Tohda, C.; Zhao, J.; Nakamura, N.; Hattori, M.; Komatsu, K. Axon-or dendrite-predominant outgrowth induced by constituents from Ashwagandha. Neuroreport 2002, 13, 1715–1720. [Google Scholar] [CrossRef]
  88. Zhao, J.; Nakamura, N.; Hattori, M.; Kuboyama, T.; Tohda, C.; Komatsu, K. Withanolide derivatives from the roots of Withaniasomnifera and their neurite outgrowth activities. Chem. Pharm. Bull. 2002, 50, 760–765. [Google Scholar] [CrossRef]
  89. Tohda, C.; Kuboyama, T.; Komatsu, K. Search for natural products related to regeneration of the neuronal network. Neurosignals 2005, 14, 34–45. [Google Scholar] [CrossRef]
  90. Liffert, R.; Hoecker, J.; Jana, C.K.; Woods, T.M.; Burch, P.; Jessen, H.J.; Gademann, K. Withanolide A: Synthesis and structural requirements for neurite outgrowth. Chem. Sci. 2013, 4, 2851–2857. [Google Scholar] [CrossRef]
  91. Vanderah, D.J.; Djerassi, C. Novel marine sterols with modified bile acid side chain from the sea pen Ptilosarcus gurneyi. Tetrahedron Lett. 1977, 18, 683–686. [Google Scholar] [CrossRef]
  92. Vanderah, D.J.; Djerassi, C. Marine natural products. Synthesis of four naturally occurring 20. beta.-H cholanic acid derivatives. J. Org. Chem. 1978, 43, 1442–1448. [Google Scholar] [CrossRef]
  93. Shingate, B.B.; Hazra, B.G.; Pore, V.S.; Gonnade, R.G.; Bhadbhade, M.M. Stereoselective syntheses of 20-epi cholanic acid derivatives from 16-dehydropregnenolone acetate. Tetrahedron 2007, 63, 5622–5635. [Google Scholar] [CrossRef]
  94. Henshall, T.; Parnell, E.W. Application of acrylonitrile to the synthesis of some reduced heterocyclic compounds. J. Chem. Soc. 1962, 123, 661–667. [Google Scholar] [CrossRef]
  95. Van Bever, W.F.; Knaeps, A.G.; Willems, J.J.; Hermans, B.K.; Janssen, P.A. Local anesthetic azabicyclo-N-alkylanilides. J. Med. Chem. 1973, 16, 394–397. [Google Scholar] [CrossRef] [PubMed]
  96. Joosten, A.; Lambert, E.; Vasse, J.L.; Szymoniak, J. Diastereoselective access to trans-2-substituted cyclopentylamines. Org. Lett. 2010, 12, 5128–5131. [Google Scholar] [CrossRef]
  97. Meyer, D.; Renaud, P. Enantioselective Hydroazidation of Trisubstituted Non-Activated Alkenes. Angew. Chem. Int. Ed. 2017, 56, 10858–10861. [Google Scholar] [CrossRef]
  98. Anaya, J.; Barton, D.H.; Gero, S.D.; Grande, M.; Hernando, J.M.; Laso, N.M. Different approaches to the asymmetric synthesis of 1,3,6-trisubstituted and 1,2,3,6-tetrasubstituted carbapenems1 from D-glucosamine. Tetrahedron Asymmetry 1995, 6, 609–624. [Google Scholar] [CrossRef]
  99. Chen, Y.L.; Leguijt, R.; Redlich, H.; Fröhlich, R. Trimethylene dithioacetals of carbohydrates, part 6: CC coupling reactions of dilithiated N-acetyl-d-glucosamine trimethylene dithioacetal derivatives. Synthesis 2006, 24, 4212–4218. [Google Scholar] [CrossRef]
  100. Kapferer, P.; Birault, V.; Poisson, J.F.; Vasella, A. Synthesis and Evaluation as Glycosidase Inhibitors of Carbasugar-Derived Spirodiaziridines, Spirodiazirines, and Spiroaziridines. Helv. Chim. Acta 2003, 86, 2210–2227. [Google Scholar] [CrossRef]
  101. Ogawa, S.; Funayama, S.; Okazaki, K.; Ishizuka, F.; Sakata, Y.; Doi, F. Synthesis of 5a-carba-hexopyranoses and hexopyranosylamines, as well as 5a, 5a′-dicarbadisaccharides, from 3, 8-dioxatricyclo [4.2. 1.02, 4] nonan-9-ol: Glycosidase inhibitory activity of N-substituted 5a-carba-β-gluco-and β-galactopyranosylamines, and derivatives thereof. Bioorg. Med. Chem. Lett. 2004, 14, 5183–5188. [Google Scholar] [CrossRef] [PubMed]
  102. Duclos, O.; Duréault, A.; Depezay, J.C. Access to polyhydroxylated cycloheptane derivatives through stereoselective nitrile oxide intramolecular cycloaddition. Synthesis of an analogue of calystegine B2. Tetrahedron Lett. 1992, 33, 1059–1062. [Google Scholar] [CrossRef]
  103. Chen, Y.L.; Redlich, H.; Bergander, K.; Fröhlich, R. d-Glucosamine trimethylene dithioacetal derivatives: Formation of six-and seven-membered ring amino carbasugars. Synthesis of (–)-calystegine B3. Org. Biomol. Chem. 2007, 5, 3330–3339. [Google Scholar] [CrossRef] [PubMed]
  104. Noreen, S.; Zahoor, A.F.; Ahmad, S.; Shahzadi, I.; Irfan, A.; Faiz, S. Novel chiral ligands for palladium-catalyzed asymmetric allylic alkylation/asymmetric Tsuji-Trost reaction: A review. Curr. Org. Chem. 2019, 23, 1168–1213. [Google Scholar] [CrossRef]
  105. Aziz, H.; Zahoor, A.F.; Ahmad, S. Pyrazole bearing molecules as bioactive scaffolds: A review. J. Chil. Chem. 2020, 65, 4746–4753. [Google Scholar] [CrossRef]
  106. Henry, G.D. De novo synthesis of substituted pyridines. Tetrahedron 2004, 29, 6043–6061. [Google Scholar] [CrossRef]
  107. Movassaghi, M.; Hill, M.D. Synthesis of substituted pyridine derivatives via the ruthenium-catalyzed cycloisomerization of 3-azadienynes. J. Am. Soc. 2006, 128, 4592–4593. [Google Scholar] [CrossRef]
  108. Chen, M.Z.; Micalizio, G.C. Three-component coupling sequence for the regiospecific synthesis of substituted pyridines. J. Am. Chem. Soc. 2012, 134, 1352–1356. [Google Scholar] [CrossRef]
Molecules 28 04367 g001 550
Figure 1. A typical Corey-Seebach reaction.
Figure 1. A typical Corey-Seebach reaction.
Molecules 28 04367 g001
Molecules 28 04367 g002 550
Figure 2. Structure of Swinholide A 1 and pironetin 2.
Figure 2. Structure of Swinholide A 1 and pironetin 2.
Molecules 28 04367 g002
Molecules 28 04367 g003 550
Figure 3. Structure of ciguatoxin 1B 3.
Figure 3. Structure of ciguatoxin 1B 3.
Molecules 28 04367 g003
Molecules 28 04367 g004 550
Figure 4. Structure of maytansine 4.
Figure 4. Structure of maytansine 4.
Molecules 28 04367 g004
Molecules 28 04367 sch001 550
Scheme 1. Synthesis of lycoplanine A 12 isomer via Corey-Seebach reagent.
Scheme 1. Synthesis of lycoplanine A 12 isomer via Corey-Seebach reagent.
Molecules 28 04367 sch001
Molecules 28 04367 sch002 550
Scheme 2. Synthesis of hetidine-based diterpenoid 17 alkaloid.
Scheme 2. Synthesis of hetidine-based diterpenoid 17 alkaloid.
Molecules 28 04367 sch002
Molecules 28 04367 sch003 550
Scheme 3. Synthesis of bisnorditerpene 26.
Scheme 3. Synthesis of bisnorditerpene 26.
Molecules 28 04367 sch003
Molecules 28 04367 sch004 550
Scheme 4. Synthesis of totarol 33 via Corey-Seebach approach.
Scheme 4. Synthesis of totarol 33 via Corey-Seebach approach.
Molecules 28 04367 sch004
Molecules 28 04367 sch005 550
Scheme 5. Synthesis of ambruticin J 41.
Scheme 5. Synthesis of ambruticin J 41.
Molecules 28 04367 sch005
Molecules 28 04367 sch006 550
Scheme 6. Total synthesis of biakamides 53 and 54.
Scheme 6. Total synthesis of biakamides 53 and 54.
Molecules 28 04367 sch006
Molecules 28 04367 sch007 550
Scheme 7. Synthesis of bisacyldigermanes 59.
Scheme 7. Synthesis of bisacyldigermanes 59.
Molecules 28 04367 sch007
Molecules 28 04367 sch008 550
Scheme 8. Synthesis of benzoyl germanium derivatives 61a–f via Corey-Seebach approach.
Scheme 8. Synthesis of benzoyl germanium derivatives 61a–f via Corey-Seebach approach.
Molecules 28 04367 sch008
Molecules 28 04367 sch009 550
Scheme 9. Synthesis of benzophenone adducts 65a−e by utilizing Corey-Seebach reaction.
Scheme 9. Synthesis of benzophenone adducts 65a−e by utilizing Corey-Seebach reaction.
Molecules 28 04367 sch009
Molecules 28 04367 sch010 550
Scheme 10. Synthesis of dithiane adducts 67 and 68.
Scheme 10. Synthesis of dithiane adducts 67 and 68.
Molecules 28 04367 sch010
Molecules 28 04367 sch011 550
Scheme 11. Synthesis of riccardin C 80 via Corey-Seebach reaction.
Scheme 11. Synthesis of riccardin C 80 via Corey-Seebach reaction.
Molecules 28 04367 sch011
Molecules 28 04367 sch012 550
Scheme 12. Synthesis of benzoin-derived diol linkers 84 and 85.
Scheme 12. Synthesis of benzoin-derived diol linkers 84 and 85.
Molecules 28 04367 sch012
Molecules 28 04367 sch013 550
Scheme 13. Synthesis of tetraphenylcyclopentadienones 89a–e.
Scheme 13. Synthesis of tetraphenylcyclopentadienones 89a–e.
Molecules 28 04367 sch013
Molecules 28 04367 sch014 550
Scheme 14. Synthesis of scleropentasides A 93 via Corey-Seebach Reaction.
Scheme 14. Synthesis of scleropentasides A 93 via Corey-Seebach Reaction.
Molecules 28 04367 sch014
Molecules 28 04367 sch015 550
Scheme 15. Synthesis of withanolide A 99.
Scheme 15. Synthesis of withanolide A 99.
Molecules 28 04367 sch015
Molecules 28 04367 sch016 550
Scheme 16. Synthesis of cholanic acid derivatives 107 by utilizing Corey-Seebach approach.
Scheme 16. Synthesis of cholanic acid derivatives 107 by utilizing Corey-Seebach approach.
Molecules 28 04367 sch016
Molecules 28 04367 sch017 550
Scheme 17. Synthesis of rodocaine 113 via Corey-Seebach reaction.
Scheme 17. Synthesis of rodocaine 113 via Corey-Seebach reaction.
Molecules 28 04367 sch017
Molecules 28 04367 sch018 550
Scheme 18. Synthesis of D-glucosamine derivatives 123 via Corey-Seebach approach.
Scheme 18. Synthesis of D-glucosamine derivatives 123 via Corey-Seebach approach.
Molecules 28 04367 sch018
Molecules 28 04367 sch019 550
Scheme 19. Synthesis of (−)-calystegine B3 132 by utilizing Corey-Seebach reaction.
Scheme 19. Synthesis of (−)-calystegine B3 132 by utilizing Corey-Seebach reaction.
Molecules 28 04367 sch019
Molecules 28 04367 sch020 550
Scheme 20. Synthesis of substituted pyridines 137.
Scheme 20. Synthesis of substituted pyridines 137.
Molecules 28 04367 sch020
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Haroon, M.; Zahoor, A.F.; Ahmad, S.; Mansha, A.; Irfan, M.; Mushtaq, A.; Akhtar, R.; Irfan, A.; Kotwica-Mojzych, K.; Mojzych, M. The Corey-Seebach Reagent in the 21st Century: A Review. Molecules 2023, 28, 4367. https://doi.org/10.3390/molecules28114367

AMA Style

Haroon M, Zahoor AF, Ahmad S, Mansha A, Irfan M, Mushtaq A, Akhtar R, Irfan A, Kotwica-Mojzych K, Mojzych M. The Corey-Seebach Reagent in the 21st Century: A Review. Molecules. 2023; 28(11):4367. https://doi.org/10.3390/molecules28114367

Chicago/Turabian Style

Haroon, Muhammad, Ameer Fawad Zahoor, Sajjad Ahmad, Asim Mansha, Muhammad Irfan, Aqsa Mushtaq, Rabia Akhtar, Ali Irfan, Katarzyna Kotwica-Mojzych, and Mariusz Mojzych. 2023. "The Corey-Seebach Reagent in the 21st Century: A Review" Molecules 28, no. 11: 4367. https://doi.org/10.3390/molecules28114367

APA Style

Haroon, M., Zahoor, A. F., Ahmad, S., Mansha, A., Irfan, M., Mushtaq, A., Akhtar, R., Irfan, A., Kotwica-Mojzych, K., & Mojzych, M. (2023). The Corey-Seebach Reagent in the 21st Century: A Review. Molecules, 28(11), 4367. https://doi.org/10.3390/molecules28114367

Article Metrics

Back to TopTop