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Special Issue "Synthesis of Bioactive Compounds from the Chiral Pool"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Organic Synthesis".

Deadline for manuscript submissions: closed (15 June 2016)

Special Issue Editors

Guest Editor
Prof. Dr. Carlo Siciliano

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, I-87036 Arcavacata di Rende, Italy
Website | E-Mail
Interests: synthesis of biomolecules and their analogues; amino acid and peptide chemistry; modification of natural amino acids; chiral templates; design and synthesis of protease inhibitors; steroid chemistry
Guest Editor
Dr. Constantinos M. Athanassopoulos

Department of Chemistry, University of Patras, GR-26504, Rion, Patras, Greece
Website | E-Mail
Interests: synthetic organic chemistry; asymmetric synthesis; chiral templates; amino acid and peptide chemistry; medicinal chemistry

Special Issue Information

Dear Colleagues,

Chiral pool synthesis is a well-known and widespread approach for the design and preparation of chiral compounds of biological and pharmacological interest. This particularly important and versatile strategy employs, as starting materials, simple and complex enantiopure compounds readily available from the arsenal of natural sources. The most common components of the chiral pool are monosaccharides and amino acids. The use of these cheap starting materials is of great importance and helpful if the synthetic target compounds display strong similarities to the structure of the enantiopure natural precursors. Moreover, the use of the chiral pool is especially noticeable and fruitful when meandering multistep approaches to enantiopure bioactive compounds may be required. The strategy based on natural sources of chiral compounds is also of great aid in all cases of synthetic procedures characterized by considerable losses in total yields, and when suitable enantiopure scaffolds may be difficult to achieve. The aim of this Special Issue is to gather an inspiring anthology for the dissemination of the most recent acquisitions in the field of design, preparation, and characterization of enantiopure compounds starting from the chiral pool. Reviews, feature articles, and original research papers that focus on new divergent and convergent total syntheses of bioactive natural compounds and their analogues starting from the chiral pool are all welcomed.

Prof. Dr. Carlo Siciliano
Dr. Constantinos M. Athanassopoulos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • asymmetric synthesis
  • enantiopure chiral templates
  • total synthesis
  • bioactive compounds

Published Papers (7 papers)

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Research

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Open AccessArticle Backstabbing P-gp: Side-Chain Cleaved Ecdysteroid 2,3-Dioxolanes Hyper-Sensitize MDR Cancer Cells to Doxorubicin without Efflux Inhibition
Molecules 2017, 22(2), 199; doi:10.3390/molecules22020199
Received: 2 December 2016 / Revised: 18 January 2017 / Accepted: 18 January 2017 / Published: 25 January 2017
Cited by 1 | PDF Full-text (771 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
P-glycoprotein (P-gp, ABCB1) over-expression, causing a multi-drug resistant (MDR) phenotype, is a major problem in cancer chemotherapy that urgently requires novel approaches. Our previous studies showed certain ecdysteroid derivatives as promising chemo-sensitizers against MDR and non-MDR cancer cell lines while also exerting mild
[...] Read more.
P-glycoprotein (P-gp, ABCB1) over-expression, causing a multi-drug resistant (MDR) phenotype, is a major problem in cancer chemotherapy that urgently requires novel approaches. Our previous studies showed certain ecdysteroid derivatives as promising chemo-sensitizers against MDR and non-MDR cancer cell lines while also exerting mild to moderate inhibition of P-gp function. Here we report the preparation of a set of substituted 2,3-dioxolane derivatives of poststerone, a known in vivo metabolite of 20-hydroxyecdysone (20E). In contrast with previously studied ecdysteroid dioxolanes, the majority of the new compounds did not inhibit the efflux function of P-gp. Nevertheless, a strong, dose dependent sensitization to doxorubicin was observed on a P-gp transfected cancer cell line and on its susceptible counterpart. We also observed that the MDR cell line was more sensitive to the compounds’ effect than the non-MDR. Our results showed for the first time that the chemo-sensitizing activity of ecdysteroids can be fully independent of functional efflux pump inhibition, and suggest these compounds as favorable leads against MDR cancer. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Figure 1

Open AccessCommunication Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists
Molecules 2016, 21(8), 1027; doi:10.3390/molecules21081027
Received: 31 May 2016 / Revised: 31 July 2016 / Accepted: 2 August 2016 / Published: 6 August 2016
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Abstract
Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the
[...] Read more.
Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl d-Aspartate (NMDA) receptor antagonists. The indolo[2,3-a]quinolizidine scaffold was obtained using the following key steps: (i) a stereoselective cyclocondensation of (S)- or (R)-tryptophanol with appropriate racemic δ-oxoesters; (ii) a stereocontrolled cyclization on the indole nucleus. The synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA receptor antagonists and one compound was identified to be 2.9-fold more potent as NMDA receptor blocker than amantadine (used in the clinic for Parkinson’s disease). This compound represents a hit compound for the development of novel NMDA receptor antagonists with potential applications in neurodegenerative disorders associated with overactivation of NMDA receptors. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Open AccessArticle A New Class of Glucosyl Thioureas: Synthesis and Larvicidal Activities
Molecules 2016, 21(7), 925; doi:10.3390/molecules21070925
Received: 13 April 2016 / Revised: 4 July 2016 / Accepted: 12 July 2016 / Published: 16 July 2016
PDF Full-text (931 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A novel series of glucosyl thioureas were synthesized in good overall yields (up to 37% over four steps) from d-glucose and primary amines, and their larvicidal activities toward Mythimna separata Walker were also investigated. This new class of glucosyl thioureas demonstrated low
[...] Read more.
A novel series of glucosyl thioureas were synthesized in good overall yields (up to 37% over four steps) from d-glucose and primary amines, and their larvicidal activities toward Mythimna separata Walker were also investigated. This new class of glucosyl thioureas demonstrated low to moderate growth inhibition activity of Mythiman separata Walker, with a growth inhibitory rate of up to 47.5% at a concentration of 100.0 mg/L in acetone. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Open AccessArticle Synthesis of Chiral, Enantiopure Allylic Amines by the Julia Olefination of α-Amino Esters
Molecules 2016, 21(6), 805; doi:10.3390/molecules21060805
Received: 24 May 2016 / Revised: 14 June 2016 / Accepted: 14 June 2016 / Published: 21 June 2016
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Abstract
The four-step conversion of a series of N-Boc-protected l-amino acid methyl esters into enantiopure N-Boc allylamines by a modified Julia olefination is described. Key steps include the reaction of a lithiated phenylalkylsulfone with amino esters, giving chiral β-ketosulfones, and the
[...] Read more.
The four-step conversion of a series of N-Boc-protected l-amino acid methyl esters into enantiopure N-Boc allylamines by a modified Julia olefination is described. Key steps include the reaction of a lithiated phenylalkylsulfone with amino esters, giving chiral β-ketosulfones, and the reductive elimination of related α-acetoxysulfones. The overall transformation takes place under mild conditions, with good yields, and without loss of stereochemical integrity, being in this respect superior to the conventional Julia reaction of α-amino aldehydes. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Review

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Open AccessReview (+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †
Molecules 2016, 21(9), 1197; doi:10.3390/molecules21091197
Received: 6 August 2016 / Revised: 1 September 2016 / Accepted: 2 September 2016 / Published: 8 September 2016
Cited by 1 | PDF Full-text (5451 KB) | HTML Full-text | XML Full-text
Abstract
In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the
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In this review the synthetic work in the field of aphidicolane, stemodane and stemarane diterpenoids, in which readily available (+)-podocarpic acid (4) was used as chiral template for the construction of their polycyclic structures, is described as it developed along the years. In the frame of this work (+)-podocarpic acid (4) was a very useful tool in a model study leading to the syntheses of tetracyclic ketones 7 and 8, models of key intermediates 5a and 6 in the syntheses of (+)-aphidicolin (1) and (+)-stemodin (2a), respectively. (+)-Podocarpic acid (4) was also converted into (+)-2-deoxystemodinone (2d), allowing confirmation of the stemodane diterpenoids absolute configuration, into (+)-aphidicol-15-ene (36) and into Stemodia chilensis tetracyclic diterpenoid (+)-19-acetoxystemodan-12-ol (2f), allowing confirmation of its structure. (+)-Podocarpic acid (4) was then extensively used in the work which led to the synthesis of (+)-stemar-13-ene (57) and (+)-18-deoxystemarin (3b). Finally, (+)-4 was converted into (+)-2-deoxyoryzalexin S (66), which made it possible to demonstrate that the structure of (+)-66 could not be attributed to a Chilean Calceolaria isolated diterpenoid to which this structure had been assigned. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Open AccessReview Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis
Molecules 2016, 21(7), 951; doi:10.3390/molecules21070951
Received: 15 June 2016 / Revised: 7 July 2016 / Accepted: 18 July 2016 / Published: 21 July 2016
Cited by 3 | PDF Full-text (3806 KB) | HTML Full-text | XML Full-text
Abstract
Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can
[...] Read more.
Chiral pool α-amino acids have been used as powerful tools for the total synthesis of structurally diverse natural products. Some common naturally occurring α-amino acids are readily available in both enantiomerically pure forms. The applications of the chiral pool in asymmetric synthesis can be categorized prudently as chiral sources, devices, and inducers. This review specifically examines recent advances in substrate-controlled asymmetric reactions induced by the chirality of α-amino acid templates in natural product synthesis research and related areas. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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Open AccessReview The Chiral Pool in the Pictet–Spengler Reaction for the Synthesis of β-Carbolines
Molecules 2016, 21(6), 699; doi:10.3390/molecules21060699
Received: 27 April 2016 / Revised: 18 May 2016 / Accepted: 24 May 2016 / Published: 27 May 2016
Cited by 3 | PDF Full-text (4732 KB) | HTML Full-text | XML Full-text
Abstract
The Pictet–Spengler reaction (PSR) is the reaction of a β-arylethylamine with an aldehyde or ketone, followed by ring closure to give an aza-heterocycle. When the β-arylethylamine is tryptamine, the product is a β-carboline, a widespread skeleton in natural alkaloids. In the natural occurrence,
[...] Read more.
The Pictet–Spengler reaction (PSR) is the reaction of a β-arylethylamine with an aldehyde or ketone, followed by ring closure to give an aza-heterocycle. When the β-arylethylamine is tryptamine, the product is a β-carboline, a widespread skeleton in natural alkaloids. In the natural occurrence, these compounds are generally enantiopure, thus the asymmetric synthesis of these compounds have been attracting the interest of organic chemists. This review aims to give an overview of the asymmetric PSR, in which the chirality arises from optically pure amines or carbonyl compounds both from natural sources and from asymmetric syntheses to assemble the reaction partners. Full article
(This article belongs to the Special Issue Synthesis of Bioactive Compounds from the Chiral Pool)
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