Search Results (34)

Mandelic acid, an aromatic α-hydroxy acid, has become a valuable scaffold in polymer chemistry, providing a rare combination of chemical reactivity and stereochemical control due to its aromatic ring, carboxylic acid group, and stereogenic center. In this work, racpoly(mandelic acid) (PMA) was synthesized via Dean–Stark Azeotropic Polycondensation, Steglich polyesterification with diisopropylcarbodiimide and 4-(dimethylamino)pyridinium p-toluenesulfonate, and a two-stage melt polycondensation. In the melt polycondensation synthesis titanium butoxide, titanium isopropoxide, p-toluenesulfonic acid, and sulfuric acid were investigated as appropriate catalysts. The synthesized samples were characterized using various techniques, such as intrinsic viscosity, Gel Permeation Chromatography, Differential Scanning Calorimetry, Dielectric Relaxation Spectroscopy, Thermogravimetric Analysis, Water Contact Angle measurements as well as enzymatic and aquatic hydrolysis tests. Although PMA has been synthesized before, this work provides the first comprehensive structure–property–degradation map for poly(mandelic acid) synthesized by melt and azeotropic polycondensation and Steglich polyesterification from the L,D-mandelic acid, combining detailed molecular weight analysis, thermal characterization, wettability, hydrolysis and dielectric probing of molecular dynamics. Full article

In addition to well-known traditional synthetic illicit drugs like cocaine, amphetamines, and heroin, an increasing number of new psychoactive substances (NPS) are appearing on the global drug market. Among them, cathinones represent a prominent class. These amphetamine-like compounds contain a stereogenic center, resulting in the possible presence of two enantiomers. Pure enantiomers of cathinone derivatives are not commonly available, and their production is cost-intensive. Thus, there is very little knowledge about the possible distinct effects of single enantiomers of cathinones. The objective of this study was to evaluate the stability of a set of eight cathinone derivatives, namely 3-methylethcathinone, 3-methylmethcathinone, 4-methylethcathinone, 4-methylmethcathinone, ethylone, 3,4-trimethylene-α-ethylaminovalerophenone, 3,4-tetramethylene-α-pyrrolidinovalerophenone, and 3,4-trimethylene-α-pyrrolidinobutiophenone, over a six-month period. Any racemization that may have occurred under different storage and solution conditions was monitored and compared. Pure enantiomeric fractions were collected on a multi-milligram scale using semi-preparative HPLC under isocratic normal-phase conditions. A Phenomenex Lux^® i-Cellulose-5, 5 μm 250 × 10 mm column containing cellulose tris(3,5-dichlorophenylcarbamate) served as the chiral selector. The tests showed that aqueous conditions, pH, temperature, chemical structure, sunlight, and oxygen influence compound stability. The long-term storage of cathinone derivative enantiomers was found to be optimal as solids under deep-freezing conditions or in a slightly acidified solvent where they are protected from air and light. Full article

Perimidine derivatives are versatile heterocycles with growing significance in medicinal chemistry and materials sciences. However, their structural variety remains limited. This study focused on the synthesis and crystal structure characterization of a new perimidine-based molecule. A bicyclic perimidine lactone, (1S,4R)-4,7,7-trimethyl-1-(1H-perimidin-2-yl)-2-oxabicyclo[2.2.1]heptan-3-one (1), was synthesized through an intramolecular dehydration of a monoamide intermediate formed from 1,8-diaminonaphthalene and (1S)-(–)-camphanic chloride under basic conditions. The product was purified and crystallized from acetone, giving single crystals suitable for X-ray diffraction. Structural analysis revealed two stereogenic centers and crystallization in the chiral tetragonal P4₃2₁2 space group, with stabilization through N—H···O and C—H···N hydrogen bonds as well as C—H···π interactions. Full article

Streptomyces sp. AWH31-250, isolated from a tidal mudflat in the Nakdong River estuary in Busan, Republic of Korea, was found to produce two novel p-aminoacetophenone derivatives, mohangic acid H (1) and mohangiol (2). Their planar structures were established by comprehensive 1D and 2D NMR spectroscopy, mass spectrometry, and UV analysis, possessing a shorter carbon-chain with a diene moiety, whereas known mohangic acids A–F bear a longer carbon-chain with a triene moiety. The absolute configurations of the key stereogenic centers were determined via computational DP4+ calculations and bioinformatic analysis of the ketoreductase domain sequence from the biosynthetic gene cluster. Based on the careful gene analysis along with whole-genome sequencing, the first plausible biosynthetic pathway of mohangic acids A–G and mohangiol was proposed. Mohangic acid H (1) and mohangiol (2) displayed moderate inhibitory activity against Candida albicans isocitrate lyase with IC₅₀ values of 21.37 and 21.12 µg/mL, respectively. Full article

A stereoselective and scalable strategy for the synthesis of phosphorus-containing bicyclic and tricyclic compounds from 1-phenylphosphin-2-en-4-one 1-oxide is presented. This activated dienophile, available in both racemic and enantiopure forms, undergoes smooth [4+2] cycloadditions with acyclic and cyclic dienes, affording products with excellent yields and controlled stereochemistry. Notably, the cis/trans-fusion of the cycloadducts (phosphadecalones and phosphahexahydrochrysene) can be selectively controlled by fine-tuning the conditions of microwave-assisted cycloaddition reaction. The influence of temperature, time, and steric effects on cis/trans and endo/exo selectivity was examined in detail. The molecular structure, including the absolute configuration, of eight products has been determined by X-ray crystallography. These analyses further established the endo-selective nature of the cycloaddition, favoring the P=O face of the dienophile. Post-cycloaddition transformations of selected P-stereogenic phosphadecalone, such as isomerization, reduction and deoxygenation, demonstrate the synthetic versatility of the resulting products. Full article

The development of new chiral ligands with simple and modular structure represents a challenging direction in the design of efficient homogeneous transition metal catalysts. Herein, we report on the asymmetric hydrogenation of prochiral ketones catalyzed by the iridium complexes of simple alkane-diyl-based P,N,O-type chiral ligands with a highly modular structure. The role of (i) the P-N and N-O backbone in the potentially tridentate ligands, (ii) the number, position and relative configuration of their stereogenic elements and (iii) the effect of their NH and OH subunits on the activity and enantioselectivity of the catalytic reactions are studied. The systematic variation in the ligand structure and the comparative catalytic experiments shed light on different mechanistic aspects of the iridium-catalyzed reaction. The catalysts containing the simple alkane-diyl-based ligands with central chirality provided high enantioselectivities (up to 98% ee) under optimized reaction conditions and proved to be active and selective even at very high substrate concentrations (100 mmol substrate/mL solvent). Full article

This paper presents the efficient reduction of phosphinoylacetic acid esters and 3-phosphorylated coumarin to their corresponding phosphino-boranes using BH₃-THF complexes. Optimized conditions for the reduction of phosphinoylacetic acid esters resulted in high yields of phosphinoborates. The straightforwardness and efficiency of the process were demonstrated for diarylphosphinoylacetic acid ethyl esters, as well as P-stereogenic L-menthyl esters, where the simultaneous reduction of the strong P=O bond and the ester group was exclusively observed for the first time. The study also highlighted the significant influence of steric effects with bulky substituents, such as the menthol group or the 1-naphthyl substituent at phosphorus, on the reduction efficiency. However, the reduction of 3-phosphorylated coumarins produced an unexpected reaction product: a 2,3-dihydrobenzofuran derivative. The present findings provide valuable information on the direct reduction of phosphine oxides and related compounds, demonstrating the versatility of borane complexes in synthetic chemistry, and provide new perspectives for studying the problems of symmetry and asymmetry in the chemistry of such transformations. Full article

This paper presents the general synthesis of a comprehensive group of P-chiral phosphinyl derivatives with a natural coumarin-type motif. A chiral substituent was attached at the third position of the coumarin molecule via the Knoevenagel procedure using readily available P-chiral phoshinylacetic acid esters without loss of enantiomeric purity. The application of salicylaldehyde-based derivatives allowed the incorporation of substituents of different electron character into the backbone of these coumarins making them suitable for subsequent chemical modifications. As a result, we gained access to six achiral (2a–g) and a large number ((S_p)-4a–f, (S_p)-6a–e and (R_p)-8a) of new potential chiral ligand precursors, pharmaceuticals, etc. with an imbedded phosphinyl group with evidenced biological activity based on the natural coumarin backbone. The molecular structure, including absolute configuration, was determined for seven compounds. Full article

Five undescribed pentaketide derivatives, (R)-6,8-dihydroxy-4,5-dimethyl-3-methylidene-3,4-dihydro-1H-2-benzopyran-1-one (1), [(3S,4R)-3,8-dihydroxy-6-methoxy-4,5-dimethyl-1-oxo-3,4-dihydro-1H-isochromen-3-yl]methyl acetate (2), (R)-5, 7-dimethoxy-3-((S)-(1-hydroxyethyl)-3,4-dimethylisobenzofuran-1(3H)-one (4b), (S)-7-hydroxy-3-((S)-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran 1(3H)-one (5), and a p-hydroxyphenyl-2-pyridone derivative, avellaneanone (6), were isolated together with the previously reported (R)-3-acetyl-7-hydroxy-5-methoxy-3,4-dimethylisobenzofuran-1(3H)-one (3), (R)-7-hydroxy-3-((S)-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran-1(3H)-one (4a) and isosclerone (7), from the ethyl acetate extract of a culture of a marine sponge-derived fungus, Hamigera avellanea KUFA0732. The structures of the undescribed compounds were elucidated using 1D and 2D NMR, as well as high-resolution mass spectral analyses. The absolute configurations of the stereogenic carbons in 1, 4b, 5, and 6 were established by X-ray crystallographic analysis. The absolute configurations of C-3 and C-4 in 2 were determined by ROESY correlations and on the basis of their common biosynthetic origin with 1. The crude fungal extract and the isolated compounds 1, 3, 4b, 5, 6, and 7 were assayed for their growth inhibitory activity against various plant pathogenic fungi viz. Alternaria brassicicola, Bipolaris oryzae, Colletotrichum capsici, C. gloeosporiodes, Curvularia oryzae, Fusarium semitectum, Lasiodiplodia theobromae, Phytophthora palmivora, Pyricularia oryzae, Rhizoctonia oryzae and Sclerotium rolfsii. Full article

1,4- and 1,2-additons of secondary phosphine oxides to (1R)-myrtenal and (1S)-myrtanal were evaluated as potential routes to P,C-stereogenic phosphine oxides bearing additional hydroxyl or aldehyde functions. 1,4-Additions of racemic secondary phosphine oxides to (1R)-myrtenal were found to offer moderate to good stereoselectivity which shows some promise for utility in kinetic resolution processes, especially at lower conversions. In case of 1,2-additions making the process doubly asymmetric by using an enantiomerically pure secondary phosphine oxide as substrate turned out to be practical. The stereochemical course of the addition reactions under study is presented. The P-resolved 1,2-addition products were demonstrated to undergo facile reduction by BH₃ at room temperature leading to the formation of the corresponding α-hydroxyphosphine-boranes with clean inversion of configuration at the P-centre. All P,C-stereogenic phosphine oxides and boranes that were isolated in the form of a single diastereoisomer were assigned their absolute configurations by means of X-ray crystallography and/or 2D NMR spectral techniques. Full article

The aim of the research described in this publication is two-fold. The first is a detailed description of the synthesis of a series of compounds containing a stereogenic heteroatom, namely the optically active P-stereogenic derivatives of tert-butylarylphoshinic acids bearing sulfur or selenium. The second is a detailed discussion dedicated to the determination of their structures by an X-ray analysis. Such a determination is needed when considering optically active hetero-oxophosphoric acids as new chiral solvating agents, precursors of new chiral ionic liquids, or ligands in complexes serving as novel organometallic catalysts. Full article

A focused library of 1-adamantyl arylthiophosphonates was prepared in racemic form. An enantioseparation method was developed for P-stereogenic thiophosphonates using (S)-1-phenylethylamine as the resolving agent. Under optimized conditions, three out of the five arylthiophosphonates were prepared in enantiopure form (ee > 99%). The subsequent desulfurization of optically active arylthiophosphonates gave the corresponding H-phosphinates without significant erosion of enantiomeric purity (ee = 95–98%). Hence, this reaction sequence can be considered an alternative method for the preparation of 1-adamantyl aryl-H-phopshinates. The absolute configuration of the (S)-1-adamantyl phenylphosphonothioic acid was assigned using single-crystal XRD and it allowed the confirmation that the removal of the P = S group proceeds with retention of configuration. The organocatalytic applicability of (S)-1-adamantyl phenylphosphonothioic acid was also evaluated as a P-stereogenic Brønsted acid. Full article

An unreported isocoumarin, (3S,4R)-4-hydroxy-6-methoxymellein (2), an undescribed propylpyridinium anthraquinone (4), and an unreported C-glucosyl resorcinol derivative, acetyl carnemycin E (5c), were isolated, together with eight previously reported metabolites including p-hydroxybenzaldehyde (1), 1,3-dimethoxy-8-hydroxy-6-methylanthraquinone (3a), 1,3-dimethoxy-2,8-dihydroxy-6-methylanthraquinone (3b), emodin (3c), 5[(3E,5E)-nona-3,5-dien-1-yl]benzene (5a), carnemycin E (5b), tajixanthone hydrate (6a) and 15-acetyl tajixanthone hydrate (6b), from the ethyl acetate extract of the culture of a marine sponge-derived fungus, Aspergillus stellatus KUFA 2017. The structures of the undescribed compounds were elucidated by 1D and 2D NMR and high resolution mass spectral analyses. In the case of 2, the absolute configurations of the stereogenic carbons were determined by comparison of their calculated and experimental electronic circular dichroism (ECD) spectra. The absolute configurations of the stereogenic carbons in 6a and 6b were also determined, for the first time, by X-ray crystallographic analysis. Compounds 2, 3a, 3b, 4, 5a, 5b, 5c, 6a, and 6b were assayed for antibacterial activity against four reference strains, viz. two Gram-positive (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212) and two Gram-negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), as well as three multidrug-resistant strains. However, only 5a exhibited significant antibacterial activity against both reference and multidrug-resistant strains. Compound 5a also showed antibiofilm activity against both reference strains of Gram-positive bacteria. Full article

Organophosphorus compounds with stereogenic phosphorus and carbon atoms have received increasing attention. In this regards, primary phosphines with a stereogenic carbon atom adjacent to the phosphorus atom were synthesized by the reduction in phosphonates and phosphonoselenoates with a binaphthyl group. Their oxidized products, i.e., phosphine oxides with a stereogenic tetrasubstituted carbon atom, were found to undergo BEt₃-mediated radical addition to cyclohexene to give P-stereogenic secondary phosphine oxides with a diastereoselectivity of 91:9. The products were characterized by ordinary analytical methods, such as Fourier transform infrared spectroscopy; ¹H, ¹³C, and ³¹P NMR spectroscopies; and mass spectroscopy. Computational studies on the phosphorus-centered radical species and the obtained product implied that the thermodynamically stable radical and the adduct may be formed as a major diastereomer. The radical addition to a range of alkenes took place in an anti-Markovnikov fashion to give P-stereogenic secondary phosphine oxides. A variety of functional groups in the alkenes were tolerated under the reaction conditions to afford secondary phosphine oxides in moderate yields. Primary phosphines with an alkenyl group, which were generated in situ, underwent intramolecular cyclization to give five- and six-membered cyclic phosphines in high yields after protection by BH₃. Full article

The resolution of racemic 1-phenylphosphin-2-en-4-one 1-oxide (2), was achieved through the fractional crystallization of its diastereomeric complexes with (4R,5R)-(−)-2,2-dimethyl -α,α,α′,α′-tetraphenyl-dioxolan-4,5-dimethanol (R,R-TADDOL) followed by the liberation of the individual enantiomers of 2 by flash chromatography on silica gel columns. The resolution process furnished the two enantiomers of 2 of 99.1 and 99.9% e.e. at isolated yields of 62 and 59% (counted for the single enantiomer), respectively. The absolute configurations of the two enantiomers were established by means of X-ray crystallography of their diastereomerically pure complexes, i.e., (R)-2•R,R)-TADDOL and (S)-2•(R,R)-TADDOL. The structural analysis revealed that in the (R)-2•(R,R)-TADDOL complex, the P-phenyl substituent occupied a pseudoequatorial position, whereas in (S)-2•(R,R)-TADDOL, it appeared in both the pseudoequatorial and the pseudoaxial positions in four symmetrically independent molecules. Concurrent conformational changes of the TADDOL molecules were best described by the observed changes of a pseudo-torsional CO...OC angle that could be considered as a possible measure of TADDOL conformation in its receptor–ligand complexes. The structural analysis of the (R,R)-TADDOL molecule revealed that efficiency of this compound for use as an effective resolving factor comes from its ability to flexibly fit its structure to both enantiomers of a ligand molecule, producing a rare case of resolution for both pure enantiomers with one chiral separating agent. The resolved (R)-2 was used to assign the absolute configuration of a recently described (−)-1-phenylphosphin-2-en-4-one 1-sulfide by chemical correlation. In addition, an attempted stereoretentive reduction of (R)-2 by PhSiH₃ at 60 °C revealed an unexpectedly low barrier for P-inversion in 1-phenylphosphin-2-en-4-one. Full article