Search Results (4)

The review is devoted to the theoretical and synthetic aspects of the stereochemistry of organophosphorus compounds. Organophosphorus compounds are not only widely exist in biologically active pharmaceuticals and agrochemicals, but also have widespread applications in material science and organic synthesis as ligands for transition metal complexes. One of the mainstreams for the development in this field is the creation of biologically active organophosphorus compounds that are searched and used as drugs or plant-protecting agents, which leads to the elaboration of advanced methods and monitoring, yielding up-to-date approaches to perform synthesis in an environmentally friendly manner. The review consists of two parts. The first part presents methods for the asymmetric synthesis of organophosphorus compounds using asymmetric organocatalysis and metal complex catalysis. In the review is described the nature of the chirality generation in the prebiotic period, the mechanisms of asymmetric induction, and double stereodifferentiation are discussed. The use of these methods for the preparation of chiral phosphorus analogs of natural compounds (phosphono-isonorstatin, phosphono-GABOB, phosphacarnitine, bis-phosphonates, and others) is described. Some data concerning of λ⁵-phosphanediones as metaphosphate anion analogues are also reported. The second part of the presented review shows examples of the use of these methods for the synthesis of phosphorus analogues of natural compounds—chiral phosphonoamino acids and hydroxyphosphonates: phosphonoaspartic acid, phosphonoglutamic acid, phosphonohomoproline, chiral bis-phosphonates. The reaction of dehydration aromatization with the formation of pho sphono isoindolinones, including isoindolinone bis-phosphonates, has been studied. Some of the synthesized compounds showed biological activity as protein tyrosine phosphatase inhibitors. A phosphonic analogue of iso-norstatine was synthesized. A stereoselective method for the synthesis of tetradecapentaenoic acid derivatives was developed. Full article

Hydroxy fatty acids (HFAs) constitute a class of lipids, distinguished by the presence of a hydroxyl on a long aliphatic chain. This study aims to expand our insights into HFA bioactivities, while also introducing new methods for asymmetrically synthesizing unsaturated and saturated HFAs. Simultaneously, a procedure previously established by us was adapted to generate new HFA regioisomers. An organocatalytic step was employed for the synthesis of chiral terminal epoxides, which either by alkynylation or by Grignard reagents resulted in unsaturated or saturated chiral secondary alcohols and, ultimately, HFAs. 7-(S)-Hydroxyoleic acid (7SHOA), 7-(S)-hydroxypalmitoleic acid (7SHPOA) and 7-(R)- and (S)-hydroxymargaric acids (7HMAs) were synthesized for the first time and, together with regioisomers of (R)- and (S)-hydroxypalmitic acids (HPAs) and hydroxystearic acids (HSAs), whose biological activity has not been tested so far, were studied for their antiproliferative activities. The unsaturation of the long chain, as well as an odd-numbered (C17) fatty acid chain, led to reduced activity, while the new 6-(S)-HPA regioisomer was identified as exhibiting potent antiproliferative activity in A549 cells. 6SHPA induced acetylation of histone 3 in A549 cells, without affecting acetylated α-tubulin levels, suggesting the selective inhibition of histone deacetylase (HDAC) class I enzymes, and was found to inhibit signal transducer and activator of transcription 3 (STAT3) expression. Full article

Samarium is an efficient reducing agent, a radical generator in cyclization and a cascade addition reaction. Interestingly, samarium metal has crucial impact on numerous C-C and C-X (X = hetero atom) bond forming transformations. It has been established as an exceptional chemo-selective and stereoselective reagent. The reactivity of the samarium catalyst/reagent is remarkably enhanced in the presence of various additives, ligands and solvents through effective coordination and an increase in reduction potential. It has inherent character to act as electron donor for a wide range of transformations including the asymmetric version of various reactions. This review accentuates the developments in samarium-mediated/catalyzed asymmetric organic synthesis over the past 12 years, where the chirality has been induced from ligand, a nearby asymmetric center within the substrate or through coordination directed stereospecific reactions. Full article

Diazo compounds are versatile reagents in chemical synthesis and biology due to the tunable reactivity of the diazo functionality and its compatibility with living systems. Much effort has been made in recent years to explore their accessibility and synthetic potential; however, their preparation through stereoselective enzymatic asymmetric synthesis has been scarcely reported in the literature. Alcohol dehydrogenases (ADHs, also called ketoreductases, KREDs) are powerful redox enzymes able to reduce carbonyl compounds in a highly stereoselective manner. Herein, we have developed the synthesis and subsequent bioreduction of nine α-diazo-β-keto esters to give optically active α-diazo-β-hydroxy esters with potential applications as chiral building blocks in chemical synthesis. Therefore, the syntheses of prochiral α-diazo-β-keto esters bearing different substitution patterns at the adjacent position of the ketone group (N₃CH₂, ClCH₂, BrCH₂, CH₃OCH₂, NCSCH₂, CH₃, and Ph) and in the alkoxy portion of the ester functionality (Me, Et, and Bn), were carried out through the diazo transfer reaction to the corresponding β-keto esters in good to excellent yields (81–96%). After performing the chemical reduction of α-diazo-β-keto esters with sodium borohydride and developing robust analytical conditions to monitor the biotransformations, their bioreductions were exhaustively studied using in-house made Escherichia coli overexpressed and commercially available KREDs. Remarkably, the corresponding α-diazo-β-hydroxy esters were obtained in moderate to excellent conversions (60 to >99%) and high selectivities (85 to >99% ee) after 24 h at 30 °C. The best biotransformations in terms of conversion and enantiomeric excess were successfully scaled up to give the expected chiral alcohols with almost the same activity and selectivity values observed in the enzyme screening experiments. Full article