Current Organic Chemistry - Volume 21, Issue 13, 2017

This review updates recent applications of asymmetric aziridination, azirination, thiirination, epoxidation, and cyclopropanation in the total synthesis of biologically active compounds, including natural products, using chiral substrates or chiral catalysts, covering the literature since 2000. The interest towards these synthetic methodologies of chiral three-membered rings has increased in the last decade, dictated either by the biological activities that display many naturally occurring products bearing a three-membered unit or by the ring strain of three-membered rings making them useful precursors of many more complex interesting molecules. Classic as well as modern protocols in asymmetric aziridinations, azirinations, epoxidations, thiirinations, and cyclopropanations have been widely applied as key steps of a number of syntheses of important products. Although the use of chiral substrates and auxiliaries is still highly employed particularly in asymmetric aziridination and cyclopropanation, the development of enantioselective catalytic methodologies has witnessed exponential growth during the last decade. The present review is subdivided into three parts, dealing successively with the use of chiral nitrogen-containing three-membered rings, chiral epoxides and thiiranes, and chiral cyclopropanes in total synthesis.

Oligo- and polysaccharides have complicated structures because of the structurally different monosaccharide units and differences in stereo- and regioarrangements of glycosidic bonds. As enzymatic reactions proceed in highly regio- and stereo-controlled manner, these are well accepted as a powerful tool for the precise synthesis of well-defined oligo- and polysaccharides. For example, α-glucan phosphorylase has increasingly been identified as the crucial and useful catalyst to provide oligo- and polysaccharide substrates with various structures, which are difficult to synthesize by conventional chemical synthetic approaches. This enzyme catalyzes the polymerization of α-D-glucose 1-phosphate (Glc-1-P) from a maltooligosaccharide primer to produce pure amylose. After the discussion on the principle reaction manner and specificity by α-glucan phosphorylase catalysis, the present review discloses the synthesis of various amylose diblock copolymers by α-glucan phosphorylase-catalyzed enzymatic polymerization using polymeric primers with a maltooligosaccharide moiety at the chain end. The following chemoenzymatic approach including α-glucan phosphorylase-catalyzed enzymatic polymerization is also disclosed. When bio-related polymeric primers with multiple maltooligosaccharide chains are used for enzymatic polymerization, amylose-grafted bio-related polymers, e.g., amylose-grafted polysaccharides and polypeptides, are produced. Based on the fact that α-glucan phosphorylase exhibits weak specificity for substrate recognition, the next section deals with the synthesis of non-natural oligo- and polysaccharides by α-glucan phosphorylase-catalyzed glycosylation using analog substrates of Glc-1-P, which have monosaccharide residues different from Glc. The last section describes the preparation of amylose inclusion supramolecules with polymeric guests from α-glucan phosphorylase- catalyzed enzymatic polymerization in the presence of guest polymers. This polymerization system has been referred to as “vine-twining polymerization.”

In recent years, chiral guanidines have attracted considerable interest in organic synthesis because of their unique structural features and strongly basic properties. Compounds belonging to this structural class can act as not only Brønsted bases but also through a hydrogen bond activation mode either of the nucleophile or of the electrophile, and have consequently been widely used in asymmetric organic catalysis, delivering high levels of selectivity and activity. The Michael reaction is one of the most common methods of forming C-C and C-H bonds and has been used in many successful cases as an important transformation of industrial production of several bioactive molecules. In this review, series of classical chiral guanidines with “privileged” scaffolds were summarized, and recent reports describing the usage of chiral guanidines as organocatalysts in enatioselctive Michael reactions of carbon and hetero-nucleophiles to different olefins were described. Furthermore, the transition state models to elucidate how these chiral guanidines affect stereoselectivities in the conjugate additions were demonstrated, and the potential industrial applications of these methodologies were discussed as well.

Background and Objective: Continuing our researches in the field of heterocyclic chemistry, the study on the chemical properties of compounds simultaneously containing different heterocycles such as fused thieno[2,3-b]pyridines, fused triazoles has been carried out. Moreover, their possible antimicrobial activity against some gram-positive and gram-negative bacilli strains has been evaluated. Methods: Starting from the hydrazino derivative of cyclopenta[4',5']pyrido[3',2':4,5]thieno[3,2-d]pyrimidines 1 by reflux with triethyl orthoformate or formic acid, some substituted isomeric cyclopenta[4',5'] pyrido[3',2':4,5] thieno[2,3-e][1,2,4]triazolopyrimidines 2 and 3 have been synthesized. Results: 10-Alkyl(aryl)-8,9-dihydro-7H-cyclopenta[4',5']pyrido[3',2':4,5]thieno[2,3-e] [1,2,4]triazolo[4,3-c] pyrimidines 2 and 10-isobutyl-3-(methylthio)-8,9-dihydro-7H-cyclopenta[4',5']pyrido[3',2':4,5]thieno[2,3-e] [1,2,4]t riazolo[4,3-c]pyrimidine 5 gave the Dimroth rearrangement in both basic and acidic media. By reaction with formic acid or with triethyl orthoformate, 4-alkyl-7-hydrazino-9-(methylthio)-2,3-dihydro-1H-cyclopenta[ 4',5'] pyrido[3',2':4,5]thieno[3,2-d]pyrimidines 13 furnished 10-alkyl-5-(methylthio)-8,9-dihydro-7Hcyclopenta[ 4',5'] pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidines 14. In turn, compounds 14 gave with potassium carbonate 10-isobutyl-5-(methylthio)-8,9-dihydro-7H-cyclopenta[4',5']pyrido[3', 2':4,5]thieno [2,3-e][1,2,4]tria-zolo[1,5-c]pyrimidine 15 and with amines 10-alkyl-8,9-dihydro-7H-cyclopenta[4', 5']pyrido [3',2':4,5]thieno[2,3-e][1,2,4]triazolo [1,5-c]pyrimidin-5-amines 16 by contemporary substitution of the SCH3 group with amines and Dimroth rearrangement. Conclusion: Several cyclopenta[4',5']pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolopyrimidines have been synthesized. The study of their reactivity evidenced that Dimroth rearrangement in case of 10-alkyl(aryl)-8,9- dihydro-7H-cyclopenta[4',5']pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidines 2 as well as 10-isobutyl-3-(methylthio)-8,9-dihydro-7H-cyclopenta[4',5']pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolo[4,3-c] pyrimidine 5 occurred in both acidic and basic media. The biological activity of the synthesized compounds against some gram-positive bacteria and gram-negative bacilli strains was examined evidencing some interesting relation between the structure of the examined compounds and their antimicrobial activity.