Application of the Synthetic Aminosugars for Glycodiversification:  Synthesis and Antimicrobial Studies of Pyranmycin

Abstract

A divergent approach was employed for the synthesis of aminosugars, from which a novel library of aminoglycoside antibiotics (pyranmycins) was synthesized. Pyranmycins have comparable antibacterial activity as neomycin, a clinically used aminoglycoside antibiotic, against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Mycobacterium smegmatis. In addition, pyranmycins, like streptomycin, are bacteriocidal while isoniazid (INH) is bacteriostatic. Therefore, pyranmycins may provide new therapeutic options in the treatment against tuberculosis. Several members of pyranmycins also manifest modest anti-Tat and anti-Rev activities, which may aid in the development of new anti-HIV agents. Although the antibacterial activity of pyranmycins against aminoglycoside resistant bacteria is less than expected, the synthetic methodologies of utilizing a library of aminosugars can be a model for future studies of glycodiversification or glycorandomization.

Antifungal amphiphilic aminoglycosides

“…Several observations indicate membrane perturbation as the primary antibacterial action of these compounds and not ribosome interaction to cause protein translation misreading. 4,10,11,23,28 …”

Study of the Glycosidation Properties of 1‐Thiomannosazidopyranosides and 1‐Thiomannosaziduronic Acid Esters

“…[35] In the first instance, known 4-azidothiofucose donor 22 [36] was condensed with 1-thiomannosaziduronic acid ester 9 under the agency of Ph 2 SO/Tf 2 O to afford, in a chemoselective fashion, α-linked thiodisaccharide 24 in 55 % yield. No deterioration of disaccharide 24 in the presence of the transiently formed diphenyl(phenylthio)sulfonium triflate was detected.…”

Metathesis and Macrocycles with Embedded Carbohydrates

“…Reduction of the alkenes and subsequent debenzylation and removal of acetate and TFA protecting groups gave 55 and 56, respectively. [29] A similar strategy was used to prepare 58 and 60 from 57 and 59 respectively, which were derived from C-glycosides. The RCM reaction proceeded in 73-95 % yields.…”