Synthesis of 33-(R,S)-Bromo-33-deoxyoligomycin A

Lysenkova, Lyudmila N.; Saveljev, Oleg Y; Королев, А. М.; Даниленко, В. Н.; Bekker, Olga B.; Mavletova, D. A.; Vatlin, Aleksey A.; Omelchuk, Olga A.; Shchekotihin, Andrey E.

doi:10.6060/mhc160422s

Cited by 5 publications

(3 citation statements)

References 7 publications

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“…[6] Для пергидроолигомицина (3) Так, C. krusei обладает природной устойчивостью к флу-коназолу, применяемого для системного и местного ле-чения грибковых инфекций. Большинство клинических изолятов C. albicans чувствительны к флуконазолу, C. tropicalis занимает промежуточное положение, а 15 % изолятов C. glabrata устойчивы к флуконазолу.…”

Section: молекулярный докингunclassified

“…[3] Previously a series of modifications at the side chain and chemical transformation of the lactone moiety of 1 have been developed. [4][5][6][7][8] However, all derivatives modificated at the lactone moiety were less potent than 1. [7,8] Recently a new derivative, 2,3-dihydrooligomycin A (2), has been obtained by a microbiological method.…”

Section: Corresponding Author E-mail: Shchekotikhin@mailrumentioning

confidence: 99%

“…[3] Ранее нами был разработан ряд эффективных ме-тодов химической трансформации олигомицина А (1) как по боковой цепи (положение 33), так и по макро-лактонному кольцу. [4][5][6][7][8] Установлено, что изменение структуры макролактона значительно снижает актив-ность антибиотика. [7,8] Однако недавние исследования биологических свойств 2,3-дигидроолигомицина А (2) (Рисунок 1), полученного микробиологическим путем, показали, что восстановление двойной 2С-3С связи приводит к повышению активности в отношении дрож-жей S. cerevisiae.…”

Section: Introductionunclassified

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Synthesis and Biological Activity of 2,3,16,17,18,19-Hexahydrooligomycin A

Omelchuk¹,

Belov²,

Цветков³

et al. 2016

MHC

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Section: молекулярный докингunclassified

Section: Corresponding Author E-mail: Shchekotikhin@mailrumentioning

confidence: 99%

Section: Introductionunclassified

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Synthesis and Biological Activity of 2,3,16,17,18,19-Hexahydrooligomycin A

Omelchuk¹,

Belov²,

Цветков³

et al. 2016

MHC

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Verification of oligomycin A structure: synthesis and biological evaluation of 33-dehydrooligomycin A

et al. 2017

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Although, the structure of oligomycin A (1) was confirmed by spectroscopic and chemical evaluations, some crystallographic data cast doubt on the originally adopted structure of the side 2-hydroxypropyl moiety of this antibiotic. It was suggested that the side chain of the oligomycin is enol-related (2-hydroxy-1-propenyl). To clarify this matter we synthesized and evaluated 33-dehydrooligomycin A (2) prepared by the Kornblum oxidation of 33-O-mesyloligomycin A (3) by dimethyl sulfoxide. NMR data for 33-dehydrooligomycin (2) and results of quantum chemical calculations have shown that this derivative exists in the keto rather than in the enol tautomer 2a. The in vitro antimicrobial activity of 2 was approximately two times weaker in comparison with oligomycin A against Streptomyces fradiae ATCC-19609 and reference Candida spp. strains and similar activity against certain filamentous fungi. The docking binding estimate of 2 with FFATP synthase showed a slight decrease in binding affinity for 2 when compared with oligomycin A; that correlated with its activity against S. fradiae ATCC 19609 that is supersensitive to oligomycin A. The in vitro antiproliferative activities of 2 are also discussed.

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Main trends in the design of semi-synthetic antibiotics of a new generation

Olsufyeva¹,

Yankovskaya²

2020

Russ. Chem. Rev.

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This review summarizes main advances achieved by Russian researchers in the synthesis and characterization of semi-synthetic antibiotics of a new generation in the period from 2004 to 2019. The following classes of compounds are considered as the basis for modification: polycyclic antibacterial glycopeptides of the vancomycin group, classical macrolides, antifungal polyene macrolides, the antitumour antibiotic olivomycin A, antitumour anthracyclines and broad-spectrum antibiotics, in particular, oligomycin A, heliomycin and some other. Main trends in the design of modern anti-infective and antitumour agents over this period are considered in relation to original natural antibiotics, which have been independently discovered by Russian researchers. It is shown that a new type of hybrid structures can, in principle, be synthesized based on glycopeptides, macrolides and other antibiotics, including heterodimers containing a new benzoxaborole pharmacophore. The review addresses the influence of the length of the spacer between two antibiotic molecules on the biological activity of hybrid structures. A combination of genetic engineering techniques and methods of organic synthesis is shown to be useful for the design of new potent antifungal antibiotics based on polyenes of the amphotericin B group. Many new semi-synthetic analogues exhibit important biological properties, such as a broad spectrum of activity and low toxicity. Emphasis is given to certain aspects related to investigation of a broad range of biological activity and mechanisms of action of new derivatives. The bibliography includes 101 references.

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Synthesis of 33-(R,S)-Bromo-33-deoxyoligomycin A

Cited by 5 publications

References 7 publications

Synthesis and Biological Activity of 2,3,16,17,18,19-Hexahydrooligomycin A

Synthesis and Biological Activity of 2,3,16,17,18,19-Hexahydrooligomycin A

Verification of oligomycin A structure: synthesis and biological evaluation of 33-dehydrooligomycin A

Main trends in the design of semi-synthetic antibiotics of a new generation

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