Total Synthesis and Absolute Configuration of Simpotentin, a Potentiator of Amphotericin B Activity

Masaki Ohtawa; Eri Shimizu; Atsushi Saito; Sayuri Sakamoto; Ai Waki; Ariko Kondo; Akiho Yagi; Ryuji Uchida; Hiroshi Tomoda; Tohru Nagamitsu

doi:10.1021/acs.orglett.9b01945

Total Synthesis and Absolute Configuration of Simpotentin, a Potentiator of Amphotericin B Activity

Org Lett. 2019 Jul 19;21(14):5596-5599. doi: 10.1021/acs.orglett.9b01945. Epub 2019 Jun 27.

Authors

Affiliations

¹ Laboratory of Synthetic Natural Products Chemistry and Medicinal Research Laboratories, School of Pharmacy , Kitasato University , 5-9-1 Shirokane , Minato-ku, Tokyo 108-8641 , Japan.
² Faculty of Pharmaceutical Sciences , Tohoku Medical and Pharmaceutical University , 4-4-1 Komatsushima, Aoba-ku , Sendai-shi , Miyagi 891-8558 , Japan.

PMID: 31246478
DOI: 10.1021/acs.orglett.9b01945

Abstract

The total synthesis of simpotentin (1), a new potentiator of amphotericin B activity against Candida albicans, was achieved. Our research results enabled the access of all stereoisomers of 1 and the elucidation of the unknown absolute configuration of 1. Furthermore, one of the stereoisomers is a better amphotericin B potentiator than 1 and is an excellent lead compound for the development of a novel amphotericin B potentiator.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amphotericin B / pharmacology*
Candida albicans / drug effects
Chemistry Techniques, Synthetic
Drug Synergism
Mannosides / chemical synthesis
Mannosides / chemistry*
Mannosides / pharmacology*
Microbial Sensitivity Tests
Pyrans / chemical synthesis*
Pyrans / chemistry
Pyrans / pharmacology*
Stereoisomerism

Substances

Mannosides
Pyrans
simpotentin
Amphotericin B