16元大环内酯的酰基衍生物。I. 3"-O-丙酰基柱晶白霉素A5（TMS-19-Q）的合成与生物学性质

Acyl derivatives of 16-membered macrolides. I. Synthesis and biological properties of 3"-O-propionylleucomycin A5 (TMS-19-Q).

作者信息

Sakakibara H, Okekawa O, Fujiwara T, Otani M, Omura S

出版信息

J Antibiot (Tokyo). 1981 Aug;34(8):1001-10. doi: 10.7164/antibiotics.34.1001.

DOI:10.7164/antibiotics.34.1001

PMID:7319915

Abstract

Using leucomycin A5 (1), 3"-O-propionylleucomycin A5 (7) was synthesized by the following synthetic route: 2"-O-acetylation, 3,9-di-O-trimethylsilylation, 3"-O-propionylation, 3,9-di-O-detrimethylsilylation and 2'-O-deacetylation. Acylation of the 3"-tertiary hydroxyl group of 2'-O-acetyl-3,9-di-O-trimethylsilylleucomycin A5 with propionyl chloride in the presence of tribenzylamine at 70 degrees C gave a 3"-O-propionyl derivative in 96% yield. The structure of the final compound, 3"-O-propionylleucomycin A5 (7) was confirmed by means of mass, 1H-NMR and 13C-NMR spectrometry and chemical degradations. 3"-O-Propionylleucomycin A5 (7) showed higher antibacterial activity in vitro and higher serum levels than its mother antibiotic. The biological properties of 7 also were compared with those of josamycin and midecamycin.

摘要

采用柱晶白霉素A5（1），通过以下合成路线合成了3''-O-丙酰基柱晶白霉素A5（7）：2''-O-乙酰化、3,9-二-O-三甲基硅烷基化、3''-O-丙酰化、3,9-二-O-脱三甲基硅烷基化和2'-O-脱乙酰化。在70℃下，在三苄胺存在下，用丙酰氯对2'-O-乙酰基-3,9-二-O-三甲基硅烷基柱晶白霉素A5的3''-叔羟基进行酰化反应，得到产率为96%的3''-O-丙酰基衍生物。通过质谱、1H-NMR和13C-NMR光谱以及化学降解对最终化合物3''-O-丙酰基柱晶白霉素A5（7）的结构进行了确证。3''-O-丙酰基柱晶白霉素A5（7）在体外显示出比其母体抗生素更高的抗菌活性和更高的血清水平。还将7的生物学特性与交沙霉素和麦迪霉素的生物学特性进行了比较。