Aurisides A and B, Cytotoxic Macrolide Glycosides from the Japanese Sea Hare Dolabella auricularia

Abstract

Bioassay-guided fractionation of the cytotoxic constituents of the Japanese sea hare Dolabella auricularia led to the isolation of two novel cytotoxic compounds, aurisides A (1) and B (2). Their gross structures were established by spectroscopic analysis including the 2D NMR technique. On the basis of the NOESY spectral analysis and the degradation experiments, their absolute stereostructures were determined to be 14-membered macrolide glycosides that contain a bromine-substituted conjugated diene structure, a cyclic hemiacetal moiety, and a 2,4-di-O-methyl-L-rhamnopyranoside part. Aurisides A (1) and B (2) show cytotoxicity against HeLa S(3) cells with IC(50) values of 0.17 and 1.2 &mgr;g/mL, respectively.

The Cyanobacterial Origin of Potent Anticancer Agents Originally Isolated from Sea Hares

“…The potent biological activity of the scytophycins, microfilament-depolymerizing agents [81], has also stimulated various synthetic endeavors [82]. Other Dolabella isolates that are non-nitrogenous yet likely of cyanobacterial origin are aurisides A (55) and B (56) [83]. These compounds are glycoside macrolides and remarkably close to the three known glycoside macrolides (57−59) subsequently isolated from marine cyanobacteria [84− 86] (Fig.…”

Integrated approaches to the configurational assignment of marine natural products

“…are recent additions to a group of cytotoxic glycosidic 14-membered ring macrolides from various marine organisms; others include aurisides A ( 161 ) clxxxix and B and dolastatin 19 ( 162 ) cxc from the sea slug Dolabella auricularia , callipeltoside A ( 163 ) from the sponge Callipelta sp., cxci and lyngbyaboulloside ( 164 ) from the cyanobacteria Lyngbya bouillonii . cxcii Configurational assignment of auriside A ( 161 ) by combined J coupling and NOESY analysis which established the complete RC.…”

Total Synthesis, Stereochemical Reassignment, and Biological Evaluation of (−)‐Lyngbyaloside B

“…[1] Marine macrolide glycosides constitute a growing family of structurally and biologically intriguing natural products that are supposed to be of cyanobaterial origin [2] and continue to attract intense attention from the synthetic community. [1] Marine macrolide glycosides constitute a growing family of structurally and biologically intriguing natural products that are supposed to be of cyanobaterial origin [2] and continue to attract intense attention from the synthetic community.…”