Peloruside B, a potent antitumor macrolide from the New Zealand marine sponge Mycale hentscheli: isolation, structure, total synthesis, and bioactivity.
Peloruside B (2), a natural congener of peloruside A (1), was isolated in sub-milligram quantities from the New Zealand marine sponge Mycale hentscheli. Peloruside B promotes microtubule polymerization and arrests cells in the G(2)/M phase of mitosis similar to paclitaxel, and its bioactivity was comparable to that of peloruside A. NMR-directed isolation, structure elucidation, structure confirmation by total synthesis, and bioactivity of peloruside B are described in this article. The synthesis features Sharpless dihydroxylation, Brown's asymmetric allylboration reaction, reductive aldol coupling, Yamaguchi macrolactonization, and selective methylation.
Singh
A Jonathan
AJ
Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand.
Xu
Chun-Xiao
CX
Xu
Xiaoming
X
West
Lyndon M
LM
Wilmes
Anja
A
Chan
Ariane
A
Hamel
Ernest
E
Miller
John H
JH
Northcote
Peter T
PT
Ghosh
Arun K
AK
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000302:isolation & purification* / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009520:New Zealand; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry*
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; D018942:Macrolides; C414085:peloruside A; C547698:peloruside B; D017239:Paclitaxel