Total synthesis, stereochemical reassignment, and biological evaluation of (-)-lyngbyaloside B.
(-)-Lyngbyaloside B is a 14-membered macrolide glycoside isolated from the marine cyanobacterium Lyngbya sp. as a cytotoxic substance by Moore and co-workers. The first total synthesis of (-)-lyngbyaloside B and the reassignment of its stereostructure is described. The synthesis features an Abiko-Masamune aldol reaction, a vinylogous Mukaiyama aldol reaction, and a macrocyclization involving an acyl ketene intermediate for the construction of the macrocyclic backbone, which contains an acylated tertiary alcohol. The antiproliferative activity of selected compounds against a small panel of human cancer cell lines is also reported.
Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan). hfuwa@m.tohoku.ac.jp.
Haruhiko
H
Fuwa
Yuta
Y
Okuaki
Naoya
N
Yamagata
Makoto
M
Sasaki
D000447:Aldehydes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000458:Cyanobacteria / Q000737:chemistry / Q000378:metabolism; D003500:Cyclization; D018922:HL-60 Cells; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013237:Stereoisomerism
D000447:Aldehydes; D000970:Antineoplastic Agents; D018942:Macrolides; C473445:lyngbyaloside B; C116609:3-hydroxybutanal
aldol reactions; macrolide glycosides; natural products; structure determination; total synthesis