Enantiospecific synthesis and cytotoxicity evaluation of ligudentatol: a programmed aromatization approach to the 2,3,4-trisubstituted phenolic motif via visible-light-mediated group transfer radical cyclization.
A facile enantiospecific approach to (+)-ligudentatol (1) and (-)-ligudentatol (ent-1) is reported. The approach features the construction of a trisubstituted phenolic motif fused to a chiral aliphatic ring by a sequence of visible-light-mediated radical seleno transfer cyclization, bromination, concomitant selenoxide elimination-dehydrobromination, and demethoxycarbonylation, namely, a programmed aromatization. Biological evaluation of the enantiomers of ligudentatol obtained by the present route revealed for the first time their cytotoxicity towards various cancer cell lines.
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan), Fax: (+81) 6-6879-8214.
Gamal A I
GA
Moustafa
Hiroshi
H
Suizu
Hiroshi
H
Aoyama
Masayoshi
M
Arai
Shuji
S
Akai
Takehiko
T
Yoshimitsu
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization; D006801:Humans; D008027:Light; D015394:Molecular Structure; D009284:Naphthols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry*; D013237:Stereoisomerism
D000972:Antineoplastic Agents, Phytogenic; D009284:Naphthols; D010636:Phenols; C000597300:ligudentatol
cytotoxicity; natural products; radical reactions; seleno transfer; total synthesis