Total Synthesis and Biological Evaluation of Siladenoserinol A and its Analogues. (22nd March 2018)

• Record Type: Journal Article
• Authors: Yoshida, Masahito; Saito, Koya; Kato, Hikaru; Tsukamoto, Sachiko; Doi, Takayuki
• Is Part Of: Angewandte Chemie. Volume 130:Number 18(2018)
• Page Start: 5241
• Page End: 5244
• Publication Date: 2018-03-22
• Subjects: Bicycloketale -- Naturstoffe -- Inhibitoren -- Siladenoserinol A -- Totalsynthesen; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201801659
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: The total synthesis of siladenoserinol A, an inhibitor of the p53–Hdm2 interaction, has been achieved. AuCl3 ‐catalyzed hydroalkoxylation of an alkynoate derivative smoothly and regioselectively proceeded to afford a bicycloketal in excellent yield. A glycerophosphocholine moiety was successfully introduced through the Horner–Wadsworth–Emmons reaction using an originally developed phosphonoacetate derivative. Finally, removal of the acid‐labile protecting groups, followed by regioselective sulfamate formation of the serinol moiety afforded the desired siladenoserinol A, and benzoyl and desulfamated analogues were also successfully synthesized. Biological evaluation showed that the sulfamate is essential for biological activity, and modification of the acyl group on the bicycloketal can improve the inhibitory activity against the p53–Hdm2 interaction.