Total Synthesis and Biological Evaluation of Siladenoserinol A and its Analogues

Masahito Yoshida, Koya Saito, Hikaru Kato, Sachiko Tsukamoto, Takayuki Doi

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5147-5150
Number of pages4
JournalAngewandte Chemie - International Edition
Volume57
Issue number18
DOIs
Publication statusPublished - 2018 Apr 23

Keywords

  • bicycloketals
  • inhibitors
  • natural products
  • siladenoserinol A
  • total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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