Catalyst-controlled asymmetric synthesis of fostriecin and 8-epi-fostriecin

Keisuke Maki, Rie Motoki, Kunihiko Fujii, Motomu Kanai, Takayasu Kobayashi, Shinri Tamura, Masakatsu Shibasaki

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97 Citations (Scopus)

Abstract

Catalytic asymmetric synthesis of the natural antibiotic fostriecin (CI-920) and its analogue 8-epi-fostriecin and evaluation of their biological activity are described. We used four catalytic asymmetric reactions to construct all of the chiral centers of fostriecin and 8-epi-fostriecin; cyanosilylation of a ketone, Yamamoto allylation, direct aldol reaction, and Noyori reduction, two of which were developed by our group. Catalytic enantioselective cyanosilylation of ketone 13 produced the chiral tetrasubstituted carbon at C-8. Both enantiomers of the product cyanohydrin were obtained with high enantioselectivity by switching the center metal of the catalyst from titanium to gadolinium. Yamamoto allylation constructed the C-5 chiral carbon in the α,β-unsaturated lactone moiety. A direct catalytic asymmetric aldol reaction of an alkynyl ketone using LLB catalyst constructed the chirality at C-9 with the introduction of a synthetically versatile alkyne moiety, which was later converted to cis-vinyl iodide, the substrate for the subsequent Stille coupling for the triene synthesis. Noyori reduction produced the secondary alcohol at C-11 from the acetylene ketone 6 with excellent selectivity. Importantly, all the stereocenters were constructed under catalyst control in this synthesis. This strategy should be useful for rapid synthesis of stereoisomers of fostriecin.

Original languageEnglish
Pages (from-to)17111-17117
Number of pages7
JournalJournal of the American Chemical Society
Volume127
Issue number48
DOIs
Publication statusPublished - 2005 Dec 7

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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