Total Synthesis of Calicheamicin γ1I. 3. The Final Stages

K. C. Nicolaou, C. W. Hummel, M. Nakada, K. Shibayama, E. N. Pitsinos, H. Saimoto, Y. Mizuno, K. U. Baldenius, A. L. Smith

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119 Citations (Scopus)

Abstract

The first total synthesis of calicheamicin γ1I (1) has been achieved. The stereoselective glycosidation, joining the appropriately functionalized aglycon 3 with the oligosaccharide fragment 2, was realized using Schmidt’s trichloroacetimidate methodology. Segment 4, equipped with the photolabile 2-nitrobenzyl group at the reducing end, was synthesized using similar chemistry to that applied to the synthesis of its methyl glycoside counterpart (see accompanying paper). Stereoselective reduction of oxime 31, obtained from the coupling product, with NaCNBH3 in the presence of BF3-OEt2, late in the synthetic scheme, generated the desired alkoxylamine 32 and its A-4 isomer 32-epi. Installment of the allylic trisulfide and appropriate deprotections allowed transformation of 32 and 32-epi to calicheamicin γ1I (1) and its A-4 epimer 1-epi, respectively.

Original languageEnglish
Pages (from-to)7625-7635
Number of pages11
JournalJournal of the American Chemical Society
Volume115
Issue number17
DOIs
Publication statusPublished - 1993 Aug 1
Externally publishedYes

ASJC Scopus subject areas

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

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    Nicolaou, K. C., Hummel, C. W., Nakada, M., Shibayama, K., Pitsinos, E. N., Saimoto, H., Mizuno, Y., Baldenius, K. U., & Smith, A. L. (1993). Total Synthesis of Calicheamicin γ1I. 3. The Final Stages. Journal of the American Chemical Society, 115(17), 7625-7635. https://doi.org/10.1021/ja00070a006