Total synthesis of calicheamicin γ1 I. 3. The final stages

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

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

The first total synthesis of calicheamicin γ1 I (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 γ1 I (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
Publication statusPublished - 1993 Aug 25
Externally publishedYes

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Oximes
Glycosides
Oligosaccharides
Joining
Isomers
trichloroacetamide

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Nicolaou, K. C., Hummel, C. W., Nakada, M., Shibayama, K., Pitsinos, E. N., Saimoto, H., ... Smith, A. L. (1993). Total synthesis of calicheamicin γ1 I. 3. The final stages. Journal of the American Chemical Society, 115(17), 7625-7635.

Total synthesis of calicheamicin γ1 I. 3. The final stages. / Nicolaou, K. C.; Hummel, C. W.; Nakada, Masahisa; Shibayama, K.; Pitsinos, E. N.; Saimoto, H.; Mizuno, Y.; Baldenius, K. U.; Smith, A. L.

In: Journal of the American Chemical Society, Vol. 115, No. 17, 25.08.1993, p. 7625-7635.

Research output: Contribution to journalArticle

Nicolaou, KC, Hummel, CW, Nakada, M, Shibayama, K, Pitsinos, EN, Saimoto, H, Mizuno, Y, Baldenius, KU & Smith, AL 1993, 'Total synthesis of calicheamicin γ1 I. 3. The final stages', Journal of the American Chemical Society, vol. 115, no. 17, pp. 7625-7635.
Nicolaou KC, Hummel CW, Nakada M, Shibayama K, Pitsinos EN, Saimoto H et al. Total synthesis of calicheamicin γ1 I. 3. The final stages. Journal of the American Chemical Society. 1993 Aug 25;115(17):7625-7635.
Nicolaou, K. C. ; Hummel, C. W. ; Nakada, Masahisa ; Shibayama, K. ; Pitsinos, E. N. ; Saimoto, H. ; Mizuno, Y. ; Baldenius, K. U. ; Smith, A. L. / Total synthesis of calicheamicin γ1 I. 3. The final stages. In: Journal of the American Chemical Society. 1993 ; Vol. 115, No. 17. pp. 7625-7635.
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