Total synthesis of spicamycin

Tamotsu Suzuki, Sayaka T. Suzuki, Iwao Yamada, Yoshiaki Koashi, Kazue Yamada, Noritaka Chida

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Abstract

The first total synthesis of one of the spicamycin congeners, SPM VIII (3), is described. A preliminary model study for construction of the characteristic N-glycoside linkage in spicamycin using tetra-O-benzyl-β-D-mannopyranosylamine (13) and halopurines 5 revealed that Pd-catalyzed conditions successfully provided the coupling products 14 and 15 in good yields. It was also shown that thermal anomerization of the N-glycosides easily occurred, which resulted in the predominant formation of the β-anomer as the thermodynamically favored compound, and the activation energy of anomerization of 15 was estimated to be ca. 30 kcal/mol. The novel aminoheptose unit of spicamycin 6 was prepared stereoselectively by carbon elongation of an acyclic aldehyde, prepared by ring cleavage reaction of a highly functionalized cyclohexane derived from naturally abundant myo-inositol. The Pd-catalyzed coupling reaction of the β-heptopyranosylamine 6 with protected 6-chloropurine 5d, followed by deprotection, provided spicamycin amino nucleoside 2, whose condensation with dodecanoylglycine completed the total synthesis of 3. This study confirmed the proposed unique structure of a novel nucleoside antibiotic.

Original languageEnglish
Pages (from-to)2874-2880
Number of pages7
JournalJournal of Organic Chemistry
Volume67
Issue number9
DOIs
Publication statusPublished - 2002 May 3

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ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Suzuki, T., Suzuki, S. T., Yamada, I., Koashi, Y., Yamada, K., & Chida, N. (2002). Total synthesis of spicamycin. Journal of Organic Chemistry, 67(9), 2874-2880. https://doi.org/10.1021/jo010925c