Total synthesis and biological evaluation of (-)-apicularen A and its analogues.

Abstract

The total synthesis of (-)-apicularen A (1), a highly cytostatic 12-membered macrolide, and its analogues is described. The convergent and distinct approach not only provides 1, but also opens the opportunity to synthesize C10-C11 functional analogues of 1. The key steps of the total synthesis include assembling of iodoalkene 12 and aldehyde 13by Nozaki-Hiyama-Kishi (NHK) coupling, stereospecific construction of 2,6-trans-disubstituted dihydropyran by Pd(II)-catalyzed 1,3-chirality transfer reaction, and Yamaguchi macrolactonization. The (17E,20Z,22Z)-heptadienoylenamine moiety in the side chain is installed by an efficient Cu(I)-mediated coupling to complete the synthesis. Analogues of C11-epi-, C11-deoxy-C10-α-hydroxy-, and C10-C11 dehydrated apicularen A 3-5 were also prepared. Cytostatic activities of (-)-apicularen A and the three analogues for three different cancer cell lines are described.

• Authors: Sanjay S Palimkar, Jun'ichi Uenishi, Hiromi Ii
• Journal: The Journal of organic chemistry (J Org Chem) Vol. 77 Issue 1 Pg. 388-99 (Jan 06 2012) ISSN: 1520-6904 [Electronic] United States
• PMID: 22118352 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Bridged Bicyclo Compounds, Heterocyclic
• apicularen A
• Palladium

Topics

• Antineoplastic Agents (chemical synthesis, chemistry)
• Bridged Bicyclo Compounds, Heterocyclic (chemical synthesis, chemistry)
• Catalysis
• Cell Line, Tumor
• Humans
• Molecular Structure
• Palladium (chemistry)
• Stereoisomerism