title: 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: Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8412, Japan.
authors: Sanjay S
authors: SS
authors: Palimkar
authors: Jun'ichi
authors: J
authors: Uenishi
authors: Hiromi
authors: H
authors: Ii
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D045744:Cell Line, Tumor; D006801:Humans; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C117813:apicularen A; D010165:Palladium