An architectonic macrolide library based on a C2-symmetric macrodiolide toward pharmaceutical compositions. Issue 37 (16th September 2015)

• Record Type: Journal Article
• Authors: Nakano, Hayato; Sugawara, Akihiro; Hirose, Tomoyasu; Gouda, Hiroaki; Hirono, Shuichi; Ōmura, Satoshi; Sunazuka, Toshiaki
• Is Part Of: Tetrahedron. Volume 71:Issue 37(2015)
• Page Start: 6569
• Page End: 6579
• Publication Date: 2015-09-16
• Subjects: Macrodiolides -- Stereochemical diversity -- Natural product-inspired compounds -- Macrolactonization -- Erythromycin A; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2015.01.030
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: A stereodivergent approach to creation of a specific 14-membered macrolide library is described. We designed a new 14-membered macrolide template possessing 10 sterogenic centers, and established a new library of fully-synthesized 14-membered ring compounds. The designed macrodiolides were synthesized through a convergent approach using an Evans aldol reaction, Keck esterification, and Yamaguchi macrolactonization, or Mitsunobu macrolactonization, as key steps. Moreover, introduction of an aminosugar to a macrodiolide aglycone by Schmidt glycosylation also afforded a new macrodiolide. Comparison between the conformation analysis of the macrolides, which we designed, and NMR analysis of the synthetic macrolides, indicated our stereoisomer library has significant diversity. Graphical abstract: