Total Synthesis of Apoptolidin: Part 1. Retrosynthetic Analysis and Construction of Building Blocks

K C Nicolaou; Yiwei Li; Konstantina C Fylaktakidou; Helen J Mitchell; Heng-Xu Wei; Bernd Weyershausen

doi:10.1002/1521-3773(20011015)40:20<3849::AID-ANIE3849>3.0.CO;2-M

Total Synthesis of Apoptolidin: Part 1. Retrosynthetic Analysis and Construction of Building Blocks

Angew Chem Int Ed Engl. 2001 Oct 15;40(20):3849-3854. doi: 10.1002/1521-3773(20011015)40:20<3849::AID-ANIE3849>3.0.CO;2-M.

Authors

K C Nicolaou¹, Yiwei Li¹, Konstantina C Fylaktakidou¹, Helen J Mitchell¹, Heng-Xu Wei¹, Bernd Weyershausen¹

Affiliation

¹ Department of Chemistry and The Skaggs Institute for Chemical Biology The Scripps Research Institute 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA) Fax: (+1) 858-784-2469 and Department of Chemistry and Biochemistry University of California San Diego 9500 Gilman Drive, La Jolla, CA 92093 (USA).

PMID: 29712121
DOI: 10.1002/1521-3773(20011015)40:20<3849::AID-ANIE3849>3.0.CO;2-M

Abstract

No less than 30 stereogenic elements, a highly unsaturated 20-membered macrocyclic system, four carbohydrate units, and unique biological activity, make the natural occurring apoptolidin (1) a challenging synthetic target. The retrosynthetic analysis revealed five key building blocks-three for the construction of the macrolide ring B and two prospective pendant saccharide units-which were synthesized in a highly convergent manner and then connected. Apoptolidin's rather labile nature proved particularly challenging in the final deprotection, purification, and characterization procedures.

Keywords: apoptolidin; macrolides; natural products; total synthesis.