Work

Total Synthesis of Potent Antitumor Macrolide (–)‐Zampanolide: An Oxidative Intramolecular Cyclization‐Based Strategy

Year: 2012

Type: article

Abstract: A detailed account of the enantioselective total synthesis of (–)‐zampanolide, a macrolide marine natural product with high anticancer activity, is described. For the synthesis of the 4‐methylenetetrahydropyran unit of (–)‐zampanolide, we initially relied upon an oxidative C–H activation of an alkenyl ether and intramolecular cyclization to provide the substituted tetrahydropyran ring. However, this strategy was unsuccessful. Subsequently, we found that a cinnamyl ether is critical for the successful oxidative intramolecular cyclization reaction. The synthesis also features a cross‐metathesis reaction for the construction of a trisubstituted olefin, a ring‐closing metathesis to form a highly functionalized macrolactone, and a chiral phosphoric acid promoted formation of an N‐acyl aminal to furnish (–)‐zampanolide stereoselectively and in good yield. The synthetic (–)‐zampanolide had effects on cultured cells and on tubulin assembly consistent with the properties reported for the natural product.

Source: European Journal of Organic Chemistry

DOI: 10.1002/ejoc.201200286

Authors: Arun K. Ghosh, Xu Cheng, Ruoli Bai, Ernest Hamel

Institutions: Purdue University West Lafayette, National Institutes of Health, Frederick National Laboratory for Cancer Research, National Cancer Institute

Language: English

Topic: Organic Chemistry Synthesis Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Purdue University, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences

Awards: DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORS, Design & Synthesis of Nonpeptide Protease Inhibitors