Work

Evolution of the Total Synthesis of (−)-Okilactomycin Exploiting a Tandem Oxy-Cope Rearrangement/Oxidation, a Petasis−Ferrier Union/Rearrangement, and Ring-Closing Metathesis

Year: 2009

Type: article

Abstract: An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (1), as well as assignment of the absolute configuration, has been achieved exploiting a convergent strategy. Highlights of the synthesis include a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers, a Petasis-Ferrier union/rearrangement to construct the highly functionalized tetrahydropyranone inscribed within the 13-membered macrocycle ring, employing for the first time a sterically demanding acetal, an intramolecular chemoselective acylation to access an embedded bicyclic lactone, and an efficient ring-closing metathesis (RCM) reaction to generate the macrocyclic ring.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja8084669

Authors: Amos B. Smith, Todd Bosanac, Kallol Basu

Institutions: Monell Chemical Senses Center, University of Pennsylvania

Language: English

Topic: Synthetic Organic Chemistry Methods

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Cancer Institute

Awards: Antitumor Agents: Structure and Synthesis, G1761111181, Chrolactomycin and Okilactomycin: Novel Antitumor Agents, G6506144607