Work

Total Synthesis of Potent Antitumor Agent (−)‐Lasonolide A: A Cycloaddition‐Based Strategy

Year: 2008

Type: article

Abstract: A detailed account of the enantioselective total synthesis of (-)-lasonolide A is described. Our initial synthetic route to the top tetrahydropyran ring involved Evans asymmetric alkylation as the key step. Initially, we relied on the diastereoselective alkylation of an alpha-alkoxyacetimide derivative containing an alpha' stereogenic center and investigated such an asymmetric alkylation reaction. Although alkylation proceeded in good yield, the lack of diastereoselectivity prompted us to explore alternative routes. Our subsequent successful synthetic strategies involved highly diastereoselective cycloaddition routes to both tetrahydropyran rings of lasonolide A. The top tetrahydropyran ring was constructed stereoselectively by an intramolecular 1,3-dipolar cycloaddition reaction. The overall process constructed a bicyclic isoxazoline, which was later unravelled to a functionalized tetrahydropyran ring as well as a quaternary stereocenter present in the molecule. The lower tetrahydropyran ring was assembled by a Jacobsen catalytic asymmetric hetero-Diels-Alder reaction as the key step. The synthesis also features a Lewis acid catalyzed epoxide opening to form a substituted ether stereoselectively.

Source: Chemistry - An Asian Journal

DOI: 10.1002/asia.200800164

Authors: Arun K. Ghosh, Gangli Gong

Institution: Purdue University West Lafayette

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 Institute of General Medical Sciences

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