Mechanistic study of the oxa-Pictet-Spengler cyclization in the synthesis of pyranonaphthoquinones

ORGN 170

Clark N. Eid, eidc@wyeth.com1, Jaechul Shim2, and Jack Andrew Bikker, bikkerj@wyeth.com1. (1) Chemical & Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, (2) Department of Chemical and Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965
Abstract-The oxa-Pictet-Spengler cyclization has been reported to provide only the kinetically derived syn-products in the asymmetric syntheses of pyranonaphthoquinones.  Our application of the oxa-Pictet-Spengler cyclization in the syntheses of (+)-7-deoxyfrenolicin B and (+)-7-deoxykalafungin produced only the thermodynamically derived anti-products.  The mechanistic details behind these opposite stereochemical outcomes will be reported.  We also provide insight on the epimerization of the precursor hydroxylactones in the presence of strong Lewis acids and the consequence this has on access to other diastereomers via this synthetic route.

 

 

Physical Organic Chemistry, Combinatorial and Process Chemistry, New Reactions and Methodology, Peptides, Proteins and Amino Acids
8:00 PM-10:00 PM, Sunday, April 6, 2008 Morial Convention Center -- Hall A, Poster

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008