Skeletally diverse sultams via Dieckman cyclization

ORGN 75

Thiwanka Samarakoon, smtikiri@mail.ku.edu, Daniel Barrera, and Paul R. Hanson, phanson@ku.edu. Department of Chemistry, University of Kansas, 1251 Wescoe Hall Dr, NIH Center of Excellence in Chemical Methodologies and Library Development (KU-CMLD), Lawrence, KS 66045-7582
Sultams (cyclic sulfonamides) although not found in nature, have shown potent biological activity. Our efforts towards the development of an array of diverse sultam (cyclic sulfonamides) skeletons derived from beta-keto sultams are presented. This strategy employs a Dieckman-type cyclization to synthesize a number of core beta-keto sultams. The core sultam was generated via the sulfonylation of a variety of amino esters followed by a one-pot, sequential N-alkylation and Dieckman cyclization. The chemistry of the core sultam was then probed with reduction, Wittig reactions, Knoevenagel condensations, Michael additions and Robinson annulations to yield a number of skeletally different sultams. Further investigation of the chemistry of the core scaffold is being probed for its chemistry toward building structurally different motifs.