Self-regeneration of stereocenters: a practical enantiospecific synthesis of LFA-1 antagonist BIRT-377.
[reaction: see text] An efficient enantiospecific synthesis of the LFA-1 antagonist BIRT-377 has been achieved in 43% overall yield in eight steps. The key transformations involve the stereospecific formation of the trans imidazolidinone 7, subsequent alkylation, and the efficient hydrolysis of disubstituted imidazolidinone 9. The process is practical, robust, and cost-effective; it has been successfully implemented in the pilot plant to produce multikilogram quantities of the drug BIRT-377.
Yee
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Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Old Ridgebury Road, P.O. Box 368, Ridgefield, Connecticut 06877-0368, USA. nyee@rdg.boehringer-ingelheim.com
D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D048289:Imidazolidines; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D013237:Stereoisomerism
C400461:BIRT 377; D007093:Imidazoles; D048289:Imidazolidines; D007166:Immunosuppressive Agents; D016169:Lymphocyte Function-Associated Antigen-1