title: Stereodivergent synthesis of the LFA-1 antagonist BIRT-377 by porcine liver esterase desymmetrization and Curtius rearrangement.
abstract: The LFA-1 inhibitor and leukocyte adhesion suppressor BIRT-377 was prepared in high enantiomeric excess by desymmetrization of dimethyl 2-p-bromobenzyl-2-methylmalonate, followed by condensation of the resulting carboxylic acid with 3,5-dichloroaniline, saponification of the remaining ester and Curtius rearrangement as the key steps. When Curtius rearrangement preceded the condensation step, (ent)-BIRT-377 was similarly obtained in high ee.
authors.affiliation: Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary AB, CanadaT2N 1N4. tgback@ucalgary.ca.
authors.forename: Aaron
authors.initials: A
authors.lastname: Johnson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Saunders
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Back
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D004950:Esterases / Q000378:metabolism*; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D013237:Stereoisomerism; D013552:Swine
chemical_list: C400461:BIRT 377; D048289:Imidazolidines; D016169:Lymphocyte Function-Associated Antigen-1; D004950:Esterases