Stereodivergent synthesis of the LFA-1 antagonist BIRT-377 by porcine liver esterase desymmetrization and Curtius rearrangement.

Highly diastereoselective alkylation of aziridine-2-carboxylate esters: enantioselective synthesis of LFA-1 antagonist BIRT-377.

Total synthesis of LFA-1 antagonist BIRT-377 via organocatalytic asymmetric construction of a quaternary stereocenter.

A catalytic route for enantioselective total synthesis of cell adhesion inhibitor BIRT-377 is described. The quaternary stereocenter was constructed through l-proline-derived, tetrazole-catalyzed direct asymmetric alpha-amination of 3-(4-bromophenyl)-2-methylpropanal with dibenzyl azodicarboxylate. In the course of these studies, a one-pot trifluoro acetylation/selective benzyloxycarbonyl depro...

Cutting edge: a small molecule antagonist of LFA-1-mediated cell adhesion.

LFA-1 (CD18,CD11a) is a cell-adhesion molecule that mediates critical immunological processes. In this paper we report the discovery and characterization of (R)-5-(4-bromobenzyl)-3-(3, 5-dichlorophenyl)-1,5-dimethylimidazolidine-2,4-dione (BIRT 377), an orally bioavailable small molecule that interacts specifically with LFA-1 via noncovalent binding to the CD11a chain and prevents LFA-1 from bi...

Curtius rearrangement and Wolff homologation of functionalized peroxides

The Curtius and Wolff rearrangements of peroxide-containing alkanoyl azides and diazoketones provide an effi cient entry to peroxysubstituted amines, isocyanates, carbamates, and peroxyalkanoates. Scheme 2. Substrate preparation. Reagents and conditions: (a) tBuO2H, CsOH; (b) KMnO4; (c) m-CPBA; (d) t-BuO2H, BF3OEt2; (e) H2CrO4. 7456 DUSSAULT & XU IN TETRAHEDRON LETTERS 45 (2004) 2. Curtius rear...

Total synthesis of (+/-)-acetomycin and design of esterase-resistant analogs.

The synthesis of acetomycin and related analogs was investigated. Acetomycin was synthesized from diethyl allyl(methyl)malonate in 6.5% yield over 18 steps. The total number of steps was improved compared to our previous synthesis; i.e., four steps shorter, and the total yield was 4.5% greater than the previous synthesis. Acetomycin analogs with benzoyloxy and pivaloyloxy groups, instead of an ...