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

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

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

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, (e...

Organocatalytic asymmetric multicomponent cascade reaction via 1,3-proton shift and [3+2] cycloaddition: an efficient strategy for the synthesis of oxindole derivatives.

An efficient and powerful organocatalytic cascade reaction was achieved for the synthesis of biologically important chiral spiro[pyrrolidin-3,2'-oxindoles] using very simple and readily available starting materials. Three C-C bonds and four contiguous stereogenic centers including one quaternary stereocenter were established in a single operation with reasonable yields and good stereoselectivity.

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...

Observation of neighboring ortho-hydroxyl group participation in organocatalytic asymmetric sequential Michael-lactonization reactions: synthesis of highly substituted chiral spirodihydrocoumarins.

A general approach to asymmetric synthesis of highly substituted spirodihydrocoumarins with a quaternary stereocenter was achieved through neighboring ortho-hydroxyl group induced sequential Michael-lactonization reactions on 2-(2-nitrovinyl)phenols with alkyl cyclopentanone-2-carboxylates in the presence of a catalytic amount of quinine-NH-thiourea followed by p-TSA.