Novel Chiral Auxiliary for Attempted Resolution of Key Roxifiban Intermediate: A Simple Diastereoselective Coupling Approach for the Synthesis of Roxifiban

Abstract

This article describes a simple method for the synthesis of roxifiban, a potent glycoprotein GP IIb-IIIa receptor antagonist, by a diastereoselective coupling approach to give .99.9% optical purity. We have also described an attempt to resolve the key synthetic intermediate by diastereomeric ester formation. Although we have been able to separate two diastereomeric esters, the removal of the chiral auxiliary led to partial racemization.

Heterocyclizations of functionalized heterocumulenes with C,N-, C,O-, and C,S-binucleophiles: XIII. Synthesis of dialkyl 2-oxo-3-allyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylates and their reaction with arylhydroxymoyl chlorides

“…Yet the effect of the substituents at nitrogen atoms remains practically nonstudied to a certain extent because of the lack of methods of the selective functionalization of the nitrogen atoms with biophore moieties. To the latter the isoxazoline heterocycle certainly belongs for among its derivatives substances are found with a wide range of the biologic action [5][6][7][8].The analysis of publications [9-11] reveals a limited number of isoxazoline derivatives linked to the other heterocycles by a methylene bridge. It was therefore feasible to extend our method [12] of 3-arylpyrimidinedicarboxylates synthesis on their 3-allyl analogs and to use the latter for building up an isoxazoline ring.…”

“…Yet the effect of the substituents at nitrogen atoms remains practically nonstudied to a certain extent because of the lack of methods of the selective functionalization of the nitrogen atoms with biophore moieties. To the latter the isoxazoline heterocycle certainly belongs for among its derivatives substances are found with a wide range of the biologic action [5][6][7][8].…”