Paul Grover

Rapid access to enantiopure bupropion and its major metabolite by stereospecific nucleophilic substitution on an α-ketotriflate

Abstract A stereospecific method for the synthesis of enantiopure α-aminoketone from its corresponding α-hydroxy-ketone via the triflate intermediate is discussed. This strategy provides a rapid and efficient route for the preparation of either enantiomer of bupropion and its biologically active hydroxylated metabolite.

Rigid aminoalcohol backbone as a highly defined chiral template for the preparation of optically active tertiary α-hydroxyl acids

Abstract Constrained aminoalcohol derived-ketoester or amides have provided a new entry for the production of enantiopure acid 1 for (S)-oxybutynin.

Effective tuning of the arene and alkanesulfinamides for highly enantioselective synthesis of (S)-4-chlorophenylphenylmethylamine, a key intermediate for antihistamic (S)-cetirizine

High diastereoselectivity (>94%) has been achieved in the phenylMgBr addition process to chlorophenyl aldimine derived from the new and sterically hindered triisopropylbenzene sulfinamide (TIPBSA) in the synthesis of a key intermediate of (S)-Cetirizine. Surprisingly, under the same reaction conditions, toluenesulfinamide derived chlorophenyl aldimine provided only 10% ee.

Practical chemical and enzymatic technologies for (S)-1,4-benzodioxan-2-carboxypiperizine intermediate in the synthesis of (S)-doxazosin mesylate

Abstract ( S )-1,4-Benzodioxan-2-carboxypiperazine ( S )- 2 , the key chiral intermediate for the synthesis of ( S )-doxazosin, was prepared utilizing two approaches: (i) enzymatic resolution of ethyl 1,4-benzodioxan-2-carboxylate with an esterase ( Serratia ) followed by amide formation; (ii) direct resolution of 1,4-benzodioxan-2-carboxypiperazine 2 with d -tartaric acid. An efficient process for the conversion of ( S )- 2 to ( S )-doxazosin mesylate was developed (80% yield, 99.9% e.e.).

First preparation of enantiomerically pure sibutramine and its major metabolite, and determination of their absolute configuration by single crystal X-ray analysis

Abstract Racemic sibutramine was resolved with dibenzoyl- d -tartaric acid, and the absolute stereochemistry of sibutramine was determined by single crystal X-ray crystallography of its dibenzoyl d -tartrate. The major active metabolite (desmethylsibutramine) was obtained by demethylation of sibutramine with DEAD. Enantiomeric purity of sibutramine was determined by HPLC on an Ultron ES-OVM column.

In vitro and in vivo evaluation of O-alkyl derivatives of tramadol.

Tramadol is a centrally acting opioid analgesic structurally related to codeine and morphine. O-Alkyl, N-desmethyl, and non-phenol containing derivatives of tramadol were synthesized to probe their effect on metabolic stability and both in vitro and in vivo potency.