Journal of Organic Chemistry 2001-01-01

Stereoselective Synthesis of HIV-1 Protease Inhibitor, DMP 323.

MichaelE. Pierce, GregoryD. Harris, Qamrul Islam, LilianA. Radesca, Louis Storace, RobertE. Waltermire, Ed Wat, PrabhakarK. Jadhav, GeorgeC. Emmett

Index: J. Org. Chem. 61 , 444, (1996)

Full Text: HTML

Abstract

DMP 323, a potent HIV-1 protease inhibitor, has been synthesized by an efficient stereoselective process, amenable to large scale preparations. The core C(2) symmetric diol was synthesized by a stereoselective pinacol coupling of CBZ protected D-phenylalanine. Judicious selection of protecting groups allowed cyclic urea formation under mild conditions, enhanced the ease of bis-alkylation, and led to intermediates which were easily purified without chromatography. Additionally, a one-pot, high yield process was developed to prepare the alkylating agent, 4-[(triphenylmethoxy)methyl]benzyl chloride from 1,4-benzenedimethanol.

Related Compounds

Related Articles:

Preparation of Aminoalkyl Chlorohydrin Hydrochlorides: Key Building Blocks for Hydroxyethylamine-Based HIV Protease Inhibitors.

2001-01-01

[J. Org. Chem. 61 , 3635, (1996)]

Cyclic HIV protease inhibitors: synthesis, conformational analysis, P2/P2' structure-activity relationship, and molecular recognition of cyclic ureas.

1996-08-30

[J. Med. Chem. 39 , 3514, (1996)]

Inhibitors of HIV-1 proteinase containing 2-heterosubstituted 4-amino-3-hydroxy-5-phenylpentanoic acid: synthesis, enzyme inhibition, and antiviral activity.

1994-09-16

[J. Med. Chem. 37 , 3079, (1994)]

Improved cyclic urea inhibitors of the HIV-1 protease: synthesis, potency, resistance profile, human pharmacokinetics and X-ray crystal structure of DMP 450.

1996-04-01

[Chem. Biol. 3 , 301, (1996)]

Liu, C. et al.

[Org. Process Res. Dev. 1 , 45, (1997)]

More Articles...