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Vanadium( II )‐ and Niobium( III )‐Induced, Diastereoselective Pinacol Coupling of Peptide Aldehydes to Give a C 2 ‐Symmetrical HIV Protease Inhibitor
Author(s) -
Kammermeier Bernhard,
Beck Gerhard,
Holla Wolfgang,
Jacobi Detlev,
Napierski Bernd,
Jendralla Heiner
Publication year - 1996
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.19960020312
Subject(s) - pinacol , chemistry , epimer , stereoselectivity , vanadium , peptide , protease , stereochemistry , medicinal chemistry , protease inhibitor (pharmacology) , combinatorial chemistry , organic chemistry , enzyme , human immunodeficiency virus (hiv) , catalysis , biochemistry , medicine , family medicine , antiretroviral therapy , viral load
Peptide aldehydes 15 a–c are prepared without epimerization from enantiomerically pure ( S )‐α‐amino acids (Scheme 3). Reductive pinacol homocoupling of 15 a–c , induced by vanadium complex 11 or niobium complex 16 in refluxing THF, yields C 2 ‐symmetrical ( S,R,R,S )‐configurated 6a , 6b and 2 , respectively, with moderate to high stereoselectivity (Scheme 4). In a novel protocol for the preparation and utilization of THF solutions of 11 , the isolation of air‐sensitive intermediates can be avoided and the potent HIV protease inhibitor 2 prepared in enantio‐ and diastereomerically pure form on a kilogram scale without chromatographic purification. The ( S,R,R,S ) selectivity of the pinacol homocouplings is confirmed by means of an independent, stereochemically unequivocal synthesis of 6 a and 2 from D ‐mannitol 4 (Scheme 1).