An efficient synthesis of a key intermediate for the preparation of the rhinovirus protease inhibitor AG7088 via asymmetric dianionic cyanomethylation of N-Boc-l-(+)-glutamic acid dimethyl ester

Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors

“…Since the primary substrate specificity residue of 3Cpro and 3CLpro is a glutamine residue, a glutamine surrogate 15,16 was therefore utilized in the P1 site of the inhibitors. Like others, 17,18 we found that a hydrophobic amino acid such as leucine residue at the P2 site enhances the recognition.…”

Design and Synthesis of Peptidomimetic Severe Acute Respiratory Syndrome Chymotrypsin-like Protease Inhibitors

“…12 The resulting amine salt was treated with Na 2 CO 3 at reflux for 6 h to afford lactam ester 16. 13 Selective reduction of the ester group in the presence of the lactam was carried out with LiBH 4 (1 N solution in THF) in CH 2 Cl 2 to provide alcohol 17 in 91% yield. Alcohol 17 was converted into desired lactam fragment 18 by a one-pot oxidation followed by Wittig reaction of the resulting aldehyde with carbethoxyphosphorane in DMSO in 90% yield.…”

Synthesis and Evaluation of Keto-Glutamine Analogues as Potent Inhibitors of Severe Acute Respiratory Syndrome 3CLpro

“…However, the corresponding extended tetrapeptides 4a-d and 8a-d (entries 2-5, [9][10][11][12] are much more potent, indicating that both the tetrapeptide and keto-phthalhydrazide moieties are required for inhibition. Also, the cyclic glutamine analogues 8a-d (entries 9-12) exhibit better inhibition compared to the acyclic derivatives (compounds 4a-d, entries 2-5).…”