An expedient synthesis of N(alpha)-protected-L-tetrahydrofuranylglycine and its application in the synthesis of novel substrate based inhibitors of HIV-1 protease.
Z- and Fmoc-L-tetrahydrofuranylglycines have been obtained from L-vinylglycine through dipolar cycloaddition reaction, and its Fmoc derivative has been applied in the synthesis of modified S9 and S10 substrates of HIV-1 protease. These compounds mostly acted as strong inhibitors, rather than substrates, of the protease, probably due to the favourable interactions of the tetrahydrofuranylglycine moiety at the S(2) site.
Rajesh
S
S
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Japan.
Ami
Ei'ichi
E
Kotake
Tomoya
T
Kimura
Tooru
T
Hayashi
Yoshio
Y
Kiso
Yoshiaki
Y
D005663:Furans / Q000737:chemistry / Q000494:pharmacology; D005998:Glycine / Q000737:chemistry / Q000494:pharmacology; D016333:HIV Protease / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D005663:Furans; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D016333:HIV Protease; D005998:Glycine