Design and synthesis of novel fluoropeptidomimetics as potential mimics of the transition state during peptide hydrolysis

被引：24

作者：

Annedi, SC

Li, WY

Samson, S

Kotra, LP

机构：

[1] Univ Toronto, Fac Pharm, Mol Design & Informat Technol Ctr, Toronto, ON M5S 2S2, Canada

[2] Univ Toronto, Dept Chem, Toronto, ON M5S 2S2, Canada

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2003年 / 68卷 / 03期

关键词：

D O I：

10.1021/jo026310c

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

alpha-Fluoroamino acids were targeted in our ongoing efforts to design novel fluoropeptidomimetics (1) as potential protease inhibitors. alpha-Fluoroglycine derivative (2) and alpha-fluoro-beta-aminoethanethiol derivatives (3-9) were synthesized for the first time en route to obtain the peptidomimetic moiety 1. The stability of 2-9 was investigated under organic as well as aqueous conditions. The stability of 3-9 under acidic and basic conditions, the effect of substitution at C-2 position, and potential biological activities are discussed.

引用

收藏

页码：1043 / 1049

页数：7

相关论文

共 30 条

[1] Molecular recognition of protein-ligand complexes: Applications to drug design [J].

Babine, RE ;

Bender, SL .

CHEMICAL REVIEWS, 1997, 97 (05) :1359-1472

[2] Synthesis of α-heterosubstituted glycine derivatives from dihaloethanamides [J].

Bailey, PD ;

Baker, SR ;

Boa, AN ;

Clayson, J ;

Rosair, GM .

TETRAHEDRON LETTERS, 1998, 39 (42) :7755-7758

[3] Selectfluor™ reagent F-TEDA-BF4 in action:: Tamed fluorine at your service [J].

Banks, RE .

JOURNAL OF FLUORINE CHEMISTRY, 1998, 87 (01) :1-17

[4] CHEMOSELECTIVITY OF THE REACTION OF DICHLOROBORANES WITH FUNCTIONAL AZIDES - EFFICIENT FUNCTIONALIZED SECONDARY AMINE SYNTHESIS [J].

CARBONI, B ;

VAULTIER, M ;

CARRIE, R .

TETRAHEDRON, 1987, 43 (08) :1799-1810

[5] LOSS OF THE TERT-BUTYLOXYCARBONYL (BOC) PROTECTING GROUP UNDER BASIC CONDITIONS [J].

CURRAN, TP ;

POLLASTRI, MP ;

ABELLEIRA, SM ;

MESSIER, RJ ;

MCCOLLUM, TA ;

ROWE, CG .

TETRAHEDRON LETTERS, 1994, 35 (30) :5409-5412

[6]

DEREK HRB, 1997, TETRAHEDRON, V53, P14565

[7] PREPARATION AND PROPERTIES OF N(ALPHA)DI-TERT-BUTOXYCARBONYL AMINO-ACIDS - APPLICABILITY IN THE SYNTHESIS OF LEU-ENKEPHALIN [J].

GUNNARSSON, K ;

RAGNARSSON, U .

ACTA CHEMICA SCANDINAVICA, 1990, 44 (09) :944-951

[8] FLUORINATION OF SULFUR-CONTAINING AMINO-ACIDS - REACTION OF XENON DIFLUORIDE WITH CYSTEINE DERIVATIVES [J].

HUANG, XL ;

BLACKBURN, BJ ;

AUYEUNG, SCF ;

JANZEN, AF .

CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1990, 68 (03) :477-479

[9] Syntheses of 1,4-benzothiazepines and 1,4-benzoxazepines via cyclizations of 1-[2-arylthio(oxy)ethyl]-5-benzotriazolyl-2-pyrrolidinones and 3-benzotriazolyl-2-[2-arylthio(oxy)ethyl]-1-isoindolinones [J].

Katritzky, AR ;

Xu, YJ ;

He, HY ;

Mehta, S .

JOURNAL OF ORGANIC CHEMISTRY, 2001, 66 (16) :5590-5594

[10] KINETIC EVIDENCE FOR THE OCCURRENCE OF A STEPWISE MECHANISM IN HYDRAZINOLYSIS OF PHTHALIMIDE [J].

KHAN, MN .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (14) :4536-4541