Fluorinated β2- and β3-Amino Acids: Synthesis and Inhibition of α-Chymotrypsin

被引：33

作者：

Peddie, Victoria ^{[1
,2
]}

Pietsch, Markus ^{[1
]}

Bromfield, Karen M. ^{[3
]}

Pike, Robert N. ^{[4
]}

Duggan, Peter J. ^{[5
]}

Abell, Andrew D. ^{[1
]}

机构：

[1] Univ Adelaide, Sch Chem & Phys, Adelaide, SA 5005, Australia

[2] Univ Canterbury, Dept Chem, Christchurch 1, New Zealand

[3] Monash Univ, Ctr Green Chem, Clayton, Vic 3800, Australia

[4] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[5] CSIRO Mol & Hlth Technol, Clayton, Vic 3169, Australia

来源：

SYNTHESIS-STUTTGART | 2010年 / 11期

基金：

澳大利亚研究理事会;

关键词：

beta-amino acids; fluorination; crystal structure; alpha-chymotrypsin; inhibitor; AMINO-ACIDS; ENANTIOSELECTIVE SYNTHESIS; PEPTIDYL AMINOPEPTIDASES; CATALYZED HYDROGENATION; PROTEOLYTIC STABILITY; ASYMMETRIC-SYNTHESIS; CALPAIN INHIBITORS; SERINE PROTEASES; TRANSITION-STATE; SUBSTRATE;

D O I：

10.1055/s-0029-1218743

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The synthesis of a series of alpha-fluorinated beta(2)- and beta(3)-amino acid derivatives is described. Stereoselective fluorination at the alpha-carbon of the beta(3)-amino acids was achieved by deprotonation with lithium diisopropylamide followed by treatment with N-fluorobenzenesulfonimide. Fluorination of beta(2)-amino acids employed the chiral auxiliary (4R)-4-benzyl-2-oxazolidinone. The alpha-fluorinated amino acids and their non-fluorinated precursors were found to competitively inhibit alpha-chymotrypsin.

引用

页码：1845 / 1859

页数：15

共 76 条

[1] Ring-deactivated hydroxymethylpyrroles as inhibitors of α-chymotrypsin [J].

Abell, AD ;

Nabbs, BK .

BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (03) :621-628

[2] Synthesis and X-ray crystallographic structure of leucine-phenylalanyl succinimide-based pseudopeptides [J].

Abell, AD ;

Oldham, MD .

JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (05) :1509-1513

[3] SYNTHESIS OF CYCLIC ACYLATED ENAMINO ESTER DIPEPTIDE ANALOGS VIA THE BROMOLACTONIZATION OF A KETO ACID PHOSPHORANE [J].

ABELL, AD ;

TAYLOR, JM .

JOURNAL OF ORGANIC CHEMISTRY, 1993, 58 (01) :14-15

[4] Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors [J].

Abell, Andrew D. ;

Jones, Matthew A. ;

Coxon, James M. ;

Morton, James D. ;

Aitken, Steven G. ;

McNabb, Stephen B. ;

Lee, Hannah Y-Y ;

Mehrtens, Janna M. ;

Alexander, Nathan A. ;

Stuart, Blair G. ;

Neffe, Axel T. ;

Bickerstaff, Roy .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2009, 48 (08) :1455-1458

[5] Stereoselective synthesis of β-amino-α-fluoro esters via diastereoselective fluorination of enantiopure β-amino enolates [J].

Andrews, PC ;

Bhaskar, V ;

Bromfield, KM ;

Dodd, AM ;

Duggan, PJ ;

Duggan, SAM ;

McCarthy, TD .

SYNLETT, 2004, (05) :791-794

[6] Design and synthesis of novel fluoropeptidomimetics as potential mimics of the transition state during peptide hydrolysis [J].

Annedi, SC ;

Li, WY ;

Samson, S ;

Kotra, LP .

JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (03) :1043-1049

[7]

[Anonymous], 1998, SHELX 97

[8] CHYMOTRYPSIN - MOLECULAR AND CATALYTIC PROPERTIES [J].

APPEL, W .

CLINICAL BIOCHEMISTRY, 1986, 19 (06) :317-322

[9] Antibiotic and hemolytic activity of a β2/β3 peptide capable of folding into a 12/10-helical secondary structure [J].

Arvidsson, PI ;

Ryder, NS ;

Weiss, HM ;

Gross, G ;

Kretz, O ;

Woessner, R ;

Seebach, D .

CHEMBIOCHEM, 2003, 4 (12) :1345-1347

[10]

Arvidsson PI, 2001, CHEMBIOCHEM, V2, P771, DOI 10.1002/1439-7633(20011001)2:10<771::AID-CBIC771>3.0.CO

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