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Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: a key intermediate for dipeptidyl peptidase IV inhibitors.

ABSTRACT: An alternative and practical synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile was achieved. Reaction of L-proline with chloroacetyl chloride was followed by conversion of the carboxylic acid moiety of the resulting N-acylated product into the carbonitrile via the corresponding amide intermediate. The synthesized pyrrolidine derivative was utilized to prepare DPP-IV inhibitor Vildagliptin.

SUBMITTER: Singh SK

PROVIDER: S-EPMC2486489 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: a key intermediate for dipeptidyl peptidase IV inhibitors.

Singh Santosh Kumar SK Manne Narendra N Pal Manojit M

Beilstein journal of organic chemistry 20080612

An alternative and practical synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile was achieved. Reaction of L-proline with chloroacetyl chloride was followed by conversion of the carboxylic acid moiety of the resulting N-acylated product into the carbonitrile via the corresponding amide intermediate. The synthesized pyrrolidine derivative was utilized to prepare DPP-IV inhibitor Vildagliptin. ...[more]

PMID: 18941490

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Project description:Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor-associated angioedema. This case-control study tested the hypothesis that dipeptidyl peptidase IV activity and antigen are decreased in sera of patients with a history of angiotensin-converting enzyme inhibitor-associated angioedema. Fifty subjects with a history of angiotensin-converting enzyme inhibitor-associated angioedema and 176 angiotensin-converting enzyme inhibitor-exposed control subjects were ascertained. Sera were assayed for angiotensin-converting enzyme activity, aminopeptidase P activity, aminopeptidase N activity, dipeptidyl peptidase IV activity, and antigen and the ex vivo degradation half-lives of bradykinin, des-Arg(9)-bradykinin, and substance P in a subset. The prevalence of smoking was increased and of diabetes decreased in case versus control subjects. Overall, dipeptidyl peptidase IV activity (26.6+/-7.8 versus 29.6+/-7.3 nmol/mL per minute; P=0.026) and antigen (465.8+/-260.8 versus 563.1+/-208.6 ng/mL; P=0.017) were decreased in sera from individuals with angiotensin-converting enzyme inhibitor-associated angioedema compared with angiotensin-converting enzyme inhibitor-exposed control subjects without angioedema. Dipeptidyl peptidase IV activity (21.5+/-4.9 versus 29.8+/-6.7 nmol/mL per minute; P=0.001) and antigen (354.4+/-124.7 versus 559.8+/-163.2 ng/mL; P=0.003) were decreased in sera from cases collected during angiotensin-converting enzyme inhibition but not in the absence of angiotensin-converting enzyme inhibition. The degradation half-life of substance P correlated inversely with dipeptidyl peptidase IV antigen during angiotensin-converting enzyme inhibition. Environmental or genetic factors that reduce dipeptidyl peptidase IV activity may predispose individuals to angioedema.

Dataset Information

Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: a key intermediate for dipeptidyl peptidase IV inhibitors.

Publications

Synthesis of (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile: a key intermediate for dipeptidyl peptidase IV inhibitors.

Similar Datasets

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