Document Detail


Stereoselectivity and regioselectivity in nucleophilic ring opening in derivatives of 3-phenylisoxazolo[2,3-a]pyrimidine. Unpredicted dimerization and ring transformation. Syntheses of derivatives of pyrimidinylmethylamine, pyrimidinylmethylamino acid amides, and alpha-amino-2-pyrimidinylacetamides.
MedLine Citation:
PMID:  15255723     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The nucleophilic ring opening of the isoxazolone ring in 2-oxo-3-phenylisoxazolo[2,3-a]pyrimidine derivatives by optically active amino acid amides and ephedrine led to pyrimidinylmethylamino acid amides. Using amides of different L-amino acids and (-)-ephedrine resulted in different degrees of stereoselectivity. The degree of streoselectivity depended mostly on the nucleophile used. When applying hydroxy amines such as ephedrine, the attack via the secondary amino group was found as the favored regioselectivity. Upon replacement of the oxo group in position 2 in the phenylisoxazolo[2,3-a]pyrimidine system by an imino group, it was expected that the spontaneous decarboxylation that follows the ring opening would not take place, thus achieving amino acid amide derivatives of 2-pyrimidinylacetamide, which are closely related to pyrimidoblamic acid, an important constituent of Bleomycins, used in cancer therapy. However, by heating 5,7-dimethyl-2-imino-3-phenylisoxazolo[2,3-a]pyrimidine in solution, it underwent an unprecedented dimerization process that involved both the phenyl and the imino group. After protecting the imino group by acetylation, the ring opening by nucleophiles was possible, resulting in the formation of derivatives of 2-pyrimidinylacetamide. 2-Acetylimino-5,7-dimethyl-3-phenylisoxazolo[2,3-a]pyrimidine also underwent a ring transformation, yielding an interesting indolone derivative. Selectivity in ring opening and mechanisms of dimerization and ring transformation are discussed.
Authors:
Gury Zvilichovsky; Isra Gbara-Haj-Yahia
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of organic chemistry     Volume:  69     ISSN:  0022-3263     ISO Abbreviation:  J. Org. Chem.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-16     Completed Date:  2004-09-17     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2985193R     Medline TA:  J Org Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4966-73     Citation Subset:  IM    
Affiliation:
Department of Organic Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. gury@vms.huji.ac.il
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MeSH Terms
Descriptor/Qualifier:
Amides / chemical synthesis,  chemistry
Amines / chemical synthesis*,  chemistry*
Amino Acids / chemical synthesis,  chemistry
Dimerization
Methylamines / chemical synthesis*,  chemistry*
Molecular Structure
Oxazoles / chemical synthesis*,  chemistry*
Pyrimidines / chemical synthesis*,  chemistry*
Stereoisomerism
Chemical
Reg. No./Substance:
0/2-oxo-3-phenylisoxazolo(2,3-a)pyrimidine; 0/Amides; 0/Amines; 0/Amino Acids; 0/Methylamines; 0/Oxazoles; 0/Pyrimidines; 0/pyrimidinylmethylamine

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