Document Detail


New neplanocin analogues. IX. A practical preparation of (6'R)-6'-C-methylneplanocin A (RMNPA), a potent antiviral agent, and the determination of its 6'-configuration. Diastereoselective deamination by adenosine deaminase.
MedLine Citation:
PMID:  9023976     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously synthesized (6'R)- and (6'S)-6'-C-methylneplanocin A's (2a and 2b, respectively), and found that one of them has a potent antiviral activity, though its 6'-configuration has not been confirmed. This report describes the determination of the 6'-configuration and practical preparation of the antivirally active diastereomer. The 6'-configuration of the active diastereomer was determined as R by the modified Mosher's method as well as by synthesizing 2b from the known cyclopentenone derivative 10. A practical method for preparing the 6'R-diastereomer was developed by using diastereoselective deamination with Ado deaminase as the key step. Treatment of the diastereomeric mixture of 2a and 2b, which was prepared via an addition reaction of Me3Al with the 6'-formyl derivative 3, with Ado deaminase from calf intestine, deaminated 2b selectively to give the corresponding (6'S)-inosine congener 5, and left the desired 2a not deaminated. After silica gel column chromatography, 2a was obtained in a pure form.
Authors:
S Shuto; T Obara; S Yaginuma; A Matsuda
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chemical & pharmaceutical bulletin     Volume:  45     ISSN:  0009-2363     ISO Abbreviation:  Chem. Pharm. Bull.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-03-24     Completed Date:  1997-03-24     Revised Date:  2001-11-28    
Medline Journal Info:
Nlm Unique ID:  0377775     Medline TA:  Chem Pharm Bull (Tokyo)     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  138-42     Citation Subset:  IM    
Affiliation:
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenosine / analogs & derivatives*,  chemical synthesis,  chemistry,  isolation & purification
Adenosine Deaminase / chemistry*
Antiviral Agents / chemical synthesis*,  chemistry*
Chromatography, Gel
Deamination
Stereoisomerism
Chemical
Reg. No./Substance:
0/Antiviral Agents; 138571-54-7/6'-C-methylneplanocin A; 58-61-7/Adenosine; EC 3.5.4.4/Adenosine Deaminase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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