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2,2-Disubstituted 4-Acylthio-3-oxobutyl Groups as Esterase- and Thermo-labile Protecting Groups of Phosphodiesters.
MedLine Citation:
PMID:  23272806     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Five different 2,2-disubstituted 4-acylthio-3-oxobutyl groups have been introduced as esterase-labile phosphodiester protecting groups that additionally are thermolabile. The phosphotriesters 1, 2 and 3 were prepared to determine the rate of the enzymatic and non-enzymatic removal of such groups at 37 ºC and pH 7.5 by HPLC-ESI-MS. Additionally, 1H NMR spectroscopic monitoring was used for structural characterization of the intermediates and products. When treated with Hog Liver Esterase, these groups were removed by enzymatic deacylation followed by rapid chemical cyclization to 4,4-disubstituted dihydrothiophen-3(2H)-one. The rate of the enzymatic deprotection could be tuned by the nature of the 4-acylthio substituent, the benzoyl group and acetyl groups being removed 50 and 5 times as fast as the pivaloyl group. No alkylation of glutathione could be observed upon the enzymatic deprotection. The half-life for the non-enzymatic deprotection varied from 0.57 h to 35 h depending on the electronegativity of the 2-substituents and the size of the acylthio group. The acyl group evidently migrates from the sulphur atom to C3-gem-diol obtained by hydration of the keto group and the exposed mercapto group attacks on C1 resulting in departure of the protecting group as 4,4-disubstituted 3-acyloxy-4,5-dihydrothiophen with concomitant release of the desired phosphodiester.
Authors:
Emilia Kiuru; Zafar Ahmed; Harri Lonnberg; Leonid Beigelman; Mikko Ora
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-28
Journal Detail:
Title:  The Journal of organic chemistry     Volume:  -     ISSN:  1520-6904     ISO Abbreviation:  J. Org. Chem.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985193R     Medline TA:  J Org Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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