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- Title
4-Acetylthio-2,2-dimethyl-3-oxobutyl Group as an Esterase- and Thermo-Labile Protecting Group for Oligomeric Phosphodiesters.
- Authors
Leisvuori, Anna; Lönnberg, Harri; Ora, Mikko
- Abstract
(4-Acetylthio-2,2-dimethyl-3-oxobutyl)-protected oligomeric phosphodiesters 1 and 2 were synthesized and removal of the protecting groups in the presence and absence of hog liver esterase was followed at pH 7.5 and 37 °C. Phosphotriesters 1 and 2 were successfully converted into the desired fully deprotected phosphodiesters 3 and 4, respectively. Some cleavage of internucleosidic P-O bonds took place, which reduced the yield of 3 and 4. Non-enzymatic removal of the protecting group was only modestly retarded by accumulation of negative charge on the molecule. With 1, the half-lives for the departure of the first and second protecting groups were 7.8 and 10.7 h, respectively, and with 2, 6.2 and 7.2 h, respectively. After 4 d, 70 % of both starting materials 1 and 2 were converted into the unprotected phosphodiester. The presence of hog liver esterase (2.6 units mL-1) resulted in fast removal of the first protecting group (τ1/2 2.7 min and 36 min with 1 and 2, respectively), but the appearance of fully deprotected 3 and 4 was accelerated only by a factor of 2, consistent with dramatic retardation of the enzymatic reaction upon accumulation of the negative charge.
- Subjects
PRODRUGS; OLIGONUCLEOTIDES; CHEMICAL kinetics; PHARMACEUTICAL chemistry; ORGANIC chemistry research
- Publication
European Journal of Organic Chemistry, 2014, Vol 2014, Issue 26, p5816
- ISSN
1434-193X
- Publication type
Article
- DOI
10.1002/ejoc.201402412