A1 Journal article – refereed

4-Acetylthio-2,2-dimethyl-3-oxobutyl group as an esterase- and thermo-labile protecting group for oligomeric phosphodiesters

List of Authors: Anna Leisvuori, Harri Lönnberg, Mikko Ora

Publisher: Wiley-VCH

Publication year: 2014

Journal: European Journal of Organic Chemistry

Issue number: 26

Number of pages: 11

ISSN: 1434-193X

DOI: http://dx.doi.org/10.1002/ejoc.201402412

(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.

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