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4‐Acetylthio‐2,2‐dimethyl‐3‐oxobutyl Group as an Esterase‐ and Thermo‐Labile Protecting Group for Oligomeric Phosphodiesters
Author(s) -
Leisvuori Anna,
Lönnberg Harri,
Ora Mikko
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201402412
Subject(s) - chemistry , phosphodiester bond , protecting group , cleavage (geology) , esterase , yield (engineering) , enzyme , stereochemistry , leaving group , molecule , biochemistry , organic chemistry , catalysis , alkyl , geotechnical engineering , rna , materials science , fracture (geology) , engineering , metallurgy , gene
(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 (τ 1/2 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.