Premium
Reverse Stereoselectivity in the Lipase‐Catalyzed Hydrolysis of Diacetylated Pyrimidine Acyclonucleosides
Author(s) -
Kołodziejska Renata,
Studzińska Renata
Publication year - 2016
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201600931
Subject(s) - chemistry , lipase , hydrolysis , pyrimidine , stereoselectivity , catalysis , ring (chemistry) , enzyme , selectivity , burkholderia , stereochemistry , enzymatic hydrolysis , organic chemistry , biology , bacteria , genetics
The enzymatic hydrolysis of the prochiral acetyl groups of pyrimidine acyclonucleoside derivatives was catalyzed effectively by lipase Amano PS from Burkholderia cepacia (BCL) to give monoacetates with a high optical purity. The stereopreference of BCL depends on the structure of the substrates. The BCL‐catalyzed hydrolysis of the unsubstituted acyclonucleoside 2‐{[2,4‐dioxo‐3,4,5,6,7,8‐hexahydroquinazolin‐1(2 H )‐yl]methoxy}propane‐1,3‐diyl diacetate is enantiotopically selective (pro‐ R ). After the reaction, the enantiomerically pure 2‐ S isomer was obtained. The additional group on the ring caused a dramatic change in the stereopreference of the enzyme‐catalyzed deacylation compared to that of the unsubstituted compound, and the reverse chiral preference was observed. The enzymatic deacylation of prochiral ester groups of acyclonucleoside analogs substituted at C‐6 and C‐8 in 2,4‐dioxo‐3,4,5,6,7,8‐hexahydroquinazoline ring led to the 2‐ R isomer (pro‐ S selectivity).