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25‐Hydroxyvitamin D 3 Synthesis by Enzymatic Steroid Side‐Chain Hydroxylation with Water
Author(s) -
Warnke Markus,
Jung Tobias,
Dermer Juri,
Hipp Karin,
Jehmlich Nico,
von Bergen Martin,
Ferlaino Sascha,
Fries Alexander,
Müller Michael,
Boll Matthias
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201510331
Subject(s) - hydroxylation , chemistry , monooxygenase , regioselectivity , substrate (aquarium) , enzyme , vitamin d and neurology , biocatalysis , yield (engineering) , steroid , catalysis , enzyme catalysis , cytochrome p450 , side chain , potassium ferricyanide , stereochemistry , organic chemistry , biochemistry , reaction mechanism , medicine , oceanography , materials science , polymer , endocrinology , hormone , metallurgy , geology
The hydroxylation of vitamin D 3 (VD 3 , cholecalciferol) side chains to give 25‐hydroxyvitamin D 3 (25OHVD 3 ) is a crucial reaction in the formation of the circulating and biologically active forms of VD 3 . It is usually catalyzed by cytochrome P450 monooxygenases that depend on complex electron donor systems. Cell‐free extracts and a purified Mo enzyme from a bacterium anaerobically grown with cholesterol were employed for the regioselective, ferricyanide‐dependent hydroxylation of VD 3 and proVD 3 (7‐dehydrocholesterol) into the corresponding tertiary alcohols with greater than 99 % yield. Hydroxylation of VD 3 strictly depends on a cyclodextrin‐assisted isomerization of VD 3 into preVD 3 , the actual enzymatic substrate. This facile and robust method developed for 25OHVD 3 synthesis is a novel example for the concept of substrate‐engineered catalysis and offers an attractive alternative to chemical or O 2 /electron‐donor‐dependent enzymatic procedures.