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(ω‐2,ω‐2,ω‐3,ω‐3)‐Tetradeuterio‐fatty acids for mechanistic studies of enzyme‐catalyzed hydroxylation reactions
Author(s) -
Horner John H.,
Newcomb Martin
Publication year - 2012
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2959
Subject(s) - chemistry , catalysis , alkylation , hydroxylation , lauric acid , enzyme , fatty acid , alcohol , fatty alcohol , cytochrome p450 , organic chemistry , stereochemistry
Among the thousands of cytochrome P450 enzymes known, many selectively hydroxylate the hydrocarbon tail of fatty acids at the terminal (ω) position and the ω‐1, ω‐2, and ω‐3 positions. A general method for synthesis of (ω‐2,ω‐2,ω‐3,ω‐3)‐tetradeuterio‐fatty acids that can be used in mechanistic studies of cytochromes P450 is illustrated by the synthesis of 9,9,10,10‐tetradueteriododecanoic (lauric) acid and 13,13,14,14‐tetradeuteriohexadecanoic (palmitic) acid. Deuterium is introduced early in the synthesis by reduction of the THP ether of 4‐heptyn‐1‐ol with deuterium gas to give a common labeled intermediate, 4,4,5,5‐tetradeuterioheptan‐1‐ol. This alcohol is converted to the corresponding tosylate that is used to alkylate O‐protected (ω‐1)‐alkyn‐1‐ols to give, eventually, long‐chain alcohols that are oxidized to the corresponding fatty acids. An important experimental detail is that relatively large amounts of Wilkinson's catalyst were used to limit isotopic scrambling. Copyright © 2012 John Wiley & Sons, Ltd.