Synthesis of 9,9,9-trideutero-1,4-dihydroxynonane mercapturic acid (d3-DHN-MA), a useful internal standard for DHN-MA urinalysis.
Racemic 1,4-dihydroxynonane mercapturic acid (DHN-MA) and 9,9,9-trideutero-1,4-dihydroxynonane mercapturic acid (d3-DHN-MA) are synthesized on a 400-mg scale (overall yield approximately 40%) by a two-step sequence involving Michael addition of N-acetyl-L-cysteine to methyl 4-hydroxynon-2(E)-enoate or methyl 9,9,9-trideutero-4-hydroxynon-2 (E)-enoate, followed by reduction of the intermediate adducts with lithium borohydride. The requisite starting methyl esters are obtained, respectively, from heptanal or 7,7,7-trideuteroheptanal and methyl 4-chlorophenylsulfinylacetate via a sulfoxide piperidine and carbonyl reaction described in the literature. The 7,7,7-trideuteroheptanal is easily prepared by classical methods in four steps from 6-bromo-1-hexanol. 13C NMR data indicate that DHN-MA as well as d3-DHN-MA are obtained as mixtures of four diastereomers. Preliminary results show that d3-DHN-MA could be used as an internal standard for mass spectrometric quantification of DHN-MA in human urine.
Chantegrel
B
B
Laboratoire de Chimie Organique INSA-Lyon, Bâtiment Jules Verne, 17 Avenue Jean Capelle, 69621 Villeurbanne, France. Bernard.Chantegrel@insa-lyon.fr
Deshayes
C
C
Doutheau
A
A
Steghens
J P
JP
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000652:urine*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D012015:Reference Standards; D016482:Urinalysis / Q000379:methods
C480284:9,9,9-trideutero-1,4-dihydroxynonane mercapturic acid; D000111:Acetylcysteine