Title: Simplified synthesis of individual stereoisomers of the 4-hydroxynonenal adducts of deoxyguanosine.

Authors: Christov, Plamen P; Hawkins, Edward K; Kett, Nathan R; Rizzo, Carmelo J

Published In Tetrahedron Lett, (2013 Aug 07)

Abstract: We previously reported the synthesis of the 1,N(2)-deoxyguanosine adducts of 4-hydroxynonenal, an important product of lipid peroxidation, which involved the nucleophilic aromatic substitution reaction of an O(6)-protected-2-fluoroinosine with 4-amino-1,2,5-trihydroxydecanal followed by periodate oxidation of the vicinal diol.(3) An improved synthesis of the amino triols has been developed. The syn and anti diasteromers of a key intermediate, 4-nitro-5-hydroxy-1-decene, were synthesized by a Henry reaction and separated; each diastereomer was further separated into individual enantiomers by chiral supercritical fluid chromatography. Of note, dihydroxylation of the terminal olefin under conventional conditions with catalytic OsO4 and a tertiary amine oxide as the stoichiometric oxidant led to scrambling of stereochemistry at C4. The scrambling was not observed when t-butylhydroperoxide was used as the oxidant.

PubMed ID: 23935223

MeSH Terms: No MeSH terms associated with this publication