Synthesis of deoxytetrahydrouridine.
The alpha-hydroxyamido functionality of 2'-deoxytetrahydrouridine (dTHU) makes this seemingly simple and generally useful compound difficult to obtain. Reported synthetic strategies produce extremely poor yields and multiple products, and full characterization data is not available. Described herein is a two-step approach for synthesizing dTHU in increased yields and purity; stability concerns are also addressed. Catalytic reduction (5% Rh/alumina) of 2'-deoxyuridine, followed by reduction with sodium borohydride as a limiting reagent, produces dTHU and limits formation of side products. Evidence was obtained for formation of a methoxy-substituted analogue during purification. By this strategy, dTHU of >95% purity can be obtained in 40% yield on a 150 mg scale.
Norton
Jolanna
J
Department of Medicinal Chemistry, The Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Matsuo
Hiroshi
H
Sturla
Shana J
SJ
D015394:Molecular Structure; D013237:Stereoisomerism; D013767:Tetrahydrouridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D013767:Tetrahydrouridine; C052729:2'-deoxytetrahydrouridine