Collect. Czech. Chem. Commun. 2003, 68, 931-950

Synthesis of Optically Active N6-Alkyl Derivatives of (R)-3-(Adenin-9-yl)-2-hydroxypropanoic Acid and Related Compounds

Marcela Krečmerová*, Miloš Buděšínský, Milena Masojídková and Antonín Holý

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic


Reaction of ethyl (R)-oxiranecarboxylate (2a) with various nucleobases (adenine, 6-chloropurine, thymine, cytosine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one and 4-methoxypyrimidin-2(1H)-one) afforded ethyl 3-substituted-2-hydroxypropanoates 4-10. Enantioselectivity of this reaction is dependent on the type of the base: 6-chloropurine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one, thymine and cytosine gave optically pure R enantiomers. In other cases, partial or complete racemization occurred. Optically pure ethyl (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoate (5a) was hydrolyzed to give (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoic acid (11). Reactions of 11 with various primary or secondary amines led to N6-substituted (R)-3-(adenin-9-yl)-2-hydroxypropanoic acids 14-19. Enantiomeric purity was determined from 1H NMR spectra measured in the presence of (-)-(R)-1-(9-anthryl)-2,2,2-trifluoroethan-1-ol.

Keywords: Oxirane ring opening; Enantiomeric purity determination; Acyclic nucleoside analogues; Nucleosides; S-Adenosyl-L-homocysteine hydrolase inhibitors; SAH hydrolase; Adenine; Purines; Epoxides; Antivirals.

References: 24 live references.