Collect. Czech. Chem. Commun. 1979, 44, 593-612

Synthesis of racemic and optically active erythro- and threo-9-(2,3,4-trihydroxybutyl)adenines and related compounds

Antonín Holý

Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6


Reduction of diethyl 2,3-O-isopropylidene-DL-tartrate (II) with lithium aluminium hydride afforded 2,2-dimethyl-1,3-dioxolane-threo-4,5-dimethanol (III) which was transformed to the monotosyl derivative VI. Reaction of this compound with sodium salt of adenine, followed by acidic deblocking, gave 9-(DL)-threo-(2,3,4-trihydroxybutyl)adenine (IX). Analogously, 9-(DL)-erythro-(2,3,4-trihydroxybutyl)adenine (XVII) was prepared from diethyl meso-tartrate (XI) via the diol XIII and the tosyl derivative XV. 1,3-O-Benzylidene-D-threitol (D-XVIII) was converted successively into the 4-O-tosyl derivative XIX and the 2-O-benzoyl-4-O-tosyl derivative XX. Reaction of the compound XX with sodium salt of adenine, followed by removal of the protecting groups in the intermediate XXI, afforded 9-(D)-threo-(2,3,4-trihydroxybutyl)adenine (D-XXII); analogously, 1,3-O-benzylidene-L-threitol (L-XVIII) was transformed into the 9-(L)-threo-derivative L-XXII. The D-threo-derivative D-XXII was prepared also from 5-O-tosyl-3-O-benzoyl-1,2-O-isopropylidene-α-D-xylofuranoside (XXIII) or from 3-O-benzyl derivative XXIX by condensation with sodium salt of adenine, followed by acidic hydrolysis, degradation of the 1,2-diol grouping by sodium periodate and sodium borohydride, and methanolysis or hydrogenolysis. An analogous procedure was used for preparation of 1-(D)-threo-(2,3,4-trihydroxybutyl)uracil (D-XXVII). Methyl 2,3-O-isopropylidene-5-benzoyl-6-tosyl-D-mannofuranoside (XXXVI) was transformed to the 5-(adenin-9-yl) derivative XXXVII which after hydrolysis of the dioxolane ring, followed by cleavage of the cis-diol with sodium periodate, reduction with sodium borohydride and methanolysis, afforded 9-(D)-erythro-(2,3,4-trihydroxybutyl)adenine (D-XL). The L-enantiomer (L-XL) was obtained from 5-O-(adenin-9-yl)-3-O-benzoyl-1,2-O-isopropylidene-β-L-arabinofuranoside (XXXIIIb) by acidic cleavage, degradation of the intermediate XXXIV with periodate and methanolysis.