Collect. Czech. Chem. Commun. 1996, 61, 442-457

Intramolecular Cyclization of Some Acyclic Nucleoside Analogs

Zlatko Janeba, Antonín Holý, Hana Votavová and Milena Masojídková

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


Reaction of stereoisomeric 8-bromo-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (8) with concentrated aqueous ammonia, sodium hydride, potassium tert-butoxide, or 1,8-diazabicyclo[5,4,0]undec-7-ene afforded 4e-O,8-anhydro-9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines 9 (derivatives of 1,3-oxazepino[2,3-e]adenine). The CD spectra of optically active stereoisomers of 9 have been studied and it was found that for threo isomers 9a and 9b their character corresponds to 5'-O,8-cycloadenosine. The compounds 9 were also prepared by oxidative cyclization of 9-(2,3-O-isopropylidene-2,3,4-trihydroxybutyl)adenines (7) with lead(IV) acetate in benzene. Reaction of 9-(4-hydroxybutyl)adenine (14) with lead(IV) acetate smoothly afforded the seven-membered ring derivative, 4'-O,8-anhydro-9-(4-hydroxybutyl)adenine (15); no anhydro products with five-, six-, and eight-membered ring were found. 2',3'-O-Isopropylideneinosine (16) reacted with lead(IV) acetate to give 5'-O,8-cyclo-2',3'-O-isopropylideneinosine (17) whereas 9-(4-hydroxybutyl)hypoxanthine (18) afforded no cyclic products.

Keywords: Nucleosides; Acyclic analogs; Purine derivatives.