Purines. LVII. Regioselective Alkylation of N⁶, 9-Disubstituted 8-Oxoadenines : Syntheses of the Sea Anemone Purine Caissarone and Some Positional Isomers and Analogues

Abstract

The first total synthesis of caissarone hydrochloride (1), a constituent of the sea anemone Bunodosoma caissarum, has been accomplished via a two-step route starting from N⁶, 9-dimethyl-8-oxoadenine (3), which is obtainable from 9-methyladenine (5) through a four-step route. The key step in the synthesis is the regioselective methylation of 3 at N(3), which has been designed on the basis of a methylation study of N⁶-benzyl-9-methyl-8-oxoadenine (11). Some positional isomers (19, 24, and 31) and analogues (8, 26, and 32) of 1 have also been synthesized. A ¹H-NMR spectroscopic study has suggested that the free base (23) of caissarone is capable of forming a hetero-base pair (such as 41) with 2', 3', 5'-tri-O-acetylguanosine (40) in Me₂SO-d₆.