Synthesis of Tetrahydrodiazepinopurines by Ring-Closing Metathesis

Abstract

The tetrahydrodiazepinopurine ring system B (n = 1), the core of asmarine, isolated from the marine sponge Raspailia sp., was synthesized via ring-closing metathesis (RCM) for the first time. Similarly, the diazocino analogue B (n = 2) was obtained. For the former, 6-chloropurine was treated with allyl amine or allyl alcohol in the presence of pyridine to give intermediate A. The formation of C-9-alkylated product A rather than the C-7 product is significant because normally in such reactions a mixture of N-7 and N-9 alkylation derivatives is obtained. Interestingly, the RCM was achieved only in the case of the X = N-Boc derivative giving excellent yield (95%) of product, while others, with X = H, Me, failed even at elevated temperatures. Removal of N-Boc protection before double bond reduction failed for the B (n = 1) product, a reaction which was successful for B with n = 2.