Four carhocyclic analogues of the ribonucleoside coformycin. including the recently isolated natural product 2, have been synthesised in racemic form. The syntheses were achieved in a convergent and direct manner via palladium(O) catalysed coupling between diazepinones 15 and 16 and the allylic acetate 5. Coformycin (1) is a naturahy occuning nucleoside of potential use in cancer and viral chemotheraphy,t . and possesses herbicidal properdes of agrochemical interest.2 Recently workers at Chesterford Park isolated and characterised the carhocyclic analogue 2 of coformycin, which also exhibits herbicidal activity.3 This paper describes the total synthesis of (f)-carbocyclic coformycin (2) and of three other novel carbocyclic analogues of coformycin. HO %_ _ (P 1" HO XN 'u' .-/"" _ Hd + &H 1 x-o 2 x=cHs
Our initial studies focused on transformation of the carhocyclic purine 34 via an analogous route to that previously reported for the conversion of purine ribonucleoside to coformycin (1).5 However, while this route did furnish low yields of carhocyclic isocoformycin (4) the desired compound 2 was never detected (Scheme I).6 Subsequently, we conceived that carbocyclic nucleosides such as 2 would he available via a palladium(O) catalysed coupling between the aglycone and the cyclopentenyl acetate 5 or 6. This approach has recently been successfully exploited by ourselves and several other groups for the synthesis of carhocyclic nucleosi&s.7.s.9.10..