Synthesis of a cyclic tetrameric purine by successive cross-coupling reactions and subsequent Pd-catalyzed cyclization

摘要

The tetrameric N-benzyl-protected purine (quaterpurine) 2 was synthesized and characterized as its palladium complex [2.Pd]. The synthesis commenced with the Pd-catalyzed cross-coupling of 8-zincated 9-benzyl-6-chloro-8-iodopurine (9) and 9-benzyl-6-iodopurine (11) establishing the first C-6/ C-8 bond. The sequence was repeated twice after iodo-dechlorination at C-6' (C-6") of the respective dimer 12 and trimer 15. The final ring closure was achieved at the tetrameric 6"'-chloro-8-iodoquaterpurine 3b by a reductive intramolecular cross-coupling with hexamethylditin in the presence of Pd-2(dba)(3) and P(2-furyl)(3). The overall yield in the eight step sequence was 17% starting from 9-benzyl-6-chloropurine (8), the immediate precursor of 11. Other strategies to combine the purine fragments, i.e. by dimer/dimer bond formation or by regioselective cross-coupling, were not successful. (C) Wiley-VCH Verlag GmbH & Co.