Synthesis of purine- and pyrimidine-substituted heptadienes. The stereochemistry of cyclization and cyclopolymerization products

A series of 1,6-heptadienes, substituted in the 4 position with nucleic acid bases 1-6, have been synthesized via Mitsunobu condensations. Guanine, adenine, thymine, and uracil derivatives can be prepared directly by coupling the protected base with 1,6-heptadien-4-ol (7). However, coupling protected cytosine and 7 gives an O-alkylated product. Thus, the cytosine derivative must be prepared from the uracil-substituted heptadienes via the triazole. The free-radical addition of CCl(4) and BrCCl(3) to these adducts was investigated. In all cases, both 1:1 and 1:2 adducts were obtained. The 1:1 adduct was identified as the cyclized product of the initially formed 5-hexen-1-yl radical. The cyclization takes place in a stereospecific manner, with only one of the four possible diastereomers resulting. NMR studies indicate that all substituents are cis in this product. In the case of the addition of CCl(4) to the uracil-substituted heptadiene, this conclusion was confirmed by an X-ray structure determination of the isolated cyclized product. The free-radical-initiated cyclocopolymerizations of 1-6 with SO(2) gave 1:1 copolymers with cis-linked five-membered rings. Two-dimensional NMR studies on poly(2-SO(2)) showed predominately the cis-syn isomer while poly(6-SO(2)) has an approximately equal amount of cis-syn and cis-anti isomers.