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

Article abstract of DOI:10.1021/jo026379k

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 CCl₄ and BrCCl₃ 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 CCl₄ 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 SO₂ gave 1:1 copolymers with cis-linked five-membered rings. Two-dimensional NMR studies on poly(2-SO₂) showed predominately the cis-syn isomer while poly(6-SO₂) has an approximately equal amount of cis-syn and cis-anti isomers.