Acyclo Nucleosides and Nucleotides: Synthesis, Conformation and Other Properties, and Behaviour in Some Enzyme Systems, of 2′,3′-Seco Purine Nucleosides, Nucleotides and 3′:5′-Cyclic Phosphates, Analogues of cAMP and cGMP

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Abstract
The 3′:5′-cyclic phosphates of 2′,3′-secoadenosine and guanosine, structural analogues of cAMP and cGMP, were synthesized by cyclization of the 5′-phosphates of 2′,3′-secoadenosine and guanosine, respectively. The 2′,3′-seco-3′:5′-cAMP was converted to the IM P analogue by nitrous acid deamination, and to the 8-bromo analogue by bromination. Chemical phosphorylation of 2′,3′-secoadenosine gave four products, the major one of which, in 50% yield, was 2′,3′-seco-3′:5′-cAMP, identical to that obtained by the cyclization reaction above. The three other products have been tentatively identified. The conformations in solution of the seco nucleosides, their 5′-monophosphates, and their 3′:5′-cyclic phosphates, were determined with the aid of 1H , 13C and 31P NMR spectroscopy, particular attention being devoted to orientations about the C-O bonds and the glycosidic bond, and the results compared with crystallographic data available for the 2′,3′-seco congener of ribofuranosyl benzimidazole. The findings are briefly discussed in relation to substrate and inhibitor properties in some enzyme systems. Some of the foregoing compounds have been examined as potential enzyme substrates and inhibitors. In particular, the seco 3′:5′-cyclic phosphates are resistant to cAMP cyclic phos­ phodiesterase of mammalian origin, but are slowly hydrolyzed by purified higher plant cyclic nucleotide phosphodiesterase to the corresponding monophosphates.

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