Direct alkylation via a free radical reaction was utilized to prepare 8-tert-butylguanosine-5′- phosphate; this was dephosphorylated with alkaline phosphatase to give the parent nucleoside. The 8- (α-hydroxyisopropyl) derivatives of 5′-GMP and guanosine were prepared in an analogous manner. The foregoing products, which are necessarily in the syn conformation about the glycosidic bond because of the bulky 8-substituents (van der Waals’ radii 3.5-4 Å), were characterized by elementary analysis, UV spectra and 1HNMR spectroscopy. The changes in chemical shifts of H (1′), H (2′) and H (3′) of each of the foregoing derivatives, relative to those for guanosine and 5′-GMP, were consistent with their being in the syn conformation and, furthermore, pointed to guanosine and 5′-GMP being predominantly anti, in aqueous medium or DMSO. They also demonstrated that, contrary to the prevailing opinion, 8-bromo-5′-GMP and 8-bromoguanosine are not necessarily exclusively in the syn conformation in solution. While 8-bromoadenosine-5′-phosphate was slowly dephosphorylated by snake venom 5′-nucleoti- dase, the 8-tert-butyl and 8-(α-hydroxyisopropyl) derivatives of 5′-GMP were fully resistant to this enzyme.
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Pless et al. (1978) studied this question.