2‘-Deoxyribonucleosides (2‘-deoxyadenosine (1), 2‘-deoxycytidine (2), thymidine (3)) singly enriched with 13C at C2‘ have been prepared and used to obtain one-, two-, and three-bond 13C−1H and 13C−13C spin-coupling constants involving C2‘. Coupling data are interpreted with assistance from complementary 3 J HH data (PSEUROT analysis), furanose structural parameters obtained from molecular orbital calculations, structure-coupling correlations found for J CH and J CC in carbohydrates, and calculated J values. Spin couplings in 1−3 involving C1‘ and C2‘ are also compared to corresponding values in ribonucleosides in order to assess the effects of nucleoside structure and conformation on J values within the furanose ring. 1 J C2 ‘ ,H2 ‘ R and 1 J C2 ‘ ,H2 ‘ S in 1−3 and 1 J C2 ‘ ,H2 ‘ in ribonucleosides depend on C−H bond orientation; 1 J C1 ‘ ,H1 ‘ in 1−3 and in ribonucleosides exhibits a similar dependence. The latter couplings appear to be essentially unaffected by N-glycoside torsion. 1 J CC values depend on the number and distribution of electronegative substituents on the C−C fragment. A modified projection curve is proposed to aid in the interpretation of 2 J C2 ‘ ,H1 ‘ values; the presence of N substitution at C1‘ causes a shift to more negative couplings relative to the O-substituted analog. In contrast, 2 J C1 ‘ ,H2 ‘ is essentially unaffected by the same change in the electronegative substituent at C1‘. 2 J CC values within the furanose ring are determined by two coupling pathways; in one case (i.e., 2 J C1 ‘ ,C3 ‘), the observed coupling is shown to be the algebraic sum of the two couplings arising from each pathway. 3 J CH and 3 J CC values depend in general on appropriate molecular dihedral angles as expected (Karplus relationships); however, 3 J C2 ‘ ,H4 ‘ values exhibit unexpected behavior, thus suggesting potential limitations in its use as a structural probe.

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Five new tetracaine analogues were synthesized and evaluated for potency of blockade of cyclic nucleotide-gated channels relative to a multiply charged tetracaine analogue described previously (4). Increased positive charge at the tertiary amine end of tetracaine results in higher potency and voltage dependence of block. Modifications that reduce the hydrophobic character at the butyl tail are deleterious to block. The tetracaine analogues described here have apparent affinities for CNGA1 channels that vary over nearly 8 orders of magnitude.