CONFORMATIONALLY CONSTRAINED ANALOGS OF DAG .8. CHANGES IN PK-C BINDING-AFFINITY PRODUCED BY ISOSTERIC GROUPS OF THE 3-O-ACYL FUNCTION IN 2-DEOXY-L-RIBONOLACTONES

Syntheses of a series of 2-deoxy-L-ribonolactones modified at C-3 with groups isosteric to the 3-O-acyl moiety of the parent 3-O-tetradecanoyl-2-deoxy-L-ribonolactone (1) are reported. Lipophilicity of the molecules was kept constant by maintaining invariant the length of the aliphatic chain. Compound 5 was identified as having an affinity equal to that of 1 in a competitive binding assay that measured the ability of the ligands to displace [H-3]-phorbol-12,13-dibutyrate from PK-C. The reverse ester function in 5 makes this compound more stable than 1 by preventing beta-elimination. Other changes in 1 led to a reduction in affinity.