1-(2'-deoxy-BETA-D-ribofuranosyl)-1,2-Dihydropyrimidine-2-one-5'- monophosphate (2'-deoxyzebularine monophosphate) was identified as a very potent inhibitor of deoxycytidilate deaminase. The parent nucleoside was prepared by a new synthetic approach. A large-scale adaptation of the synthesis of 2'-deoxyzebularine worked well. Synthesis of the 5'- monophosphate in sufficient amounts for biological testing is in progress. Comparative studies with the 5'-monophosphate of tetrahydrouridine are planned. A large number of mono- and bis-butyrolactones have been synthesized and shown to be very stereoselective in the manner in which they activate protein kinase C (PK-C). These compounds function as conformationally constrained analogues of diacylglycerol. The level of potency achieved is now submicromolar. A more refined structure-activity analysis is expected to yield compounds effective at nanomolar concentrations. This structurally vital information will be put to use in the design of PK-C inhibitors.
