LATENT INHIBITORS .11. THE SYNTHESIS OF 5-SPIROCYCLOPROPYL DIHYDROOROTIC ACID

Approaches to the synthesis of 5-spirocyclopropyldihydroorotic acid ar e described. Difficulties were encountered in the lack of reactivity o f diethyl 2-oxobutandicarboxylate and its derivatives towards cyclopro panation. Potential intermediates were prepared from ethyl 4-acetoxy-3 -oxobutanoate but rearrangements involving ring expansion of the cyclo propane ring and hindrance towards condensation reactions of the keton e prevented formation of the pyrimidine. A successful route involving Strecker synthesis of a precursor aminoacid from ethyl 1-formylcyclopr opane-1-carboxylate in which the formyl group was converted into the c orresponding the urea led to the target compound.