THE SYNTHESIS OF DERIVATIVES OF CYCLIC NUCLEOTIDES

In this paper we reported the method of synthesis of c-AMP, c-GMP, c-CMP, c-UMP and their derivatives for studying their biological activities.The acyl derivatives of c-GMP and c-UMP were prepared from c-GMP and c-UMP by acylation with acid anhydride in dried pyridine. The infrared and ultraviolet spectra of these acyl derivatives were studied. According to the data of spectra we suggest that the structures of acyl derivatives of c-CMP are N⁶, O²'-diacyl-c-CMP and the structures of acyl derivatives of c-UMP are N¹, O²'-diacyl-c-UMP.c-AMP was treated in pyridine with morpholine or piperidine in the presence of DCC to give 6-(N, N'-dicyclohexylguanidino)-purine riboside 3',5'-cyclic phosphoramidates. Under the same conditions, c-AMP could not react with imidazole, acetylglycine or glycine ethyl ester, but some condensation products of DCC and imidazole, acetyl glycine or glycine ethyl ester were obtained respectively.Tri-n-butylammonium salt of N⁶,0²'-dibutyryl-c-AMP reacted with POCI₃ in chloroform to give an active intermediate, which reacted immidiately with morpholine, piperidine and diethylamine to give the corresponding adenosine 3',5'-cyclic phosphoramidates. The butyryl group at N⁶ or 0²' of c-AMP was hydrolyzed under various conditions.It was found that the active intermediates formed from N⁶,O²'-dibutyryl-c-AMP and POCI₃ could not react with alcohols to obtain the corresponding phosphotriesters, cleavage of riboside-purine linkage occurred, instead, to give the adenine hydrochloride. Silver salt of c-AMP reacted with alkyl iodide to give the corresponding phosphotriestets.