Download Enhanced Fusion Method for Purine Nucleoside Synthesis: Acid-catalyzed Reactions of N(9)- and more Summaries Chemistry in PDF only on Docsity! September, 1964] SHORT COMMUNICATIONS 1389 SHORT COMMUNICATIONS An Improved Fusion Method for the Synthesis of Purine Nucleosides. The Acid-catalyzed Reactions of N(9)- or N(9)-Acylpurines with Acylated Sugars By Yoshiharu IsHrno, Akira HosoNO, Sadanori ISOME, Akira MARUYAMA and Tetsuo SATO (Received May 25, 1964) In previous papers1) from our laboratory, the acid-catalyzed fusion reaction of purines with acylated sugars has been reported. Re- cently, the method has been applied to the synthesis of nucleosides of D-xylose,2a) 2-deoxy- D-ribose,2b,3) and deoxyaminosugars.3) The extensive experiments on the acidic catalysts for this reaction made it clear that the compounds formulated as R-SO3H, picric acid, and many inorganic acidic compounds were effective. It is of great interest that amphoteric acids, such as sulfanilic and sulfa- mic acids, showed fairly good catalytic effects.4) On the other hand, perspective observation of the reactivity of purine derivatives in the fusion reaction made us aware of the fact that there is no rational correlation between the reactivity of purines and the polar effect of their substituent groups on the reaction centers, though such correlation was confirmed in the fusion reaction of phenols with acylated su- gars.3) Accordingly, it was deduced that this fact was probably due to the fusibility of purine derivatives.4b,c) In fact, the reactions of purines with a high fusibility, such as 2,6-dichloropurine(I)[m. p. 181℃(decomp.)5)],halogenopurines, and theo- phylline, proceeded in a homogeneous state to yield the corresponding purine nucleosides, 2,6-dichloro-9-(2',3',5'-tri-O-acetyl-β-D-ribofur- anosy1)purine(II)4b,c){m. p.158～159℃,[α]21.5D. -5 .7°(c 1.05, chloroform), λEtOHmax 253 mμ (ε, 6100)and 274.5 mμ(ε,9800),λEtOHmin 258 mμ (ε, 5800)},and others, generally in a good yield (40～80% yield of the theoretical yileds)4). On the other hand, amino- or hydroxypurines with extremely high melting points were usual- ly hard to fuse on the reaction and were not practically reactive.4) These results have led to the suggestion that easily-fusible purine derivatives might be favorable for the fusion reaction. Thereupon, purines which are acylated at a nitrogen atom of the imidazole nucleus and have much lower melting points than those of the parent purines have been applied to the reaction. Birkofer6) prepared diacyladenines by refiux- ing adenine with excess acid anhydrides. Montgomery7) also obtained monoacethlyalo- genopurines by refluxing diaminohalogeno- pyrimidines with ethyl orthoformate in acetic anhydride. He deduced from the infrared spectra that the acetyl group should be linked to a nitrogen atom of the imidazole moiety of the purine nucleus. The melting points of these acyl purines are much lower(30～200℃) than those of the parent purine. We have newly obtained acyl derivatives of theophylline (Ｎ(7)-acetyl, m. p. 156～157℃; 1) T. Sato, T. Simadate and Y. Ishido J. Chem. Soc. Japan, Pure Chem. Sec. (Nippon Kagaku Zasshi), 81, 1440, 1442 (1960); T. Simadate, Y. Ishido, and T. Sato, ibid., 82, 938 (1961); T. Simadate, ibid., 82, 1261 (1961); Y. Ishido and T. Sato, This Bulletin, 34, 1347 (1961). 2) a) W. W. Lee, A. P. Martinez, G. L. Tong and L. Goodman, Chem. Ind. (London), 1963,2007; b) M. J. Robins, W. A. Bowles and R. K. Robins, J. Am. Chem. Soc., 86, 1251 (1964). 3) Y. Ishido, T. Matsuba, A. Hosono and T. Sato, International Symposium on the Chemistry of Natural Products, Kyoto, Japan, April. 1964. 4) a) Y. Ishido and T. Sato, 15th Annual Meeting of Chemical Society of Japan, _ Kyoto, April, 1962;b) Y. Ishido, Doctoral Thesis, Tokyo Institute of Technology, Japan. March, 1963; c) Y. Ishido, A. Hosono, Y.Kikuchi and T. Sato; Y. Ishido, A. Hosono, Y. Kikuchi and T. Sato; Y. Ishido, A. Hosono, Y. Kikuchi, S. Isome, A. Maruyama, and T. Sato, 17th Annual Meeting of the Chmical Society of Japan, Tokyo, Japan, March, April, 1964. 5) G. B. Elion and G. H. Hitchings, J. Am. Chem. Soc., 78, 3508 (1956). 6) L. Birkofer, Ber., 76, 769 (1943). 7) J. A. Montgomery, J. Am. Chem. Soc., 78, 1928 (1956).
