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), λEtOHmax253 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).
