4066
JACK
J. Fox, N. C. YUNG,IRIS TEMPE EN
ASD
MAXHOFFER
VOl. s3
[COSTRIBUTION FROM THE DIVISION O F NUCLEOPROTEIN CHEXISTRY, SLOAS-KETrERISG INSTITUTE FOR CANCER RESEARCH; SLOAN-KETTERING DIVISION OF CORNELL UNIVERSITY MEDICAL COLLEGE, NEWYORK21, N. Y., AND HOFFMANN LAROCHE, INC.,NUTLEY, N. J . ]
Nucleosides.
XII. Direct Synthesis of 2 ’-Deoxycytidine and its cu-AnomeP BY JACK J. Fox, NAISHUNC. YUNG,IRISWEMPENAND MAXHOFFER RECEIVED M A Y 8, 1961
The direct synthesis of 2’-deoxycytidine (V), a naturally-occurring constituent of deoxyribonucleic acid, was achieved w u the mercuri process involving the condensation of 3,5-di-0-(p-chlorobenzoyl)-2-deoxy-~-ribosy1 chloride (11) with A‘-
acetylcytosinemercury (I). The a-anomer ( V I ) of V also was obtained from this reaction. The synthesis of I1 from 2deoxy-Dribose is described. The optical rotations of this anomeric pair ( V and VI) as well as those of their acylated intermediates do not conform t o Hudson’s rules of isorotation. The synthesis of other fully acylated derivatives of 2-deoxg-~ribofuranose from pre-formed purine-2’-deoxy-~-ribonucleosides also is described.
In recent years, several papers have appeared dealing with the synthesis of 2‘-deoxy-~-ribofuranosyl nucleosides. I n earlier papers3 such syntheses were achieved by conversion of pre-formed ~-P-Daldopentofuranosyl-pyrimidines or -purines to their corresponding 2’-deoxy derivatives by elaborate, though elegant, reactions. Other reports4 have dealt with the conversion of 2/-deoxyuridine4“ and thymidine4” to 2/-deoxycytidine and its 5methyl analog via a thiation procedure. More recently, the direct synthesis of 2/-deoxy-~-ribofurano~yl-pyrimidines~~~ and -purinesfi from suitably-protected derivatives of %deoxy-~-ribosehas been accomplished. This paper deals with the direct synthesis of 2’-deoxycytidine7 and its aanomer by the mercuri process for pyrimidine nucleoside synthesiss employed previously in the preparation of cytidine. Required for this synthesis was a suitablyprotected 3,5-di-0-acyl-2-deoxy-~-ribosyl halide for condensation with a proper mercuri-pyrimidine. N-Acetylcyto~inemercury~was employed since mono-mercuripyrimidines*~5~10 are relatively more reactive in these condensation reactions than monochloromercuripyrimidines or dipyrimidylmercury derivatives. I t was found, further, that 3,5di-O-(p-chlorobenzoyl)-2-deoxy-~-ribosyl chloride (11) served well in this condensation reaction with (1) This investigation was supported in p a r t b y funds from t h e X a tional Cancer Institute, National Institutes of H e a l t h , Public Health Service (Grant No. 3190). (2) -4 preliminary commiinicaiiNer. R . Duschinsky. J. J Fox and h-.C. T u n g , J . A m C h e m . Soc., 81, 411.1 (1959). (3) (a) D. M. Brown, D. B. Parihar, C . B. Recse a n d A . 12 ‘Yodi1 Pvoc. Chem. Soc., 321 (1937): J . Chfm. . S G C , 3035 (IS,%); (h) (; Shaw and R. N. \Tarretier, Pi.m [ ‘ / I P ? V ,So , 81 (1958); J . Cheiri. SOF. I.Shostakovskii, E. N. Prliezhaeva a n d L. 5 '. T s y m b a l , are shown in Fig. 2. Z h i i u . Obshch. Khim., 26, 739 (19%);
C . A , , SO, 14564 (1956). ( 5 ) B. I. Zfikhant'ev a n d V. L. Lapenko, Zhiiu. Obsliclz. Khiiiz., a7, 2~172,2840(1957); c. A , , 52, 8054, 8056 ( 1 g . m . (6) S. Kunichika a n d Y . Sakabibara, K o g y o K a g a k u Zassha. 6 0 , 701 (1957); C . A . , 63, 10009 (1959).
(7) H. W. Kircher, Aitol. Cizetiz., 32, 1103 (1960). (8) K . Freudenberg a n d E . Plankenhorn, A n n . . 636, 257 (1938). (9) R.L. Sundberg, C. M . hlccloskey, D. E . Rees and G . H . Coleman, J . A m . Chem. Soc., 67. 1080 (1945).
