414 D. M. BROWN AND A. R. TODD 



derived from each of the other three nucleosides were also produced^^-'is 

 put a new complexion on the polynucletide problem. The a and h nucleotides 

 were shown^® to be the 2'- and 3 '-phosphates of the corresponding nucleo- 

 sides (i.e., Ila and b), although not necessarily respectively, and much sub- 

 sequent work has confirmed this conclusion. The acid-catalyzed intercon- 

 version of the isomeric a and b nucleotides,^^'^^ which will be discussed later, 

 rendered invalid the conclusion of Levene and Harris that their isolated 

 nucleotides were 3 '-phosphates, since their degradative method could not 

 really distinguish between the 2'- and 3 '-isomers. Very recent studies*^"^" 

 have provided strong evidence for the view that the a nucleotides are the 

 2 '-phosphates (Ila), and the h nucleotides the 3 '-phosphates (lib), of the 

 respective nucleosides. While additional confirmation"^ of these findings 

 would no doubt be desirable, it is reasonable to accept them for the pur- 

 poses of our discussion. On their validity rests any final conclusion regard- 

 ing the absolute orientation of the internucleotidic linkages in intact ribo- 

 nucleic acids. 



The salient points in the chemistry of the nucleoside-2'- and -3 '-phos- 

 phates [cf. Baddiley, Chapter 4] may be briefly restated. Their intercon- 

 version in acid solution to an equilibrium mixture^^''^^ has been shown*« 

 by analogy with the glycerol-a- and -|3-phosphates^i-^^ to depend on migra- 

 tion of the phosphoryl group via an intermediate cyclic 2 ',3 '-phosphate 

 (III). The intermediate cychc 2 ',3 '-phosphates have been synthesized ^^ 

 and shown to possess the predicted properties, i.e., they are unstable and 



« W. E. Cohn, J. Am. Chem. Soc. 72, 1471 (1950). 



« W. E. Cohn, J. Am. Chem. Soc. 72, 2811 (1950). 



** H. S. Loring, N. G. Luthy, H. W. Bortner, and L. W. Levy, J. Am. Chem. Soc. 72, 



2811 (1950). 

 « W. E. Cohn, J. Cellular Comp. Physiol, 38, Suppl. 1, 21 (1951). 

 ^6 D. M. Brown and A. R. Todd, J. Chem. Soc. 1952, 44. 

 « H. S. Loring, M. L. Hammell, L. W. Levy, and H. W. Bortner, J. Biol. Chem. 196, 



821 (1952). 

 « L. F. Cavalieri, J. Am. Chem. Soc. 74, 5804 (1952); 75, 5268 (1953). 

 " J. J. Fox, L. F. Cavalieri, and N. Chang, J. Am. Chem. Soc. 75, 4315 (1953). 

 ''0 J. X. Khym, D. G. Doherty, E. Volkin, and W. E. Cohn, J. Am. Chem. Soc. 75, 



1262 (1953). 

 ''»» This has recently been given in the case of the isomeric adenylic acids by X-ray 



analysis (D. M. Brown, G. D. Fasman, D.I. Magrath, A. R. Todd, W. Cochran, 



and M. M. Woolfson, Nature 172, 1184, 1953), by chemical synthesis {loc. cit.; D. 



M. Brown, G. D. Fasman, D. I. Magrath, and A. R. Todd, J. Chem. Soc. 1954, 



1448), and by degradation (J. X. Khym and W. E. Cohn, J. Am. Chem. Soc. 76, 



1818, 1954). 

 " M. C. Bailly, Compt. rend. 206, 1902 (1938); 208, 443 (1939). 

 62 P. E. Verkade, J. C. Stoppelenburg, and W. D. Cohen, Rec. trav. chim. 59, 886 



(1940). 

 " E. Chargaff, J. Biol. Chem. 145, 455 (1942). 

 " D. M. Brown, D. I. Magrath, and A. R. Todd, J. Chem. Soc. 1952, 2708. 



