CHEMISTRY OF NUCLEOSIDES AND NUCLEOTIDES 



153 



NH2 



NH2 



N^N^NCeHsCU' 

 NH, 



N^NHj 

 NH, 



N^ 

 [f^NHRi 



K^NH-CHS 



NH, 



Ri 



. N. ^N 



NH: 



1 



f 



N 



RiHN 



H 



N. ^N 



R 



R= glycosyl 



Ri = acetylated glycosyl 



NH, 



mixtures of 9-glycosides and 7-glycosylaminopurinesJ^ The general method 

 has been used for the synthesis of 9-D-xylopyranosyl-/^ 9-D-ribopyranosyl-/* 

 9-D-mannopyranosyl-,'^® 9-D-glucop3"ranosyl-adenine/^ 9-D-xylopyranosyl-2- 

 methylthioadenine/^ and 9-D-glucopyranosyHsoguanine7^ 



Whereas the glycosides prepared by the general route are undoubtedly 

 9-/3-glycosides,^®' ^^' ''*• ^^ periodate titration shows that they are pyrano- 

 sides. In order to ensure a furanose structure in the glycosidic residue it is 

 necessary to start with a suitably protected aldehydo-sugar. For the syn- 

 thesis of adenosine^" along these lines 2,3,4-triacetyl-5-benzyl-D-ribose is 

 condensed with 4,6-diamino-2-methylthiopyrimidine to give a Schiff base. 

 A methylthio residue at position 2 is necessary to increase the reactivity of 

 the aminopja-imidine. After removal of the acetyl groups with methanolic 

 ammonia rearrangement occurs to the glycofiu-anoside. This is coupled 

 with diazotized 2,5-dichloroaniline, acetylated, and then reduced with zinc 

 and acetic acid to the amine, thioformylated, and cyclized. The 2-methyl- 

 thio and 5'-benzyl groups are removed by hydrogenolysis with nickel, then 

 acetyl groups removed with sodium methoxide, giving adenosine. 



It is important in this synthesis to protect the 5-position in the initial 

 sugar derivative with a benzyl or similar group. When acetyl or benzojd 

 groups are used in this connection, mixtures of furanosides and pyranosides 



" G. W. Kenner and A. R. Todd, J. Chem. Soc. 1946, 852. 



" G. W. Kenner, B. Lythgoe, and A. R. Todd, J. Chem. Soc. 1944, 652. 



■'* J. Baddiley, G. W. Kenner, B. Lythgoe, and A. R. Todd, /. Chem. Soc. 1944, 657. 



" A. Holland, B. Lythgoe, and A. R. Todd, J. Chem. Soc. 1948, 965. 



'« G. A. Howard, B. Lythgoe, and A. R. Todd, /. Chem. Soc. 1945, 556. 



" K. J. M. Andrews, Nity Anand, A. R. Todd, and A. Topham, /. Chem. Soc. 1949, 



2490. 

 '» G. A. Howard, G. W. Kenner, B. Lythgoe, and A. R. Todd, J. Chem. Soc. 1946, 855. 

 ^^ G. A. Howard, G. W. Kenner, B. Lythgoe, and A. R. Todd, J. Chem.. Soc. 1946, 861. 

 «« G. W. Kenner, C. W. Taylor, and A. R. Todd, J. Chem. Soc. 1949, 1620. 



