3963
E.J. REIST, L. GOODMAN, R. R . SPENCER AND B. R. BAKER [CONTRIBUTION FROM THE STANFORD
Potential Anticancer Agents.l
IV.
Vol. 80
RESEARCH INSTITUTE]
Synthesis of Nucleosides Derived from 6-DeoxyD-Allofuranose
BY ELMERJ. REIST,LEONGOODMAN, ROLAND R. SPENCER AND B. R. BAKER RECEIVED FEBRUARY 4, 1958 6-Amino- and 2,6-diamino-9-(6’-deoxy-D-allofuranosyl)-puriiie, members of a class of 9-(C-alkyl-~-ribofuranosyl)-purines, have been synthesized starting with L-rhamnose.
The search for potential antagonists of nucleo- nofuranosyl nucleosides (V) have been synthesizedY tide metabolism recently has received added ein- and found to be inactive. It can be seen, however, phasis after the limited success of agents such as 6- that the configuration of the sugar moiety a t Cd’ mercaptopurine in cancer chemotherapy.2 Consid- has been changed with respect to ribofuranose in erable work has been done on the synthesis of addition to possessing the desired methyl for hy“fraudulent” nucleosides in which the sugar moiety drogen substitution a t C5’. It was the belief of has been modified from the naturally occurring the authorsg that the lack of biological activity ribofuranose configuration (I). X u c h of this work could be due to the inversion of configuration a t has been concentrated in the replacement or in- C4’. version of the various hydroxyl groups and in anomerization about the C1’ of the glycoside. Thus, replacement of the 2’-hydroxyl3 or the 3‘hydroxylAaof the natural ribose nucleoside (I) with an amino group leads to an inactive compound. Inversion of the Cz’-hydroxyl of IV gave the isomeric arabinose nucleoside (II), which was devoid of a ~ t i v i t y . Similar ~ results were obtained when the configuration a t C,’ of IV was changed from the natural 6- to the a-anomer.6 The replacement of the C5’-hydroxyl of the riboside (I) by hydrogen4b also gave a biologically inactive material. Modification of the riboside (I) a t C3’ 011 the other hand, gave active compounds. Thus W - D - X ~ ~ O furanosyladcnine (111), a compound which differs Oh NY, Cd from the corresponding riboside in the configuraI!I Iv tion of the C3’-hydroxyl, proved to be active against Adenocarcinoma 755.7 Similarly, 6-dimethylCtl, Ch, amino- 9 - (3’- amino-3I-deoxy-;3-D-ribofuranosyl)-purine (IV), the amino nucleoside derived from the antibiotic puromyciii, proved to be biologically active. I t seenied of interest to synthesize iiucleositles a* 3ti 2H 311 CP, which were identical in all respects with the 1>-1 ‘
