Synthesis of 9-[2-(2-hydroxymethyl-2-methyl-, -(2-acetoxymethyl-2-methyl-, -(2,2-di(hydroxymethyl)-, and -(2,2-Di(acetoxymethyl)-1,3-dioxan-5-yl)ethyl] derivatives of guanine and 2-aminopurine

✍ Scribed by Dae-Kee Kim; Namkyu Lee; Young-Woo Kim

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2000
• Tongue: English
• Weight: 554 KB
• Volume: 37
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570370515

✦ Synopsis

Abstract

Synthesis of 9‐[2‐(2‐hydroxymethyl‐2‐methyl‐, ‐(2‐acetoxymethyl‐2‐methyl‐, ‐(2,2‐di(hydroxymethyl)‐, and ‐(2,2‐di(acetoxymethyl)‐1,3‐dioxan‐5‐yl)ethyl] derivatives of guanine and 2‐aminopurine, 2–9, has been accomplished in seven to eight step sequences from readily available 1‐(tert‐butyldiphenylsilyloxy)‐acetone, 1,3‐di(tert‐butyldiphenylsilyloxy)acetone, and the diol 10. Formation of cyclic ketals 11 and 12 was carried out successfully under an acidic condition using a catalytic amount of methanesulfonic acid along with excess anhydrous copper(II) sulfate in toluene. Subsequent reactions of desilylation, acetylation, hydrogenolysis, and bromination afforded the key intermediates 19 and 20, which were coupled with 2‐amino‐6‐chloropurine to produce the purine compounds 21 and 22 in good yields. Guanine derivatives 2–5 were obtained from 21 and 22 by hydrolysis and acetylation, while the dechlorination and hydrolysis of 21 and 22 yielded the 2‐aminopurine compounds 6–9.