Itaya T, Mizutani A, Takeda M, Shioyama C
Chem Pharm Bull (Tokyo). 1989 Feb;37(2):284-91. doi: 10.1248/cpb.37.284.
Acid- or base-catalyzed acylation of 1-benzylwye (7) provided the 7-substituted derivatives 9, 10, and 11 in poor yields. Although the reactions of lithiated 7 with electrophiles gave the 2-substituted derivatives 14, 15, 17, 20, 21, and 22, lithiation of 1-benzyl-7-bromo-2-chlorowye (23) followed by treatment with Me2CHCH2CHO (13) successfully introduced a side chain at the 7-position to afford 1-benzyl-2-chloro-7-(1-hydroxy-3-methylbutyl)wye (24). Cyclization of 1-benzyl-3-methylguanine (5) with 3-bromo-2-butanone followed by catalytic hydrogenolysis afforded 7-methylwye (2b), the hypermodified base isolated from archaebacterial transfer ribonucleic acids. A more efficient route for the synthesis of 2b has been developed via a series of reactions: the Vilsmeier-Haack reaction of 7, reduction with NaBH4, and catalytic hydrogenolysis over Pd-C.
1-苄基怀碱（7）的酸催化或碱催化酰化反应产率较低，得到了7-取代衍生物9、10和11。尽管锂化的7与亲电试剂反应得到了2-取代衍生物14、15、17、20、21和22，但1-苄基-7-溴-2-氯怀碱（23）锂化后用异丁醛（13）处理，成功地在7位引入了侧链，得到1-苄基-2-氯-7-(1-羟基-3-甲基丁基)怀碱（24）。1-苄基-3-甲基鸟嘌呤（5）与3-溴-2-丁酮环化，随后催化氢解得到7-甲基怀碱（2b），这是从古细菌转移核糖核酸中分离出的超修饰碱基。通过一系列反应开发了一种更有效的合成2b的路线：7的Vilsmeier-Haack反应、用NaBH₄还原以及在Pd-C上催化氢解。
