Synthesis of 8-Substituted Xanthines and Their Oxidative Skeleton Rearrangement to 1-Oxo-2,4,7,9-tetraazaspiro[4,5]dec-2-ene-6,8,10-triones

Abstract

The synthesis of a number of 8‐(dialkylamino)‐ and 8‐alkoxyxanthines (3 and 6, respectively) is described. Treatment of 3 with m‐chloroperoxybenzoic acid (m‐CPBA) gave by a novel rearrangement 3‐(disubstituted amino)‐4,7,9‐trimethyl‐1‐oxo‐2,4,7,9‐tetraazaspiro[4,5]dec‐2‐ene‐6,8,10‐triones 10. Also, the corresponding 3‐alkoxy‐subtituted spiro compounds 12 were obtained by an analogus treatment of 8‐alkoxyxanthines 6. In attempts to elucidate a tentative mechanism for this rearrangement 8‐[(dialkylamino)methyl]caffeines 7 when treated with m‐CPBA did not undergo the rearrangement but only yielded the expected N‐oxide derivatives 16. This result seems to indicate that a necessary structure element for this rearrangement to occur is an atom with an unshared pair of electrons to be attached to the 8‐position of the investigated xanthines. In agreement with this statement is the fact that N‐oxides of 8‐[(dialkylamino)methyl]caffeines 16 do not undergo the novel rearrangement but rather give the expected Meisenheimer rearrangement or the Cope elimination depending upon reaction conditions.

Synthesis, biological evaluation and Structure Activity Relationships (SARs) study of 8-(substituted)aryloxycaffeine

“…As a part of our interest (Mohideen et al, 2013;Rahman et al, 2009;Sono et al, 1994;Zimmer et al, 1999) on searching new biological active molecules, a series of 8-(substituted)-aryloxycaffeine (3a-m) were synthesized from 8-bromocaffeine (2). Initially, 8-bromocaffeine (2) was prepared using bromine and sodium acetate in acetic acid at 60°C from commercially available 1.…”

Studies on the Synthesis, Structural Characterization and Biological Activities of Novel Caffeine Derivatives Containing Substituted-Piperazine Moiety

“…同时, 哌嗪环具有低毒、易形成多个氢 键或离子键的特点, 以及调节药物脂水分配系数和酸碱 平衡常数等功能, 常作为药物设计的药效团被引入到不 同类型的结构中以改变母体结构的性质 [11][12] ; 其在农药 领域的报道主要体现在杀菌活性方面, 例如, 杀菌剂嗪 胺灵(Triforine) [13] 结构中即含有哌嗪结构. 我们在近年 的研究中发现, 一些含哌嗪基团的杂环衍生物可对多种 常见农作物致病真菌表现出具有优异的杀菌活性 [14][15][16][17][18] , 部分结构具有较好的除草活性 [15][16] , 对酮醇酸还原异构 酶(KARI)表现出良好的抑制活性 [16] , 一些化合物还具 有较好的杀虫活性 [19] [22] 179 ℃); 1 H NMR (400 MHz, CDCl 3 ) δ: 3.75 (s, 3H, NCH 3 ), 3.53 (s, 3H, NCH 3 ), 3.39 (s, 3H, NCH 3 ), 3.27～ 3.21 (m, 4H, piperazine-CH 2 ), 3.09～3.02 (m, 4H, piperazine-CH 2 ), 1.72 (s, 1H, piperazine-NH); 13 [23][24] 对方法对 3～4 龄东方 粘 虫 (Mythimna separata Walker) 和 小 菜 蛾 (Plutella xylostella L.)进行测试. 抑菌测试采用离体平皿法 [25] ,…”