Molecular Design and Synthesis of Novel 6-Carbon-Substituted Cytokinin Analogs

1-去氮杂嘌呤衍生物作为高活性细胞分裂素的新候选物，经过精心设计和制备。为了与已制备的衍生物进行比较，设计合成了7-芳基乙基和7-烷基乙基取代的1-二氮杂嘌呤。重要的中间体7-碘- 1-咪唑[4,5-b]嘧啶-三乙酰核苷在钯和铜的催化下与具有不同取代基的末端炔进行Sonogashira偶联，生成1-去氮嘌呤的7-炔基三乙酰核苷衍生物。得到的7-炔基三乙酰核苷用甲醇氨水解去除乙酰基保护基团。去保护的核苷进一步用1NHC1水解得到7-烷基基- 1 -去氮杂嘌呤衍生物的游离碱。最后制备了6个核苷和6个游离碱基作为新的细胞分裂素类似物。得到的7-烷基基核苷还与甲基巯基烷钠反应，得到了7-烷基基核苷的Z和E几何异构体。在这5个加成案例中，有4个案例中，Z异构体比对应的E异构体占优势；烷基核苷的1-萘基衍生物由于萘基取代基的体积较大，只能得到一个Z异构体。对这类7-烯基衍生物制备了9个新的衍生物。通过烟草Culls繁殖试验和苋菜幼苗Betacyanine形成试验对得到的细胞分裂素类似物的生物学活性进行了评价。在1-去氮杂嘌呤7位上含有脂肪取代基的化合物中，4-甲基戊基衍生物显示出中等的细胞分裂素活性。另一方面，具有芳香取代基的化合物对3-甲苯基乙炔和3-氟苯基乙炔衍生物表现出较强的活性。3-甲氧基苯乙基衍生物是最有效的细胞分裂素类似物之一，与传统的N^6取代的细胞分裂素Benzyladenine （BA）几乎相当或更好。因此，在1-去氮杂嘌呤环7位引入3-甲氧基苯基乙基取代基是一种非常有效的强细胞分裂素类似物的药物设计。此外，由于该化合物具有中等的荧光活性，3-甲氧基苯基醚。Tnyl衍生物将有助于研究细胞分裂素在活的植物细胞内的掺入、分布和降解的机理。少

As novel candidates of highly active cytokinins, 1-deazapurine derivatives were designed carefully and synthesized in preparative scale. To compare with the derivatives which have been prepared, some 7-arylethynyl- and 7-alkylethynyl-substituted 1-deazapurines were designed and synthesized. The important intermediate, 7-iodo-l-imidazo[4,5-b]pyrimidine-triacetyl riboside vas subjected to the Sonogashira Coupling with terminal alkynes with various substituents using Pd and Cu as catalysts to yield 7-alkynyl triacetyl-riboside derivatives of 1-deazapurines. The obtained 7-alkynyl triacetyl-ribosides were deprotected by hydrolysis with methanolic ammonia to remove acetyl protective groups. The deprotected ribosides were further hydrolyzed with 1NHC1 to obtain free bases of 7-alkynyl-l-deazapurine derivatives. Six ribosides, and six free bases were finally prepared as novel cytokinin analogs. The obtained 7-alkynykl-riboseides were also subjected to the reaction with sodium methylmercaptane … More to yield the Z and E geometrical isomers of 7-alkenyl-l-deazapurine ribosides. Four of five cases of this addition, Z isomers were predominant to the corresponding E isomer; the 1-Naphthyl derivative of alkenyl-ribosides gave an only Z isomer because of the bulkiness of naphthyl substituent. Nine novel derivatives were prepared for this type of 7-alkenyl-derivatives.The biological activities of the obtained cytokinin analogs were estimated by Tobacco Culls propagation test and Betacyanine formation test with Seedling of Amaranthus Among the compounds with aliphatic substituents on 7-position of 1-deazapurine, the 4-methylpentinyl derivative showed a moderate cytokinin activity. On the other hand, compounds with aromatic substituents showed strong activity in case of 3-methothypenylethynyl and 3-fluorophenylethynyl derivatives. The 3-methothyphenylethynyl derivative was one of the most effective cytokinin analogs, and was almost equivalent and/or more better than the traditional N^6substituted cytokinin, Benzyladenine (BA). Therefore, the introduction of 3-methoxyphenylethynyl substituent at the 7-position of 1-deazapurine ring was revealed as quite effective drug-design for strong cytokinin analogs. Moreover, because the compound has a moderate fluorescence activity, the 3-methoxyphenyleth.tnyl derivative will be useful for mechanistic studies for the incorporation, distribution and degradation of cytokinin within the living plant cell. Less