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

1-脱氮嘌呤衍生物是一类新型的高活性细胞分裂素类化合物。为了与已有的1-脱氮嘌呤衍生物进行比较，我们设计并合成了7-芳基乙炔基和7-烷基乙炔基取代的1-脱氮嘌呤衍生物。以7-碘-1-咪唑并[4，5-B]嘧啶三乙酰核苷为重要中间体，以Pd和Cu为催化剂，与不同取代基的末端炔进行Sonogashira偶联反应，得到1-脱氮嘌呤的7-炔基三乙酰核苷衍生物。将得到的7-炔基三乙酰基-核苷通过用甲醇氨水解来脱保护以除去乙酰基保护基。脱保护的核苷用1 NHCl进一步水解以获得7-炔基-1-脱氮嘌呤衍生物的游离碱。最终制备了六种核苷和六种游离碱作为新型细胞分裂素类似物。所得的7-炔基-核糖也与甲硫醇钠反应 ...更多信息 得到7-烯基-1-脱氮嘌呤核苷的Z和E几何异构体。这种加成的五种情况中有四种，Z异构体相对于相应的E异构体占优势;烯基核苷的1-萘基衍生物由于萘基取代基的庞大性而仅产生Z异构体。对这类7-烯基衍生物进行了9个新的衍生物的合成，并通过烟草茎段增殖试验和苋属植物幼苗的β-花青形成试验，对所合成的细胞分裂素类似物的生物活性进行了评价。在1-去氮嘌呤7-位上带有脂肪族取代基的化合物中，4-甲基戊基衍生物表现出中等的细胞分裂素活性。另一方面，在3-甲氧基苯乙炔基和3-氟苯乙炔基衍生物的情况下，具有芳香族取代基的化合物显示出强活性。3-甲氧基苯乙炔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取代的细胞分裂素苄基腺嘌呤（BA）几乎相当或更好。因此，在1-脱氮嘌呤环的7-位上引入3-甲氧基苯乙炔基取代基被揭示为强细胞分裂素类似物的相当有效的药物设计。此外，由于该化合物具有中等的荧光活性，该3-甲氧基苯基乙炔基衍生物将可用于活植物细胞内细胞分裂素的掺入、分布和降解的机理研究。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