NOVEL METHOD FOR THE PRODUCTION OF TAXANE DITERPENES

(1)紫杉醇、紫杉醇类似物和新的碱性和中性紫杉醇类化合物从东北红豆杉（Taxus cuspidata）（a）我们检测了生长在日本仙台、松本、若奈、旭川和丰臣5个不同地方的日本红豆杉的针叶和茎中紫杉醇的含量。紫杉醇的分离得率分别为0.0022%、0.0006%、0.0043%、0.0033%、0.0007%。结果表明：25 Kg新鲜可再生的红豆杉针叶和茎，在2000 ~ 2005年间，可获得较好的经济效益。生长在若奈的cuspidata产生1 g紫杉醇。我们还分离了新的碱性和中性紫杉烷类化合物，并主要通过光谱方法确定了它们的结构。(b)我们检测了42种紫杉烷类化合物作为多药耐药癌细胞调节剂的生物活性，发现11种紫杉烷类化合物显示出较强的活性。其中紫杉烷类化合物NN-1和NN-11在细胞系筛选试验中也显示出抗肿瘤活性，结果表明它们是一种新型的抗肿瘤试剂。(2)紫杉醇、紫杉烷的生产 ...更多信息 类似物、云南红豆杉碱C及其相关化合物的研究。尖齿的采用愈伤组织培养技术，对红豆杉幼茎进行了愈伤组织诱导。生长在仙台的虎杖产生twxol和14种紫杉醇，包括6种紫杉醇类似物。紫杉醇的产量为263 mg/1 Kg干愈伤组织，紫杉烷的总产量为16.6g/1 Kg干愈伤组织。其中5种紫杉烷类化合物在愈伤组织培养物中以优异的产率产生，但在针叶和茎中不产生，作为多药耐药癌细胞的调节剂显示出高活性。产物的产率和种类很大程度上取决于添加剂和条件。（3）生物活性紫杉烷的部分合成。由于生物活性紫杉碱NN-1、NN-3、NN-7、NN-14和5-肉桂酰基-10-乙酰氧基紫杉碱II的天然来源非常有限，因此，它们是从紫杉碱合成的，紫杉碱是红豆杉针叶和嫩茎中最丰富的产物。cuspidata，在良好的yoilds，以保持足够量的样品在这些化合物的体内测定。少

(1) Taxol, Taxol analogs, and New Basic and Neutral Taxoids from Taxus cuspidata(a) We examined the content of taxol in needles and stems of Japanese yew, Taxuscuspidata grown in different 5 places in Japan, Sendai, Matumoto, Wakkanai, Asahikawa, and Toyotomi. The isolated yields of taxol are 0.0022%, 0.0006%, 0.0043%, 0.0033%, 0.0007% based on the weight of fresh needles and stems respectively. The results show that 25 Kg of fresh reproducible needles and stems of T. cuspidata grown in Wakkanai, produce 1 g of taxol. We also isolated new basic and neutral taxoids and determined their structures mainly by spectroscopic method.(b) We examined biological activity of 42 taxoids as modulators of multidrug resistant cancer cells and found that 11 taxoids showed strong activity. In them taxinines NN-1 and NN-11 also showd anticancer activity in the screening assay by cell line panel, the results of which suggest that they are a new type of anticancer reagent.(2) Production of Taxol, Taxol an … More alogs, Taxuyunnanine C and Its Related Compounds by Callus Culture of T. cuspidata. The Callus cultures induced from young stems of T. cuspidata grown in Sendai produce twxol, and 14 taxoids including 6 taxol analogs. The yield of taxol is 263 mg/1 Kg dry callus and the total yield of taxoids is 16.6 g/1 Kg dry callus. In them 5 kinds of taxoids, which are produced in excellent yields in callus cultures but not produced in the needles and stems, showed high activity as the modulator of multidrug resistant cancer cell. the yields and the kinds of products largely depend on additives and conditions.(3)Partial Synthesis of Biologically, Active Taxoids. Since the very limited amount of biologically active taxinines NN-1, -3, -7, -14, and 5-cinnamoyl-10-acetoxy taxcin II were produced from natural sources, they were synthesized from taxinine, which is the most abundant product in needles and young stems of T. cuspidata, in good yoilds to keep enough amount of samples in vivo assay of these compounds. Less