NOVEL METHOD FOR THE PRODUCTION OF TAXANE DITERPENES

生产紫杉烷二萜的新方法

• 批准号: 10555320
• 负责人: ANDO masayoshi
• 金额: $ 7.74万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10555320/
• 关键词: Taxol; Taxus cuspidata; Taxane diterpene; Modulators of multidrug resistant tumor cells; P-糖蛋白質阻害剤; 新規作用抗癌剤; イチイカルス; タキソール生合成; 日本産イチイ; タキサン型ジテルペン; 耐性癌克服剤; 新規塩基性タキソイド; 新規中性タキソイド; 耐性癌克服

(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

(1)日本东北红豆杉（Taxuscuspidata）的针叶和茎中紫杉醇的含量。(a)研究了生长在日本仙台、松本、若奈、旭川和丰美5个不同地区的红豆杉（Taxuscuspidata）的针叶和茎中紫杉醇的含量。以鲜针重和鲜茎重为单位，紫杉醇的分离得率分别为0.0022%、0.0006%、0.0043%、0.0033%和0.0007%。结果表明，在Wakkanai种植的新鲜可繁殖的东北松针和茎25 Kg，可产生1 g紫杉醇。我们还分离到了新的碱性类和中性类，并主要用光谱法确定了它们的结构。(b)我们检测了42种taxoids作为多药耐药癌细胞调节剂的生物活性，发现11种taxoids表现出较强的活性。其中，紫杉醇类化合物NN-1和NN-11在细胞系面板筛选实验中也显示出抗癌活性，提示它们是一种新型的抗癌试剂。(2)利用东北柽柳愈伤组织培养生产紫杉醇、紫杉醇及其衍生物、紫杉醇云南碱C及其相关化合物。从仙台地区生长的东北杉木幼茎诱导的愈伤组织可产生两种紫杉醇和14种紫杉醇类，其中包括6种紫杉醇类似物。紫杉醇产量为263 mg/1 Kg干愈伤组织，类杉素总产量为16.6 g/1 Kg干愈伤组织。其中，5种类taxoids在愈伤组织培养中产量较高，但在针叶和茎中不产生，它们作为多药耐药癌细胞的调节剂表现出较高的活性。产品的收率和种类在很大程度上取决于添加剂和条件。(3)生物活性类Taxoids的部分合成。由于天然来源的生物活性杉素NN-1、-3、-7、-14和5-肉桂酰-10-乙酰氧基杉素II的含量非常有限，因此以杉木针叶和幼茎中含量最丰富的杉素为原料，以良好的产量进行合成，以保证这些化合物的体内检测样品的充足量。少

项目成果

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Masayoshi Ando：“(±)-(3aα,8aα)-乙基 8β-羟基-6β-甲基-2-氧代八氢-2H-环庚[b]呋喃-3α-羧酸酯的新合成方法”《有机化学》杂志。 63・4。920-929（1998）

Fumito Shimoma, Haruhiko Kusaka, Hidenori Azami, Katsuaki Wada, Toshio Suzuki, Hisahiro Hagiwara, Masayosi Ando: "Total Synthesis of (±)-Hymenolin and (±)-Parthenin"Journal of Organic Chemistry. 63(11). 3758-3763 (1998)

Fumito Shimoma、Haruhiko Kusaka、Hidenori Azami、Katsuaki Wada、Toshio Suzuki、Hisahiro Hagiwara、Masayosi Ando：“(±)-Hymenolin 和 (±)-Parthenin 的全合成”有机化学杂志 63(11)。 (1998)

安東政義: "Synthesis and Structure of Chiral (R)-2,2'-Bis-Silyl-Substituted 1,1'-Binaphthyl Derivatives"Chemistry Letters. 1245-1246 (1999)

Masayoshi Ando：“手性 (R)-2,2-双甲硅烷基取代的 1,1-联萘衍生物的合成和结构”化学快报 1245-1246 (1999)。