Research for cyotoxic macrolides for marine dinoflagellates

海洋甲藻细胞毒性大环内酯类化合物的研究

• 批准号: 13470465
• 负责人: KOBAYASHI Jun'ichi
• 金额: $ 7.42万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470465/
• 关键词: symbiotic dinoflagellate; Amphidinium; macrolide; absolute configuration; biosynthesis; 殺細胞活性

1) The absolute stereochemistries in amphidinolide C, E, G, H, T1 - T5, and W, and amphidinolide-H congeners isolated from a marine dinoflagellate Amphidinium sp., were determined on the bases of combination of NMR analyses, degradation experiments, X-ray analysis, and/or synthesis of segments.2) The biosynthetic origins of amphidinolide B, C, G, H, T1, and W were investigated on the basis of ^<13>C NMR data of ^<13>C enriched samples obtained by feeding experiments with [1-^<13>C], [2-^<13>C], and [1,2-^<13>C_2] sodium acetates in cultures of a dinoflagellate Amphidinium sp. These incorporation patterns suggested that these macrolides were generated from successive polyketide chains including isolated C_1 unit from C-2 of acetates, branched C_1 units from C-2 of acetates, "m-m" and/or "m-m-m" units derived only from C-2 of acetates.3) Cytotoxicity of amphidinolides B, D, H, G, H2, H3, H4, H5, G2, and G3 in addition to five derivatives of amphidinolide H was examined, and it was found that the presence of an allyl epoxide, an S-cis-diene moiety, and the ketone at C-20 was important for the cytotoxicity of amphidinolide H-type macrolides.

1）在NMR分析的组合基础上，确定了从海洋鞭毛鞭毛虫sp。中分离出的两栖动物C，E，G，G，H，T1 -T5和W中的绝对立体化学体以及Amphidinolide -H同类体。 X射线分析和/或片段的合成。2）根据 ^<13> c NMR数据的基础研究了两栖类药物B，C，G，H，T1和W的生物合成起源通过[1-^<13> c]，[2 - ^<13> c]和[1,2-^<13> c_2]乙酸中鞭毛脂素二氮的培养物中的[1-^<13> c]和[1,2-^<13> C_2]获得的富集样品。这些掺入模式表明，这些大花环是由连续的聚酮化合物链产生的，包括乙酸盐的C-2孤立的C_1单位，乙酸盐C-2的分支C_1单位，“ M-M”和/或仅来自C-2的单位3）两栖类药物B，D，H，G，H2，H3，H4，H5，G2和G3的细胞毒性，除了检查了二苯二酚H的五个衍生物，并发现存在Allyl Epoxide ，一个S-CIS-二烯部分和C-20时的酮对两栖动物H型大环内酯的细胞毒性很重要。

项目成果

J.Kobayashi et al.: "Amphidinolides H2〜H5, G2, and G3, New Cytotoxic 26-and 27-Membered Macrolides from Dinoflagellate Amphidinium sp"J. Org. Chem.. 67. 6585-6592 (2002)

J. Kobayashi 等：“Amphidinides H2〜H5、G2 和 G3，来自甲藻 Amphidinium sp 的新型细胞毒性 26 和 27 元大环内酯”J. Org. 67. 6585-6592 (2002)

M. Tsuda, et al.: "Biosynthetic Study of Amphidinolide B"Chem. Pharm. Bull.. 49. 1366-1367 (2001)

M. Tsuda 等：“Amphidinolide B 的生物合成研究”Chem。

K.Shimbo et al.: "Amphidinolide W, New Twelve-Membered Macrolide from Dinoflagellate Amphidinium sp"J. Org. Chem.. 67. 1020-1023 (2002)

K.Shimbo 等人：“Amphidinolide W，来自甲藻 Amphidinium sp 的新十二元大环内酯”J。

T.Kubota, et al.: "Biosynthetic Study of Amphidinolide C"Tetrahedron. 57. 134-142 (2001)

T.Kubota 等人：“Amphidinolide C”四面体的生物合成研究。

M.Tsuda, et al.: "Biosynthetic Study of Amphidinolide B"Chem. Pharm. Bull.. 49. 1366-1367 (2001)

M.Tsuda 等：“Amphidinolide B 的生物合成研究”Chem.