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)从海洋甲藻Amphidinium sp.中分离的amphidinolide C、E、G、H、T1 - T5和W以及amphidinolide-H同源物的绝对立体化学，2）通过对甲藻Amphidinium sp.培养物中的<13><13>[1-^<13>C]、[2-^<13>C]和[1，2-^ C_2]乙酸钠的~ 13 C NMR数据分析，研究了Amphidinium B、C、G、H、T_1和W的生物合成来源<13>。这些掺入模式表明，这些大环内酯是由连续的聚酮链（包括分离的C_（1，2-^ C_2））产生的。3）考察了两环内酯B、D、H、G、H2、H3、H4、H5、G2和G3以及五种两环内酯H衍生物的细胞毒性，发现烯丙基环氧化物、S-顺式二烯部分、C-20位的酮对两亲性H型大环内酯类化合物的细胞毒性有重要影响。

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)

J.Kobayashi: "Amphidinolides T2, T3, and T4, New 19-Membered Macrolides from Dinoflagellate Amphidinium sp. and Biosynthesis of Amphidinolide T1"J.Org.Chem.. 66. 134-142 (2001)

J.Kobayashi：“Amphidinolides T2、T3和T4，来自Dinoflagellate Amphidinium sp.的新19元大环内酯以及Amphidinolide T1的生物合成”J.Org.Chem.. 66. 134-142 (2001)

T.Kubota: "Absolute stereochemistry of amphidinolide C"Org.Lett.. 3. 1363-1366 (2001)

T.Kubota：“amphidinolide C 的绝对立体化学”Org.Lett.. 3. 1363-1366 (2001)

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。