STUDIES ON BIOACTIVE SUBSTANCES FROM MARINE MICROORGANISMS

海洋微生物生物活性物质的研究

• 批准号: 04453030
• 负责人: NAKAMURA Hideshi
• 金额: $ 3.01万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04453030/
• 关键词: SYMBIOTIC ALGAE; ZOOXANTHELLA; ZOOXANTHELLATOXIN; STRUCTURE DETERMINATION; 62員環ラクトン; アプリシアトキシン; スピロアセタール; ゴニオラックス; ゴニオール

Vasoconstrictive compounds, zooxanhtellatoxin-A (ZT-A) and ZT-B were isolated from a symbiotic marine dinoflagellate Symbiodinium sp. Sodium periodate oxidation of Zt-A followied by sodium borohydride reduction gave fragments containing characteristic functionalities including an exomethyoene, a diexpoxide, a sulfate, a conjugated diene, a spiroacetal, and an amide. The structures correspond to about 80% of the full structure of ZT-A.TOCSY spectra of ZT-A under various conditions enable us to connect the partial structures deduced from the degradation products. The unveiled structures were obtained by detailed analyes of HMBC, HMQC and 13-C NMR spectra. The structure of ZT-A was determined on the basis of the spectral data and chemical degradation experiments to be a novel 62-membered lactonewith and amide linkage.Model compounds of tumor-promorting sabstance, aplysiatoxin were designed on the basis of the structure-activity relationship. Synthesis of a model containing functionalities essential for biological activity was finally achieved.

从共生的海洋甲藻Symbiodinium sp.中分离到血管收缩化合物zooxanhtellatoxin-A（ZT-A）和ZT-B。ZT-A经高碘酸钠氧化，硼氢化钠还原，得到含有特征官能团的片段，包括外亚甲基、二氢氧化物、硫酸盐、共轭二烯、螺缩醛和酰胺。这些结构对应于约80%的ZT-A的完整结构。在各种条件下的ZT-A的TOCSY光谱使我们能够连接从降解产物推导出的部分结构。通过HMBC、HMQC和~（13）C NMR谱的详细分析，确定了化合物的结构。根据光谱数据和化学降解实验，确定ZT-A的结构为一个新的62元内酯，含酰胺键，并根据构效关系设计了促肿瘤活性物质-阿曲库毒素的模型化合物。合成的模型含有生物活性所必需的功能，最终实现。

项目成果

H.Nakamura: "Gonyol:Methionine-induced Sufonium Accumulation in a Dinoflagellate Gonyaulax polyedra." Tetrahedron Lett.34. 8481-8484 (1993)

H.Nakamura：“Gonyol：蛋氨酸诱导甲硫氨酸在甲藻 Gonyaulax polyedra 中积累。”

H.Nakamura: "Structure of Periodate Oxidation Products with Characteristic Partial Structures of Zooxanthellatoxin-A,a Potent Vasoconstrictive Polyol from a Symbiotic Dinoflagellate" J.Org.Chem.58. 313-314 (1993)

H.Nakamura：“高碘酸盐氧化产物的结构与虫黄藻毒素-A 的特征部分结构，一种来自共生甲藻的有效血管收缩多元醇”J.Org.Chem.58。

H.Nakamura: "Isolation of zooxanthellatoxins,novel vasoconstrictive subsances from the zooxanthella Symbiodinium sp." Toxicon. 31. 371-376 (1993)

H.Nakamura：“从虫黄藻共生藻中分离出虫黄藻毒素，一种新型血管收缩物质。”

Hideshi Nakamura: "Structwe of Periodate Oxidation Products with Characteristic Partial Sturctures of Zooxan the llatoxin-A,a Potent Vasocsrstrictive Polyol form a Sombiotic Dinotlagellate" Journal of Organic Chemistry. 58. 313-314 (1993)

Hideshi Nakamura：“高碘酸盐氧化产物的结构，具有虫黄毒素-A 的特征部分结构，是一种形成生物体甲藻的有效血管限制性多元醇”有机化学杂志。

T.Asari: "Structures of Periodate Oxidation Products with a Conjugated Diene or an Exomethylene from Zooxanthellatoxin-A" Tetrahedron Lett.34. 4059-4062 (1993)

T.Asari：“来自虫黄藻毒素-A 的共轭二烯或外亚甲基的高碘酸盐氧化产物的结构”四面体快报 34。