Total Synthesis of Natural Products Possessing Multiple Bioactivities and Isolation of Their Activities

具有多种生物活性的天然产物的全合成及其活性分离

• 批准号: 10102010
• 负责人: TATSUTA Kuniaki
• 金额: $ 181.63万
• 依托单位: Waseda University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10102010/
• 关键词: Bioactivity; Total synthesis; Isolation of activities; Nerve affecting; Antibiotics; Practical synthesis; Chiral synthesis; Molecular design; 抗エイズ薬; 抗痴〓薬; 抗痴呆薬

1. The total synthesis and developments of 12 kinds of natural products possessing multiple bioactivities have been accomplished : for examples : (1) central nervous affecting and antifungal products ES242s ; (2) antifungal, cholesterol lowering and nerve growth factor affecting calbistrins; (3) antibacterial and antitumor pyralomicins; (4) one of big four antibiotics, tetracycline ; (5) antitumor and antibacterial quinolactacins ; and (6) insulin receptor affecting, antitumor and anti-HIV, asterriquinones. Remarkably, a new methodology have been developed by using ^<15>N-NMR studies for clarification of the structure - activity relationship. As a result, several medicinally useful compounds were found to show stronger activities than the mother natural products.2. New sysnthetic methods have been delveloped. (1) synthesis of prenylphenols by convenient method combining three segments using palladium catalysts ; (2) direct preparation of aldehydes and ketones from the corresponding carboxylic acids ; (3) synthetic studies on natural products containing tetrahydro-pyrans and furans, and antitumor antibiotics, taxols and ustiloxins.

1.完成了12种具有多种生物活性的天然产物的全合成与开发，如：（1）中枢神经作用和抗真菌作用的产物ES 242 s，（2）抗真菌、降胆固醇和神经生长因子作用的calbistrins，（3）抗细菌和抗肿瘤的pyralomicins，（4）四大抗生素之一的四环素，（5）抗肿瘤的抗肿瘤的抗肿瘤药物。（5）抗肿瘤和抗菌的喹诺酮类;和（6）影响胰岛素受体、抗肿瘤和抗HIV的asteriquinones。值得注意的是，已经通过使用1H-NMR研究开发了一种新的方法<15>来阐明结构-活性关系。结果表明，几种具有药用价值的化合物具有比天然产物更强的活性.介绍了新的合成方法。(1)在钯催化剂作用下，通过三个链段合成异戊二烯基苯酚;（2）由相应的羧酸直接制备醛和酮;（3）含四氢吡喃和呋喃的天然产物以及抗肿瘤抗生素、紫杉醇和ustiloxins的合成研究。