Chemical Synthesis of Kendomycin and Garsubellin A

肯多霉素和加苏贝林 A 的化学合成

• 批准号: 7623852
• 负责人: Erik J. Sorensen
• 金额: $ 25.92万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-05 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623852
• 关键词: Achievement; Address; Agonist; Anabolism; Anti-Bacterial Agents; Applications Grants; Architecture; Biological; Biological Factors; Biomimetics; Calcitonin Receptor; Chemical Models; Chemical Structure; Chemicals; Chemistry; Complex; Core Assembly; Development; Disease; Endothelin Receptor Antagonist; Evolution; Exhibits; Future; Investigation; Lead; Maps; Methods; Molecular; Molecular Structure; Oxidation-Reduction; Process; Production; Property; Reaction; Research; Research Personnel; Skeleton; Structure; Therapeutic; analog; base; chemical synthesis; garsubellin A; hyperforin; innovation; insight; kendomycin; neurotransmitter biosynthesis; novel; programs; tool

DESCRIPTION (provided by applicant): This grant application addresses the chemical synthesis problems of two architecturally complex natural products, kendomycin and garsubellin A. The broad objectives of the research program are to develop innovative strategies for the efficient synthesis of molecular agents possessing therapeutic potential for the treatment of diseases and to develop powerful chemical methods of broad utility in the production of the compounds required in biomedical investigations. The specific aims of the present proposal are: 1) the achievement of an efficient total synthesis of kendomycin, a potent endothelin receptor antagonist and calcitonin receptor agonist that exhibits pronounced antibacterial, antitumor, and anti-osteoporotic activities, using a novel macroglycosylation approach; 2) the development of innovative strategies based on a mechanistically degenerative tandem approach that are appropriate for the expeditious synthesis of the core skeleton of kendomycin; 3) the establishment of a chemical model to gain insights into the biosynthesis of kendomycin through a total synthesis using a biomimetic cascade approach based on novel internal redox and macro-Michael addition processes; and 4) the achievement of a concise total synthesis of garsubellin A, a potent neurotrophic agent that induces the biosynthesis of neurotransmitters, using a multicomponent tandem approach that allows for rapid assembly of the core structure of hyperforin natural products. The proposed synthetic investigations take advavantage of multicomponent cascade approaches which most efficiently address the problem of constructing complex molecular structures. Thus, the chemistry we seek to develop through this grant application can be extended in many ways to bring significant advances in the chemical synthesis of bioactive compounds.

描述（由申请人提供）：该授权申请解决了两种结构复杂的天然产物，肯多霉素和garsubellin A的化学合成问题。该研究计划的广泛目标是开发具有治疗疾病的治疗潜力的分子制剂的有效合成的创新策略，并开发在生物医学研究中所需的化合物的生产中具有广泛实用性的强大化学方法。本发明的具体目的是：1）使用新的宏糖基化方法实现有效的全合成肯多霉素，其是一种有效的内皮素受体拮抗剂和降钙素受体激动剂，具有显著的抗菌、抗肿瘤和抗肿瘤活性;（二）在机械退化串联方法的基础上制定创新战略，适用于快速综合（3）建立了一个化学模型，通过仿生级联方法，基于新的内部氧化还原和大分子Michael加成过程，研究了Kendomycin的生物合成;和4）实现了Garsubellin A的简明全合成，Garsubellin A是一种诱导神经递质生物合成的有效神经营养剂，使用允许金丝桃素天然产物的核心结构的快速组装的多组分串联方法。所提出的合成研究采用多组分级联方法的优点，这些方法最有效地解决了构建复杂分子结构的问题。因此，我们寻求通过这项赠款申请开发的化学可以在许多方面扩展，以在生物活性化合物的化学合成方面取得重大进展。

项目成果

Concise synthesis of the Erythrina alkaloid 3-demethoxyerythratidinone via combined rhodium catalysis.

• DOI: 10.1021/ol102535u
• 发表时间: 2010-12-17
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Joo, Jung Min;David, Ramoncito A.;Yuan, Yu;Lee, Chulbom
• 通讯作者: Lee, Chulbom

A highly enantio- and diastereoselective 1,3-dimethylallylation of aldehydes.

醛的高度对映选择性和非对映选择性 1,3-二甲基烯丙基化。

• DOI: 10.1016/j.tet.2006.07.070
• 发表时间: 2006
• 期刊: Tetrahedron
• 影响因子: 2.1
• 作者: Yuan,Yu;Lai,AmyJ;Kraml,ChristinaM;Lee,Chulbom
• 通讯作者: Lee,Chulbom

Enantioselective Total Synthesis of (+)-Garsubellin A.

• DOI: 10.1002/anie.202109193
• 发表时间: 2021-10-11
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Jang D;Choi M;Chen J;Lee C
• 通讯作者: Lee C

Total synthesis of kendomycin: a macro-C-glycosidation approach.

• DOI: 10.1021/ja0447154
• 发表时间: 2004-10
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Yu Yuan;H. Men;Chulbom Lee