CAREER: New Annulative Methods for the Synthesis of Complex Meroterpenes

职业生涯：合成复杂间萜的新环形方法

基本信息

批准号：
1554544
负责人：
Thomas Maimone
金额：
$ 60.55万
依托单位：
University of California-Berkeley
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2021-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1554544&HistoricalAwards=false
关键词：
CAREER New Annulative Methods Synthesis

项目摘要

With this CAREER Award, the Chemical Synthesis Program of the Division of Chemistry is supporting the research of Professor Thomas Maimone of the University of California, Berkeley. Professor Maimone is developing new tools for organic synthesis that are designed to facilitate the construction of complex polycyclic compounds. One tool allows new rings to be added to a molecular structure, and another allows the size of the ring to be changed by an oxidation reaction. Professor Maimone is applying these synthetic tools to develop rapid and efficient syntheses of molecular structures in a family of natural product called polycyclic polyprenylated acylphloroglucinols. Members of this family of are protect neurons and have potential use for the treatment of neurodegenerative conditions such as Alzheimer's disease. This work is expected to have broad applications in the field of organic synthesis as well as medicinal chemistry. As the educational component of his project, Professor Maimone is developing a research symposium that focuses on introducing community college students to synthetic organic chemistry research. A hands-on research component has been designed for intensive summer research under the mentorship of a UC-Berkeley graduate chemistry student. In addition to activities at the community college level, this CAREER Award also supports research activities at the elementary school level as part of the Bay Area Scientists in Schools(BASIS) program in the Berkeley and Oakland unified school districts. Both of these endeavors are expected to increase interest in science fields, particularly chemistry, across a highly diverse student body representative of the larger Bay Area community.Professor Maimone is developing new synthetic reactions to facilitate the construction of complex polycyclic compounds. The simple feedstock chemical diketene is being developed as a novel annulation reagent. In addition, this research describes the study of oxidative carbon-carbon bond rearrangements promoted by hypervalent iodine complexes. These two steps work together to produce the conserved bicyclo [3.3.1] nonane trione motif of the polycyclic polyprenylated acylphloroglucinols. Members of this family show a variety of biological activities, including inhibition of neurotransmitter reuptake (hyperforin) and choline acetyltransferase enhancement (garsubellin A). The new synthetic methods and access to this family of natural products may have applications in the fields of organic synthesis and medicinal chemistry. The educational plan includes the development of new course material on the synthesis of heterocycles, which is targeted towards advanced undergraduate chemistry majors and graduate students. Many chemists work in the pharmaceutical industry where such knowledge of heterocyclic chemistry is important.

凭借这一职业奖，化学系的化学合成项目正在支持加州大学伯克利分校 Thomas Maimone 教授的研究。 Maimone 教授正在开发新的有机合成工具，旨在促进复杂多环化合物的构建。一种工具允许将新环添加到分子结构中，另一种工具允许通过氧化反应改变环的大小。 Maimone 教授正在应用这些合成工具来开发一种称为多环聚异戊二烯化酰基间苯三酚的天然产物家族的分子结构的快速有效合成。该家族的成员可以保护神经元，并具有治疗阿尔茨海默病等神经退行性疾病的潜在用途。这项工作有望在有机合成和药物化学领域具有广泛的应用。作为其项目的教育组成部分，迈蒙教授正在举办一个研究研讨会，重点向社区学院的学生介绍合成有机化学研究。在加州大学伯克利分校化学研究生的指导下，为密集的夏季研究设计了实践研究部分。除了社区大学层面的活动外，该职业奖还支持小学层面的研究活动，作为伯克利和奥克兰联合学区湾区学校科学家 (BASIS) 计划的一部分。这两项努力预计将增加代表大湾区社区的高度多样化的学生群体对科学领域，特别是化学的兴趣。Maimone 教授正在开发新的合成反应，以促进复杂多环化合物的构建。简单的原料化学双烯酮正在被开发为一种新型成环试剂。此外，本研究还描述了高价碘配合物促进氧化碳-碳键重排的研究。这两个步骤共同产生多环聚异戊二烯化酰基间苯三酚的保守双环[3.3.1]壬烷三酮基序。该家族的成员表现出多种生物活性，包括抑制神经递质再摄取（金丝桃素）和增强胆碱乙酰转移酶（garsubellin A）。新的合成方法和获取该天然产物家族可能在有机合成和药物化学领域得到应用。该教育计划包括开发关于杂环合成的新课程材料，针对高级化学专业本科生和研究生。许多化学家在制药行业工作，其中杂环化学知识非常重要。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Programmable meroterpene synthesis Nat Commun 11, 508 (2020). https://doi.org/10.1038/s41467-020-14354-5

可编程联萜合成 Nat Commun 11, 508 (2020)。

DOI：
10.1038/s41467-020-14354-5
发表时间：
2020-01
期刊：
Nature communications
影响因子：
16.6
作者：
Shen, X.;Ting, C. P.;Xu, G.;Maimone, T. J.
通讯作者：
Maimone, T. J.

Annulative Methods in the Synthesis of Complex Meroterpene Natural Products

复杂二萜天然产物的合成方法

DOI：
10.1021/acs.accounts.0c00781
发表时间：
2021-02
期刊：
Accounts of Chemical Research
影响因子：
18.3
作者：
Shen, Xingyu;Thach, Danny Q.;Ting, Chi P.;Maimone, Thomas J.
通讯作者：
Maimone, Thomas J.

Traversing Biosynthetic Carbocation Landscapes in the Total Synthesis of Andrastin and Terretonin Meroterpenes

穿越安德拉斯汀和毛地黄素半萜全合成中的生物合成碳正离子景观

DOI：
10.1002/anie.201705654
发表时间：
2017-08
期刊：
Angewandte Chemie International Edition
影响因子：
0
作者：
Xu, Gong;Elkin, Masha;Tantillo, Dean J.;Newhouse, Timothy R.;Maimone, Thomas J.
通讯作者：
Maimone, Thomas J.

Annulative Methods Enable a Total Synthesis of the Complex Meroterpene Berkeleyone A

环形方法实现了复杂 Merterpene Berkeleyone A 的全合成