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Asymmetric Synthesis of Antitumor Natural Products

抗肿瘤天然产物的不对称合成

基本信息

批准号：
8249103
负责人：
JOHN A PORCO
金额：
$ 32.71万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2014-04-30
项目状态：
已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Asymmetric Synthesis of Antitumor Natural Products The proposed research program reflects the interest of the Principal Investigator, John A. Porco, Jr., and his group in new chemical reaction development and the synthesis of biorelevant molecules using efficient approaches. Their overall goal is to develop and refine new synthetic methodologies for the asymmetric syntheses of diazobenzofluorene natural products, the epidithiidiketopiperazine (ETP) natural products, and the recently isolated kibdelones, three classes of complex natural products with demonstrated antitumor activity. They will apply the methodologies developed to the chemical synthesis of complex targets including FL-120B', lomaiviticin B, and the ambewelamides/scabrosin esters, and kibdelones A, B, and C. In collaborative studies with investigators at Boston University, the NIH Chemical Genomics Center (NCGC), and the National Cancer Institute (NCI), Porco and colleagues will assay the biological activity of natural and unnatural compounds produced during the course of this research. Their proposal is organized into three core projects reflecting their fundamental interest in new reaction methodology development, mechanistic studies, and applications towards the synthesis of biologically active molecules. The aims of the proposed project are: " To develop an efficient asymmetric synthesis of the diazobenzofluorenes FL-120B' and lomaiviticin B and evaluate the DNA cleavage properties of synthetic compounds. " To complete the syntheses of the epidithiodiketopiperazine (ETP) natural products vertihemiptellide A, the ambewelamides/scabrosin esters, and rostratin A. " To complete the asymmetric syntheses and absolute configuration assignment of the polycyclic xanthone antitumor agents kibdelones A , B, and C.

项目总结/摘要抗肿瘤天然产物的不对称合成拟议的研究计划反映了首席研究员John A.小波尔科和他集团在新的化学反应的发展和生物相关分子的合成，使用高效接近。他们的总体目标是开发和完善新的合成方法，重氮苯并芴天然产物、环二硫二酮哌嗪（ETP）天然产物的合成，以及最近分离的三类复杂天然产物kibdelones具有抗肿瘤活性，活动他们将把开发的方法应用于复杂目标的化学合成， FL-120 B ′、洛麦维他星B和琥珀酰胺/苦蒿素酯，以及基布地隆A、B和C。在与波士顿大学、NIH化学基因组学中心（NCGC）和国家癌症研究所（NCI），Porco及其同事将分析天然和研究过程中产生的非天然化合物。他们的建议分为三个核心部分项目反映了他们在新反应方法学开发，机理研究，以及在合成生物活性分子方面的应用。拟议项目的目标是： the reaction mixture was stirred at room temperature for 10 minutes B 并评估合成化合物的DNA切割特性。 “为了完成epidithiodiketopiperazine（ETP）天然产物vertihemiptellide A的合成，琥珀酰胺/糙皮苷酯和rostratin A。 the mechanism of nanoparticles and nanoparticles are discussed.“ 氧杂蒽酮抗肿瘤剂基布得酮A、B和C。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Total syntheses of graphisin A and sydowinin B.

DOI：
10.1021/ol301107m
发表时间：
2012-06-01
期刊：
ORGANIC LETTERS
影响因子：
5.2
作者：
Little, Andrew;Porco, John A., Jr.
通讯作者：
Porco, John A., Jr.

Polycyclic xanthone natural products: structure, biological activity and chemical synthesis.

DOI：
10.1039/c3np20122h
发表时间：
2013-03
期刊：
Natural product reports
影响因子：
11.9
作者：
Winter DK;Sloman DL;Porco JA Jr
通讯作者：
Porco JA Jr

Synthesis and biological evaluation of ABCD ring fragments of the kibdelones.

DOI：
10.1002/anie.201007613
发表时间：
2011-03-07
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
影响因子：
16.6
作者：
Sloman, David L.;Mitasev, Branko;Scully, Stephen S.;Beutler, John A.;Porco, John A., Jr.
通讯作者：
Porco, John A., Jr.

Enantioselective total synthesis and biological evaluation of (+)-kibdelone A and a tetrahydroxanthone analogue.