Asymmetric Synthesis of Antitumor Agents

抗肿瘤药物的不对称合成

基本信息

批准号：
7049557
负责人：
JAMES S. PANEK
金额：
$ 35.09万
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：
1994
资助国家：
美国
起止时间：
1994-01-13 至 2008-03-31
项目状态：
已结题

项目摘要

This research proposal reflects our interest in the development of new reaction processes and reagents in the areas of asymmetric catalysis and acyclic stereocontrol. The objectives that we intend to pursue will focus on the development and application of chiral silane reagents, although intensive activity in methodology development is outside the scope of this program. A new direction to be pursued during the budget period of this proposal will focus on the improvement of a existing reaction methodology concerning catalytic asymmetric carbene insertions into heteroatom-hydrogen bonds. We will also continue the development of double stereodifferentiating reactions and applications to the synthesis of anti-tumor antibiotics derived from terrestrial sources as well as marine sources. We intend to continue our efforts aimed at the completion of the asymmetric synthesis of herbimycin A, gledanamycin, and reblastatin. It is our objective to synthesize cyclotrienin and analogs. Cytotrienin A will be evaluated for its effect on the mitogene- activated protein kinase pathway using Saccharomyces cerevisiae as a model organism and genome-wide transcription polling techniques. It is our continuing objective to complete the asymmetric synthesis of ulapualide A, and confirm its stereochemical assignment. It is our continuing aim to identify and develop chiral metal catalysts for the catalyzed asymmetric intermolecular carene insertion reactions into heteroatom-hydrogen (cf Si-H and Sn-H) bonds. Although an in-depth mechanistic evaluation is outside the scope of this program, it is our short term objective to develop a number of useful synthetic transforms using this methodology, which include new approach to the synthesis of new chiral allylic silanes and stannanes.

这项研究计划反映了我们对不对称催化和非环状立体控制领域新反应过程和试剂开发的兴趣。我们打算追求的目标将集中于手性硅烷试剂的开发和应用，尽管方法开发的密集活动超出了该计划的范围。该提案预算期间要追求的新方向将侧重于改进有关催化不对称卡宾插入杂原子-氢键的现有反应方法。我们还将继续开发双立体分化反应并将其应用于陆地来源和海洋来源的抗肿瘤抗生素的合成。我们打算继续努力，以完成除草霉素A、格莱霉素和Reblastatin的不对称合成。我们的目标是合成环三烯酸及其类似物。将使用酿酒酵母作为模型生物和全基因组转录轮询技术来评估细胞三烯蛋白 A 对有丝分裂原激活蛋白激酶途径的影响。我们的持续目标是完成ulapualide A的不对称合成，并确认其立体化学归属。我们的持续目标是识别和开发手性金属催化剂，用于催化不对称分子间蒈烯插入杂原子-氢（参见 Si-H 和 Sn-H）键的反应。尽管深入的机理评估超出了该计划的范围，但我们的短期目标是使用该方法开发许多有用的合成转化，其中包括合成新手性烯丙基硅烷和锡烷的新方法。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Annulations of enantioenriched allenylsilanes with in situ generated iminium ions: stereoselective synthesis of diverse heterocycles.

DOI：
10.1021/ol802618p
发表时间：
2009-01-15
期刊：
Organic letters
影响因子：
5.2
作者：
Brawn RA;Panek JS
通讯作者：
Panek JS

Synthesis of reblastatin, autolytimycin, and non-benzoquinone analogues: potent inhibitors of heat shock protein 90.

DOI：
10.1021/jo1000109
发表时间：
2010-05-07
期刊：
JOURNAL OF ORGANIC CHEMISTRY
影响因子：
3.6
作者：
Wrona, Iwona E.;Gozman, Alexander;Taldone, Tony;Chiosis, Gabriela;Panek, James S.
通讯作者：
Panek, James S.

Stereoselective additions of chiral (E)-crotylsilanes to thionium ions: asymmetric synthesis of homoallylic thioethers.

手性 (E)-巴豆基硅烷与锍离子的立体选择性加成：同烯丙基硫醚的不对称合成。