首页> 外文学位 >Synthetic and biological studies of (+)-phorboxazole A: Second-generation total synthesis of (+)-phorboxazole A. Synthesis and biological evaluation of phorboxazole analogues. Progress toward the gram-scale synthesis of (+)-chlorophorboxazole A.

【24h】

Synthetic and biological studies of (+)-phorboxazole A: Second-generation total synthesis of (+)-phorboxazole A. Synthesis and biological evaluation of phorboxazole analogues. Progress toward the gram-scale synthesis of (+)-chlorophorboxazole A.

机译：（+）-phorboxazole A的合成和生物学研究：（+）-phorboxazole A的第二代全合成。phorboxazole类似物的合成和生物学评估。克级合成（+）-氯代荧光唑A的研究进展。

获取原文

获取原文并翻译 | 示例

页面导航

摘要
著录项
相似文献
相关主题

摘要

This dissertation describes synthetic and biological studies related to the marine natural product, (+)-phorboxazole A. Specifically, a convergent second generation total synthesis of (+)-phorboxazole A, the total synthesis and biological evaluation of phorboxazole analogues and the synthesis of seventy-two milligrams of a sub-nanomolar phorboxazole congener, (+)-chlorophorboxazole A will be described.; Chapter one details the isolation, structure elucidation and biological activity of (+)-phorboxazole A and B. Previous total syntheses of (+)-phorboxazole A and B will be described including, the Forsyth total synthesis of (+)-phorboxazole A, the Evans total synthesis of (+)-phorboxazole B and a detailed account of the Smith group first generation total synthesis of (+)-phorboxazole A.*; Chapter two will detail the more efficient and convergent Smith group second generation total synthesis of (+)-phorboxazole A. Several highlights of the synthesis include the late stage Stille union of advanced oxazole stannane sidechain and macrocyclic vinyl iodide fragments to construct the complete phorboxazole carbon backbone. The oxazole stannane sidechain was the tetrahydropyranyl hemiacetal and thus completion of the sidechain. Construction of the macrocyclic vinyl iodide called upon the Petasis-Ferrier union/rearrangement tactic to assemble the two 2,6 cis-tetrahydropyran moieties. Utilizing olefination protocols, the E and Z-macrocyclic olefins were constructed and thus completion of the macrocyclic vinyl iodide.*; Chapter three will detail the design, total synthesis and biological evaluation of simplified phorboxazole analogues. Modification of the phorboxazole sidechain and macrocycle afforded structurally and synthetically simplified congeners, wherein highly potent antitumor activity was discovered when evaluated against a panel of human tumor cell lines. Specifically, exchange of the phorboxazole C(45-46) E-vinyl bromine for the corresponding vinyl chlorine revealed a congener that displayed sub-nanomolar (nM) antitumor activity.*; Chapter three will also describe the synthesis of seventy-two milligrams of the sub-nanomolar phorboxazole analogue, (+)-chlorophorboxazole A. Specifically, a comparison between the analogue and large-scale synthetic routes toward an advanced vinyl chloride sidechain will be detailed as well as the ultimate conversion to (+)-chlorophorboxazole A.*; *Please refer to dissertation for diagrams.

机译：本论文描述了与海洋天然产物（+）-phorboxazole A有关的合成和生物学研究。具体而言，是（+）-phorboxazole A的聚合第二代全合成，phorboxazole类似物的总合成和生物学评估以及与之相关的合成。将描述72毫克的亚纳莫尔佛波唑同类物，（+）-氯佛波唑A。第一章详细介绍了（+）-phorboxazole A和B的分离，结构阐明和生物学活性。将介绍（+）-phorboxazole A和B的先前合成方法，包括（+）-phorboxazole A的Forsyth全合成，（+）-佛波唑B的Evans全合成和史密斯集团第一代（+）佛波唑A的全合成的详细说明。第二章将详细介绍更有效和收敛的Smith组第二代全合成（+）-佛波唑A。合成的几个亮点包括晚期恶唑锡烷侧链的Stille结合和大环乙烯基碘片段构成完整的佛波唑碳骨干。恶唑锡烷侧链为四氢吡喃基半缩醛，因此完成了侧链。大环乙烯基碘的构建要求使用Petasis-Ferrier结合/重排策略来组装两个2,6顺式-四氢吡喃部分。利用烯烃化方案，构建了E和Z-大环烯烃，从而完成了大环乙烯基碘。第三章将详细介绍简化的佛波唑类似物的设计，全合成和生物学评估。 phorboxazole侧链和大环的修饰提供了结构和合成简化的同类物，其中当针对一组人类肿瘤细胞系进行评估时，发现了高效的抗肿瘤活性。具体地说，将佛波唑C（45-46）E-乙烯基溴换成相应的氯乙烯，揭示了同类物，其表现出亚纳摩尔（nM）抗肿瘤活性。第三章还将描述72毫克亚纳莫尔佛波唑类似物（+）-氯佛波唑A的合成。具体而言，将类似物与大规模合成路线的高级氯乙烯侧链比较如下：以及最终转化为（+）-氯代虫唑A. *; *请参考论文的图表。

著录项

作者
Razler, Thomas M.;
展开▼
作者单位

University of Pennsylvania.;

展开▼
授予单位 University of Pennsylvania.;
学科 Chemistry Organic.
学位 Ph.D.
年度 2006
页码 416 p.
总页数 416
原文格式 PDF
正文语种 eng
中图分类有机化学;
关键词

相似文献

外文文献
中文文献
专利

1. Phorboxazole synthetic studies: Design, synthesis and biological evaluation of phorboxazole A and hemi-phorboxazole A related analogues [J] . Smith III A.B., Hogan A.-M.L., Liu Z., Tetrahedron . 2011,第27a28期

机译：邻苯二酚合成研究：邻苯二酚A和半邻苯二酚A相关类似物的设计，合成和生物学评估
2. Synthetic studies towards phorboxazole A. Stereoselective synthesis of the C3-C19 bis-oxane oxazole portion of the phorboxazole macrolide [J] . Pattenden Gerald., Plowright Alleyn T. Tetrahedron letters: The International Journal for the Rapid Publication of Preliminary Communications in Organic Chemistry . 2000,第6期

机译：对phorboxazole A的合成研究。phorboxazole大环内酯的C3-C19双-恶烷恶唑部分的立体选择性合成
3. Synthesis and biological evaluation of phorboxazole congeners leading to the discovery and preparative-scale synthesis of (+)-chlorophorboxazole A possessing picomolar human solid tumor cell growth inhibitory activity [J] . Smith AB, Razler TM, Meis RM, The Journal of Organic Chemistry . 2008,第4期

机译：佛波唑同系物的合成和生物学评价，导致发现和制备规模的合成具有皮摩尔人实体瘤细胞生长抑制活性的（+）-氯佛波唑A
4. Total Synthesis and Biological Evaluation of Biologically Active Natural Cyclopeptides Toward Elucidation of the Mode of Action [C] . Masahito Yoshida 日本化学会春季年会講演予稿集 . 2018

机译：生物活性天然环肽的总合成和生物学评价待阐明的作用方式
5. Part I. Total synthesis of the marine cyclodepsipeptide apratoxin A. Part II. Structural determination and total synthesis of spongidepsin. Part III. Improved synthesis of the C3-C17 domain of phorboxazole A and synthesis of a fluorescent phorboxazole derivative. [D] . Chen, Jiehao. 2004

机译：第一部分。海洋环二肽阿普毒素A的全合成。第二部分。海绵蛋白酶的结构测定和全合成。第三部分改进的佛波唑A C3-C17结构域合成和荧光佛波唑衍生物的合成。
6. Phorboxazole Synthetic Studies: Design Synthesis and Biological Evaluation of Phorboxazole A and Hemi-Phorboxazole A Related Analogues [O] . Amos B. Smith III, Anne-Marie L. Hogan, Zhuqing Liu, -1

机译：phorboxazole合成研究：设计合成及phorboxazole a的生物学评价和半phorboxazole a相关类似物
7. Phorboxazole synthetic studies: design, synthesis and biological evaluation of phorboxazole A and hemi-phorboxazole A related analogues [O] . Amos B. Smith, Anne-Marie L. Hogan, Zhuqing Liu, 2011

机译：富池酶合成研究：富池A和Hemi-FlboBoxazle的设计，合成和生物学评价相关类似物

Synthetic and biological studies of (+)-phorboxazole A: Second-generation total synthesis of (+)-phorboxazole A. Synthesis and biological evaluation of phorboxazole analogues. Progress toward the gram-scale synthesis of (+)-chlorophorboxazole A.

摘要

著录项

相似文献

相关主题

期刊订阅