Pseudopteroxazole and Related Antitubercular Agents

拟蝶恶唑及相关抗结核药

• 批准号: 7151457
• 负责人: MICHAEL HARMATA
• 金额: $ 23.88万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7151457
• 关键词: Analgesics; Anti-Inflammatory Agents; Antitubercular Agents; Area; Biological; Biological Assay; Biological Factors; Chemistry; Closure; Coupled; Development; Diterpenes; Esters; Evaluation; Exhibits; Generations; Goals; Malaria; Methodology; Mycobacterium tuberculosis; Numbers; Play; Process; Property; Reaction; Role; Structure; System; Testing; Tuberculosis; Variant; Work; analog; antimicrobial; aspidosperma alkaloid; base; carbanion; elisabethin A; elisapterosin B; erogorgiaene; interest; novel strategies; pseudopterosins; pseudopteroxazole

DESCRIPTION (provided by applicant): The goals of this work are to develop syntheses of antitubercular agents based on natural product leads. This will involve the total synthesis of the natural products pseudopteroxazole, seco-pseudopteroxazole, erogorgiaene, ileabethin, elisapterosin B and elisabethin A. Testing of targets and intermediates will be performed by the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF). A unifying methodology will be developed in pursuing these goals. This involves the synthesis of enantiomerically pure benzothiazines through the intramolecular, stereoselective addition of sulfoximine carbanions to unsaturated esters. The development of this methodology will be coupled with aspects of other new chemistry to achieve the synthetic goals. Of particular importance will be the development of a stereoselective, intramolecular radical ring closure reaction as a means of establishing a six-membered ring. Two approaches to this general type of process will be explored. Benzothiazine chemistry will be further developed, particularly in the context of the synthesis of elisabethin A, during which the study of benzothiazine carbanions as nucleophiles in Michael addition reactions will be undertaken. The compounds to be prepared in this study will contribute to the goal of developing chemotherapeutics for tuberculosis. Since the targets are related to pseudopterosins, compounds with potent analgesic and antiinflammatory properties, the work will have an impact in this area as well. More generally, the methodology to be developed should have extremely broad impact, as it can be applied to the generation of stereogenic centers in a large number of compounds of biological and medicinal interest.

描述（由申请人提供）：这项工作的目标是开发基于天然产物先导物的抗结核药物的合成。这将涉及天然产物假卟啉恶唑、次假卟啉恶唑、依绿霉素、依绿白素、elisapterosin B和elisisabethin a的全合成。靶点和中间体的检测将由结核病抗菌药物获取和协调机构（TAACF）进行。

项目成果

Oxidation of 4-methoxyanilines to 1,4-benzoquinones using ceric ammonium nitrate (CAN).

• DOI: 10.1016/j.tetlet.2010.11.070
• 发表时间: 2011-01-26
• 期刊: TETRAHEDRON LETTERS
• 影响因子: 1.8
• 作者: Chen, Yugang;Ying, Weijiang;Harmata, Michael
• 通讯作者: Harmata, Michael

Benzothiazines in organic synthesis. Stereoselectivity in the intermolecular Michael addition reactions of benzothiazines.

有机合成中的苯并噻嗪。

• DOI: 10.1021/ol701863y
• 发表时间: 2007
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Harmata,Michael;Chen,Yugang;Barnes,CharlesL
• 通讯作者: Barnes,CharlesL

Benzothiazines in synthesis. Further studies of the intramolecular, stereoselective addition of sulfonimidoyl carbanions to alpha,beta-unsaturated functional groups.

苯并噻嗪的合成。

• DOI: 10.1021/jo900151d
• 发表时间: 2009
• 期刊: The Journal of organic chemistry
• 作者: Harmata,Michael;Rayanil,Kanok-on;Espejo,VinsonR;Barnes,CharlesL
• 通讯作者: Barnes,CharlesL

Preparation of S-2-halophenyl-2,1-benzothiazines.

S-2-卤代苯基-2,1-苯并噻嗪的制备。

• DOI: 10.1016/j.tet.2021.131991
• 发表时间: 2021
• 期刊: Tetrahedron
• 影响因子: 2.1
• 作者: Garimalla,Aswin;Harmata,Michael
• 通讯作者: Harmata,Michael

Benzothiazines in synthesis. A formal total synthesis of pseudopteroxazole.

• DOI: 10.1021/jo9009112
• 发表时间: 2009-08-07
• 期刊: JOURNAL OF ORGANIC CHEMISTRY
• 影响因子: 3.6
• 作者: Harmata, Michael;Cai, Zhengxin;Chen, Yugang
• 通讯作者: Chen, Yugang