CHEMICAL SYNTHESIS OF NOVEL NATURAL PRODUCTS

新型天然产物的化学合成

• 批准号: 2734621
• 负责人: DAVID R WILLIAMS
• 金额: $ 18.13万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-04-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734621
• 关键词: alkaloids; analgesics; antifungal agents; antiinflammatory agents; antineoplastics; antiviral agents; biological products; chemical structure function; chemical synthesis; cyclic compound; oxazoles; pyridinones

DESCRIPTION: (adapted from applicant's abstract) This is a broadly directed program to investigate fundamental advances in chemical synthesis of novel biologically active natural products. The major areas have been categorized by distinct structural motifs and bioactivity. I. Novel Marine Oxazoles. Research will execute a synthesis of Hennoxazole A, a promising lead in the search for new antiviral agents. While this unique bis-oxazole also displays peripheral analgesic activity comparable to indomethacin, its unusual structure and antiviral significance (IC50 0.6 m/mL), make this a compelling case for chemical synthesis. Phorboxazole A exhibits remarkable antitumor activity in all 60 NCI cell lines, and is one of the most potent cytostatic macrocycles yet discovered. Chemical studies will explore enantioselective allylstannane condensations with aldehydes as a convergent construction of carbohydrates which are C-linked to a heterocyclic core. Overall a general approach to novel nucleosides is detailed. II. Novel Anti-Infective Cyclitols. Studies for synthesis of funiculosin and related 4-hydroxy-2-pyridinones will provide novel C-linked heterocyclic cyclitols as potent antifungal agents. Funiculosin shows in vivo antifungal potency comparable to griseofulvin with low toxicity. The Saegusa oxidation will be explored as a ring closure event, and internal conjugate additions in funiculosin, as well as apiosporamide, will be examined as a relevant chemical feature of bioactivity. III. Polycyclic Marine Alkaloids. Zoanthamine is an alkaloid with anti-inflamatory and analgesic effects. Proposed studies will investigate Pd(O)-catalyzed cross-coupling reactions for ring closure. Studies of the Michael reaction will be exploited for stereocontrolled formation of quaternary carbons in ring annelation processes. IV. Large-Ring Carbocycles. Efforts to complete synthesis studies of the lankacidins are described. These macrocyclic antitumor agents exhibit important antibiotic effects against resistant organisms. New strategies for macrocyclization are introduced. Acyl nitrene insertions for preparation of lankacyclinol are described.

描述：（改编自申请人的摘要）这是一个广泛指导的 调查新型化学合成基本进步的计划 生物活性天然产物。 主要领域已分类 通过不同的结构基序和生物活性。 I.新型海洋加沙唑。 研究将执行Hennoxazole A的综合，这是一个有希望的领导 寻找新的抗病毒剂。 而这个独特的bis-oxazole也 显示外周镇痛活性与吲哚美辛相当 异常结构和抗病毒意义（IC50 0.6 m/ml），使其成为 引人入胜的化学合成案例。 phorbasazole a展品出色 所有60个NCI细胞系中的抗肿瘤活性，是最有效的 尚未发现细胞稳定大环。 化学研究将探索 对映选择性的丙烯酸醛与醛凝结为收敛性 碳水化合物的构造是C链接到异环芯的。 总体而言，详细介绍了一种新型核苷的一般方法。 ii。 小说 抗感染环醇。 研究曲霉及相关的合成研究 4-羟基-2-吡啶酮将提供新型的C连锁杂环环醇 作为有效的抗真菌剂。 曲霉素显示体内抗真菌效力 与毒性低的谷物硫素相当。 Saegusa氧化将是 作为环闭环事件探索，内部共轭添加 funiculosin和apioporamide将被检查为相关 生物活性的化学特征。 iii。 多环生物碱。 Zoanthamine是一种具有抗炎和镇痛作用的生物碱。 拟议的研究将研究PD（O）催化的交叉偶联反应 为了闭环。 对迈克尔反应的研究将被利用 圆环碳中的第四纪碳的立体控制形成 过程。 iv。 大环碳弹性。 完成综合的努力 描述了Lankacidins的研究。 这些大环抗肿瘤 药物对抗性生物具有重要的抗生素作用。 引入了大环化的新策略。 酰基硝基插入 描述了用于制备Lankacyclinol。