SYNTHESIS OF POLYPROPIONATE DERIVED NATURAL PRODUCTS

聚丙酸酯衍生天然产物的合成

• 批准号: 2608980
• 负责人: JAMES S. PANEK
• 金额: $ 18.34万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2608980
• 关键词: allyl compound; aminoacid analog; biological products; drug design /synthesis /production; macrolide antibiotics; oligomycins; propionates; silanes; stereochemistry

DESCRIPTION: (Principal Investigator's) This research proposal reflects our general interest in the development of new reagents in the context of acyclic stereocontrol. Once the reaction methodology has achieved success in the development stage, it is used in the asymmetric synthesis of complex organic molecules that may have relevance in the treatment of human diseases. The long term objectives are the eventual achievement of the asymmetric synthesis of th macrolide antibiotics, rutamycin B, oligomycin C, oleanolide, discodermolide, and the proteosome inhibitor lactacystin. In this regard, we intend to 1. explore the scope of double stereodifferentiating reactions of chiral allylsilane reagents with chiral aldehyde partners. This study will be used to determine their potential utility for polypropionate assemblage as well as vicinal amino alcohols. As a new direction for this technology we will develop novel approaches to the synthesis of new allylsilane reagents bearing C-centered chirality; allylsilanes and beta-substituted (E)-crotylsilanes. These approaches include the development of chiral Lewis acids to promote asymmetric (2,3) and (3,3)-sigmatropic processes. 2. Pursue the completion of the synthesis of polypropionate derived macrolide antibiotics, rutamycin B and oligomycin C. 3. Pursue the total synthesis of the macrolide antibiotic oleanolide. 4. Pursue the total synthesis of the microtubule stabilizing agent discodermolide. 5. Pursue the total synthesis of unusual amino acid (+)-lactacystin.

描述：（主要研究者）本研究提案反映了我们的 在开发新试剂的背景下， 无环立体控制 一旦反应方法学取得成功 在开发阶段，它被用于配合物的不对称合成， 可能与人类疾病治疗相关的有机分子 疾病 长期目标是最终实现 大环内酯类抗生素，如他霉素B，寡霉素C， 齐墩果酸、discodermolide和蛋白体抑制剂lactacystin。 在 在这方面，我们打算1. 探索双重范围 手性烯丙基硅烷试剂与手性 醛类伴侣。 这项研究将用于确定其潜力 用于聚丙酸酯组合物以及邻位氨基醇。 作为 我们将开发新的方法来实现这项技术的新方向， 具有C-中心手性的新型烯丙基硅烷试剂的合成; 烯丙基硅烷和β-取代的（E）-巴豆基硅烷。 这些方法 包括手性刘易斯酸的发展，以促进不对称（2，3） 和（3，3）-σ迁移过程。 2. 追求合成的完成 聚丙酸衍生的大环内酯类抗生素，如鲁塔霉素B和寡霉素 C. 3. 进行大环内酯类抗生素齐墩果酸的全合成。 4. 进行微管稳定剂的全合成 discodermolide 5. 追求稀有氨基酸的全合成 （+）-lactacystin。