Highly stereoselective synthesis of complex natural products.

复杂天然产物的高度立体选择性合成。

• 批准号: 09307051
• 负责人: YONEMITSU Osamu
• 金额: $ 5.06万
• 依托单位: Okayama University of Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09307051/
• 关键词: macrolide; stereoselective synthesis; lactonization; conformation; protecting group; computational chemistry; 不斉アルドール反応; 立体選択的反応; マクロライト

The purpose of this research was to develop a new synthetic methodology of a series of complex natural macrolides through convenient and efficient syntheses of many fragments and their couplings, starting from inexpensive materials such as glucose. The following results were mainly obtained during the past three years research.Recently, we developed two methods for the construction of macro-rings ; macrolactonization and Horner-Emmons cyclization of the corresponding seco-acids and aldehyde-ketophosphonates, respectively. This methodology, combined with computer-aided conformational analysis (using both molecular mechanics and molecular orbital calculations) and structural design of key intermediates, was now applied to synthetic studies of tedanolide, an antitumor marine macrolide. Two fragments, C1-C12 and C13-C23, were synthesized stereoselectively staring from methyl hydroxyisobutyrates and coupled to give a seco-acid, which converted efficiently to an 18-mombered lactone, a key intermediate for the synthesis of tedanolide. Stereoselective syntheses of new fragments, which will be converted to another seco-acid, the corresponding lactone, and tedanolide more reasonably, were also completed.

本研究的目的是开发一种新的合成方法，通过方便、高效地合成许多片段及其偶联物，从葡萄糖等廉价材料开始，合成一系列复杂的天然大环内酯。在过去三年的研究中，主要获得了以下结果：最近，我们发展了两种构造宏环的方法；相应的二酸和醛酮膦酸的大内酯化和霍纳-埃蒙斯环化。该方法结合计算机辅助构象分析（使用分子力学和分子轨道计算）和关键中间体的结构设计，现已应用于抗肿瘤海洋大环内酯丹丹内酯的合成研究。从羟基异丁酸甲酯出发，立体选择性地合成了C1-C12和C13-C23两个片段，并偶联得到一个仲酸，该仲酸有效地转化为18元内酯，这是合成丹丹内酯的关键中间体。新片段的立体选择性合成也完成了，这些新片段将更合理地转化为另一种仲酸、相应的内酯和丹丹内酯。

项目成果

O.Yonemitsu: "Toal Synthesis of (±)-Acetomycin"Chem.Pharm.Bull.. 47. 517-523 (1999)

O.Yonemitsu：“(±)-Acetomycin 的完全合成”Chem.Pharm.Bull.. 47. 517-523 (1999)

O.Yonemitsu: "Stereoselective and Efficient Synthesis of the C13-C2 Part of Tedanolide"Synlett. 780-782 (1999)

O.Yonemitsu：“Tedanolide C13-C2 部分的立体选择性和高效合成”Synlett。

O. Yonemitsu: "Synthetic Studies of Halichondrin B. Synthesis of the C16-C36 Unit." Chem. Pharm. Bull.46. 1199-1216 (1998)

O. Yonemitsu：“软海绵素 B 的合成研究。C16-C36 单元的合成。”

Zheng, B. -Z.; Maeda, H.; Mori, M.; Kusaka, S.; Yonemitsu, O.; Matsushima, T.; Nakajima, N.; Uanishi, J.: "Synthetic Studies of 18-Membered Antitumor Macrolide, Tedanolide. 5. Streoselective Sunthesis of the C13-C23 Part via Condensation of Two Fragments,

郑，B.-Z.；

O.Yonemitsu: "Coupling of Consecutive Pyridine Ring Units for Oligopyridine Synthesis"Heterocycles. 50. 341-351 (1999)

O.Yonemitsu：“用于寡聚吡啶合成的连续吡啶环单元的偶联”杂环。