Synthetic studies of hybrid macrolides.

杂化大环内酯类的合成研究。

• 批准号: 08557124
• 负责人: YONEMITSU Osamu
• 金额: $ 7.42万
• 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: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08557124/
• 关键词: macrolide; stereoselective synthesis; cyclization; glucose; protecting group; hybrid; keto-phosphonate; ケトホスホナ-ト; 立体選択的合性; マクロ環合成; ハイブリッド・マクロライド

The purpose of this research was to develop a new synthetic methodology of a series of complex natural and artificial macrolides through convenient and efficient syntheses of many fragments and their couplings starting from inexpensive materials such as glucose. The following three results were mainly obtained during the past three years research.1.Synthetic studies of natural macrolides : Recently, we developed two methods for the constructioi on of macro-rings ; macrolactonization and Horner-Emmons cycization 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 successfully applied to a highly efficient synthesis of the 18-membered lactone of tedanolide, an antitumor marine macrolide. The improved synthesis of key fragments of tedanolide was also completed.2.Synthetic studies of artificial macrolide : The enone and dienon type typical macrolides such as methynolide, pikronolide, tylonolide, carbonolides were aynthesized via coupling of the corresponding two fragments followed by Horner-Emmons cyclization. In order to obtain artificial macrolides, exchange of fragment combinations were tried, but only a few successful results were so far available.

本研究旨在开发一种新的合成方法，以葡萄糖等廉价材料为原料，通过方便高效地合成许多片段及其偶联物，合成一系列复杂的天然和人工大环内酯类化合物。在过去三年的研究中，主要获得了以下三个结果。天然大环内酯类化合物的合成研究：近年来，我们发展了两种构造大环的方法；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（利用分子力学和分子轨道计算）和关键中间体的结构设计，成功地应用于抗肿瘤海洋大环内酯丹丹内酯的18元内酯的高效合成。完成了丹丹内酯关键片段的改进合成。人工大环内酯类化合物的合成研究：采用霍纳-埃蒙斯环化法，将相应的两个片段偶联，合成了烯酮型和二烯酮型的典型大环内酯类化合物如甲基内酯、匹克诺内酯、泰诺内酯、碳内酯等。为了获得人工大环内酯类化合物，人们尝试过交换片段组合，但迄今为止只有少数成功的结果。

项目成果

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。”

Matsushima, T. ; Mori, M. ; Nakajime, N. ; Maeda, H. ; Uenishi, J. ; Yonemitsu, O.: "Synthetic Studies of Tedanolide. Stereoselective Synthesis of the C1-C7 Fragment via Highly Efficient Sharpless Dihydroxylation" Chem.Pharm.Bull.46. 1335-1336 (1998)

松岛，T.；

N. Nakajima: "Facile Synthesis of Prunasin, Linamarin and Heterodendrin." Biosci. Biotech. Biochem.62. 453-458 (1998)

N. Nakajima：“Prunasin、Linamarin 和 Heterodendrin 的简便合成”。

Nakajima, N. ; Ubukata, M.: "Facile Synthesis of Prunasin, Linamarin and Heterodendrin" Biosci.Biotechnol.Biochem.62. 453-458 (1998)

中岛，N.；

O.Yonemitsu: "A Facile Synthesis of Pikronolide." Heterocycles. 46. 105-110 (1997)

O.Yonemitsu：“吡克罗内酯的简便合成”。