Synthetic Studies of Reveromycin A : An Inhibitor of Eukaryotic Cell Growth

真核细胞生长抑制剂白霉素 A 的合成研究

• 批准号: 12672082
• 负责人: SHIMIZU Takeshi
• 金额: $ 2.18万
• 依托单位: RIKEN (The Institute of Physical and Chemical Reseach)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672082/
• 关键词: reveromycin A; inhibitor of eukaryotic cell growth; inhibitor of protein synthesis; anti-tumor agent; 6, 6-spiroacetal; asymmetric total synthesis; succinylation; reaction under high pressure; 6,6-スピロケタール; Julia olefination

Reveromybin A is a novel polyketide-type antibiotic produced by Steptomyces sp. and inhibits mitogenic activity induced by the epidennal growth factor in a mouse epidermal keratinocyte. The characteristic structural features of reveromycin A include a 1, 7-dioxaspiro[5.5]undecane moiety, that is, the 6, 6-splroacetal system bearing a hemisuccinate, two alkenyl carboxylic acids, and methyl and n.-butyl groups. The first total synthesis of reveromycin A has been designed and accomplished. Our synthesis is based on the stereoselective and convergent synthesis of the 6, 6-spiroacetal system followed by the succinylation of tertiary alcohol under high pressure and the installation of the polyene-containing side chains. We also studied the syntheses and activities of reveromycin A derivatives.

逆转菌素A是由链霉菌产生的一种新型聚酮类抗生素。并抑制由表皮生长因子诱导的小鼠表皮角质形成细胞的有丝分裂活性。反转霉素A的结构特征包括1，7-二氧杂螺[5.5]十一烷部分，即含有一个琥珀酸半酯、两个烯基羧酸、甲基和正丁基的6，6-芳香醛体系。首次设计并实现了反转霉素A的全合成。我们的合成是基于6，6-螺缩醛体系的立体选择性和聚合性合成，然后叔醇在高压下进行琥珀酸化反应，并安装含多烯的侧链。我们还研究了反转霉素A衍生物的合成和活性。

项目成果

Ebihara M: "Kanki Publishing Company"Genetic manipulations. 223. 2156-2000 (2001)

Ebihara M：“Kanki Publishing Company”基因操纵。

T.Shimizu: "Total Synthesis of Reveromycin A"Organic Lett.. 2. 2153-2156 (2000)

T.Shimizu：“Reveromycin A 的全合成”Organic Lett.. 2. 2153-2156 (2000)

T.Shimizu: "Succinylation of Tertiary Alcohols under High Pressure"Synthesis. 1027-1034 (2001)

T.Shimizu：“高压下叔醇的琥珀酰化”合成。

Shimizu, T. ; Hiramoto, K. ; Nakata, T: "Succinylation of Tertiay Alcohols under High Pressure"1027. 1034-2001

清水，T.；

T.Shimizu: "Succinylalion of Tertiary Alcohols under High Pressure"Synthesis. 1027-1034 (2001)

T.Shimizu：“高压下叔醇的丁二醛”合成。