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.

Reveromybin A是一种新型的聚酮型抗生素，由Steflyca sp.产生，并抑制小鼠表皮角质形成细胞中由表皮生长因子诱导的有丝分裂活性。回复霉素A的特征性结构特征包括1，7-二氧杂螺[5.5]十一烷部分，即带有半琥珀酸酯、两个烯基羧酸和甲基和n.丁基。首次设计并完成了回复霉素A的全合成。我们的合成是基于立体选择性和收敛合成的6，6-螺缩醛系统，然后在高压下琥珀酰化叔醇和安装的多烯侧链。我们还研究了回复霉素A衍生物的合成和生物活性。

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。