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Steponyces sp。产生的一种新型聚酮型抗生素。并抑制小鼠表皮角质形成细胞中附子生长因子诱导的有丝分裂活性。炎霉素A的特征结构特征包括A 1、7-二氧化物[5.5] undcane部分，即携带半核酸酯，两个烷基羧酸，以及甲基和甲基甲基的6个，6个丙乙酰乙酰乙乙乙化糖系统。炎霉素A的第一个总合成是设计和完成的。我们的合成基于6个6-螺旋乙乙化系统的立体选择性和收敛合成，然后在高压下琥珀醇化，并安装了含聚乙烯的侧链。我们还研究了霉素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)

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。

Shimizu,T.,Masuda,T.,Hiramoto,K.,Nakata,T: "Total Synthesis of Reveromysin A"Organic Letters. 2 . 2153-2156 (2000)

Shimizu,T.、Masuda,T.、Hiramoto,K.、Nakata,T：“Reveromysin A 的全合成”有机信件。