Asymmetric induction and desymmetrization with organometallic reagents

有机金属试剂的不对称诱导和去对称化

• 批准号: 09555285
• 负责人: NISHIYAMA Hisao
• 金额: $ 7.49万
• 依托单位: Toyohashi University of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 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-09555285/
• 关键词: asymmetric reaction; prostacyclin; organometallics; desymmetrization; cyclopentenediol; asymmetric induction; ラジカル還元; プロスタグランジン; 非対称化; ベンゾフラン; 不斉誘導; リチウム塩

New asymmetric reaction and desymmetrization method have been applied in synthetic routes for bioactive prostaglandin derivative such as prostacyclin (PGI2), which is expected as an anti-platelet drugs. First, bis (boromophenoxy) cyclopentene derivatives were examined to SN2' reaction with Grignard reagents in metal-halogen exchange and subsequent cyclization to give a precursor of prostacyclin. An authentic sample of desired compound was synthesized from optically active cycopentanediol derivative by the desymmetric process. Second, meso-diacetoxy-cyclopentene was subjected to enantioselective desymmetric cyclization with chiral palladium catalyst to give the desired cyclization product as a precorsor in over 95% ee in high yield. Finally, above process was applied for optically active prostacycline, chiral Beraprost. In addition, non chiral Beraprost was also synthesized via new several routes.

新型的不对称反应和去对称化方法已被应用于前列环素（PGI 2）等具有生物活性的前列腺素衍生物的合成中，该衍生物有望成为抗血小板药物。首先，研究了双（硼苯氧基）环戊烯衍生物与格氏试剂在金属-卤素交换中的SN 2 '反应，然后环化得到前列环素的前体。以旋光环戊二醇衍生物为原料，通过去对称法合成了目标化合物的真实样品。第二步，在手性钯催化剂作用下，内消旋二乙酰氧基环戊烯进行不对称环化反应，得到了95%ee以上的环化前体，收率较高。最后，将上述方法应用于光学活性前列环素、手性贝前列素。此外，非手性贝前列素也通过新的几条路线合成。

项目成果

H.Nishiyama,ら他5名: "Synthesis of Optically Active Cyclopenta[b] benzofuran as a Precursor of m-phenylenprostacylin"Synlett. 930-932 (1998)

H. Nishiyama 等人和其他 5 人：“作为间苯前列环素前体的光学活性环戊二烯[b]苯并呋喃的合成”Synlett 930-932 (1998)。

H. Nishiyama, ら他4名: "Asymmetric induction in intramolecular SN'2 reaction"Synlett. 1147-1148 (1999)

H. Nishiyama 等人和其他 4 人：“分子内 SN2 反应中的不对称诱导”Synlett 1147-1148 (1999)

H.Wakita,ら他4名: "Synthesis of 5,6,7-trinor-4.8-inter-m-phenylene PGI_2 and Beraprost"Tetrahedron. 55. 2449-2474 (1999)

H. Wakita 等人和其他 4 人：“5,6,7-三降-4.8-间-亚苯基 PGI_2 和贝前列素的合成”Tetrahedron，55。2449-2474 (1999)

H.Nishiyama,N.Sakata,et al.: "Synthesis of Optically Active Cyclopenta[b]benzofuran as a Precursor of m-Prostacyclin" Synlett. 930-931 (1998)

H.Nishiyama、N.Sakata 等人：“作为间前列环素前体的光学活性环戊二烯[b]苯并呋喃的合成”Synlett。

H. Nishiyama, ら他5名: "Synthesis of optically Active Cyclopenta[b]benzofuran as a Precursor of m-phenyleneprostacylin"Synlett. 930-932 (1998)

H. Nishiyama 等人和其他 5 人：“作为间亚苯基前列环素前体的光学活性环戊二烯并呋喃的合成”Synlett 930-932 (1998)。