Efficient synthetic method for biologically active compounds and their synthetic intermediates by new carbon-carbon bond formation reactions.

通过新型碳-碳键形成反应有效合成生物活性化合物及其合成中间体的方法。

• 批准号: 03555177
• 负责人: UENO Yoshio
• 金额: $ 9.98万
• 依托单位: Nagoya Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03555177/
• 关键词: Prostaglandin; Destannylselenenylation; Alkylcyloalkenone; Vinyl anion equivalent; Punaglandin; 2-アリル-2-シクロペンテノン; 脱シリルセレノ化反応; 脱スタニルチオ化反応; α-ケトビニルアニオン; 2-置換α、β-不飽和カルボニル

This project deals with the study on the short and efficient synthesis of the synthetic intermediates of prostaglandins and punaglandins, both of which are known to have important biological activities related to the deseases of old people including cancer.Treatment of 2-(phenylseleno)-2-cyclopenten(or cyclohexen)-1-one with tributylstannyllithium gave the enolate witch was then trapped with allyl iodide to afford the allylated cycloalkenone. Destannylselenenylation could be effected by numerous reagents such as tetrabutylammonium fluoride, bases, Lewis acids, or by thermal and photo treatments, giving 2-allyl-2-cylcoalken-1-one in high yields. According to this protocol, the key intermediate for prostaglandins and their analogs could be prepared in high yield directly from chiral 4-siloxy-2-cyclopenten-1-one. The method comprises the shortest and the most convenient process ever known. In the above procedure the phenylthio and trialkylsilyl groups were shown to be able to be substituted for the phenylseleno and the tributylstannyl groups, respectively.The three-component coupling of 2-(phenylseleno)-2-cyclopenten-1-one, tributylstannyllithium, and aldehydes led to a high yield preparation of 2-(1-hydroxyalkyl)-2-cyclopenten-1-ones, which opened a way to the efficient synthesis of punaglandins and their analogs.

本项目致力于合成前列腺素和刺激素的短而高效的合成中间体的研究，这两个化合物都具有重要的生物活性，与包括癌症在内的老年人的疾病有关。用三丁基锡锂处理2-(苯基硒)-2-环戊烯(或环己烯)-1-酮，然后用烯丙基碘捕获它，得到烯丙基环烯酮。许多试剂，如四丁基氟化铵、碱、Lewis酸，或通过热处理和光处理，可以高产率地产生2-烯丙基-2-环烷基-1-酮。根据该方案，从手性4-硅氧基-2-环戊烯-1-酮可以直接高产率地合成前列腺素及其类似物的关键中间体。该方法包括迄今已知的最短和最方便的过程。在上述步骤中，苯硫基和三烷基硅基可以分别取代苯基亚硒基和三丁基锡基。2-(苯基亚硒基)-2-环戊烯-1-酮、三丁基锡基锂和醛的三组分偶联反应高产率地制备了2-(1-羟基烷基)-2-环戊烯-1-酮，为高效合成刺激素及其类似物开辟了一条新途径。

项目成果

楠田 晋也: "A Novel Vinyl Anion Equivalent.An Extremely Short Synthesis of 2-Substituted 2-Cycloalkenones and Prostaglandin Key Intermediates Via Destanny Iselenenylation." J.Org.Chem.57. 3145-3152 (1992)

Shinya Kusuda：“新型乙烯基阴离子等效物。通过 Destanny Iselenenylation 进行 2-取代 2-环烯酮和前列腺素关键中间体的极短合成。”J.Org.Chem.57（1992）。

Shinya Kusuda: "An extremely short synthesis of the prostaglandin key intermediate through a novel vinyl anion equivalent" Tetrahedron Letters. 32. 1325-1326 (1991)

Shinya Kusuda：“通过新型乙烯基阴离子等效物对前列腺素关键中间体进行极短的合成”四面体快报。

楠田 晋也: "Vinyl Anion Equivalents Part IV.Efficient Synthesis of 2-(1-Hydroxyalkyl)-2-cyclopenten-1-ones" Bull.Chem.Soc.Jpn.

Shinya Kusuda：“乙烯基阴离子当量第 IV 部分。2-(1-羟基烷基)-2-环戊烯-1-酮的高效合成”Bull.Chem.Soc.Jpn。

Shinya Kusuda: "A novel vinyl anion equivalent. An extremely short synthesis of 2-substituted 2-cycloalkenones and prostaglandin key intermediates via destannylselenenylation." J.Org.Chem.57. 3145-3152 (1992)

Shinya Kusuda：“一种新型乙烯基阴离子等价物。通过去锡锡烯基化，以极短的时间合成 2-取代的 2-环烯酮和前列腺素关键中间体。”

楠田 晋也: "A Novel Vinyl Anion Equivalent.An Extremely Short Synthesis of 2-Substituted 2-Cycloalkenones and Prostaglandin Key Intermediates via Destannylselenenylation." J.Ory.Chem.57. 3145-3152 (1992)

Shinya Kusuda：“新型乙烯基阴离子等效物。通过脱斯坦基硒化作用极短地合成 2-取代的 2-环烯酮和前列腺素关键中间体。J.Ory.Chem.57”。