Syntheses of Alkaloids Using Palladium-Catalyzed Asymmetric Synthesis

采用钯催化不对称合成法合成生物碱

• 批准号: 09470478
• 负责人: MORI Miwako
• 金额: $ 6.4万
• 依托单位: HOKKAIDO UNIVERSITY
• 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-09470478/
• 关键词: palladium complex; π-allyl palladium complex; asymmetric synthesis; pretazetine; crinamine; kinetic resolution; haemanthidine; carbonyl-ene reaction; (+)-crinamine; (-)-haemanthidine; (+)-pretazettine; π-アリルパラジウム錯体; カルボニエルエン反応; 速度論的分割; 不斉合成

Palladium-catalyzed asymmetric synthesis of methyl 2-arylcyciohexenyl carbonate was realized using (S)-BINAPO as a chiral ligand. Using this method, we succeeded in the total syntheses of (-)-mesembrane and (-)-mesembrine by combination of palladium-catalyzed amidation followed by zirconium-promoted cyclization. The Amaryllidaceae alkaloids have been of interest as synthetic targets due to their wide range of biological activities. Over 100 alkaloids have been isolated from memberes of the Amaryllidaceae, and most of these may be classified into eight skeletally homogeneous subgroups. We accomplished the first asymmetric total syntheses of the crinane-type alkaloids, (+)-crinamine, (-)-haemanthidine, and (+)-pretazettine. The starting cyclohexenyl amine was obtained by palladium-catalyzed asymmetric amination in 80% yield and with 74% ee. The product was recrystalyzed from MeOH. Interestingly, (-)-cyclohexenyl amine derivative with 99% ee was obtained from the mother liquor. Intramolecular carbonyl-ene reaction proceeds in a highly stereoselective manner to give hexahydroindole derivative as the sole product. In the Lewis acid-catalyzed carbonyl-ene reaction, an interesting rearrangement product was isolated in high yield. From this product, the above alkaloids, (+)-crinamine, (-)-haemanthidine, and (+)-pretazettine, were synthesized in very few steps. The structure of intermediary palladium complex was confirmed by X-ray crystallography.

以（S）-BINAPO为手性配体，钯催化不对称合成了2-芳基环己烯基碳酸甲酯。利用这种方法，我们成功地通过钯催化的酰胺化和锆促进的环合相结合的方法全合成了（-）-中膜和（-）-中膜。石蒜科生物碱因其广泛的生物活性而成为合成目标。从石蒜科植物中已分离出100多种生物碱，其中大部分可分为8个同源的亚组。我们首次完成了三种海百合烷型生物碱（+）-海百合胺、（-）-海百合定和（+）-pretazettine的不对称全合成。以钯催化不对称胺化反应制得环己烯基胺，收率80%，ee值74%。有趣的是，从母液中获得具有99%ee的（-）-环己烯基胺衍生物。分子内羰基-烯反应以高度立体选择性的方式进行，得到作为唯一产物的六氢吲哚衍生物。在刘易斯酸催化的羰基-烯反应中，以高产率分离出一种有趣的重排产物。从该产物，上述生物碱，（+）-crinamine，（-）-haemanthidine，和（+）-pretazettine，合成在非常少的步骤。中间体钯配合物的结构通过X射线晶体学进行了确认。

项目成果

Yoshihiro Sato et al.: "A Novel Asymmetric Cyclization of ω-Formyl-1,3-dienes Catalyzed by a Zerovalent Nickel Complex in the Presence of Silanes"J.Am.Chem.Soc.. (in press). (2000)

Yoshihiro Sato 等人：“在硅烷存在下零价镍配合物催化的 ω-甲酰基-1,3-二烯的新型不对称环化”J.Am.Chem.Soc.（出版中）。

Toyoki Nishimata and Miwako Mori: "First Asymimetric Total Syntheses of (+)-Crinamine, (-). -Haeman_thicline, and (+)-Pretazettine"J. Org. Chem.. 63. 7586-7587 (1998)

Toyoki Nishimata 和 Miwako Mori：“( )-Crinamine、(-).-Haeman_thicline 和 ( )-Pretazettine 的首次不对称全合成”J。

Y.Sato: "Total Synthe'sis of Prostaglandin F_<2α>via Nickel-Promoted Stereoselective Cyclization of 1,3-Diene and Aldehyde" Synlett. 734-736 (1997)

Y.Sato：“通过镍促进的 1,3-二烯和醛的立体选择性环化进行前列腺素 F_2α 的全合成”Synlett 734-736 (1997)。

Yoshihiro Sato, Nozomi Saito, and Miwako Mori: "A Novel Asymnletric Cyclization of ω-Formy1-1,3-dienes Catalyzed by a Zerovalent Nickel Complex in the Presence of Silanes"J. Am. Chem. Soc.. (in press). (2000)

Yoshihiro Sato、Nozomi Saito 和 Miwako Mori：“硅烷存在下零价镍配合物催化的 ω-Formy1-1,3-二烯的新型不对称环化”J. Soc. (2000)

Alice Emi Imai, et al.: "Stereospecific Synthesis of (+)- and (-)-Cyclooctenone Derivatives Using a Ring Expansion Reaction with Me_3SiSnBu_3 and CsF"J.Am. Chem. Soc.. 121. 1217-1225 (1999)

Alice Emi Imai 等人：“使用 Me_3SiSnBu_3 和 CsF 进行扩环反应立体定向合成 ( )- 和 (-)-环辛烯酮衍生物”J.Am.