Study on the Synthesis of Chiral Abnormal Amino Acids Using the Chirality Reproduction Protocol

利用手性再现方案合成手性异常氨基酸的研究

• 批准号: 09640638
• 负责人: UNO Hidemitsu
• 金额: $ 2.24万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-09640638/
• 关键词: Glutamic Acid; Siloxypyrrole; Michael Addition; Double Stereoselection; Nitroalkene; Thermozymocidin; ISP-I; ニトロエチレン; 2,6-ジアミノ-6-ヒドロキシメチルピメリン酸

In order to develop a method for preparation of bioactive seine derivatives from glutamic acid as a chiral source, stereoselective alkylation of (3R)-5-TBSoxy-3-phenyl-1H-pyrrolo[1,2-c]oxazole (1) has been investigated. Before the investigation, stereoselectivity in the reaction of TBSOP (N-t-butoxycarbony1-2-t-butyldimethylsiloxypyrrole) with aldehydes was examined as the model reaction. In the presence of boron trifluoride etherate, TBSOP reacted with aromatic aldehydes preferrably to give threo products, while erythro products were mainly obtained in the presence of tin tetrachloride. The comlpetely reverse selectivity was observed in the reaction of TBSOP with aliphatic aldehydes. This selectivity could be reasonably explained by considering the transition states, similar discussion of which could be expanded to the reaction of 1 with aldehydes. Next, the reaction of 1 with nitroethylene was carried out to give the product which was derived from the same face attack of nitrcethylen … More e with the 3-phenyl group. On the other hand, the opposite face-attacked product was preferrably obtained in the reaction with other nitro olefins. The nitro group was removed from these major products in good yields. The products were successfully transformed to the aimed alpha-alkylserine derivatives via dihydoxylation with osmium tetroxide followed by the lactam ring cleavage with lead tetraacetate. In order to prepare thermozymocidin and ISP-I, double stereoselection in the reaction of 1 with chiral glyceraldehyde derivative was investigated. In the presence of titanium tetrachloride, the reaction of 1 with R-2-TBSoxy-propionaldehyde gave the desired product which had the required stereochemistry for thermozymocidin in 55% yield. On the other hand, the reaction of I with (S)-2-TBSoxy-propionaldehyde in the presence of zinc chloride gave the product with the required stereochemistry for ISP-I in 60% yield. This method was proved to be applicable for introduction of required stereochemistries for thermozymocidin and ISP-I and the adducts were successfully converted to the basic skeleton of thermozymocidin and ISP-I by the similar method described above. Less

为了开发一种以谷氨酸为手性源制备生物活性丝氨酸衍生物的方法，对(3R)-5-TBSoxy-3-苯基-1H-吡咯并[1,2-c]恶唑(1)的立体选择性烷基化进行了研究。在研究之前，以TBSOP（N-叔丁氧基羰基1-2-叔丁基二甲基甲硅烷氧基吡咯）与醛的反应作为模型反应来检查立体选择性。在三氟化硼醚合物存在下，TBSOP与芳香醛反应优先生成苏式产物，而在四氯化锡存在下主要得到赤式产物。在TBSOP与脂肪醛的反应中观察到完全相反的选择性。这种选择性可以通过考虑过渡态来合理解释，类似的讨论可以扩展到 1 与醛的反应。接下来，1与硝基乙烯进行反应，得到产物，该产物源自硝基乙烯与3-苯基的同一面攻击。另一方面，优选在与其他硝基烯烃的反应中获得相反的面攻击产物。以良好的产率从这些主要产物中除去硝基。通过用四氧化锇进行二羟基化，然后用四乙酸铅进行内酰胺环裂解，将产物成功转化为目标α-烷基丝氨酸衍生物。为了制备Thermozymocidin和ISP-I，研究了1与手性甘油醛衍生物反应中的双重立体选择。在四氯化钛存在下，1与R-2-TBS氧基丙醛反应得到所需产物，其具有热酶杀菌素所需的立体化学，产率55%。另一方面，I与(S)-2-TBS氧基丙醛在氯化锌存在下反应得到具有ISP-I所需立体化学的产物，产率60%。该方法被证明适用于引入thermozymocidin和ISP-I所需的立体化学，并且通过上述类似方法将加合物成功转化为thermozymocidin和ISP-I的基本骨架。较少的

项目成果

H.Uno et al.: "Highly Soluble Poly(1,3,4-trisubtituted-2,5-pyrrolenevinylenes)" Tetrahedron Lett. 39. 5397-5400 (1998)

H.Uno 等人：“高度可溶的聚（1,3,4-三取代-2,5-吡咯亚乙烯基）”四面体快报。

H.Uno et al.: "Stereoselective Isomerization of Tetrakistrifluoromethyl Tetraaryl [4] Radialenes to the Type II (All-Z) Isomers." Chem.Lett.1998. 105-106 (1998)

H.Uno 等人：“四三氟甲基四芳基 [4] 辐射烯立体选择性异构化为 II 型（全 Z）异构体”。

H. Uno, N. Mizobe, Y. Yamaoka, and N. Ono: "Stereochemical Change in the Lewis Acid-promoted Reaction of 2-Silyloxypyrrole Derived from (L)-Glutamic Acid. Synthesis of a Lactacystin Analogue"Heterocycles. 48. 635-640 (1998)

H. Uno、N. Mizobe、Y. Yamaoka 和 N. Ono：“路易斯酸促进的 (L)-谷氨酸衍生的 2-甲硅烷氧基吡咯反应中的立体化学变化。乳胞素类似物的合成”杂环。

H.Uno et al.: "A New Synthesis of Benzoporphyrins using 4,7-dihydro-4,7-ethano-2H-isoindole as a Synthon of Isoindole." J.Chem.Soc.,Chem.Commun. 1661-1662 (1998)

H.Uno 等人：“使用 4,7-二氢-4,7-ethano-2H-isoindole 作为异吲哚的合成物，新合成苯并卟啉。”

H.Uno et al.: "Stereocontrolled Mukaiyama-type Aldol Reaction of Siloxypyrroles Derived from (S) -Glutamic Acid." Synlett,. 1997. 390-392 (1997)

H.Uno 等人：“源自 (S)-谷氨酸的硅氧基吡咯的立体控制 Mukaiyama 型羟醛反应。”