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

为了开发以谷氨酸为手性源制备具有生物活性的丝氨酸衍生物的方法，研究了(3R)-5- tbsosy -3-苯基- 1h -吡咯[1,2-c]恶唑(1)的立体选择性烷基化反应。在研究之前，研究了TBSOP （n -t-丁基羰基1-2-t-丁基二甲基硅氧基吡咯）与醛反应的立体选择性作为模型反应。在三氟化硼醚存在下，TBSOP与芳香醛优先反应生成三价产物，而在四氯化锡存在下主要生成赤价产物。TBSOP与脂肪醛的反应具有完全的反向选择性。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。接着，将1与亚硝基进行反应，得到亚硝基与3-苯基同面反应的产物。另一方面，与其他硝基烯烃反应可得到相反的面攻产物。从这些主要产品中去除硝基，收率很高。产物经四氧化锇二羟基化，再经四乙酸铅内酰胺环裂解，成功转化为目标α -烷基丝氨酸衍生物。为了制备热酵素和isp - 1，研究了1与手性甘油醛衍生物的双立体选择反应。在四氯化钛的存在下，1与r -2- tbsoy -丙醛反应，得到立体化学性质符合产率55%的产物。另一方面，在氯化锌的存在下，I与(S)-2- tbsoy -丙醛反应，产物具有ISP-I所需的立体化学性质，产率为60%。这种方法被证明是适用于引入所需的立体化学的热酵素和ISP-I和加合物成功转化为热酵素和ISP-I的基本骨架类似的方法。少

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