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

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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