High Stereoselectivity Asymmetric Synthesis Of Alpha 3 Methyl.alpha.-amino Acid Methodology Research

Fluorine atoms is the smallestⅦatoms in the periodic table, the van der Walls radius is larger than that of hydrogen and lesser than that of oxygen, it is the most electronegative of all elements. Because of the unique properties, it can affect the physicochemical properties when incorporated of fluorine into organic compounds. Accordingly, the biologically activity of pharmaceutical could be modulated by introuding fluorine or fluorine group. Natural amino acids is of indispensable part of peptide and protein in the body, which involved in biology processes, plays a vital role. Meanwhile, parts of amino acids and peptide compounds had significant activity on anti-cancer, antivirus, antibacterial and so on. However, there are some defects on stability, cell permeability and conformation when peptide as drug candidates. Moderating the peptide and protein by incorporating fluorine into natural amino acids is the focus of the organofluorie chemistry and biochemistry. Highly stereoselective construction of quaternary chiral center with a CF3 grouop is one of the hardest challenge. Lower toxicity than CH2F and CHF2, CF3 has advantage as drug candidate.Due to the strong bond energy of C-F, the metabolic stability of petide can be enhanced. CF3 is the most lipophilic group, bioavailability increase as well as lipophilicity. The electron density of neighboring functional group changes resulting by the stong electronegative of CF3, which affect the hydrogen bond and polar electrostatic interactions between protein and acceptor.While interacting with enzyme, the secondary structure of protein was influcened as a result of CF3’s bulkiness.This paper reaveals the high diastereoselectivy outcome by changing the substrates’ratio and Indium powder equilvlent while running the allylation of (R)-Ethy1 3,3,3-trifluoro-2-(2-methoxy-l-phenylethylimino)propanoate on gram-scale. We investigated the versatile transform of the allyl group and the ester funtional group,we got varity of flourine-containing buliding block.We also developed the methodology of highly diastereoselective synthesis of quaternary a-trifluormethyl a-amino acids by addition of benzylzinc reagent to (R)-Ethy1 3,3,3-trifluoro-2-(2-methoxy-l-phenylethylimino)propanoate.We performed the reaction at different temperature or under diverse ratios to investigate influence of them.We obtained the desirable products with highly distereoselctive(dr>20:1). We broden the substrate scope, found this reaction be suitable for varity functional group substitute of benzylzin regants and kinds of chiral imines based on the auxiliary (R)-2-methoxy-l-phenylethanamine.We ascertain the absolute the configuration by the X-ray crystallographic of compound after hydrogenation of the a-benzyl a-trifluormethyl a-amino acids analogue.