Study On The Highly Stereoselective Synthesis Of 1-Aminocyclopropane-1-carboxylic Acid Derivatives

I -Arninocyclopropane- I -carboxyli c Acids(Accs), also referred to as 2,3-methanoamino acids, constitute an important family of conformationally constrained natural amino acids, found in plants and microorganisms generally unbound or simple linked as dipeptides. Due to their diverse documented biological activities, such as plant growth regulator, herbicides, sweet- tasters, enzyme inhibitors and their use in conformation restricted peptides, they are attracting special attention of scientists.Among the considerable cyclopropane amino acid derivatives, most researches were on 2-substituted or 2,2-disubstituted cyclopropane amino acids while studies on 2,3-disubstituted cyclopropane amino acid derivatives have not been touched nearly. Because of the increasing of steric constraint after the introduction of two aromatIc rings 2 3-diaryl cyclopropane amino acid derivatives will have more unique properties such as fluorescent characteristic, etc. So the subject of this thesis is the synthesis of 2,3-diaryl cyclopropane amino acid derivatives.In part one is classified under four different approaches the numerous stereoselective preparations of 2,3-niethanoamino acids recently reported in the literature. They are (I )alkylatioii of a glycine equivalent with I 2-electrophile (2)the use of diazo compounds on double bond (3)asymmetric ylide reactions on a , f3 di (lehydroalni noaci ds (4) den vai ion 1mm CYC I opropare(me den i vat i yes.In part two are reported the highly stereoselective(100%) synthesis of thirteen new 2, 3-diaryl cyclopropane amino acid derivatives. The key step is 1,3-dipolar addition of phenykliazornethane to24-aryl idene-2-phenyl-5(4H)-oxazolones, followed by the extrusion of N2.In the first step 4-arylidene-2-phenyl-5(4H)-oxazolones were obtained by Erlenmeyer reaction from hippuric acid and aromatic aldehydes. In the second step 4-arylidene--2--phenyl-5(4H)-oxazolones reacted with phenyldiazomethane in toluene at r. t. for 8~---48hrs to give five spirocyclopropane derivatives in high yields. The two aromatic rings at the cyclopropane ring occupy a trans relationship preferentially, as confirmed by X-ray crystallography. In the third step spirocyelopropane derivatives were readily converted into the corresponding methyl esters in nearly quantitative yields by treatment with absolute methanol containing catalytic amounts of sodium methoxide. In the fourth step hydrolysis of methyl esters with 4MHCI/HOAc furnished the corresponding 2,3-diaryl cyelopropane amino acid hydrochloride in good yields.All the products containing three-membered ring were identified on the basis of their analytical data, such as JR and 'I-I-NMR.The results indicate that the strategy we used to synthesize 2,3-diaryl eyclopropane amino derivatives has significant advantages:common available materials, mild reaction conditions, simple operations, high yields and above all the high stereoselectivity. It can be expected that after the incorporating of chiral centers into 4-aryl idene-2-phenyl-5(4F1)-oxazolones, cyclopropane amino acids with three stereogenic centers will be achieved by using the same strategy.