This paper demonstrates how l-m-tyrosine 1 can be synthesized on larger-scale via enzyme-catalyzed kinetic resolution of N-acyl m-tyrosine methyl ester 4. N-Acyl m-tyrosine methyl ester 4 was prepared by a modification of Erlenmeyer’s azalactone synthesis followed by hydrogenation of the resultant dehydroamino acid 12. The optimized four-step synthesis utilizes cheap and readily available starting materials and circumvents difficult purification protocols.
The synthesis of heterocyclic compounds containing the 7-membered ring system [1,4]diazepane-2,5-dione is described. The aim of this study was to elaborate the solid phase and solution synthesis of eight representatives of the cyclic scaffold and to investigate their chemical stability and their conformational properties. The solid phase synthesis was performed on aminomethyl polystyrene resin using 5-(4-formyl-3,5-dimethoxyphenoxy)valeric acid as a backbone linker system (BAL-linker). After attachment of the α-and β-amino acid and deprotection of the amino function, the dipeptide ester was obtained. The molecule was cyclized on the solid support by treatment with NaOMe in MeOH/NMP. The product was cleaved from the resin by TFA. For the solution pathway the linear dipeptides were synthesized by coupling of the BOCprotected L-α-amino acid with the β 2 -amino acid ester (EDC/HOBT). After N -and C-terminal deprotection of the dipeptide, the linear species was cyclized with EDC/HOBT at a concentration of 3 mM in DMF. The products showed high chemical stability after storage in DMSO at room temperature for weeks. The x-ray and two dimensional NMR investigations were performed to investigate the conformation of the molecules. Three types of configuration could be distinguished by NMR, depending on the substitution pattern of the cyclic compounds. The x-ray results confirmed the NMR observations. In general the 7-membered rings showed rigidity, thus they could represent optimal scaffolds for new receptor ligands.
a-Aminomethylation of (R)-DIOZ-alkylated (DIOZ ¼ 4-isopropyl-5,5-diphenyloxazolidin-2-one) substrates is a key step in the asymmetric synthesis of b 2 -amino acids, but it is unfortunately often accompanied by formation of transcarbamation by-products. Aminomethylation was tested using a range of electrophiles, and the amount of by-product formation was assessed in each case. Benzyl N-[(benzyloxy)methyl]carbamate electrophile 3d is unable to form this by-product due to its inherent benzyl substitution. Use of electrophile 3d showed an improved impurity profile in aminomethylation, thus leading to easier intermediate purification.
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