349148-27-2

Upstream product

• 100-39-0 benzyl bromide 
• 80974-42-1 (S)-N-tert-butyloxycarbonylaspartic acid dibenzyl ester 

Downstream Products

• 349148-28-3 (2R,3S)-2-benzyl-3-(tert-butyloxycarbonylamino)-4-hydroxybutanoic acid benzyl ester 

Relevant academic research and scientific papers

Mechanistic insight into the inactivation of carboxypeptidase A by α-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid, a novel type of irreversible inhibitor for carboxypeptidase A with no stereospecificity

On the basis of the active site topology and enzymic catalytic mechanism of carboxypeptidase A (CPA), a prototypical zinc-containing proteolytic enzyme, α-benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (1), was designed as a novel type of mechanism-based inactivator of the enzyme. All four possible stereoisomers of the inhibitor were synthesized in an enantiomerically pure form starting with optically active aspartic acid, and their CPA inhibitory activities were evaluated to find that surprisingly all of the four stereoisomers inhibit CPA in a time dependent manner. The inhibited enzyme did not regain its enzymic activity upon dialysis. The inactivations were prevented by 2-benzylsuccinic acid, a competitive inhibitor that is known to bind the active site of the enzyme. These kinetic results strongly support that the inactivators attach covalently to the enzyme at the active site. The analysis of ESI mass spectral data of the inactivated CPA ascertained the conclusion from the kinetic results. The values of second-order inhibitory rate constants (kobs/[I]o) fall in the range of 1.7-3.6 M-1 min-1. The lack of stereospecificity shown in the inactivation led us to propose that the ring cleavage occurs by the nucleophilic attack at the 2-position rather than at the 5-position and the ring opening takes place in an addition-elimination mechanism. The tetrahedral transition state that would be generated in this pathway is thought to be stabilized by the active site zinc ion, which was supported by the PM3 semiemprical calculations. In addition, a-benzyl-2-oxo-1,3-oxazolidine-5-acetic acid (18), a structural isomer of i was also found to inactivate CPA in an irreversible manner, reinforcing the nucleophilic addition-elimination mechanism. The present study demonstrates that the transition state for the inactivation pathway plays a critical role in determining stereochemistry of the inactivation.

Synthesis of optically active 2-alkyl-3,4-iminobutanoic acids. β-amino acids containing an aziridine heterocycle

All four stereoisomers of 2-alkyl-3,4-iminobutanic acid, a novel class of β-amino acids bearing a chemically versatile aziridine ring, were synthesized starting with aspartic acid. The synthetic strategy involves the introduction of an alkyl group at the β-position of fully protected optically active aspartic acid followed by the construction of an aziridine ring making use of the α-carboxylate and α-amino groups. The α-carboxylate was reduced to the corresponding alcohol, which was then subjected to cyclization to form an aziridine ring with the N-protected amino group. Removal of the protection groups yielded the target compounds.

Irreversible inhibition of zinc-containing protease by oxazolidinone derivatives. Novel inactivation chemistry

α-Benzyl-2-oxo-1,3-oxazolidine-4-acetic acid (BOOA) having (αR,4S) and (αS,4R) configurations were designed and synthesized as a novel type of mechanism-based inactivators for carboxypeptidase A (CPA), and kinetic analysis demonstrated that they indeed in