177472-10-5

Upstream product

• 60079-12-1 β-Methyl α-tert-butyl (2S)-N-(benzyloxycarbonyl)aspartate 
• 3160-47-2 N-(benzyloxycarbonyl)-L-aspartic acid 4-methyl ester 
• 149598-20-9 (2S,3R)-N-tert-butyloxycarbonyl-3-methylaspartic acid dimethyl ester 
• 130622-08-1 dimethyl N-tert-butoxycarbonyl-L-aspartate 
• 501-53-1 benzyl chloroformate 

Downstream Products

• 349148-40-9 (2R,3S)-3-(benzyloxycarbonylamino)-4-hydroxy-2-methylbutanoic acid methyl ester 
• 349148-44-3 (2R,3S)-3,4-(benzyloxycarbonylimino)-2-methylbutanoic acid methyl ester 
• 112346-93-7 (3R,4S)-3-methyl-4-N-(benzyloxycarbonylamino)butyrolactone 

Relevant academic research and scientific papers

Structure-Guided Design of a "bump-and-Hole" Bromodomain-Based Degradation Tag

Chemical biology tools to modulate protein levels in cells are critical to decipher complex biology. Targeted protein degradation offers the potential for rapid and dose-dependent protein depletion through the use of protein fusion tags toward which protein degraders have been established. Here, we present a newly developed protein degradation tag BRD4BD1L94V along with the corresponding cereblon (CRBN)-based heterobifunctional degrader based on a "bump-and-hole"approach. The resulting compound XY-06-007 shows a half-degradation concentration (DC50, 6 h) of 10 nM against BRD4BD1L94V with no degradation of off-targets, as assessed by whole proteome mass spectrometry, and demonstrates suitable pharmacokinetics for in vivo studies. We demonstrate that BRD4BD1L94V can be combined with the dTAG approach to achieve simultaneous degrader-mediated depletion of their respective protein fusions. This orthogonal system complements currently available protein degradation tags and enables investigation into the consequences resulting from rapid degradation of previously undruggable disease codependencies.

PROTEIN TAG TO INDUCE LIGAND DEPENDENT DEGRADATION OF PROTEIN/PROTEIN-FUSIONS

Disclosed is a dTAG system comprising small molecule degraders of mutant BET family protein-tagged proteins via recruitment of an E3 ubiquitin ligase and uses thereof.

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.

Mapping the aspartic acid binding site of Escherichia coli asparagine synthetase B using substrate analogs

Novel inhibitors of asparagine synthetase, that will lower circulating levels of blood asparagine, have considerable potential in developing new protocols for the treatment of acute lymphoblastic leukemia. We now report the indirect characterization of th