114744-85-3

Upstream product

• 1161-13-3 N-Cbz-L-Phe 
• 1117-97-1 N,0-dimethylhydroxylamine 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 62750-39-4 ((S)-1-Benzyl-2-imidazol-1-yl-2-oxo-ethyl)-carbamic acid benzyl ester 
• 121-44-8 triethylamine 
• 543-27-1 isobutyl chloroformate 

Downstream Products

• 111491-96-4 (S)-3-(N-(benzyloxycarbonyl)amino)-4-phenyl-2-butanone 
• 114744-89-7 ((S)-1-Benzyl-2-oxo-butyl)-carbamic acid benzyl ester 
• 1059597-07-7 (S)-benzyl 3-oxo-1-phenylhex-5-en-2-ylcarbamate 
• 863650-75-3 benzyl (S)-(3-oxo-1-phenylpent-4-yn-2-yl)carbamate 
• 871210-05-8 2(S)-(benzyloxycarbonylamino)-6,6,7,7,8,8,9,9,10,10,11,11,11-tridecafluoro-1-phenyl-undecan-3-one 
• 960374-25-8 benzyl (S)-4-methyl-3-oxo-1-phenylpent-4-en-2-ylcarbamate 
• 863650-78-6 benzyl [(1S,3E)-1-benzyl-4-diethylamino-2-oxobut-3-enyl]carbamate 
• 863650-92-4 benzyl {(1S)-2-phenyl-1-[1-(6-phenylpyridazin-3-yl)-1H-pyrazol-5-yl]ethyl}carbamate 
• 863650-86-6 benzyl [(1S)-2-phenyl-1-(1-phenyl-1H-pyrazol-5-yl)ethyl]carbamate 
• 863650-90-2 benzyl {(1S)-2-phenyl-1-[1-(pyrimidin-2-yl)-1H-pyrazol-5-yl]ethyl}carbamate 
• 863650-89-9 benzyl {(1S)-2-phenyl-1-[1-(pyridin-2-yl)-1H-pyrazol-5-yl]ethyl}carbamate 

Relevant academic research and scientific papers

Probing α-Amino Aldehydes as Weakly Acidic Pronucleophiles: Direct Access to Quaternary α-Amino Aldehydes by an Enantioselective Michael Addition Catalyzed by Br?nsted Bases

The high tendency of α-amino aldehydes to undergo 1,2-additions and their relatively low stability under basic conditions have largely prevented their use as pronucleophiles in the realm of asymmetric catalysis, particularly for the production of quaternary α-amino aldehydes. Herein, it is demonstrated that the chemistry of α-amino aldehydes may be expanded beyond these limits by documenting the first direct α-alkylation of α-branched α-amino aldehydes with nitroolefins. The reaction produces densely functionalized products bearing up to two, quaternary and tertiary, vicinal stereocenters with high diastereo- and enantioselectivity. DFT modeling leads to the proposal that intramolecular hydrogen bonding between the NH group and the carbonyl oxygen atom in the starting α-amino aldehyde is key for reaction stereocontrol.

An efficient, stereocontrolled and versatile synthetic route to bicyclic partially saturated privileged scaffolds

Herein, we describe the development of a simple, high yielding and stereocontrolled strategy for the synthesis of a series of triazolopiperazines and other biologically relevant fused scaffolds from optically active amino acids. This route was applied to the synthesis of 22 scaffolds containing new, previously inaccessible vectors and used to access a novel analogue of ganaplacide.

Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity

Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.

Method for preparing isoptopenyl ketone compound

The invention discloses a method for preparing an isoptopenyl ketone compound. The method comprises the following steps: 1, dissolving a compound of formula IV and ethyl phosphate in an organic solvent, adding an ethyl phosphate activator, completing a reaction, and terminating the reaction by using a quenching agent to prepare a compound V; and 2, carrying out a condensation reaction on the compound of formula V and formaldehyde in a solvent in the presence of an alkali in order to prepare the isoptopenyl ketone compound. The method has the advantages of simplicity, high efficiency, low cost, and suitableness for industrial production.

An Environmentally Sustainable Mechanochemical Route to Hydroxamic Acid Derivatives

An operationally simple, and cost efficient conversion of carboxylic acids into hydroxamic acid derivatives via a high-energy mechanochemical activation is presented. This ball milling methodology was applied to a wide variety of carboxylic acids dramatically improving purification issues associated with this class of molecules, which still remain one of the main bottlenecks of classical methodologies. (Figure presented.).

Aminooxylation Horner-Wadsworth-Emmons Sequence for the Synthesis of Enantioenriched γ-Functionalized Vinyl Sulfones

An operationally simple protocol for the synthesis of γ-hydroxy vinyl sulfones has been developed using a proline-based aldehyde aminooxylation, followed by a vinyl sulfone forming Horner-Wadsworth-Emmons olefination. The adducts, formed in high enantiopurity, were subsequently converted to γ-azido vinyl sulfones, and azide-alkyne click chemistry enabled the synthesis of vinyl sulfone-based triazoles as potential nonpeptidic cysteine protease inhibitors. (Chemical Equation Presented).

α-Amino Aldehydes as Readily Available Chiral Aldehydes for Rh-Catalyzed Alkyne Hydroacylation

Readily available α-amino aldehydes, incorporating a methylthiomethyl (MTM) protecting group on nitrogen, are shown to be efficient substrates in Rh-catalyzed alkyne hydroacylation reactions. The reactions are performed under mild conditions, employing a small-bite-angle bis-phosphine ligand, allowing for good functional group tolerance with high stereospecificity. Amino aldehydes derived from glycine, alanine, valine, leucine, phenylalanine, isoleucine, serine, tryptophan, methionine, and cysteine were successfully employed, as was an enantiomerically enriched α-OMTM-aldehyde derived from phenyllactic acid. The synthetic utility of the α-amino enone products is demonstrated in a short enantioselective synthesis of the natural product sphingosine.

EPOXYKETONE COMPOUNDS FOR ENZYME INHIBITION

The present disclosure relates to novel compounds and pharmaceutical compositions thereof which are useful as inhibitors of proteasomes. The compounds provided herein have improved proteasome potency and selectivity, and increased aqueous solubility, and

Bifunctional amino sulfonohydrazide catalyzed direct asymmetric mannich reaction of cyclic ketimines with ketones: Highly diastereo-and enantioselective construction of quaternary carbon stereocenters

A bifunctional amino sulfonohydrazide which contains multiple sites for hydrogen bonding with substrates was found to enhance reactivity and enantioselectivity in the direct asymmetric Mannich reaction of N-sulfonyl cyclic ketimines with ketones. In this efficient transformation, not only methyl ketones but also cyclic ketones can be employed to provide a general methodology to construct tetrasubstituted α-amino ester in a stereoselective manner. The synthetic utility of a substituted amino ester product is demonstrated by the synthesis of biologically active spirotetrahydrofuran.

PEPTIDOMIMETIC COMPOUNDS AND ANTIBODY-DRUG CONJUGATES THEREOF

This invention relates to peptidomimetic linkers and anti-body drug conjugates thereof, to pharmaceutical compositions containing them, and to their use in therapy for the prevention or treatment of cancer.