16257-32-2

Upstream product

• 150-30-1 Phenylalanine 
• 105838-14-0 tert-butyl N-tosyloxycarbamate 
• 130608-09-2 (R)-2-(N'-tert-Butoxycarbonyl-hydrazino)-3-phenyl-propionic acid methyl ester 
• 13673-95-5 (S)-methyl 2-hydroxy-3-phenylpropanoate 
• 150447-60-2 H-(N²-Boc)aPhe-OMe 
• 133565-26-1 Phenylalanine benzyltrimethylammonium salt 
• 150884-56-3 N-tert-butyloxycarbonyl-3-(4-cyanophenyl)oxaziridine 
• 63-91-2 L-phenylalanine 
• 102831-44-7 diethyl tert-butoxycarbonylaminomalonate 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 462100-44-3 oxaziridine-2,3,3-tricarboxylic acid 2-tert-butyl ester 3,3-diethyl ester 
• 870-46-2 t-butoxycarbonylhydrazine 
• 17585-69-2 L-phenylalanine hydrochloride 
• 828-01-3 D-phenyllactic acid 

Downstream Products

• 16257-28-6 N^β-tert.-Butyloxycarbonyl-DL-α-hydrazino-β-phenyl-propionsaeure-(p-nitro-phenylester) 
• 1202-31-9 (S)-2-hydrazinyl-3-phenylpropanoic acid 
• 16257-35-5 tert.-Butyloxycarbonyl-L-α-hydrazino-β-phenyl-propionyl-Leu-methylester 
• 16257-29-7 N^β-tert.-Butyloxycarbonyl-DL-α-hydrazino-β-phenyl-propionsaeure-(2.4.5-trichlor-phenylester) 

Relevant academic research and scientific papers

N -Amino peptide scanning reveals inhibitors of Aβ42 aggregation

The aggregation of amyloids into toxic oligomers is believed to be a key pathogenic event in the onset of Alzheimer's disease. Peptidomimetic modulators capable of destabilizing the propagation of an extended network of β-sheet fibrils represent a potential intervention strategy. Modifications to amyloid-beta (Aβ) peptides derived from the core domain have afforded inhibitors capable of both antagonizing aggregation and reducing amyloid toxicity. Previous work from our laboratory has shown that peptide backbone amination stabilizes β-sheet-like conformations and precludes β-strand aggregation. Here, we report the synthesis of N-aminated hexapeptides capable of inhibiting the fibrillization of full-length Aβ42. A key feature of our design is N-amino substituents at alternating backbone amides within the aggregation-prone Aβ16-21 sequence. This strategy allows for maintenance of an intact hydrogen-bonding backbone edge as well as side chain moieties important for favorable hydrophobic interactions. An N-amino scan of Aβ16-21 resulted in the identification of peptidomimetics that block Aβ42 fibrilization in several biophysical assays.

Synthesis and β-sheet propensity of constrained N-amino peptides

The stabilization of β-sheet secondary structure through peptide backbone modification represents an attractive approach to protein mimicry. Here, we present strategies toward stable β-hairpin folds based on peptide strand N-amination. Novel pyrazolidinone and tetrahydropyridazinone dipeptide constraints were introduced via on-resin Mitsunobu cyclization between α-hydrazino acid residues and a serine or homoserine side chain. Acyclic and cyclic N-amino peptide building blocks were then evaluated for their effect on β-hairpin stability in water using a GB1-derived model system. Our results demonstrate the strong β-sheet stabilizing effect of the peptide N-amino substituent, and provide useful insights into the impact of covalent dipeptide constraint on β-sheet folding.

Access to Enantiopure α-Hydrazino Acids for N-Amino Peptide Synthesis

Backbone N-methylation of α-peptides has been widely employed to enhance the bioavailability and bioactivity of parent sequences. Heteroatomic peptide amide substituents have received less attention due, in part, to the lack of practical synthetic strategies. Here, we report the synthesis of α-hydrazino acids derived from 19 out of the 20 canonical proteinogenic amino acids and demonstrate their use in the solid-phase synthesis of N-amino peptide derivatives.

Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides

The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good yield and purity. The scope of Tpd incorporation is demonstrated through the synthesis of constrained peptides featuring nucleophilic/electrophilic side chains and sterically encumbered α-substituted hydrazino acid residues. (Chemical Equation Presented).

N-amination of amino acids and its derivatives using N-Boc-O-tosyl hydroxylamine as an efficient NH-Boc transfer reagent: Electrophilic amination

Terminal tert-butyloxycarbonyl (Boc) protected hydrazino acids, useful intermediates for modified peptides and biologically active heterocyclic derivatives, were synthesized by electrophilic amination methodology using N-Boc-O-tosyl hydroxylamine as an ef

N-alkyloxycarbonyl-3-aryloxaziridines: Their preparation, structure, and utilization as electrophilic amination reagents

This paper reports the synthesis of a series of N-protected oxaziridines (N-Moc, Boc, Z or Fmoc) and discusses their ability to deliver their N-alkoxycarbonyl fragment to amines, enolates, sulfur, and phosphorus nucleophiles (electrophilic amination). These oxaziridines are prepared by oxidation of the corresponding imines with oxone or anhydrous MCPBA lithium salt as the source of oxygen. They transfer their N-protected fragment to primary and secondary amines to give protected hydrazines in fair to excelent yield. The nitrogen transfer to free amino acids (in form of their R4N+ salts) is particularly fast, even at low temperature, providing L (or D) N-protected α-hydrazino acids. Enolates are C-aminated to give N-protected α-amino ketones, esters, or amides in modest yield, due to a side aldol reaction of the unreacted enolate with the released benzaldehyde. With tertiary amines (Et3N), sulfides (PhSMe), and phosphines (Ph3P), amination and oxidation proceed in a parallel way; the amount of amination product increases when the temperature is lowered (kinetic control). Some of the factors that can orient the oxaziridine reactivity towards amination or oxidation of nucleophiles are considered.

Conformationally constrained nonpeptide β-turn mimetics of enkephalin

The design, synthesis and in vitro biological analysis of a family of conformationally constrained nonpeptide mimetics incorporating a 4→1 β-turn prosthetic unit to examine the proposed biological significance of this conformer is described.

Electrophilic Amination: Preparation and Use of N-Boc-3-(4-cyanophenyl)oxaziridine, a New Reagent That Transfers a N-Boc Group to N- and C-Nucleophiles

We describe the preparation of the title compound 2b via aza-Wittig reaction of N-Boc-triphenyliminophosphorane (6) with 4-cyanobenzaldehyde followed by Oxone oxidation of the resulting imine 5b.Oxaziridine 2b is a stable, crystalline solid, which transfers under mild conditions its N-Boc fragment to primary and secondary amines (to give Nβ-Boc-hydrazines) and enolates (to give N-Boc-amino drivatives).

THE PREPARATION OF 2-HYDRAZINYL ESTERS IN HIGH OPTICAL PURITY FROM 2-SULFONYLOXY ESTERS

Chiral 2-triflyloxy esters, prepared from chiral 2-hydroxy esters, react enantiospecifically with BocNHNH2 to produce optically pure 2-hydrazinyl ester derivatives in high yields.The reaction of 2-nosyloxy esters with BocNHNH2 gives 2-(Boc-hydrazinyl) esters, thus providing an efficient (albeit slow) method for the conversion of esters to 2-hydrazinyl ester derivatives.