35402-94-9

Upstream product

• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 64-04-0 phenethylamine 
• 126770-48-7 tert-butyl (S)-(1-oxo-1-(phenethylamino)-3-phenylpropan-2-yl)carbamate 
• 7524-50-7 methyl (2S)-2-amino-3-phenylpropanoate hydrochloride 
• 156-06-9 2-oxo-3-(phenyl)propionic acid 

Downstream Products

• 184956-22-7 [(R)-3-Methyl-1-((S)-1-phenethylcarbamoyl-2-phenyl-ethylcarbamoyl)-butyl]-carbamic acid tert-butyl ester 
• 63-91-2 L-phenylalanine 

Relevant academic research and scientific papers

Pd-Catalysed oxidative carbonylation of α-amino amides to hydantoins under mild conditions

The first example of palladium-catalysed oxidative carbonylation of unprotected α-amino amides to hydantoins is described here. The selective synthesis of the target compounds was achieved under mild conditions (1 atm of CO), without ligands and bases. The catalytic system overrode the common reaction pathway that usually leads instead to the formation of symmetrical ureas.

An Ugi-like Biosynthetic Pathway Encodes Bombesin Receptor Subtype-3 Agonists

Isocyanide functional groups can be found in a variety of natural products. Rhabduscin is one such isocyanide-functionalized immunosuppressant produced in Xenorhabdus and Photorhabdus gammaproteobacterial pathogens, and deletion of its biosynthetic gene cluster inhibits virulence in an invertebrate animal infection model. Here, we characterized the first "opine-glycopeptide" class of natural products termed rhabdoplanins, and strikingly, these molecules are spontaneously produced from rhabduscin via an unprecedented multicomponent "Ugi-like" reaction sequence in nature. The rhabdoplanins also represent new lead G protein-coupled receptor (GPCR) agonists, stimulating the bombesin receptor subtype-3 (BB3) GPCR.

Structure-activity relationships on phenylalanine-containing inhibitors of histone deacetylase: In vitro enzyme inhibition, induction of differentiation, and inhibition of proliferation in friend leukemic cells

Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.

Chymotrypsin inhibitory conformation induced by amino acid side chain-side chain intramolecular CH/π interaction

Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/π interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2]n-C6H5 (n = 0-4) have been assayed for chymotrypsin. They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (Ki = 3.6 × 10-6 M). The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition. The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically. The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active. When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (Ki = 6.1 × 107 M; this dipeptide is one of the most potent chymotrypsin inhibitors to date). 1H NMR conformational analyses of these dipeptide amide derivatives show the CH/π interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition. These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S1 site, while the hydrophobic core constructed by D-Leu-Phe CH/π interaction fits the chymotrypsin S2 or S1′ site.