80152-39-2

Upstream product

• 3397-35-1 Z-L-leucine hydroxysuccinimide ester 
• 61-90-5 L-leucine 
• 100-46-9 benzylamine 
• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 3392-09-4 Boc-Leu-ONSu 
• 66866-44-2 Boc-Leu-O-COO-isoBu 
• 88333-03-3 Benzyl isocyanide 
• 2018-66-8 Z-Leu-OH 
• 7517-19-3 methyl (L)-leucinate hydrochloride 
• 844865-39-0 (S)-2-Benzylamino-4-methyl-pentanoic acid benzylamide 
• 186581-53-3 diazomethane 
• 28117-45-5 (2S)-2-benzyloxycarbonylamino-4-methyl-pentanoic acid benzylamide 
• 118283-03-7 1-benzyloxycarbamoyl-3-methyl-butyl-carbamic acid tert-butyl ester 
• 844865-32-3 (1R,2R,3R,4S)-3-[Benzyl-((S)-1-benzylcarbamoyl-3-methyl-butyl)-amino]-7-oxa-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid methyl ester 

Downstream Products

• 141381-80-8 tert-butyl (2S)-2-{[(2S)-1-(benzylamino)-4-methyl-1-oxopentan-2-yl]carbamoyl}pyrrolidine-1-carboxylate 
• 917392-68-8 (2S)-2-butylamino-4-methyl-pentanoic acid benzylamide 
• 1404563-22-9 (S)-N-benzyl-2-(1H-imidazol-1-yl)-4-methylpentanamide 
• 1404563-67-2 1-[(1S)-1-(benzylcarbamoyl)-3-methylbutyl]-3-butyl-1H-imidazol-3-ium triflamide 
• 1404563-39-8 1-[(1S)-1-(benzylcarbamoyl)-3-methylbutyl]-3-butyl-1H-imidazol-3-ium iodide 
• 98818-68-9 [(1S,2S,4R)-1-Benzyl-4-((S)-1-benzylcarbamoyl-3-methyl-butylcarbamoyl)-2-hydroxy-5-phenyl-pentyl]-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Study on anti-proliferative activity in cancer cells and preliminary structure–activity relationship of pseudo-peptide chiral thioureas

In our previous studies, we have shown that thiourea compounds containing phosphate esters have potent antitumor activity and can be used as a novel strategy for the development of antitumor agents. Herein, a series of novel phosphonate thioureas 5–38 have been synthesized, which were fully characterized by 1H NMR,13C NMR spectrum, elemental analysis. Three human cancer cell lines (Bcap-37, BGC-823, and PC-3) have been used to investigate these compounds’ antitumor activities. After the summarization of the structure–activity relationships, we found that the variation of R, R1, and R2 in these novel phosphonate thioureas contribute to the antitumor activities. All these SAR-guided efforts may lead to novel antitumor drugs in the market in the near future.

Protecting-Group-Free Amidation of Amino Acids using Lewis Acid Catalysts

Amidation of unprotected amino acids has been investigated using a variety of ‘classical“ coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions.

Mechanistic implications of the enantioselective addition of alkylzinc reagents to aldehydes catalyzed by nickel complexes with α-amino amide ligands

The enantioselective alkylation of aldehydes catalysed by nickel(ii)-complexes derived from α-amino amides was studied by means of density functional theory (DFT) and ONIOM (B3LYP:UFF) calculations. A mechanism was proposed in order to investigate the origin of enantioselectivity. The chirality-determining step for the alkylation was the formation of the intermediate complexes with the involvement of a 5/4/4-fused tricyclic transition state. The predominant products predicted theoretically were of (S)-configuration, in good agreement with experimental observations. The scope of the reaction was examined and high yields and enantioselectivities were observed for the enantioselective addition of Et2Zn and Me2Zn to aromatic and aliphatic aldehydes.

C2 symmetrical nickel complexes derived from α-amino amides as efficient catalysts for the enantioselective addition of dialkylzinc reagents to aldehydes

A series of C2 symmetrical 1:2 Ni:L complexes derived from α-amino amides were studied for the enantioselective addition of dialkylzinc reagents to aldehydes. Different structural elements on the ligands seem to play an important role in determining the observed enantioselectivity. Through optimization of structure and reaction conditions, the best ligand provided secondary alcohols in excellent yields (up to 98%) and enantioselectivity of up to 99% ee for (R)-enantiomer. A transition state model has been proposed to explain the observed enantioselectivities based on computational calculations at the DFT level. Very interestingly, calculations suggest a coordination model of the aldehyde to the metal complex through association of a lone pair of the carbonyl oxygen to the hydrogen atom of an amino group.

NEW COMPOUNDS

The invention provides compounds of the formula I wherein Q is aryl or heterocyclyl any of which is optionally substituted; Z is O, S, NRa or S(=O)p; Y is NH, NHNH, CH2NH, O, S or S(=O)p; n is 0, 1, 2 or 3; m is 0, 1 or 2; p is 1 or 2; Ra is H or C1-C4alkyl; R1 is hydrogen, C1-C6alkyl, C0-C3alkanediylC3-C7cycloalkyl, C0-C3alkanediylaryl or C0- C3alkanediylheterocyclyl; R2 is hydrogen or C1-C6alkyl; X' is hydrogen, fluoro, hydroxy, amino or C1-C6alkoxy; X" is hydrogen, or when X' is fluoro, then X" may also be fluoro; R3is C1-C6alkyl; R4' is C1-C6alkyl; R4" is H or C1-C6alkyl; or R4' and R4" together with the carbon atom to which they are attached define a C3-C6cycloalkyl; W is C1-C6alkyl, C3-C7cycloalkyl, aryl or heterocyclyl any of which is optionally substituted; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof. The compounds of the invention are inhibitors of aspartyl proteases such as renin and are among other things useful for the treatment of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency.

Synthesis of hydantoins from enantiomerically pure α-amino amides without epimerization

A method for the preparation of enantiomerically pure hydantoins from optically pure α-amino amides utilizing triphosgene is described. We also propose that the racemization observed with 1,1′-carbonyldiimidazole (CDI) for this type of reaction is due to

Circular dichroism studies on absolute configuration assignment of peptidomimetics with a terminal chiral 3-arylpropionic acid unit

The relationship between the molecular structure of peptidomimetics 1 and their chiroptical properties has been studied using circular dichroism spectroscopy. It was demonstrated that the sign of the Cotton effects occurring around 230 and 270 nm enables the direct assignment of stereochemistry at C-1 and C-3 carbon atoms. The TD-DFT calculations of the circular dichroism (CD) spectrum of one of the model compounds confirm the absolute stereochemistry assignment made experimentally. Thus, CD spectroscopy proved to be a simple, reliable and general tool for the determination of the absolute configuration of the stereogenic centers of peptidomimetics with a terminal 3-arylpropionic group.

PEPTIDIC COMPOUNDS

The present invention provides a compound of formula (I), (II), (III) and (IV) as defined herein and pharmaceutically acceptable derivatives thereof. The present invention further provides use of the compounds of the present invention in the treatment of bacterial infection and in the treatment of HIV infection. Also provided are pharmaceutical compositions comprising the compounds of the present invention.

A novel highly selective chiral auxiliary for the asymmetric synthesis of L- and D-α-amino acid derivatives via a multicomponent ugi reaction

(Chemical Equation Presented) This paper describes the synthesis of a bicyclic β-amino acid scaffold in both pure enantiomeric forms and its application as chiral auxiliary in an intramolecular version of the Ugi multicomponent reaction (U-5C-4CR) to prepare α-amino acid derivatives of both D- and L-series in a straightforward and very stereoselective manner. The mild conditions required for the Ugi condensation and for the removal of the chiral auxiliary make this method very attractive to prepare a wide range of differently structured N-alkylated and unalkylated amino acid derivatives.

Arecoline Tripeptide Inhibitors of Proteasome

The 26S proteasome is a multicatalytic protease complex that plays an essential role in intracellular protein degradation. We have synthesized and tested a series of arecoline peptide derivatives where the peptide portion derives from a screening of tripe