90068-06-7

Upstream product

• 58107-67-8 Benzyloxycarbonylproline Isobutylamide 
• 1148-11-4 N-Benzyloxycarbonyl-L-proline 
• 1236255-06-3 pyrrolidine-2-carboxylic acid isobutylamide hydrochloride 
• 78-81-9 isobutylamine 
• 147-85-3 L-proline 

Downstream Products

• 116287-70-8 {(S)-1-[(S)-2-((S)-2-Isobutylcarbamoyl-pyrrolidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-ethyl}-carbamic acid benzyl ester 
• 116287-67-3 Benzyloxycarbonylalanyl-proline Isobutylamide 

Relevant academic research and scientific papers

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.

Direct amidation of unprotected amino acids using B(OCH2CF3)3

A commercially available borate ester, B(OCH2CF3)3, can be used to achieve protecting-group free direct amidation of α-amino acids with a range of amines in cyclopentyl methyl ether. The method can be applied to the synthesis of medicinally relevant compounds, and can be scaled up to obtain gram quantities of products.

Compounds binding to the S2-S3 pockets of thrombin

A set of compounds designed to bind to the S2-S3 pockets of thrombin was prepared. These compounds included examples with no interactions in the S1 pocket. Proline, a common P2 in many thrombin inhibitors, was combined with known P3 residues and P1 substituents of varying size and lipophilicity. Binding constants were determined using surface plasmon resonance (SPR) biosensor technology and were found to be in good agreement with results from an enzyme assay. A dramatic increase in affinity (100-1000 times) was seen for compounds incorporating an amino group capable of forming a hydrogen bond with gly216 in the protein backbone. The ligand efficiency was increased by including substituents that form stronger hydrophobic interactions with the P1 pocket. The binding mode was confirmed by X-ray analysis, which revealed the anticipated binding motif that included hydrogen bonds as well as a tightly bound water molecule. A QSAR model indicated that hydrogen bonding and lipophilicity were important for the prediction of binding constants. The results described here may have implications for how directed compound libraries for shallow protein pockets, like S2 and S3 in serine proteases, can be designed.

INHIBITORS OF PANCREATIC AND LEUKOCYTE ELASTASE

Tho following alkylamides of ω-carboxyalkanoyldi- and tripeptides of the Ala-Pro or Ala-Ala-Pro sequence have been prepared: ethylamide-, propylamide-, and isobutylamide of 3-carboxypropionylalanyl-proline, ethylamide of 3-carboxypropionylalanyl-alanyl-pr