67675-32-5

Upstream product

• 67-56-1 methanol 
• 127862-68-4 2-Benzyloxycarbonylamino-hexanoic acid 2,2,2-trifluoro-ethyl ester 
• 127862-66-2 2-Benzyloxycarbonylamino-butyric acid 2,2,2-trifluoro-ethyl ester 
• 21754-55-2 L-norleucine methyl ester 
• 501-53-1 benzyl chloroformate 
• 100-51-6 benzyl alcohol 
• 96789-62-7 (S)-2-Isocyanato-hexanoic acid methyl ester 
• 100945-15-1 N-(benzyloxycarbonyl)phosphonoglycine trimethyl ester 
• 226895-29-0 methyl-2-(benzyloxycarbonylamino)-2-hexenoate 

Downstream Products

• 119005-54-8 2<3-oxo-4(S)-N-(benzyloxycarbonyl)-aminooctyl>-1,3-dioxane 
• 119005-55-9 Z-Nle-Ψ(CO-CH2)-Gly-OH 
• 119038-24-3 Z-Nle-Ψ(CO-CH2)-Gly-OSu 
• 119005-50-4 Z-Nle-Ψ(CO-CH2)-Gly-Trp-Nle-Asp-Phe-NH2 
• 119005-51-5 Boc-Tyr-Nle-Ψ(CO-CH2)-Gly-Trp-Nle-Asp-Phe-NH2 
• 117038-50-3 Boc-Tyr(SO3H)-Nle-Ψ(CO-CH2)-Gly-Trp-Nle-Asp-Phe-NH2 
• 1416992-33-0 C₂₁H₂₉N₃O₅ 
• 39608-30-5 N-benzyloxycarbonyl-L-norleucine 
• 1416992-19-2 C₂₂H₃₁N₃O₆ 
• 1416992-41-0 C₂₁H₃₀N₃O₈S^(1-)*Na⁽¹⁺⁾ 
• 1448616-19-0 benzyl ((S)-1-(((S)-1-(benzo[d]thiazol-2-yl)-1-oxo-3-((S)-2-oxopyrrolidin-3-yl)propan-2-yl)amino)-1-oxohexan-2-yl)carbamate 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: Structure-activity relationship study

This work describes the design, synthesis, and evaluation of low-molecular weight peptidic SARS-CoV 3CL protease inhibitors. The inhibitors were designed based on the potent tripeptidic Z-Val-Leu-Ala(-pyrrolidone-3-yl)-2-benzothiazole (8; Ki = 4.1 nM), in which the P3 valine unit was substituted with a variety of distinct moieties. The resulting series of dipeptide-type inhibitors displayed moderate to good inhibitory activities against 3CLpro. In particular, compounds 26m and 26n exhibited good inhibitory activities with Ki values of 0.39 and 0.33 μM, respectively. These low-molecular weight compounds are attractive leads for the further development of potent peptidomimetic inhibitors with pharmaceutical profiles. Docking studies were performed to model the binding interaction of the compound 26m with the SARS-CoV 3CL protease. The preliminary SAR study of the peptidomimetic compounds with potent inhibitory activities revealed several structural features that boosted the inhibitory activity: (i) a benzothiazole warhead at the S1′ position, (ii) a γ-lactam unit at the S1-position, (iii) an appropriately hydrophobic leucine moiety at the S2-position, and (iv) a hydrogen bond between the N-arylglycine unit and a backbone hydrogen bond donor at the S3-position.

Carica papaya lipase catalysed resolution of β-amino esters for the highly enantioselective synthesis of (S)-dapoxetine

An efficient synthesis of the (S)-3-amino-3-phenylpropanoic acid enantiomer has been achieved by Carica papaya lipase (CPL) catalysed enantioselective alcoholysis of the corresponding racemic N-protected 2,2,2-trifluoroethyl esters in an organic solvent. A high enantioselectivity (E > 200) was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. Based on the resolution of a series of amino acids, it was found that the structure of the substrate has a profound effect on the CPL-catalysed resolution. The enantioselectivity and reaction rate were significantly enhanced by switching the conventional methyl ester to an activated trifluoroethyl ester. When considering steric effects, the substituted phenyl and amino groups should not both be large for the CPL-catalysed resolution. The mechanism of the CPL-catalysed enantioselective alcoholoysis of the amino acids is discussed to delineate the substrate requirements for CPL-catalysed resolution. Finally, the reaction was scaled up, and the products were separated and obtained in good yields (≥ 80 %). The (S)-3-amino-3- phenylpropanoic acid obtained was used as a key chiral intermediate in the synthesis of (S)-dapoxetine with very high enantiomeric excess (> 99 %). A carica papaya lipase catalysed resolution of N-protected β-phenylalanine esters has been developed. High enantioselectivity was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. After 50 % conversion, the products were separated and used as key chiral intermediates for the synthesis of (S)-dapoxetine with > 99 % ee. Copyright

Inhibition of norovirus 3CL protease by bisulfite adducts of transition state inhibitors

Noroviruses are the most common cause of acute viral gastroenteritis, accounting for >21 million cases annually in the US alone. Norovirus infections constitute an important health problem for which there are no specific antiviral therapeutics or vaccines. In this study, a series of bisulfite adducts derived from representative transition state inhibitors (dipeptidyl aldehydes and α-ketoamides) was synthesized and shown to exhibit anti-norovirus activity in a cell-based replicon system. The ED 50 of the most effective inhibitor was 60 nM. This study demonstrates for the first time the utilization of bisulfite adducts of transition state inhibitors in the inhibition of norovirus 3C-like protease in vitro and in a cell-based replicon system. The approach described herein can be extended to the synthesis of the bisulfite adducts of other classes of transition state inhibitors of serine and cysteine proteases, such as α-ketoheterocycles and α-ketoesters.

Resolution of non-proteinogenic amino acids via microbial lipase-catalyzed enantioselective transesterification

A number of non-proteinogenic amino acids bearing aliphatic side chains were resolved with moderate to good enantioselectivities (E = 15-42) through the Burkholderia cepacia lipase-catalyzed enantioselective transesterification of the 2,2,2-trifluoroethyl esters of their N-benzyloxycarbonyl derivatives with methanol as a nucleophile in diisopropyl ether.

Resolution of non-protein amino acids via Carica papaya lipase-catalyzed enantioselective transesterification

Carica papaya lipase-catalyzed transesterification of the 2,2,2-trifluoroethyl esters of N-benzyloxycarbonylated dl-amino acids carrying aliphatic side chains proceeded smoothly and, in almost all the cases, enantiospecifically (E = >200), affording the l-methyl esters and leaving the d-trifluoroethyl esters intact.

Synthesis of enantiomerically pure backbone alkyl substituted peptide nucleic acids utilizing the Et-DuPHOS-Rh+ hydrogenation of enamido esters

A series of enantiomerically pure alkyl substituted peptide nucleic acid (PNA) monomers were synthesized by incorporating novel α-amino acids produced by the Et-DuPHOS-Rh+ catalytic asymmetric hydrogenation of enamido esters.