244092-76-0

Usage

Uses

Used in Pharmaceutical Industry:
3R enantiomer is used as an intermediate for the synthesis of N-protected α-amino epoxides, which are key intermediates for HIV protease inhibitors. Its specific configuration plays a crucial role in the development of effective antiretroviral drugs, contributing to the fight against HIV and AIDS.
Used in Synthesis of Chiral Compounds:
The 3R enantiomer is also utilized in the synthesis of other chiral compounds, which are essential in various chemical and pharmaceutical applications. Its unique spatial arrangement allows for the creation of enantiomerically pure products, which are vital for the development of drugs with minimal side effects and improved efficacy.

Upstream product

• 1779-49-3 Methyltriphenylphosphonium bromide 
• 77119-85-8 N-(tert-butoxycarbonyl)-D-phenylalaninal 
• 19493-09-5 Methylenetriphenylphosphorane 
• 115186-33-9 (R)-tert-butyl (1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate 
• 18942-49-9 Boc-D-Phe-OH 
• 24424-99-5 di-tert-butyl dicarbonate 
• 756462-76-7 (R)-1-benzyl-prop-2-enylamine 

Downstream Products

• 103127-52-2 ((S)-1-benzylallyl)carbamic acid tert-butyl ester 
• 126410-30-8 (S)-1-phenylbut-3-en-2-amine 
• 220871-52-3 1(R,S)-<1'-(S)-<(tert-butyloxycarbonyl)amino>-2-phenylethyl>oxirane 
• 98760-08-8 (2R,3S)-3-[N-(tert-butyloxycarbonyl)amino]-1,2-epoxy-4-phenylbutane 
• 98760-08-8 (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 4732-10-9 (RS)-3-Amino-4-phenyl-1-butene 
• 2055172-61-5 (S)-(4-([1,1'-biphenyl]-4-yl)-1H-1,2,3-triazol-1-yl)(2-benzylpiperidin-1-yl)methanone 
• 756462-76-7 (R)-1-benzyl-prop-2-enylamine 
• 99112-94-4 (2S)-2-benzylpiperidine 
• 156474-22-5 tert-butyl [(2R,3S)]-(-)-(1-oxiranyl-2-phenylethyl)carbamate 
• 156474-21-4 tert-butyl [(2R,3R)]-(-)-(1-oxiranyl-2-phenylethyl)carbamate 

Relevant academic research and scientific papers

Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2-AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4-substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5-position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting-induced refeeding of mice, thereby emulating the effect of cannabinoid CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

Convenient method for synthesis of N-protected α-amino epoxides: Key intermediates for HIV protease inhibitors

A convenient method for synthesis of 2R,3S and 2S,3S N-Boc phenylalanine epoxides using readily available allylamine is described. Previous methods employed multistep synthetic routes from l-phenyl alanine that include use of m-chloroperbenzoic acid (m-CPBA) and a chromatographic method for purification of the desired diastereomers. Column purification could be eliminated by bringing in much improvement in the existing process. The process was further enhanced by replacing m-CPBA with oxone, an ecofriendly reagent advantageous for commercial application. The overall green process discussed involves the recovery and recycling of enantiomers of chiral allyl amines and judicial separation of diastereomers of the epoxides using simple economical methods.

Synthesis of new (-)-bestatin-based inhibitor libraries reveals a novel binding mode in the S1 pocket of the essential malaria M1 metalloaminopeptidase

The malarial PfA-M1 metallo-aminopeptidase is considered a putative drug target. The natural product dipeptide mimetic, bestatin, is a potent inhibitor of PfA-M1. Herein we present a new, efficient, and high-yielding protocol for the synthesis of bestatin derivatives from natural and unnatural N-Boc-d-amino acids. A diverse library of bestatin derivatives was synthesized with variants at the side chain of either the α-hydroxyβ-amino acid (P1) or the adjacent naturalα-amino acid (P1′). Surprisingly, we found that extended aromatic side chains at the P1 position resulted in potent inhibition against PfA-M1. To understand these data, we determined the X-ray cocrystal structures of PfA-M1 with two derivatives having either a Tyr(OMe) 15 or Tyr(OBzl) 16 at the P1 position and observed substantial inhibitor-induced rearrangement of the primary loop within the PfA-M1 pocket that interacts with the P1 side chain. Our data provide important insights for the rational design of more potent and selective inhibitors of this enzyme that may eventually lead to new therapies for malaria.

Stereochemical analysis of (hydroxyethyl)urea peptidomimetic inhibitors of γ-secretase

(Hydroxyethyl)urea peptidomimetics systematically altered at positions P2-P3′ with hydrophobic D-amino acids were synthesized. An all D-amino acid containing analogue was identified that effectively blocked γ-secretase activity in a cell-free system (IC50 = 30 nM). Systematic alteration of the stereocenters of a potent compound revealed interdependence between the various positions. Although typically less potent than their L-peptidomimetic counterparts, selected all D-amino acid containing analogues were equipotent to their counterparts in a cell-based assay when incubated for extended times.