229613-93-8

Basic information

• Product Name: (1S-4R)-4-[[(1,1-diMethylethoxy)carbonyl]aMino]- 2-Cyclopentene-1-carboxylic acid Methyl ester
• Synonyms: Peramivir Intermediate 2;methyl 2-((1R,4R)-4-((tert-butoxycarbonyl)amino)cyclopent-2-en-1-yl)acetate;(1S-4R)-4-[[(1,1-diMethylethoxy)carbonyl]aMino]- 2-Cyclopentene-1-carboxylic acid Methyl ester;Methyl 4-{[(tert-butoxy)carbonyl]aMino}-3-(pentan-3-yl)-3aH,4H,5H,6H,6aH-cyclopenta[d][1,2]oxazole-6-carboxylate;(3aR,4R,6S)-Methyl-4-((tert-butoxycarbonyl)aMino)-3-(pentan-3-yl)-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-6-carboxylate;(3aR,4R,6S,6aS)-Methyl 4-(tert-butoxycarbonyl)-3-(pentan-3-yl)-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-6-carboxylate;(3aR,4R,6S,6aS)-4-[[(1,1-DiMethylethoxy)carbonyl]aMino]-3-(1-ethylpropyl)-3a,5,6,6a-tetrahydro-4H-cyclopent[d]isoxazole-6-carboxylic Acid Methyl Ester;methyl (3aR,4R,6S,6aS)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-3-pentan-3-yl-4,5,6,6a-tetrahydro-3aH-cyclopenta[d][1,2]oxazole-6-carboxylate
• CAS NO: 229613-93-8
• Molecular Formula: C18H30N2O5
• Molecular Weight: 354.4412
• EINECS: 1308068-626-2
• Mol File: 229613-93-8.mol
• Article Data: 8

Chemical Properties

• Appearance: /
• Density: 1.227 g/cm³
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Sparingly), Methanol (Slightly)
• PKA: 11.61±0.60(Predicted)
• CAS DataBase Reference: (1S-4R)-4-[[(1,1-diMethylethoxy)carbonyl]aMino]- 2-Cyclopentene-1-carboxylic acid Methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: (1S-4R)-4-[[(1,1-diMethylethoxy)carbonyl]aMino]- 2-Cyclopentene-1-carboxylic acid Methyl ester(229613-93-8)
• EPA Substance Registry System: (1S-4R)-4-[[(1,1-diMethylethoxy)carbonyl]aMino]- 2-Cyclopentene-1-carboxylic acid Methyl ester(229613-93-8)

Safety Data

• Hazardous Substances Data: 229613-93-8(Hazardous Substances Data)

Usage

Uses

(3aR,4R,6S,6aS)-4-[[(1,1-Dimethylethoxy)carbonyl]amino]-3-(1-ethylpropyl)-3a,5,6,6a-tetrahydro-4H-cyclopent[d]isoxazole-6-carboxylic Acid Methyl Ester is an intermediate used in the synthesis of peramivir (P285500), a neuraminidase inhibitor developed as an antiviral agent for the treatment of influenza.

InChI:InChI=1S/C12H19NO4/c1-12(2,3)17-11(15)13-9-6-5-8(7-9)10(14)16-4/h5-6,8-9H,7H2,1-4H3,(H,13,15)/t8-,9+/m1/s1

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 5399-18-8 2-ethylbutyraldehyde oxime 
• 49805-57-4 2-ethylbutyraldehyde oxime 
• 168683-02-1 (1S,4R)-(-)-methyl-[[(1,1-dimethylethoxy)carbonyl]amino]cyclopent-2-ene-1-carboxylate 
• 229613-83-6 (–)-methyl (1S,4R)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride 
• 138923-03-2 (1S,4R)-(-)-methyl-4-aminocyclopent-2-en-1-carboxylate hydrochloride 
• 7796-76-1 2-ethyl-1-nitrobutane 
• 103-71-9 phenyl isocyanate 
• 316173-28-1 (3aR,4R,6S,6aS)-4-[[(1,1-dimethylethoxy)carbonyl]amino]-3-(1'-ethylpropyl)-3a,5,6,6a-tetrahydro-4H-cyclopent[d]isoxazole-6-carboxylic acid tert-butylamine 
• 77-78-1 dimethyl sulfate 
• 79200-56-9 (-)-2-azabicyclo[2.2.1]hept-5-en-3-one 
• 419563-22-7 (1S,4R)-4-aminocyclopent-2-ene-1-carboxylic acid methyl ester tartrate 

Downstream Products

• 1988779-13-0 (1S,2S,3S,4R)-methyl 3-((S)-1-amino-2-ethylbutyl)-4-(tert-butoxycarbonylamino)-2-hydroxycyclopentanecarboxylate 
• 229614-05-5 (-)-methyl (1S,2S,3R,4R)-3-[(1S)-1-(acetylamino)-2-ethylbutyl]-4-[(tert-butoxycarbonyl)amino]-2-hydroxycyclopentanecarboxylate 
• 229614-55-5 peramivir 
• 1469338-58-6 (1S,2S,3R,4R)-methyl-3-((S)-1-acetamido-2-ethylbutyl)-4-(2,3-bis(tert-butoxycarbonyl)guanidino)-2-(((3-(((E)-3-(3,4-bis(allyloxy)phenyl)acryloyl)oxy)propyl)carbamoyl)oxy)cyclopentanecarboxylate 
• 316173-29-2 3-(1-amino-2-ethyl-butyl)-4-tert-butoxycarbonylamino-2-hydroxy-cyclopentanecarboxylic acid methyl ester 

Relevant articles and documents

Substituent and solvent effects in the 1,3-dipolar cycloadditions for synthesis of anti-influenza agent peramivir and its analog

Influenza remains a health problem to humans. Peramivir is a FDA approved anti-influenza drug targeting the virus neuraminidase. The (3 + 2) cycloaddition reaction of 2-ethylbutanenitrile oxide with the cyclopentene dipolarophile derived from Vince lactam is a key step in the conventional synthesis of peramivir. Our study showed that conducting the (3 + 2) cycloaddition reactions with either aliphatic or aromatic nitrile oxide in hexane solution provided high percentage of the desired regioisomer, and the N-substituent having electron-withdrawing property is also beneficial to the regioselectivity. This study also demonstrated an alternative synthetic pathway of (?)-peramivir and the analog having a phenyl group in place of the 3-pentyl moiety.

Peramivir Phosphonate Derivatives as Influenza Neuraminidase Inhibitors

Peramivir is a potent neuraminidase (NA) inhibitor for treatment of influenza infection by intravenous administration. By replacing the carboxylate group in peramivir with a phosphonate group, phosphono-peramivir (6a), the dehydration and deoxy derivatives (7a and 8a) as well as their corresponding monoalkyl esters are prepared from a pivotal intermediate epoxide 12. Among these phosphonate compounds, the dehydration derivative 7a that has a relatively rigid cyclopentene core structure exhibits the strongest inhibitory activity (IC50 = 0.3-4.1 nM) against several NAs of wild-type human and avian influenza viruses (H1N1, H3N2, H5N1, and H7N9), although the phosphonate congener 6a is unexpectedly less active than peramivir. The inferior binding affinity of 6a is attributable to the deviated orientations of its phosphonic acid and 3-pentyl groups in the NA active site as inferred from the NMR, X-ray diffraction, and molecular modeling analyses. Compound 7a is active to the oseltamivir-resistant H275Y strains of H1N1 and H5N1 viruses (IC50 = 73-86 nM). The phosphonate monoalkyl esters (6b, 6c, 7b, 7c, 8b, and 8c) are better anti-influenza agents (EC50 = 19-89 nM) than their corresponding phosphonic acids (EC50 = 50-343 nM) in protection of cells from the viral infection. The phosphonate monoalkyl esters are stable in buffer solutions (pH 2.0-7.4) and rabbit serum; furthermore, the alkyl group is possibly tuned to attain the desired pharmacokinetic properties.

ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY

Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.