Substituent and solvent effects in the 1,3-dipolar cycloadditions for synthesis of anti-influenza agent peramivir and its analog
Journal
Tetrahedron
Date Issued
2019
Author(s)
Abstract
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. ? 2019 Elsevier Ltd
Subjects
Cycloaddition; Influenza; Nitrile oxide; Organic synthesis; Peramivir
SDGs
Other Subjects
2 ethyl n hydroxybutanimidoyl chloride; antivirus agent; methyl 3 (pentan 3 yl) 4 (2,2,2 trifluoroacetamido) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 6 carboxylate; methyl 3 (pentan 3 yl) 4 [(trifluoromethyl)sulfonamido]3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 6 carboxylate; methyl 3 (pentan 3 yl) 4 [[(2,2,2 trichloroethoxy) carbonyl]amino] 3a,5,6,6a tetrahydro 4h cyclopent[d]isoxazole 6 carboxylate; methyl 3 (pentan 3 yl) 6 (2,2,2 trifluoroacetamido) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 4 carboxylate; methyl 3 (pentan 3 yl) 6 [(trifluoromethyl) sulfonamido] 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 4 carboxylate; methyl 3 (pentan 3 yl) 6 [[(2,2,2 trichloroethoxy)carbonyl]amino] 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 4 carboxylate; methyl 3 phenyl 4 [[(2,2,2 trichloroethoxy)carbonyl] amino] 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 6 carboxylate; methyl 3 phenyl 6 [[(2,2,2 trichloroethoxy) carbonyl]amino] 3a,5,6,6a tetrahydro 4h cyclopent[d]isoxazole 4 carboxylate; methyl 4 (1,3 dioxoisoindolin 2 yl) 3 (pentan 3 yl) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 6 carboxylate; methyl 4 (1,3 dioxoisoindolin 2 yl)cyclopent 2 ene 1 carboxylate; methyl 4 (2,2,2 trifluoroacetamido)cyclopent 2 ene 1 carboxylate; methyl 4 acetamido 3 (pentan 3 yl) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 6 carboxylate; methyl 4 acetamidocyclopent 2 ene 1 carboxylate; methyl 4 tert butoxycarbonylamino 3 (1 ethylpropyl) 4,5,6,6a tetrahydro 3aH cyclopenta[d]isoxazole 6 carboxylate; methyl 4 [(2 nitrophenyl)sulfonamido] 3 (pentan 3 yl) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 6 carboxylate; methyl 4 [(2 nitrophenyl)sulfonamido]cyclopent 2 ene 1 carboxylate; methyl 4 [(tert butoxycarbonyl)amino] 3 phenyl 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 6 carboxylate; methyl 4 [(tert butoxycarbonyl)amino]cyclopent 2 ene 1 carboxylate; methyl 4 [(trifluoromethyl)sulfonamido]cyclopent 2 ene 1 carboxylate; methyl 4 [[(2,2,2 trichloroethoxy)carbonyl]amino]cyclopent 2 ene 1 carboxylate; methyl 6 (1,3 dioxoisoindolin 2 yl) 3 (pentan 3 yl) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 4 carboxylate; methyl 6 acetamido 3 (pentan 3 yl) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 4 carboxylate; methyl 6 [(2 nitrophenyl)sulfonamido] 3 (pentan 3 yl) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 4 carboxylate; methyl 6 [(tert butoxycarbonyl)amino] 3 (pentan 3 yl) 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 4 carboxylate; methyl 6 [(tert butoxycarbonyl)amino] 3 phenyl 3a,5,6,6a tetrahydro 4h cyclopenta[d]isoxazole 4 carboxylate; n hydroxybenzimidoyl chloride; peramivir; unclassified drug; unindexed drug; antiviral activity; Article; concentration response; cycloaddition; drug structure; drug synthesis; isomer; priority journal; regioselectivity; solvent effect; substitution reaction
Type
journal article