Synthesis of transition-state analogues as potential inhibitors of sialidase from Influenza virus

• Published in: Carbohydrate research Vol. 262; no. 2; pp. 297 - 310
• Main Authors: Driguez, Pierre-Alexandre, Barrere, Béatrice, Quash, Gérard, Doutheau, Alain
• Format: Journal Article
• Language: English
• Published: AMSTERDAM Elsevier Ltd 15.09.1994; Elsevier
• Subjects: Arabinose - analogs & derivatives; Arabinose - chemical synthesis; Arabinose - pharmacology; Biochemistry & Molecular Biology; Chemistry; Chemistry, Applied; Chemistry, Organic; Influenza virus; Inhibitors; l-Arabinose; Life Sciences & Biomedicine; Mannose - analogs & derivatives; Mannose - chemical synthesis; Mannose - pharmacology; Molecular Structure; Neuraminic acid; Neuraminidase - antagonists & inhibitors; Orthomyxoviridae - enzymology; Physical Sciences; Ritter reaction; Science & Technology; Sialidases; Transition-state analogues; Ritter reaction; Inhibitors; l-Arabinose; Influenza virus; Neuraminic acid; Sialidases; Transition-state analogues; 2-DEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC ACID; MECHANISM; L-ARABINOSE; TRANSITION-STATE ANALOGS; BEHAVIOR; STRUCTURAL VARIATIONS; VIBRIO-CHOLERAE SIALIDASE; C-GLYCOSIDES; NEURAMINIC ACID; NEURAMINIDASE; SIALIDASES; INFLUENZA VIRUS; N-ACETYL-4-DEOXY-D-NEURAMINIC ACID; INHIBITORS; RITTER REACTION; DERIVATIVES; N-ACETYLNEURAMINIC ACID
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/0008-6215(94)84186-1

Sodium 5-acetamido-2,6-anhydro-3,4,5-trideoxy- d- manno-non-2-enonate ( 2) has been synthesized from N-acetyl-4-deoxy-neuraminic acid methyl ester ( 4). Sodium 2,6-anhydro-3-deoxy- l- arabino-hept-2-enonate ( 3), 4-acetamido-2,6-anhydro-3,4-dideoxy- l- arabino-hept-2-enonic acid ( 18 e ), and 4-acetamido-2,6-anhydro-3,4-dideoxy- l- ribo-hept-2-enonic acid ( 18 a ) have been prepared from l-arabinose. The above compounds were investigated as inhibitors of sialidase from Influenza virus. Only compound 2 showed a significant inhibitory activity ( K i 8 × 10 −2 mM) against the enzyme.