N-MONOALKYLATION OF TETRA-O-BENZYL-D-ARABINONAMIDE - SYNTHESIS OF SOME OPEN-CHAIN ANALOGS OF N-ACETYLNEURAMINIC ACID AND THEIR EVALUATION AS SIALIDASE INHIBITORS

N-Arabinonoylglycine 2, its phospho analogue (arabinonoylamino)methylp hosphonate 14, N-arabinonoyltaurine salt 18, and [2-(arabinonoylamino) ethylidene]bis[phosphonic acid] 22 have been synthesized from D-arabin ose in seven (2 or 14), and eight steps (18 or 22a), respectively. Wit h the exception of the salt 22b, none of these compounds showed a sign ificant inhibitory activity in vitro against the sialidases of Vibrio cholerae, Salmonella typhimurium, or Influenza A (N9), or B (B/Lee/40) virus. Ammonolysis of the oxosulfonate 8 obtained by oxidation of the hydrogensulfite adduct 7 of 2,3,4,5-tetra-O-benzyl-aldehydo-D-arabino se (6) yielded the primary amide 9 (64% from 6),which was alkylated wi th the triflates 10 or 11 of benzyl glycolate and dibenzyl hydroxymeth ylphosphonate, respectively, to give the protected N-arabinonoylglycin ate 12 and the (arabinonoylamino)methylphosphonate 13 (45 and 90%, res p.), N-Alkylation of 9 with 2-bromoethyl triflate 15 followed by nucle ophilic displacement with sodium sulfite yielded the protected taurine analogue 17 (21% from 9), whereas the protected tetraethyl bis[phosph onate] 20 was formed in 90% yield by 1,4-addition of 9 to tetraethyl e thenylidenebis[phosphonate] 19. Debenzylation of 12 and 13, followed b y purification by reversed-phase HPLC gave the triethylammonium salt o f N-(D-arabinonoyl)glycine (2) and triethylammonium (D-arabinonoylamin o)methylphosphonate (14b), respectively, whereas the deprotection of 1 7 afforded the N-(D-arabinonoyl)taurine salt 18. Debenzylation of 20, followed by treatment with Me3SiBr and hydrolysis of the resulting sil yl ester gave the bis[phosphonic acid] 22a (3 steps, 88%).