Premium
N ‐Monoalkylation of Tetra‐ O ‐benzyl‐ D ‐arabinonamide: Synthesis of Some Open‐Chain Analogues of N ‐Acetylneuraminic Acid and Their Evaluation as Sialidase Inhibitors
Author(s) -
Storz Thomas,
Vasella Andrea
Publication year - 1998
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19981007)81:10<1896::aid-hlca1896>3.0.co;2-5
Subject(s) - chemistry , phosphonate , alkylation , sialidase , medicinal chemistry , hydrolysis , stereochemistry , organic chemistry , catalysis , neuraminidase , enzyme
N ‐Arabinonoylglycine 2 , its phospho analogue (arabinonoylamino)methylphosphonate 14 , N ‐arabinonoyltaurine salt 18 , and [2‐(arabinonoylamino)ethylidene]bis[phosphonic acid] 22 have been synthesized from D ‐arabinose in seven ( 2 or 14 ), and eight steps ( 18 or 22a ), respectively. With the exception of the salt 22b , none of these compounds showed a significant 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 ‐arabinose ( 6 ) yielded the primary amide 9 (64% from 6 ), which was alkylated with the triflates 10 or 11 of benzyl glycolate and dibenzyl hydroxymethylphosphonate, respectively, to give the protected N ‐arabinonoylglycinate 12 and the (arabinonoylamino)methylphosphonate 13 (45 and 90%, resp.). N ‐Alkylation of 9 with 2‐bromoethyl triflate 15 followed by nucleophilic displacement with sodium sulfite yielded the protected taurine analogue 17 (21% from 9 ), whereas the protected tetraethyl bis[phosphonate] 20 was formed in 90% yield by 1,4‐addition of 9 to tetraethyl ethenylidenebis[phosphonate] 19 . Debenzylation of 12 and 13 , followed by purification by reversed‐phase HPLC gave the triethylammonium salt of N ‐( D ‐arabinonoyl)glycine ( 2 ) and triethylammonium ( D ‐arabinonoylamino)methylphosphonate ( 14 b ), respectively, whereas the deprotection of 17 afforded the N ‐( D ‐arabinonoyl)taurine salt 18 . Debenzylation of 20 , followed by treatment with Me 3 SiBr and hydrolysis of the resulting silyl ester gave the bis[phosphonic acid] 22 a (3 steps, 88%).