A series of N6,2-disubstituted adenosine analogues have been synthesized and their functional activity measured against A2a and A1 receptors. Examples of compounds with both a lipophilic N6-substituent and amino-functionalized 2-position were highly active at the A2a receptor on the human neutrophil.

Analogues of 4-Guanidino-Neu5Ac2en (Zanamivir) have been prepared containing carbamate substituents at the 7-hydroxy position. (4S,5R,6R)-5-Acetylamino-6-[1R-[(6-aminohexyl)carbamoyloxy]-2R,3-dihydroxypropyl]-4-guanidino-5,6-dihydro-4H-pyran-2carboxylic acid and (4S,5R,6R)-5-Acetylamino-6-[1R-[heptylcarbamoyloxy]-2R,3-dihydroxypropyl]-4-guanidino-5,6-dihydro4H-pyran2-carboxylic acid were the two analogues possessing activity comparable to Zanamivir, showing potent inhibition of influenza virus sialidases and good antiviral activity in vitro.

N-Propylcarboxamides 1a,b-3a,b have been synthesised from 2,3-didehydro-2,4-dideoxy-4-amino-N-acetylneuraminic acid 4. The tertiary amides 2a,b-3a,b are highly potent but selective inhibitors of influenza A sialidase. The exceptional inhibitory activity of the dipropylamides 3a and 3b against influenza A shows that the 6-dipropylcarboxamide substituent is preferable to the polar glycerol sidechain found in the related sialidase inhibitors GG167 and 4. Copyright (C) 1996 Elsevier Science Ltd

A reinvestigation of the reaction of threo-(+/-)-2,3-dibromopentane-1,5-diol 5 with the disodium salt of catechol has shown that the product is (+/-)-1-(2,3-dihydro[1,4]benzodioxin-2-yl)propane-1,3-diol 20 and not trans-(+/-)-3-(2-hydroxyethyl)-2-(hydroxymethyl) -2,3-dihydro[1,4]benzodioxin 12, as assumed previously. Consequently trans-(+/-)-1,2,3,4,4a,10a-hexahydro[1,4]benzodioxino[2.3-c] pyridine 3 could not have been isolated earlier, and we now report its unambiguous synthesis via the epoxide 8 as well as the crystal structure of the diol 20.

A concise synthetic route to the tricarbonyl subunit (3a) in the immunosuppressant rapamycin (2), based on ruthenium-catalysed oxidation of an acetylenic amide precursor (17) is described. viz (17) → (18) → (20).