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Norbornane Mimics of Distorted β ‐ D ‐Glucopyranosides – Inhibitors of β ‐ D ‐Glucopyranosidases?
Author(s) -
Buser Stephan,
Vasella Andrea
Publication year - 2006
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/hlca.200690064
Subject(s) - chemistry , norbornane , alcohol , stereochemistry , yield (engineering) , triol , ketone , organic chemistry , materials science , diol , metallurgy
The racemic gluco ‐configured norbornanes 4 and 16 were prepared and tested as inhibitors of β‐ glucosidases. The known alcohol 5 was deprotected to provide the triol 6 . Silylation (→ 7 ), monobenzoylation (→ 8 / 9 ), and oxidation provided the regioisomeric ketones 10 and 11 . Reduction of 10 gave the desired endo ‐alcohol 13 , albeit in low yield, while reduction of the isomeric ketone 11 provided mostly the altro ‐configured endo ‐alcohol 12 . The alcohol 13 was desilylated to 14 . Debenzoylation to 15 followed by hydrogenolytic deprotection gave the amino triol 4 that was reductively aminated to the benzylamine 16 . The amino triols 4 and 16 proved weak inhibitors of the β ‐glucosidase from Caldocellum saccharolyticum ( 4 : IC 50 = 5.6 m m; 16 : IC 50 = 3.3 m m) and from sweet almonds ( 16 : IC 50 = 5.5 m m) . A comparison of 4 with the manno ‐configured norbornane 3 shows that 3 is a better inhibitor of snail β ‐mannosidase than 4 is of β‐ glucosidases, in keeping with earlier results suggesting that these β ‐glycosidases enforce a different conformational itinerary.