A stereodivergent, two-directional synthesis of stereoisomeric C-linked disaccharide mimetics.
Dipyranones, such as 1,2-bis[(2R,3S,6S)-3-hydroxy-6-methoxy-3-oxo-6H-pyran-2-yl]ethane, were exploited as templates for the synthesis of some novel C-linked disaccharide analogues. Efficient methods, such as stereoselective reduction and dihydroxylation, were developed for two-directional functionalisation of these templates. Peracetylated derivatives of ten stereoisomeric disaccharide analogues [acetic acid 4,5-diacetoxy-6-methoxy-[(3',4',5'-triacetoxy-6'-methoxytetrahydropyran- 2'-yl)ethyl]tetrahydropyran-3-yl esters] were synthesised from a virtual library of 136 compounds; furthermore, an additional eight stereoisomers could have been synthesised simply by using the enantiomeric ligand in the enantioselective step. The ability of (2S,3S,4R,5R,6R)-6-methoxy-2-[2'-((2'R,3'R,4'S, 5'R,6'S)-3',4',5'-trihydroxy-6'-methoxytetrahydropyran-2'-yl) ethyl]tetrahydropyran-3,4,5-triol to bind to the repressor protein, LacI, was estimated to be similar to that of isopropyl-beta-thiogalactoside. The disaccharide mimetics were concluded to be a new and interesting class of C-linked disaccharide mimetics with promising, though largely unstudied, biological activity.
Harding
Michael
M
Department of Chemistry, University of Leeds, Leeds, UK LS2 9JT.
Hodgson
Robert
R
Majid
Tahir
T
McDowall
Kenneth J
KJ
Nelson
Adam
A
D001426:Bacterial Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002236:Carbohydrate Conformation; D020650:Combinatorial Chemistry Techniques; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006900:Hydroxylation; D056968:Lac Repressors; D007785:Lactose / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D011714:Pyrans / Q000737:chemistry; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D013862:Thiogalactosides / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D004187:Disaccharides; D056968:Lac Repressors; D011714:Pyrans; D012097:Repressor Proteins; D013862:Thiogalactosides; D007785:Lactose