AI Article Synopsis
- The Ho crossed aldol condensation technique enables the synthesis of branched iminosugars, including enantiomers of isoDMDP, isoDGDP, and isoDAB, which are compared to their linear natural product counterparts.
- L-IsoDMDP is synthesized in 11 steps with a 45% yield from d-lyxonolactone and is identified as a strong inhibitor of gut disaccharidases, outperforming the current diabetes drug miglitol in managing hyperglycemia.
- The ability of L-isoDMDP to partially restore function in defective CFTR cells suggests its potential in treating cystic fibrosis, with a comparison to other treatments like miglustat and isoLAB.
Article Abstract
The Ho crossed aldol condensation provides access to a series of carbon branched iminosugars as exemplified by the synthesis of enantiomeric pairs of isoDMDP, isoDGDP, and isoDAB, allowing comparison of their biological activities with three linear isomeric natural products DMDP, DGDP, and DAB and their enantiomers. L-IsoDMDP [(2S,3S,4R)-2,4-bis(hydroxymethyl)pyrrolidine-3,4-diol], prepared in 11 steps in an overall yield of 45% from d-lyxonolactone, is a potent specific competitive inhibitor of gut disaccharidases [K(i) 0.081 μM for rat intestinal maltase] and is more effective in the suppression of hyperglycaemia in a maltose loading test than miglitol, a drug presently used in the treatment of late onset diabetes. The partial rescue of the defective F508del-CFTR function in CF-KM4 cells by L-isoDMDP is compared with miglustat and isoLAB in an approach to the treatment of cystic fibrosis.
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| http://dx.doi.org/10.1021/jo4005487 | DOI Listing |
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C-branched iminosugars: α-glucosidase inhibition by enantiomers of isoDMDP, isoDGDP, and isoDAB-L-isoDMDP compared to miglitol and miglustat.
J Org Chem
August 2013
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Article Synopsis
- The Ho crossed aldol condensation technique enables the synthesis of branched iminosugars, including enantiomers of isoDMDP, isoDGDP, and isoDAB, which are compared to their linear natural product counterparts.
- L-IsoDMDP is synthesized in 11 steps with a 45% yield from d-lyxonolactone and is identified as a strong inhibitor of gut disaccharidases, outperforming the current diabetes drug miglitol in managing hyperglycemia.
- The ability of L-isoDMDP to partially restore function in defective CFTR cells suggests its potential in treating cystic fibrosis, with a comparison to other treatments like miglustat and isoLAB.
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