Cyclophellitol

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Cyclophellitol
Cyclophellitol.png
Names
Preferred IUPAC name
(1S,2R,3S,4R,5R,6S)-5-(Hydroxymethyl)-7-oxabicyclo[4.1.0]heptane-2,3,4-triol
Other names
Cyclophellitol
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
  • InChI=1S/C7H12O5/c8-1-2-3(9)4(10)5(11)7-6(2)12-7/h2-11H,1H2/t2-,3-,4+,5-,6-,7+/m1/s1 checkY
    Key: YQLWKYQDOQEWRD-GEGSFZHJSA-N checkY
  • InChI=1S/C7H12O5/c8-1-2-3(9)4(10)5(11)7-6(2)12-7/h2-11H,1H2/t2-,3-,4+,5-,6-,7+/m1/s1
    Key: YQLWKYQDOQEWRD-GEGSFZHJSA-N
  • C([C@@H]1[C@H]([C@@H]([C@H]([C@H]2[C@@H]1O2)O)O)O)O
Properties
C7H12O5
Molar mass 176.168 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N (what is checkY☒N ?)

Cyclophellitol is a potent irreversible inhibitor of beta-glucosidases.[1] It is a cyclitol mimic of beta-glucose with an epoxide group in place of the acetal group found in glucosides. When recognized, cyclophellitol undergoes an acid-catalyzed ring-opening addition reaction with the catalytic nucleophile of a retaining glycoside hydrolase.[2] The resulting ester linkage cannot be hydrolyzed by the normal catalytic machinery of the enzyme, resulting in irreversible inhibition.

Cyclophellitol was originally isolated from a species of Phellinus mushroom found in Japan.[1] The first total chemical synthesis of cyclophellitol was demonstrated by Tatsuta et al.[3] Synthetic derivatives of cyclophellitol have been used for the detection of enzymes such as glucocerebrosidase, deficiency of which results in Gaucher's disease.[4]

References[edit]

  1. ^ a b Atsumi, S. et al. (1990) ‘Production, isolation and structure determination of a novel β-glucosidase Inhibitor, cyclophellitol, from phellinus sp’, The Journal of Antibiotics. Japan Antibiotics Research Association, 43(1), pp. 49–53. doi: 10.7164/antibiotics.43.49.
  2. ^ Gloster, T. M., Madsen, R. and Davies, G. J. (2007) ‘Structural basis for cyclophellitol inhibition of a β-glucosidase’, Organic and Biomolecular Chemistry. The Royal Society of Chemistry, 5(3), pp. 444–446. doi: 10.1039/b616590g.
  3. ^ Tatsuta, K. et al. (1991) ‘Syntheses and Enzyme Inhibiting Activities of Cyclophellitol Analogs’, Journal of Antibiotics. Japan Antibiotics Research Association, 44(8), pp. 912–914. doi: 10.7164/antibiotics.44.912.
  4. ^ Witte, M. D. et al. (2010) ‘Ultrasensitive in situ visualization of active glucocerebrosidase molecules’, Nature Chemical Biology. Nature Publishing Group, 6(12), pp. 907–913. doi: 10.1038/nchembio.466.