The spirocyclopropyl moiety as a methyl surrogate in the structure of l-fucosidase and l-rhamnosidase inhibitors.
Nitrogen-in-the-ring analogues of l-fucose and l-rhamnose were prepared, which feature a spirocyclopropyl moiety in place of the methyl group of the natural sugar. The synthetic route involved a titanium-mediated aminocyclopropanation of a glycononitrile as the key step. Four new spirocyclopropyl iminosugar analogues were generated, which displayed some activity towards l-fucosidase and l-rhamnosidase.
Pearson
Morwenna S M
MS
Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims, CNRS UMR 6229, UFR des Sciences Exactes et Naturelles, BP 1039, 51687 Reims Cedex 2, France.
Floquet
Nicolas
N
Bello
Claudia
C
Vogel
Pierre
P
Plantier-Royon
Richard
R
Szymoniak
Jan
J
Bertus
Philippe
P
Behr
Jean-Bernard
JB
D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005643:Fucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation; D012210:Rhamnose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors / Q000378:metabolism
D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D013141:Spiro Compounds; D005643:Fucose; D006026:Glycoside Hydrolases; C022525:alpha-L-rhamnosidase; D005644:alpha-L-Fucosidase; D012210:Rhamnose