Expeditious synthesis of tri- and tetrahydroxyazepanes from D-(-)-quinic acid as potent glycosidase inhibitors.
Several new stereoisomers of 3,4,6-trihydroxyazepanes and 7-hydroxymethyl-3,4,5-trihydroxyazepanes as well as known 3,4,5-trihydroxyazepanes were synthesized as potent glycosidase inhibitors from D-(-)-quinic acid in an efficient manner. The key step employs dihydroxylation of protected chiral 1,4,5-cyclohex-2-enetriols under RuCl3/NaIO4/phosphate buffer (pH 7) condition, followed by reductive amino cyclization. We found the choice of an appropriate protecting group to C1-OH of chiral 1,4,5-cyclohex-2-enetriols would increase the yields of cyclization. The preliminary biological data indicate some of these azepanes possess potent inhibition against alpha-mannosidase and alpha-fucosidase.
Shih
Tzenge-Lien
TL
Department of Chemistry, Tamkang University, Tamsui, Taipei County 25137, Taiwan. tlshih@mail.tku.edu.tw
Yang
Ru-Ying
RY
Li
Shiou-Ting
ST
Chiang
Cheng-Fan
CF
Lin
Chun-Hung
CH
D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011801:Quinic Acid / Q000737:chemistry*; D013237:Stereoisomerism; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001381:Azepines; D004791:Enzyme Inhibitors; D011801:Quinic Acid; D043323:alpha-Mannosidase; D005644:alpha-L-Fucosidase