Stereoselective synthesis of the glycosidase inhibitor australine through a one-pot, double-cyclization strategy.
[reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The chiral starting materials were ketone 3, derived from L-erythrulose, and alpha-alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was the highly stereoselective aldol reaction between 4 and a Z boron enolate derived from 3. Another key step was the one-pot construction of the bicyclic pyrrolizidine system by means of a three-step sequence of SN2 displacements induced by benzylamine on a trimesylate precursor.
Ribes
Celia
C
Departament de Química InorgAnica y OrgAnica, Universitat Jaume I, Castellón, E-12080 Castellón, Spain.
Falomir
Eva
E
Carda
Miguel
M
Marco
J Alberto
JA
D000447:Aldehydes / Q000737:chemistry; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007659:Ketones / Q000737:chemistry; D015394:Molecular Structure; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D004791:Enzyme Inhibitors; D007659:Ketones; D011763:Pyrrolizidine Alkaloids; C059794:australine; D006026:Glycoside Hydrolases