Synthesis of (+)-casuarine.
[formula: see text] The first synthesis of (+)-casuarine, a pentahydroxy pyrrolizidine alkaloid, is described. The key bond-forming events occur in a tandem [4 + 2]/[3 + 2] nitroalkene cycloaddition involving nitroalkene 6, chiral vinyl ether 7b, and vinyl silane 4. This process also creates five of the six stereocenters present in this potent glycosidase inhibitor. Completion of the synthesis required only four additional steps and delivered (+)-casuarine in 20% overall yield.
Denmark
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Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana 61801, USA. denmark@scs.uiuc.edu
Hurd
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D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000470:Alkaloids; D004791:Enzyme Inhibitors; D011758:Pyrroles; D011763:Pyrrolizidine Alkaloids; C409108:casuarine; D006026:Glycoside Hydrolases