A practical, enantioselective synthetic route to a key precursor to the tetracycline antibiotics.
A practical, enantioselective synthetic route to a key precursor to the tetracycline antibiotics is reported. The route proceeds in nine steps (21% yield) from the commercial substance methyl 3-hydroxy-5-isoxazolecarboxylate. Key steps in the route involve enantioselective addition of divinylzinc to 3-benzyloxy-5-isoxazolecarboxaldehyde and an endo-selective intramolecular furan Diels-Alder cycloaddition reaction. The route described has provided more than 40 g of chromatographically pure 1 with 93% ee.
Brubaker
Jason D
JD
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Myers
Andrew G
AG
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013752:Tetracycline / Q000138:chemical synthesis* / Q000737:chemistry
D000900:Anti-Bacterial Agents; D011355:Prodrugs; D013752:Tetracycline
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