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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Total synthesis of siphonazole and its O-methyl derivative, structurally unusual bis-oxazole natural products
Jörg Linder1, Alexander J Blake, Christopher J Moody
1School of Chemistry, University of Nottingham, University Park, Nottingham, UK NG7 2RD.
Abstract:
The details of the first syntheses of the unusual bis-oxazole natural products siphonazole and its O-methyl derivative are reported. The cinnamyl substituted oxazole was constructed using diazocarbonyl chemistry, whereby the cinnamamide was reacted with the rhodium carbene derived from methyl 2-diazo-3-oxobutanoate to give a beta-ketoamide that was cyclodehydrated to the corresponding oxazole-4-ester. Reduction to the corresponding aldehyde was followed by coupling with a zinc reagent derived from methyl 2-iodomethyl-5-methyloxazole-4-carboxylate, also prepared using rhodium carbene chemistry, to give, after oxidation of the resulting secondary alcohol, the desired bis-oxazole ketone. The syntheses were completed by hydrolysis of the ester and coupling of the 2,4-pentadienylamine side chain.
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