Reinvestigation of the Biomimetic Cyclization of 3,5-Diketo Esters: Application to the Total Synthesis of Cyercene A, an α-Methoxy-γ-Pyrone-Containing Polypropionate

Abstract

The biomimetic cyclization of 3,5-diketo esters was reinvestigated for the synthesis of α-methoxy-γ-pyrones. 3,5-Diketo esters were selectively synthesized via the aldol reaction of commercially available methyl 2-methyl-3-oxopentanoate with an aldehyde followed by the oxidation with AZADOL^® and PhI(OAc)₂. The DBU-promoted intramolecular transesterification of 3,5-diketo esters showed excellent reactivity in MeOH, to give the corresponding γ-hydroxy-α-pyrones in high yields under mild reaction conditions. Based on the present cyclization scheme, the total synthesis of cyercene A was achieved.

Key words

γ-pyrone - intramolecular transesterification - polyketide - cyercene A - 3,5-diketo esters

• References and Notes

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• 13b The calculated lowest-energy conformer of the 2,4-syn diastereomer is shown in Scheme 4.
• 14 See the Supporting Information for more details.
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