Total Synthesis Highlights
Total Synthesis Highlights
Total Synthesis Highlights
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The enantiomerically-pure imine 2 was readily deprotonated, and the resulting anion was<br />
condensed with the aldehyde 1 to give, after dehydration, the imine 12. The enol ether was<br />
selectively brominated. Free radical reduction led to smooth cyclization, to give 13. On unmasking<br />
of the ketone, spontaneous enamine addition ensued, to give the imine 14. Stereocontrolled<br />
reduction with NaBH 4 and protection then gave the pentacylic 15, accompanied by the<br />
diastereomer resulting from condensation of 2 with the other enantiomer of 1. These two<br />
diastereomers were readily separable by flash chromatography.<br />
To complete the synthesis, the enamide 15 was hydrolyzed by aqueous acid. In situ reduction<br />
carried the liberated ketone on to the enone, which was deprotected to give glabulimima alkaloid<br />
13 (3). Both enantiomers of 3 were prepared this way, beginning with each of the enantiomers of 4.<br />
The enantiomer derived from L-alaninol gave the same rotation as the natural product, allowing<br />
the assignment of the absolute configuration.<br />
The convergent coupling employed here allowed the ready preparation of each of the four<br />
enantiomerically-pure diastereomers of the natural product. There are real advantages to such an<br />
approach, because it provides not just one substance, the natural product, but each of the four, for<br />
further evaluation of physiological activity.<br />
54. The Corey Route to the Dolabellanes: Isoedunol and β-Araneosene