Total Synthesis Highlights

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