Total Synthesis Highlights

Although one might think of medium rings such as that of 2 as being floppy, in fact 2 has a single
preferred conformation, and diastereocontrol for the rest of the synthesis took advantage of that
preferred conformation. The diene 11 derived from 2 has one open face. Addition of methyl vinyl
ketone to that outside face gave a 1 : 2 mixture of the diastereomeric endo and exo cycloadducts.
The mixture was equilibrated to the more stable exo adduct 12. A four-step sequence then
converted 12 into 13.
The completion of the synthesis again depended on the inside-outside bias of the medium ring.
Addition of methyl magnesium chloride to the outside face of the ketone derived from 13
delivered 14 with high diastereocontrol. Epoxidation of 14, again from the outside face, led
directly to vigulariol 3. The intermediate in the MCPBA reaction is the protonated epoxide, and it
may be that the tertiary alcohol poised directly on the opposite face of the alkene opened that
activated intermediate directly.
This synthesis of vigulariol (3) is remarkably concise, with four rings and eight stereogenic
centers being assembled in just twenty steps. All of the stereogenic centers are derived from the
secondary alcohol 6. Use of the known enantiomerically-pure 6 would have delivered vigulariol (3)
in enantiomerically-pure form. This synthesis design once again illustrates the power of
conformational analysis of medium rings.
40. The Trost Synthesis of (-)-Terpestacin
(-)-Terpestacin (3), isolated from Arthrinium sp. FA1744, inhibits the formation of syncytia by
HIV-infected T cells. A key step in the total synthesis of 3 reported (J. Am. Chem. Soc. 2007, 129,
4540. ) by Barry M. Trost of Stanford University was the Ru-catalyzed cyclization of 1 to 2. This
synthesis of (-)-terpestacin (3) elegantly illustrates the power of the Trost enantioselective Pd
catalysts.