Total Synthesis Highlights

Nakamura reagent delivered the allyl group preferentially to one face of the ketone 1, to give 9.
The subsequent sigmatropic rearrangement to establish the very congested second quaternary
center of 2 then proceeded with remarkable facility, at 0°C for one hour.
Oxidative cleavage to the aldehyde followed by reductive amination gave 10, that looks as though
it could be poised for intramolecular displacement of the secondary chloride. Nonetheless, Lewis
acid mediated ionization followed by cyclization proceeded smoothly, to establish the fourth ring
of the natural product. Oxidation state adjustment then completed the synthesis of (-)-Acutumine
(3).
The face selective enone allylation followed by oxy-Cope rearrangement (1 → 2), a highlight of
the approach presented here, will have many applications in target-directed synthesis.
20.The Trost Synthesis of (-)-Ushikulide A
(-)-Ushikolide A (4), isolated from a culture broth of Streptomyces sp. IUK-102, showed powerful
activity against murine splenic lymphocyte proliferation (IC 50 = 70 nM). The most important
player in the synthesis of 4 described (J. Am. Chem. Soc. 2008, 130, 16190. ) by Barry M. Trost of
Stanford University was the ProPhenol ligand 1.
The precursor 2 was prepared by coupling the mesylate 7, the alkyne 12, and the aldehyde 13. The
first role of catalyst 1 was in mediating the enantioselective coupling of commercial 5 with 6 to
give, after saponification and CuCl decarboxylation, the mesylate 7. The preparation of 12 began
with the Noyori hydrogenation of the ester 8 to the alcohol 9 in the expected high ee. Note that
although this transformation was carried out at 1800 psi, such reductions proceed well and in