Totally Synthetic by Paul H. Docherty, 21 May 2006

Total Synthesis of Pteriatoxin A, B, C

Kishi

F. Matsuura, R. Peters, M. Anada, S. S. Harried, J. Hao, Y. Kishi, J. Am. Chem. Soc. 2006, 128, 7463-7465.

Kishi and co-workers have just completed their syntheses of the Pteriatoxins A-C, related to their prior work on Pinnatoxin A. Using two of the precursors developed for the latter work, they were able to create the straight-chain analogue, with the necessary addition of a third precursor. They then used a exo-selective Diels-Alder reaction (DA) to assemble the cyclohexene ring, completing the macrocycle.

The DA work in this paper is incredibly interesting - the protecting groups used on the diol influence the endo/exo selectivity massively, and also the rate of reaction, most dramatically in the case of TBS vs. Ac.

The other dramatic point in this DA was the guts it took to heat the substrate to 170°C!

Selected Comments

22 May, 2006 at 23:25, secret milkshake says:
better than Lewis acid, I think, in this case. Besides, spiroacetals are not all too fragile to heating if you keep the H⁺ out.

22 May, 2006 at 23:29, Uncle Bob says:
Yeah, you can logic your way into thinking “What can go wrong”, but you still have to set the dial to 170°C!!

23 May, 2006 at 6:50, secret milkshake says:
You get there by few iterations. I remember from Brian Stolz grad research Staurosporine talk some very funny cyclizations - the first used molten tBuOK (neat, at 350°C!) as a solvent and base, the other used pinacolone (tBuCOMe) at around 100°C for the Ru-catalyzed carbene insertion from nasty diazo compound. I asked him how he got to use pinacolone and he said that he went into the stockroom, loaded the cart with everything that was liquid and tried one bottle after another until he eventualy got over 30% Y. With every ambitious scheme, desperation is assured.