Written by: William Sommer, Ph.D

The total synthesis of natural compounds can lead to the discovery of new drugs and new reactions. Vintonyak and Maier investigated the synthesis of Cruentaren A.¹ This molecule is highly cytotoxic and has shown some potency as a pesticide and as an inhibitor of mitochondrial F-ATPase.² Starting the synthesis of this macromolecule, Vintonyak and Maier functionalized 2,4-dimethoxybenzoic acid using allyl bromide followed by its oxidation to the aldehyde. It was then reacted with pentynyloxazolidinone in an Evans aldol transformation to yield the desired alkyne. Following the protection of the alcohol moieties and the reduction of the ketone and of the ether, the terminal alkyne was functionalized using nBuLi and MeI. The molecule was then reacted with NaH and the desired alkyne diol to yield the di-alkyne necessary for the ring closing metathesis. Having this molecule in hand, the researchers used the ring-closing alkyne metathesis using tris(tert-butoxy)(2,2-dimethylpropylidyne)tungsten(VI). Finally, the alcohol was deprotected to yield the core structure of Cruentaren A.

In summary, an efficient route to synthesize the core structure of Cruantarene A was reported. An excellent example illustrating the efficiency of tris(tert-butoxy)(2,2-dimethylpropylidyne)tungsten(VI) for alkyne ring closing metathesis is demonstrated. The newly developed strategy should allow for the synthesis of more complex natural products.

(1) Vintonyak, V. V. and Maier, M. E. Org. Lett. 2007, 9, 655.
(2) Jundt, L. et al. Eur. J. Org. Chem. 2006, 5036.

Written by Dr. Sharbil J. Firsan

The title organometallic complex has emerged as an effective alkyne metathesis catalyst under fairly mild conditions.  The usefulness of this catalyst is illustrated by the concise and stereoselective synthesis of cis-civetone—a valuable, macrocyclic, olfactory compound.1  For a broader understanding of alkyne metathesis, including its scope, functional group tolerance, and complementarity with olefin metathesis, the recent review by Fuerstner and Davies can serve as a good starting point.2

 
 
(1) Fuerstner, A.; Seidel, G. J. Organomet. Chem. 2000, 606, 75.
(2) Fuerstner, A.; Davies, P. W. Chem. Commun. 2005, 2307.