Fawcettimine synthesis

Inubushi and cowoiicers have studied a similar unsymmetrical dialdehyde in the context of their fawcettimine synthesis." Dialdehyde (34) cyclizes under various conditions to give a mixture of enals (35 and 36 equation 100). Unexpectedly, both the Woodward and Corey methods give the same major product, providing (35) (36) ratios of 21 1 (80% yield) and 19 1 (62% yield), respectively. The opposite regioselectivity is obtained by using morpholine and camphoric acid in ether-HMPA solvent under these conditions, the (3S) (36) ratio is 1 25 and the yield is 54%. 

Another highlight of the period under review is the report of the total synthesis of the tricyclic alkaloid fawcettimine (22) (Scheme 2).9 Lewis-acid-catalysed Diels-Alder addition of butadiene to 2-allyl-5-methylcyclohex-2-enone provided the ds-octalone (23), which was modified as indicated to give the dialdehyde (24). After considerable experimentation, conditions were defined which led to regioselective ring-closure in the desired direction. The unsaturated aldehyde was treated directly with the Wadsworth-Emmons reagent to provide... 

Base treatment and Michael addition to the a,8-unsaturated ester of (42) to form a hydrindanone has been reported as a key step in a synthesis of racemic fawcettimine,6 and a novel base induced... 

The structure of the new alkaloid 27, named lycoposeiramine-C [25], was deduced to be a fawcettimine-t3q3e alkaloid possessing a double bond at the C-6 and C-7 positions of fawcettimine (11), and was finally established by X-ray crystallographic analysis (Fig. 2). Although our preliminary biological screening indicated that 27 possesses potent AChE inhibitory activity, further examination of the activity has been restricted by its limited availability in nature. In order to develop an efficient synthetic route to 27 for further examination, we planned the asymmetric total synthesis of 27. 

Synthesis ofalkaloids using radical cyclizations 12YGK1413 13H(87)527. Syntheses of fawcettimine-type Lycopodium alkaloids utilizing the Pau-son—Khand reaction 12SL2014. 

Schemp 2.15 The total synthesis of the fawcettimine class alkaloids.

As already mentioned earlier (e.g. Scheme 35), Lycopodium alkaloids have always been interesting targets in natural product syntheses (129-133). In 2007, the group of Toste reported a 13-step total synthesis of (+)-fawcettimine (273) with... 

SCHEME 11.11. Toste et al. synthesis of fawcettimine via Robinson annulation. 

Linghu X, Keimedy-Smith JJ, Toste ED. Total synthesis of (+)-fawcettimine. Angew. Chem. Int. Ed 2007 46(40) 7671-7673. 

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