Plicamine

Scheme 7.113 Microwave-assisted preparation of a (+)-plicamine precursor.

Baxendale, I.R., Ley, S.V. and Piutti, C., Total Synthesis of the Amaryllidaceae Alkaloid (+)-plicamine and its unnatural enantiomer by using solid-supported reagents and scavengers in a multistep sequence of reactions, Angew. Chem., Int. Ed. Engl., 2002, 41, 2194. 

In fact, the Eey group reported the first total synthesis of (-i-)-plicamine 188 and its enantiomer using only a combination of supported reagents and scavengers to effect all of the synthetic steps. No less than thirteen immobilized systems were used to produce the clean product. Given the relative complexity of the molecule, the synthesis is a powerful demonstration of the ability to achieve multistep transformation without conventional chromatographic methods. 

Scheme 21 -10 Synthesis of plicamine using polymer-supported reagents (Ley et The, etters R and s on the...

As an ultimate example of how polymer-supported reagents can be applied to alkaloid synthesis, their multiple applications in the synthesis of (+)-plicamine truly stands out (Scheme 18.17). In this synthesis, extensive use was made of parallel optimization methods in order to progress the forward route more rapidly. Again, microwave techniques worked especially well to achieve fast reaction times. The entire route, including optimization, was complete in just six weeks, without the need to rehearse the reactions using conventional solution-phase reagents or the requirement of separation methods. 

In the original article describing the synthesis of plicamine, extensive use was also made of the intermediate structures to deliver a range of new structural analogs for evaluation (Scheme 18.18). ... 

Scheme 18.17 Synthesis of (+)-plicamine using an extended array of polymer-supported reagents.

Scheme 3. Synthesis of plicamine and obliquine using solid-supported reagents.

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