Robinson tropinone synthetic

A number of new synthetic approaches to the tropane skeleton have been developed during recent years. The more characteristic ones are described in this section. In order to provide a representative picture of the whole field, a few of the earlier syntheses, starting from the classic ones of Willstatter and Robinson, are briefly reviewed. The earlier methods based on the transformation of the preformed tropane skeleton are noted only occasionally. However, the recently developed syntheses of the proteaceous tropane alkaloids based on new C-acylation methods for tropinone (124) are included. 

Another interesting example is the synthesis of 77-(2-thiazolyl)-nortropinon 121. Stoll and co-authors [175] described the synthesis of this drug-like product via the legendary first total synthetic approach proposed by Robinson in 1917 [176] for the natural alkoloid tropinone, also well known as a good example of biomimetic reaction. In this tandem treatment, 2-aminothiazole was reacted with succinaldehyde and acetonedicarboxylic acid yielding 77-(2-thiazolyl)-nortropinon 121 in moderate yields (Scheme 58). 

Woodward s projected synthesis of dodecahedrane was actually based upon the recognition of the symmetry present in 115. While this approach failed in this particular instance, considerations of this type might turn out to be extremely useful in the search for a short synthetic route even in cases involving rather complicated structures. The synthesis of tropinone by Robinson is probably the earliest example that illustrates the effectiveness of such an approach. This impressive accomplishment was actually achieved by utilizing symmetrical bifunctional reagents to secure the formation of a symmetrical bicyclic structure as a result of a single chemical operation (see Section 3.2.1). 

Synthesis. The first synthesis of an A. was reported in 1886 by Ladenburg, who generated coniine from a-picoline. On the hypothesis that A. are synthesized in the plant as amino add derivatives, Robinson and Schopf developed corresponding synthetic pathways and tested them under physiological conditions (see Tropinone). These studies also inspired laboratory syntheses, and some compounds were synthesized for the first time by routes similar to those occurring in the plant. Most A. for medical use are prepared from plant sources. 

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