Nature polycyclic carboxylic acids

Nature also produces complex polycyclic carboxylic acids... 

An advantage of this methodology is that a strained or complicated molecule of the natural alkaloids can be built from simple compounds, such as commercially available carboxylic acids or amines, from which enamides are prepared. In addition, on cyclization, the skeletons of complex polycyclic and multifunctionalized natural products or their precursors, which are easily converted to the target alkaloids, can be formed in one step. 

Schreiber s early efforts in this area were focused on libraries of compounds having structural features reminiscent of rigid, complex, stereochemically rich natural products. In a key early example, solid-phase split-pool synthesis was used to generate a combinatorial library of over two million complex, polycyclic compounds derived from shikimic acid [17]. A stereoselective tandem acylation-nitrone cycloaddition was used to generate 18 tetracyclic scaffolds, to which 30 alkynes were coupled using a Sonogashira reaction, 62 amines were coupled via y -lactone aminolysis, and 62 carboxylic acids were coupled by alcohol esterification (Fig. 9.1-3(c)). In addition, a portion of the solid supports were left unreacted at each of the last three steps to generate a skip codon that further increased the diversity of the library. 

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