Synthesis of Cycloprodigiosin Identifies the Natural Isolate as a Scalemic Mixture

We prepared the enantiomers of the natural product cycloprodigiosin using an expedient five-step synthetic sequence that takes advantage of a Schöllkopf–Barton–Zard (SBZ) pyrrole annulation with a chiral isocyanoacetate and a nitrocyclohexene derivative. Using chiral HPLC and X-ray crystallographic analyses of the synthetically prepared material and natural isolate (isolated from the marine bacterium Pseudoalteromonas rubra), naturally occurring cycloprodigiosin was determined to be a scalemic mixture occurring in an enantiomeric ratio of 83:17 (R)/(S) at C4'.