Abstract
Feeding studies indicated that cylindrospermopsin is an acetogenin with guani-dinoacetic acid serving as the starter unit of the polyketide chain. Cylindrospermopsin has been isolated from the cyanobacterium Cylindrospermopsis raciborskii, Umezakia natans, and Aphanizomenon ovalisporum. The relative stereochemistry of the ring carbons has been assigned based on the analysis of the coupling constants. The novel structure of cylindrospermopsin, with a guanidine embedded in a tricyclic system, six chiral centers, and polar sulfate, uracil, and guanidine functional groups, makes its synthesis challenging. Its potent toxicity makes the synthesis of cylindrospermopsin a problem. The polar functionality is a difficulty in the synthesis of cylindrospermopsin because the natural product cannot be extracted into organic solvents, making its separation from water-soluble reagents difficult. The B ring of cylindrospermopsin could be prepared by an intramolecular SN2 reaction of the guanidine on the bromoketone. Equilibration provides the desired equatorial side chain. The reduction of the ketone, deprotection, and sulfation completes the synthesis of cylindrospermopsin. The addition of acetylene to pyrimidine carboxaldehyde provides a convergent and efficient approach.