Total synthesis of nominal 4S,7R, 11S,14R Cyclocinamide B and analysis of three stereoisomers of Cyclocinamide A

The marine natural product cyclocinamide A was isolated from a Psammocinia sponge found in the waters of Papua New Guinea. The very similar natural product cyclocinamide B was isolated from the sponge Cortium sp. in Fijian waters. The cyclic tetrapeptide core of both natural products consist of two alpha-amino acids (5-bromotryptophan and asparagine) and two beta- amino acids (1,2-diaminopropionic acid and isoserine). Both have a glycine chlorinated N-methyl pyrrole dipeptide side chain. The isolation and two previous total synthetic efforts are discussed in chapter 1. Original research resulting in the total synthesis of (4S,7R,11S,14 R) cyclocinamide A and B is presented in chapters 2 and 3. Cyclocinamide is disconnected into three dipeptides: glycyl-4,5-dichloro-N-methylpyrrole, isoseryl-5-bromotryptophan and diaminopropionyl-(cyclo)asparagine. The synthesis of these three dipeptides is highlighted in chapter 2. The formation of the cyclic core and completion of the synthesis of the 4R,7 S,11R,14S isomer of cyclocinamide A and B is detailed in chapter 3. The full NMR analysis in chapter 4 of the 4R,7S,11R,14S, 4S,7S,11S,14 S and 4S,7S,11R,14 S reveals that the assignment of both cyclocinamide A and B to be incorrect and further experimentation is needed to determine the actual stereochemistry of the natural products.