Application of the DP4 Probability Method to Flexible Cyclic Peptides with Multiple Independent Stereocenters: The True Structure of Cyclocinamide A

A DP4 protocol has been successfully utilized to establish the true structure of the natural product cyclocinamide A, a flexible cyclic peptide with four isolated stereocenters. Benchmarking the necessary level of theory required to successfully predict the NMR spectra of three previously synthesized isomers of cyclocinamide A led to the prediction of the natural stereochemistry as 4S, 7R, 11R, 14S, which has been confirmed by total synthesis.