X-ray Crystal Structure of Woodinine and Conformational Analysis by Semiempirical and 1H-NMR Methods

The molecular structure of (−)-woodinine (1), a carboline-based alkaloid with antibacterial and antimycobacterial activities, was investigated by X-ray crystallographic, NMR, and semiempirical quantum chemical methods. Compound 1 was prepared by reacting 5-bromotryptamine and (S)-(−)-N-(tert-butoxycarbonyl)pyrrolidine-2-carboxyaldehyde in a Pictet−Spengler-type reaction. The debrominated analogue of 1 was methylated at the indole nitrogen with methyl methane sulfonate after deprotonation with n-BuLi. The X-ray crystal structure of 1 showed the indole ring in the expected planar conformation, the pyrrolidine ring in an envelope conformation, and a weak intramolecular hydrogen bond between the pyrrolidine nitrogen and the proton of the indole nitrogen. NMR experiments indicated that this hydrogen bond is not present in solution and that further differences exist between the crystal and the solution structures of 1. By semiempirical quantum chemical methods, different local energy minimum conformations of 1, resulting from inversions within the piperideine moiety and from rotation of the pyrrolidine ring, were calculated. The totality of all NOE signals can only be explained to originate from a population of some of these conformers, and additionally from different envelope and twisted conformations of the pyrrolidine ring.