This Is AuburnElectronic Theses and Dissertations

Synthesis, Analytical Profiles and Receptor Pharmacology of Methoxylated Derivatives and Regioisomers of the NBOMe series of Hallucinogenic Drugs




Almalki, Ahmad

Type of Degree

PhD Dissertation




The potential for designer analogue development in the NBOMe series of drugs of abuse is very high based on the methods used to synthesize this class of compounds, and the availability of a wide variety of precursor chemicals which would allow for significant structural variation. Also, since derivatives and isomers of the NBOMe drug class are difficult to differentiate by routine analytical methods, the production of designer analogues would pose significant challenges for those involved in drug detection and identification. In this study several series of NBOMe derivatives and regioisomers were synthesized with varying substituents and substitution patterns in the phenethyl aromatic ring, the N-benzyl aromatic ring, the ethyl side chain and nitrogen atom. These compounds were prepared using the basic synthetic methods reported in the literature. GCMS and other analytical methods were then explored to identify the specific NBOMe analogues and differentiate regioisomers within series of derivatives. All NBOMe derivatives prepared underwent the same fragmentation pathway in the electron ionization-mass spectrum (EI-MS) giving a base peak by the cleavage of the benzylic C-N bond to yield a benzyl cation, and ions of secondary abundance from dissociation of the phenethyl C-N bond to form an iminium cation, and from loss of CH2O from the methoxy benzyl cation. Derivatives of different molecular weight and atomic composition were readily differentiated by CI-MS and other spectroscopic means. Regioisomeric NBOME derivatives with a single methoxy group in the N-benzyl ring could be differentiated based on the relative abundances of the benzyl cation formed in the EI-MS. Regioisomeric NBOME derivatives with two methoxy groups in the N-benzyl ring were differentiated by EI-MS only after derivatization with TFA. TFAderivatization resulted in the formation of unique ions in the EI-MS as well as significant differences in the relative abundance of other key fragment ions. In addition to MS methods, regioisomeric NBOMe derivatives were also separated and identified by gas chromatographic methods. The new NBOMe compounds synthesized were tested for their receptor affinities in a variety of assays and several were found to have nanomolar affinities and high selectivity for 5-HT2 receptor subtypes.