Cannabis through the looking glass: chemo- and enantio-selective separation of phytocannabinoids by enantioselective ultra high performance supercritical fluid chromatography

By using the Inverted Chirality Columns Approach (ICCA) we have developed an enantioselective UHPSFC method to determine the enantiomeric excess (ee) of (-)-Δ(9)-THC in medicinal marijuana (Bedrocan®). The ee was high (99.73%), but the concentration of the (+)-enantiomer (0.135%) was not negligible, and it is worth a systematic evaluation of bioactivity

Dynamic HPLC on chiral stationary phases: a powerful tool for the investigation of stereomutation processes

Dynamic HPLC on enantioselective stationary phases has become a well-established technique to investigate chiral molecules with internal motions that result in stereoinversion and occur on the time scale of the separation process. Kinetic parameters for the on-column interconversion phenomena can be extracted from experimental peak profiles by computer simulation or by direct calculation methods. The technique has been used in a wide range of temperatures and is complementary in scope to dynamic NMR spectroscopy

Chirality effects on the IRMPD spectra of basket resorcinarene/nucleoside complexes

The IRMPD spectra of the ESI-formed proton-bound complexes of the R,R,R,R- and S,S,S,S-enantiomers of a bis(diamido)-bridged basket resorcin[4]arene (R and S) with cytosine (1), cytidine (2), and cytarabine (3) were measured in the region 2800– 3600 cm1. Comparison of the IRMPD spectra with the corresponding ONIOM (B3LYP/6-31(d):UFF)-calculated absorption frequencies allowed the assessment of the vibrational modes that are responsible for the observed spectroscopic features. All of the complexes investigated, apart from [R·H·3]+, showed similar IRMPD spectra, which points to similar structural and conformational landscapes. Their IRMPD spectra agree with the formation of several isomeric structures in the ESI source, wherein the N(3)-protonated guest establishes noncovalent interactions with the host amidocarbonyl groups that are either oriented inside the host cavity or outside it between one of the bridged side-chains and the upper aromatic nucleus. The IRMPD spectrum of the [R·H·3]+ complex was clearly different from the others. This difference is attributed to the effect of intramolecular hydrogen bonding interactions between the C(2’)-OH group and the aglycone oxygen atom of the nucleosidic guest upon repulsive interactions between the same oxygen atom and the aromatic rings of the host

The Quest for Secondary Pharmaceuticals: Drug Repurposing/Chiral-Switches Combination Strategy

Drug repurposing toward new medical uses and chiral switches are elements of secondary pharmaceuticals. The drug repurposing and chiral-switches strategies have mostly been applied independently in drug discovery. Drug repurposing has peaked in the search for therapeutic treatments of the Coronavirus Disease 2019 pandemic, whereas chiral switches have been overlooked. The current Perspective introduces the drug repurposing/chiral-switches combination strategy, overviewing representative cases of chiral drugs that have undergone this combination: ketamine, flurbiprofen, fenfluramine, and milnacipran. The deuterium-enabled chiral switches of racemic thalidomide analogs, a variation of the repurposing/chiral-switch combination strategy, is also included. Patenting and regulatory-exclusivity considerations of the combination strategy in the discovery of new medical uses are considered. The proposed combination creates a new synergy of its two elements, overcoming arguments against chiral switches, with better prospects for validation of patents and regulatory exclusivities. The combination strategy may be applied to chiral switches to paired enantiomers. Repurposing/chiral-switch drugs may be ‘obvious-to-try’; however, their inventions may be unexpected and their patents nonobvious. Patenting repurposing/chiral-switch combination drugs is not ‘evergreening’, ‘product hopping’, and ‘me-too’. The expected benefits and opportunities of the combined repurposing/chiral-switch strategy vis-à-vis its two elements are superior pharmacological properties, overcoming arguments against patent validities, challenges of chiral-switch patents, reduced expenses, shortened approval procedures, and higher expectations of regulatory exclusivities

Dynamic HPLC on chiral stationary phases: a powerful tool for the investigation of stereomutation processes

Dynamic HPLC on enantioselective stationary phases has become a well-established technique to investigate chiral molecules with internal motions that result in stereoinversion and occur on the time scale of the separation process. Kinetic parameters for the on-column interconversion phenomena can be extracted from experimental peak profiles by computer simulation or by direct calculation methods. The technique has been used in a wide range of temperatures and is complementary in scope to dynamic NMR spectroscopy

Tecniche cromatografiche enantioselettive: principi e stato dell'arte

Recent developments in the field of high performance enantioselective chromatography (HRGC, HPLC) are discussed in this review. Commonly used chiral stationary phases are presented according to their separation mechanism, together with application fields, advantages and limitations. Finally new chiral stationary phases at receptorial level have been introduce