Strategies and Tactics for the Synthesis of Polycyclic Alkaloids

The myrmicarin family of oligomeric natural products comprises one of the most ornate collections of polycyclic alkaloids known. The structural characterization of their unique scaffolds was accomplished through elegant spectroscopic studies. Furthermore, the synthesis of these alkaloids has attracted the attention of the synthetic community, with several syntheses of the monomeric myrmicarins completed. Significant effort has been put forth toward the synthesis of the higher order structures, though no successful approach has been reported to date. These isolation and characterization studies as well as synthetic approaches toward the family are reviewed. Chapter 2. The Evolution of Efficient, Enantioselective Total Syntheses of Monomeric Myrmicarin Alkaloids. In order to provide a family-level solution to the myrmicarin alkaloids, we adopted a strategy-level approach to their synthesis. Utilizing concepts from retrosynthetic analysis and diversity oriented synthesis, an enantioselective and highly streamlined synthesis of the monomeric myrmicarin alkaloids as well as potential dimerization precursors was established from a common intermediate with late stage diversification. Chapter 3. Dimerization Studies toward the Synthesis of Myrmicarin 430A. An alternative strategy for the synthesis of myrmicarin 430A is presented using a dienamine precursor. This approach allows for the stereoselective synthesis of the all trans stereotriad of the central cyclopentane moiety of myrmicarin 430A. Mechanistic aspects concerning the final bond closure are presented in light of quantum chemical calculations. Chapter 4. An Introduction to the Securinega Alkaloids and NHC Catalysis The Securinega alkaloids comprise a large family of tetracyclic alkaloids, many of which contain a conjugated butenolide moiety. While many distinct synthetic approaches have appeared for the synthesis of members of this family, only a relatively small number of approaches are applied to the synthesis of the butenolide portion of these natural products. The various synthetic endeavors to accessing this structural motif are presented. NHC catalysis is a growing field of research for its ability to promote unusual chemical transformations. As this field of research is of relevance to our latter studies, a brief overview of modern NHC catalysis is presented. Chapter 5. Development of an NHC-Catalyzed Cascade Reaction to Access the Core Architecture of the Securinega Alkaloids. In targeting the family of Securinega alkaloids, a retrosynthesis was devised that proposes a novel intramolecular cyclization approach of an ynal and ketone to deliver the bridging butenolide moiety of these natural products. The development of this reaction and its application toward the synthesis of various Securinega alkaloids is presented

(6aR,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetra­hydro-6H-benzo[c]­chromen-1-yl 4-methyl­benzene­sulfonate

In the crystal structure of the title compound, C28H36O4S, the p-tolyl ring is inclined at 35.8° to the aromatic ring. The cyclohexene ring adopts a boat conformation and the heterocyclic ring is in a slightly distorted screw boat conformation

Comprehensive chromatographic profiling of cannabis from 23 USA States marketed for medical purposes

In this research, cannabis varieties represent 23 USA States were assayed by GC-FID to generate their complex chemical profiles informative for plants clustering. Results showed that 45 cannabinoids and terpenoids were quantified in all plant samples, where 8 cannabinoids and 18 terpenoids were identified. Among organics, Δ9-THC, CBN (cannabinoids) and Fenchol (terpenoid) not only showed the highest levels overall contents, but also were the most important compounds for cannabis clustering. Among States, Washington, Oregon, California and Hawaii have the highest cannabis content. GC-FID data were subjected to PCA and HCA to find (1) the variations among cannabis chemical profiles as a result of growing environment, (2) to reveal the compounds that were responsible for grouping cultivars between clusters and (3) finally, to facilitate the future profile prediction and States clustering of unknown cannabis based on the chemical profile. The 23 cannabis USA States were grouped into three clusters based on only Δ9-THC, CBN, C1 and Fenchol content. Cannabis classification based on GC-profile will meet the practical needs of cannabis applications in clinical research, industrial production, patients’ self-production, and contribute to the standardization of commercially-available cannabis cultivars in USA

Linear discriminant analysis based on gas chromatographic measurements for geographical prediction of USA medical domestic cannabis

Fifty four domestically produced cannabis samples obtained from different USA states were quantitatively assayed by GC-FID to detect 22 active components: 15 terpenoids and 7 cannabinoids. The profiles of the selected compounds were used as inputs for samples grouping to their geographical origins and for building a geographical prediction model using Linear Discriminant Analysis. The proposed sample extraction and chromatographic separation was satisfactory to select 22 active ingredients with a wide analytical range between 5.0 and 1,000 μg/mL. Analysis of GC-profiles by Principle Component Analysis retained three significant variables for grouping job (Δ9-THC, CBN, and CBC) and the modest discrimination of samples based on their geographical origin was reported. PCA was able to separate many samples of Oregon and Vermont while a mixed classification was observed for the rest of samples. By using LDA as a supervised classification method, excellent separation of cannabis samples was attained leading to a classification of new samples not being included in the model. Using two principal components and LDA with GC-FID profiles correctly predict the geographical of 100% Washington cannabis, 86% of both Oregon and Vermont samples, and finally, 71% of Ohio samples

D02. NCNPR Activities at Coy Waller Complex

Corresponding author (NCNPR, School of Pharmacy): Mohamed M. Radwan, [email protected]://egrove.olemiss.edu/pharm_annual_posters/1024/thumbnail.jp

Propagation through alginate encapsulation of axillary buds of Cannabis sativa L.-an important medicinal plant

ABSTRACT Cannabis sativa L. (Cannabaceae) is an important medicinal plant well known for its pharmacologic and therapeutic potency. Because of allogamous nature of this species, it is difficult to maintain its potency and efficacy if grown from the seeds. Therefore, chemical profile-based screening, selection of high yielding elite clones and their propagation using biotechnological tools is the most suitable way to maintain their genetic lines. In this regard, we report a simple and efficient method for the in vitro propagation of a screened and selected high yielding drug type variety of Cannabis sativa, MX-1 using synthetic seed technology. Axillary buds of Cannabis sativa isolated from aseptic multiple shoot cultures were successfully encapsulated in calcium alginate beads. The best gel complexation was achieved using 5 % sodium alginate with 50 mM CaCl 2 .2H 2 O. Regrowth and conversion after encapsulation was evaluated both under in vitro and in vivo conditions on different planting substrates. The addition of antimicrobial substance -Plant Preservative Mixture (PPM) had a positive effect on overall plantlet development. Encapsulated explants exhibited the best regrowth and conversion frequency on Murashige and Skoog medium supplemented with thidiazuron (TDZ 0.5 μM) and PPM (0.075 %) under in vitro conditions. Under in vivo conditions, 100 % conversion of encapsulated explants was obtained on 1:1 potting mix-fertilome with coco natural growth medium, moistened with full strength MS medium without TDZ, supplemented with 3 % sucrose and 0.5 % PPM. Plantlets regenerated from the encapsulated explants were hardened off and successfully transferred to the soil. These plants are selected to be used in mass cultivation for the production of biomass as a starting material for the isolation of THC as a bulk active pharmaceutical

Profiles of Urine Samples Taken from Ecstasy Users at Rave Parties: Analysis by Immunoassays, HPLC, and GC-MS

The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is increasing throughout the world. They have become popular drugs, especially at all-night techno dance parties (Raves), and their detection is becoming an important issue. Presently, there are no MDMA- or MDA-specific immunoassays on the market, and detection of the designer amphetamines is dependent upon the use of commercially available amphetamine assays. The success of this approach has been difficult to assess because of the general unavailability of significant numbers of samples from known drug users. The objectives of the present study are to characterize the drug content of urine samples from admitted Ecstasy users by chromatographic methods and to assess the ability of the available amphetamine/methamphetamine immunoassays to detect methylenedioxyamphetamines. We found that, when analyzed by high-performance liquid chromatography with diode-array detection (HPLC-DAD), 64% of 70 urine samples (by gas chromatography-mass spectrometry [GC-MS]: 88% of 64 urine samples) obtained from Rave attendees contained MDMA and/or 3,4-methylenedioxyamphetamine (MDA) alone or in combination with amphetamine, methamphetamine, or other designer amphetamines such as 3,4-methylenedioxyethylamphetamine (MDEA). This suggests that the majority of the Ravers are multi-drug users. At the manufacturer's suggested cutoffs, the Abbott TDx Amphetamine/Methamphetamine II and the new Roche HS Amphetamine/MDMA assays demonstrated greater detection sensitivity for MDMA than the other amphetamine immunoassays tested (Abuscreen OnLine Hitachi AMPS, Abuscreen OnLine Integra AMPS, Abuscreen OnLine Integra AMPSX, CEDIA AMPS, and EMIT II AMPS). There is 100% agreement between each of the two immunoassays with the reference chromatographic methods, HPLC-DAD and GC-MS, for the detection of methylenedioxyamphetamine

Employing Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD)

Corresponding author (Pharmaceutics and Drug Delivery): Iman Taha, [email protected]://egrove.olemiss.edu/pharm_annual_posters_2022/1020/thumbnail.jp

Phytochemical composition and antimicrobial properties of Markhamia platycalyx (Baker) Sprague leaf

Purpose: To isolate new antimicrobial agents from the leaves of Markhamia platycalyx (Baker) Sprague and assess their phytochemical characteristics and antimicrobial activity. Methods: Different chromatographic and spectroscopic techniques (NMR and ESI-MS) were applied for the identification of antimicrobial compounds. Agar-well diffusion technique was used for determination of antimicrobial activity. Anti-HCV effects were investigated using VITROS Anti-HCV assay. Results: Eighteen compounds were isolated for the first time from this genus. These were phytol, noctacosanoic acid (OCTA), tormentic acid and β-sitosterol-3-O-(6'-O-heptadecanoyl)-β-Dglucopyranoside. The other compounds were β-sitosterol, ursolic acid (URSA), oleanolic acids, pomolic acid (POMA), 2-epi-tormentic and β-sitosterol-3-O-β-D-glucopyranoside. However, stigmasterol and acteoside, which were seen in previous studies, were also present. Total ethanol extract (TEE) was the most effective against Escherichia coli, with the lowest minimum inhibitory concentration (MIC) of 1.0 µg/mL. Acteoside, URSA and 2-epi-tormentic acid showed the highest antibacterial effect on Pseudomonas aeruginosa while 2-epi-tormentic acid and acteoside produced the least MIC on Candida glabrata. These effects were superior to those produced by standard antibiotics. However, 2-epitormentic acid and β-sitosterol-3-O-β-D-glucopyranoside had no anti-HCV effects. Conclusion: Due to the good antimicrobial properties of Markhamia platycalyx, it is a potential source of new antimicrobial drugs