Synthesis of novel cage amino acid analogues.

Thesis (M.Sc.)-University of Natal, Durban, 2001.Amino acids are important building blocks for the synthesis of a large number of biologically active compounds and drugs. Amino acids with the pentacyclo-undecane (1) and trishomocubane (2) frameworks fall into the class of conformationally constrained non-natural amino acids. Conformationally constrained amino acids are found in many naturally occurring, biologically active compounds. It was found that incorporating cage structures into drugs induces a range of positive effects: promotes transport across the cell membrane, drugs can be designed to target the central nervous system, increased receptor site specificity, and retards metabolic degradation. In the light of this, it was decided to investigate the incorporation of cage amino acids into peptides. A synthetic route has been established for the efficient synthesis of amino acids 1 and 2, and for their incorporation into peptides. Several chiral macrocyclic crown ethers and related analogues have been shown to be capable of forming complexes enantioselectively with chiral organic ammonium salts. The design and synthesis of host chiral macrocycles which are able to distinguish between the enantiomers of guest organic ammonium salts is of interest in the areas that include synthesis of enzymes, electrodes for specific ions or molecules, drugs targeted for specific sites, and enantiomer separation. A synthetic procedure has been established for the synthesis of cage annulated chiral crown ethers derived from amino acids. The advantage of using cage compounds in crown ethers is due to increased rigidity, increased solubility in non-polar solvents and increased chirality. Various techniques for the determination of enantiomeric recognition have been studied and include NMR spectroscopy, fluorescence emission spectroscopy and computational methods. The cage crown ether 3 represents a typical example of these new cage annulated, chiral crown ethers

A study of chiral pentacyclo-undecane derived macrocycles and ligands.

Thesis (PhD-Chemistry)-University of KwaZulu-Natal, Durban, 2004Several chiral macrocyclic crown ethers and related analogues have shown to be capable o

The analysis of alcohol content in hand sanitisers (in the Durban region) using gas chromatography-mass spectrometry during the COVID-19 pandemic

The COVID-19 pandemic has resulted in an unprecedented surge in the demand for alcohol-based hand sanitisers (ABHS). The Centre for Disease Control  (CDC) and World Health Organisation (WHO) recommend alcohol, i.e., isopropanol or ethanol, at a 60-95% concentration in ABHS for sufficient antiviral  protection. Consumers need to be vigilant of substandard hand sanitisers being marketed to the public. The frequent exposure of microorganisms to  alcohol concentrations below the recommended range for infection prevention may lead to resistant mutations, and above the range may be ineffective.  Therefore, this study aimed to verify the stated alcohol content in hand sanitisers from their respective labels. We analysed 50 hand sanitiser samples  available to our region in Durban, KwaZulu-Natal, South Africa, using a Shimadzu GC-MS-QP2010 Ultra equipped with a Zebron ZB-wax capillary column.  The hand sanitisers analysed had a range of 44–93% alcohol content. The data from our study also revealed that 32% (16) of hand sanitisers did not  adhere to the stated alcohol indicated on their labels. 16% (8) contained >80% and 12% (6) contained <60%, while 6% (3) of the ABHS contained  1-propanol and ethyl acetate as contaminants, respectively. This study clearly emphasises manufacturers’ exploitation of the pandemic and the need for  stricter guidelines and regulations for consistency amongst ABHS manufacturers. The public should also be more alert to the % alcohol stated (ideal    range 60-80%) on the sanitizer bottle and note one needs to rub their hands together until it feels dry

(1R,3S)-N-Benzhydryl-2-benzyl-6,7-dimeth­oxy-1-phenyl-1,2,3,4-tetra­hydro­isoquinoline-3-carbothio­amide

The title compound, C38H36N2O2S, has a heterocyclic ring that assumes a half-chair conformation. The phenyl rings of neighbouring mol­ecules align forming alternating chains parallel to [100] within the crystal packing. The absolute stereochemistry of the crystal was confirmed to be R,S at the 1- and 3-positions, respectively, by proton NMR spectroscopy. A single intra­molecular N—H⋯N hydrogen bond is observed

Synthesis, characterization and biocompatibility of a multifunctional gold nanoparticle system for the delivery of single-stranded RNA to lymphocytes

The use of RNA macromolecules as therapeutic agents for HIV and other infectious diseases is promising but limited by suboptimal delivery to the target site. With HIV infection, this is particularly challenging since lymphocytes are particularly difficult to transfect. This paper describes an innovative strategy for the intracellular delivery of a novel single-stranded RNA (oligoribonucleotide) with putative anti-HIV activity. This strategy is based on a PEGylated gold nanoparticle scaffold covalently linked to the thiol-modified oligoribonucleotide via a cleavable N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) linker molecule. The nanoparticle was then coated with a cationic polymer (polyethyleneimine) to facilitate cell entry and endosomal escape. A synthetic anti-CD4 cyclic targeting peptide was attached to the polyethyleneimine-coated nanoparticle via an SPDP linker molecule, in an attempt to enhance uptake and selectivity. Synthesis, characterization, SPDP and RNA loading, cytotoxicity and antiviral activity of the nanoparticle are described. Approximately 45 000 strands of RNA were taken up per lymphocyte. Uptake was limited by relatively inefficient loading ofRNAonto the gold nanoparticle surface (1 strand per 4.8 nm2 of nanoparticle surface area) and significant aggregation of the nanoparticle in physiological solutions. No antiviral activity was demonstrated, possibly due to insufficient intracytoplasmic delivery of the RNA.Keywords: Gold nanoparticle, polyethyleneimine, transfection, RNA deliver

(S)-2-Benzyl-N-(2,6-diisopropyl­phen­yl)-1,2,3,4-tetra­hydro­isoquinoline-3-carboxamide

The asymmetric unit of the title compound, C29H34N2O, contains two mol­ecules in which the N-containing six-membered rings assume different conformations viz. half-chair and envelope. Inter­molecular N—H⋯O hydrogen bonding via the amide groups cross-link the mol­ecules in the crystal structure

6,7-Dimeth­oxy-3-meth­oxy­carbonyl-1-(2-meth­oxy­phen­yl)-3,4-dihydro­isoquinoline 2-oxide

In the title compound, C20H21NO6, an N-oxide-based organocatalyst, the N-containing six-membered ring adopts a twisted half-chair conformation. No hydrogen bonding or π–π stacking was found within the crystal structure

(S)-Benzyl 3-phenyl­carbamoyl-1,2,3,4-tetra­hydro­isoquinoline-2-carboxyl­ate

There are two independent mol­ecules in the asymmetric unit of the title compound, C24H22N2O3. The heterocyclic ring assumes a twisted boat conformation and N—H⋯O inter­actions help to construct the three-dimensional network within the crystal packing

(1R,3S)-Methyl 2-benzyl-6,7-dimeth­oxy-1-phenyl-1,2,3,4-tetra­hydro­isoquinoline-3-carboxyl­ate

In the title compound, C26H27NO4, a precursor to novel chiral catalysts, the N-containing six-membered ring assumes a half-boat conformation. Various C—H⋯π interactions and intermolecular short contacts (C⋯H = 2.81–2.90 Å) link the mol­ecules together in the crystal structure

endo-11-(Dibenzyl­amino)­tetra­cyclo­[5.4.0.03,10.05,9]undecane-8-one

The structure of the title compound, C25H27NO, is a mono-ketone penta­cyclo­undecane (PCU) mol­ecule bearing a tertiary amine group. One of the methyl­ene groups in the PCU is disordered over two orientations with site-occupancy factors of 0.621 (7) and 0.379 (7)