A Radical-Mediated Approach to the Total Synthesis of Fluorinated Marinoquinoline A and Related Tricyclic and Tetracyclic Congeners

A radical-mediated approach to the core structure of fluorinated marinoquinoline A, N-methylated marinoquinoline A and related congeners via the use of Togni’s reagent is described

An undergraduate study for the comparison of dissolution profiles using 3D printed PVA and commercial paracetamol tablets

Three-dimensional printing (3DP) is an additive manufacturing process that can rapidly render 3D objects from computer aided design software by successively depositing polymeric materials layer by layer. A range of different 3D printing technologies are in current use, with the most prevalent methodology using Fused Deposition Modelling (FDM) technology due to a synergetic combination that merges economic and accuracy/resolution factors. In 2015, Spritam®, a solid pharmaceutical formulation which contains the anti-epileptic drug levetiracetam, became the first 3D printed medicine approved by the US Food and Drug Administration (FDA) leading to a raised interest in this type of technology so to revolutionise healthcare in the area of personalised medicines

Prospective cross sectional study on anatomical variation with special emphasis on critical anatomical landmark in patients undergoing multi detector computed tomography of paranasal sinuse

Introduction: Paranasal sinuses are best evaluated by multi-detector computed tomography. Evaluation of sphenoid sinus pneumatization, lamina papyracea, onodi cell, cribriform plate, types of optic canal and supraorbital pneumatisation are useful for evaluation of the surgical anatomy of paranasal sinuses for the radiologist which guides the surgeon to take a correct approach for surgery without major complications of crucial structures. CT is recently used as a investigation of choice in the assessment of the paranasal sinuses and surrounding structures. Aims and Objective: To study the types of anatomical variation of paranasal sinuses and osteomeatal complex and clinical importance of these various of paranasal sinus on pre-operative computed tomography. Materials and Methods: Over a period of 18 months, 104 patients referred for CT scan of PNS region G.K.General hospital were evaluated for the presence of normal variants of the paranasal region. Unenhanced CT of the PNS was performed for these patients in the coronal plane, complemented by axial views in selected cases. Results: Out of 109 patients who fulfilled inclusion criteria were studied from that most common is type II cribriform plate found in 80.7% of patients, Presence of haller cells was noted in 11.01% of individuals. Most of the uncinate process was attached to lamina papyracea in 88.9% individuals. Onodi cell was identified among 41% patients. Depending on the pneumatization of the sphenoid sinus, type I course of optic nerve was most common. Sellar variety of sphenoid sinus was more common observed in 82.5% patients. Presence of supraorbital pneumatization was identified in 72.4% patients among total subjects. Conclusion: The presence of anatomical variants does not indicate a predisposition to sinus pathology but these variations may predispose patients to increased risk of intraoperative complication

Tuneable radical cyclisations: a tin-free approach towards tricyclic and spirocyclic heterocycles via a common precursor

A novel common precursor approach towards both tricyclic and spirocyclic heterocycles is described. Cyclisations are based on thiyl radical/isocyanide methodology and avoid the use of tin

Crafting mono- and novel bis-methylated pyrroloquinoxaline derivatives from a shared precursor and its application in the total synthesis of marinoquinoline A

The synthesis of mono- and novel bis-methylated pyrrolo[1,2-a]quinoxalines through the addition of unstable methyl radicals to aryl isocyanides is described contingent upon the reaction conditions employed. The strategy has been effectively employed in the total synthesis of the natural product marinoquinoline A

Antivirals for broader coverage against human coronaviruses

Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome that is 27–31 kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and nine accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple roles in the replication cycle and immune evasion (1). There are seven known human CoVs that most likely appeared after zoonotic transfer, the most recent being SARS-CoV-2, responsible for the COVID-19 pandemic. Antivirals that have been approved by the FDA for use against COVID-19 such as Paxlovid can target and successfully inhibit the main protease (MPro) activity of multiple human CoVs; however, alternative proteomes encoded by CoV genomes have a closer genetic similarity to each other, suggesting that antivirals could be developed now that target future CoVs. New zoonotic introductions of CoVs to humans are inevitable and unpredictable. Therefore, new antivirals are required to control not only the next human CoV outbreak but also the four common human CoVs (229E, OC43, NL63, HKU1) that circulate frequently and to contain sporadic outbreaks of the severe human CoVs (SARS-CoV, MERS and SARS-CoV-2). The current study found that emerging antiviral drugs, such as Paxlovid, could target other CoVs, but only SARS-CoV-2 is known to be targeted in vivo. Other drugs which have the potential to target other human CoVs are still within clinical trials and are not yet available for public use. Monoclonal antibody (mAb) treatment and vaccines for SARS-CoV-2 can reduce mortality and hospitalisation rates; however, they target the Spike protein whose sequence mutates frequently and drifts. Spike is also not applicable for targeting other HCoVs as these are not well-conserved sequences among human CoVs. Thus, there is a need for readily available treatments globally that target all seven human CoVs and improve the preparedness for inevitable future outbreaks. Here, we discuss antiviral research, contributing to the control of common and severe CoV replication and transmission, including the current SARS-CoV-2 outbreak. The aim was to identify common features of CoVs for antivirals, biologics and vaccines that could reduce the scientific, political, economic and public health strain caused by CoV outbreaks now and in the future

Room temperature DBN initiated phospha‐Brook rearrangement of α‐hydroxyphosphonates to phosphates

A series of substituted aryl phosphate esters have been synthesized from their α‐hydroxyphosphonates substrates, using DBN (1,5 diazabicyclo(4.3.0)non‐5‐ene) at room temperature, via a phospha‐Brook rearrangement. The aryl‐substrate dependence of the rearrangement was explored, and excellent yields of the phosphate esters were achieved irrespective of whether the aryl moiety was activated or unactivated. A plausible mechanism for the rearrangement has been proposed. Based on the low temperature 31P‐NMR, the mechanism of the phospha‐Brook rearrangement is proposed to take place via an oxaphosphirane intermediate

Three-Dimensional Printing of a Scalable Molecular Model and Orbital Kit for Organic Chemistry Teaching and Learning

Three-dimensional (3D) chemical models are a well-established learning tool used to enhance the understanding of chemical structures by converting two-dimensional paper or screen outputs into realistic three-dimensional objects. While commercial atom model kits are readily available, there is a surprising lack of large molecular and orbital models that could be used in large spaces. As part of a program investigating the utility of 3D printing in teaching, a modular size-adjustable molecular model and orbital kit was developed and produced using 3D printing and was used to enhance the teaching of stereochemistry, isomerism, hybridization, and orbitals

3D‐printed polypropylene continuous‐flow column reactors: exploration of reactor utility in SNAr reactions and the synthesis of bicyclic and tetracyclic heterocycles

3D printing has the potential to transform the way in which chemical reactions are carried out due to its low‐cost, ease‐of‐use as a technology and its capacity to expedite the development of iteratively enhanced prototypes. In this present study, we developed a novel, low‐cost polypropylene (PP) column reactor that was incorporated into an existing continuous‐flow reactor for the synthesis of heterocycles. The utility and solvent resistance of the printed devices were explored in SNAr reactions to produce substituted aniline derivatives and in the synthesis of bicyclic and tetracyclic heterocycles. Using this approach, a range of heterocyclic compounds was synthesised including the core structure of the natural product (±)‐γ‐lycorane and structurally complex compounds based on the tetracyclic core of the erythrina alkaloids

Peri-substituted dithianaphthalenes as sources of reactive intermediates in organic chemistry

This thesis reports the application of 1,8 dithianaphthalenes (peri-substituted dithianaphthalenes) as sources of, and as a means of stabilising, reactive intermediates in organic chemistry. Three peri-substituted trisulfide-2-oxides (49, 58 and 103) were prepared by reacting 1,8-naphthalene dithiols with thionyl chloride in the presence of pyridine. The trisulfide-2-oxides 49, 58 and 103 were shown to act as sulfur monoxide transfer reagents with dienes. ortho-Substituents on the naphthalene ring increased the rate and lowered the temperature at which SO transfer occurred. Treatment of the resulting sulfoxides under Pummerer conditions afforded the corresponding thiophenes. SO transfer was applied in a formal synthesis of Plavix® and the naturally occurring thioperillene. Mechanistic studies on the SO transfer reaction indicated that the rate-determining step was independent of the diene, and first-order with respect to trisulfide-2-oxide. C-H abstraction from cycloheptatriene suggested formation of triplet SO. vic-Disulfoxides are reactive intermediates in the oxidation of thiosulfinates to thiosulfonates. The oxidation of 1,8-naphthalene disulfides was investigated. Cyclic voltammetry demonstrated that electron-rich 3,8-dimethoxynaphtho[1,8-cd][1,2]dithiole (87) was easier to oxidise than the parent naphthalene disulfide 50. Treatment of 87 with one equiv. of oxidant resulted in formation of thiosulfonate 206 and disulfide 87, suggesting disproportionation of thiosulfinate 205. Oxidation of t-Bu-substituted disulfide, 3,8-di-tert-butylnaphtho[1,8-cd][1,2]dithiole (65), afforded the isolable trans vic-disulfoxide 217. Isomerisation of 217 occurred thermally and photochemically, generating cis vic-disulfoxide 225 and thiosulfonate 224. Complete rearrangement of 217 to the thiosulfonate 224 occurred in refluxing mesitylene, establishing trans-217 as the most stable vic-disulfoxide to date. Bis(sulfonyl)hydroxylamine 284 is proposed as a potential source of nitric oxide (NO) or nitroxy (HNO). 284 was prepared by formal N-insertion into the S(O)-S(O)$_2$ bond of sulfinyl sulfone 228, prepared in turn through oxidation of disulfide 50. Bis(sulfonyl)hydroxylamine 284 was found to be stable both thermally and photochemically. Investigations into the oxidation of t-Bu-substituted disulfide resulted in the isolation of sulfinic anhydride, 295, from disulfide 65. Desulfonylation occurred when 295 was heated in H$_2$O/1,4-dioxane. Deuterium incorporation occurred on running the reaction in D$_2$O/1,4-dioxane. Refluxing 295 in PhCl resulted in deoxygenation to disulfide 65