The Crisis of Identity in Post-Revolutionary Cuban Film: A Sociological Analysis of Strawberry and Chocolate

This paper analyzes Tomás Gutiérrez Alea and Juan Carlos Tabío´s Strawberry and Chocolate (1993) from the sociological perspective of film as a cultural text informed by the political, historical, and social world in which it is produced. A symbolic interactionist/cultural studies model is used as a guide for the interpretive and qualitative methods utilized in approaching the film. Of particular interest to the sociological analysis of the film is the changing political context of the Cuban Revolution during the “special period” of the early 1990s, the use of stereotypes in the characterization of the actors, and finally its representation of gender and sexuality as a reflection of the revolutionary discourse in Cuba. The paper concludes with reflections on the importance of film to sociological study and theory in general, using Strawberry and Chocolate as a salient example

Synthesis, Discovery and Delivery of Therapeutic Natural Products and Analogs

Small molecule drug discovery relies heavily on synthetic organic chemistry to develop novel chemical entities that elicit desirable therapeutic effects. The development of targeted chemical syntheses is of paramount importance to access molecules for biological evaluation and is usually considered the bottleneck in most drug discovery campaigns. Targets for chemical syntheses commonly draw inspiration from molecules of natural origin. Nature harbors a wealth of chemical diversity that has established itself over millions of years through chemical and biological evolution. Organisms have an inherent ability to protect themselves from predators and harmful environments. In doing so, many of them evolve to produce chemical defenses in order to survive in their environments. Unfortunately, most bioactive natural products are not present in large abundance and require chemical syntheses for evaluation of their therapeutic potential. Antibiotic resistance has become a major health concern that is creating a health and financial burden on society. There is an unmet need to develop new antibiotics to combat the ever-evolving microbes. Drug-resistant bacteria capable of adopting biofilm morphology become increasingly resistant to antibiotic treatment, threatening the life of the patient. A series of marine natural products (MNPs) have recently been identified to exhibit promising activity against methicillin resistant Stahphylococcus aureus (MRSA) biofilms. One of the most potent compounds in the series was the MNP membranolide. The intriguing biological properties of membranolide have led us to develop an enantioselective synthesis of the natural product and related analogs for further evaluation against MRSA biofilms (outlined in chapter 2). Microbial infections are not limited to bacteria. Parasitic and amoebic pathogens can cause infections as well, with the latter being underrepresented in drug discovery. The lack of research and development in the area of amoebic infections may be partly due to the rarity of occurrence. However, some amoebic infections have extremely high mortality rates, such as those caused by Naegleria fowleri, presenting a dire need for new therapeutics. Phytocannabinoid natural products have been found to exhibit anti-proliferation activity against N. fowleri and represent a class of compounds that may aid in the efforts in combatting its infections. A novel chemical synthesis is disclosed in chapter 3 that gives rise to tetrahydrocannabinol (THC) and cannabidiol (CBD) and related analogs to further evaluate and understand their biological activity. Furthermore, these compounds could be effective treatments against a myriad of other clinical indications including but not limited to pain, inflammation, anxiety and even Alzheimer’s disease. The cannabinoids are well-known for their unique biological and physiochemical properties; however, they lack ideal pharmacokinetic profiles to become successful therapeutics. Their poor absorption through traditional delivery routes can be addressed either by analog development or different drug delivery methods. The low oral bioavailability and high lipophilicity of the cannabinoids has prompted the development of a transdermal route for their delivery. Throughout chapter 4, a novel transdermal delivery system for the cannabinoids is discussed including the first use of a skin PAMPA assay to assist in the transdermal patch development for the cannabinoids

Practical and Scalable Installation of Neglected S(VI) Functionality with Applications to the Enantiospecific Synthesis of Pharmaceuticals

Sulfoximines and related sulfonimidoyl groups have been largely ignored for decades until their value was demonstrated in biological settings. The realization of their importance has ushered in a new wave of discovery and pharmaceutical applications. In attempts to remove the “neglected” description of the lesser-known S(VI) groups, a practical and modular approach for a-substituted heterocycles bearing sulfonimidoyl functional groups was developed. A variety of sulfoximines containing diverse functionality and complexity were rapidly introduced in an enantiospecific fashion with good to excellent yields. Pharmaceutically important heterocyclic scaffolds were shown to undergo the facile nucleophilic substitution, while sulfoximines, sulfonimidamides and sulfondiimines were all demonstrated to be compatible nucleophiles. The utility and practicality of the method was exhibited in target- and diversity-oriented syntheses of four sulfoximine-containing pharmaceuticals including ceralasertib, an ATR inhibitor currently in clinical trials. The introduction of underexplored sulfur functionality to common heterocyclic pharmacophores provides a practical platform for rapid analog development that is expected to aid future efforts in the discovery sciences.</p

Synthesis of cannabinoids

Provided are synthesis processes and intermediates for preparing cannabinoids and analogs

Synthesis of cannabinoids

Provided are synthesis processes and intermediates for preparing cannabinoids and analogs

Synthesis of cannabinoids

Provided are synthesis processes and intermediates for preparing cannabinoids and analogs

Asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides, and sulfonimidamides enabled by an enantiopure bifunctional S(VI) reagent

An increased interest to expand the three-dimensional chemical space for the design of new materials and medicines has created a demand for isosteric replacement groups of commonly used molecular functionality. The structural and chemical properties of chiral S(VI) functional groups provide unique spatial and electronic features compared to their achiral sulfur- and carbon-based counterparts. Manipulation of the S(VI) center to introduce structural variation with stereochemical control has remained a synthetic challenge. The stability of sulfonimidoyl fluorides and the efficiency of sulfur fluorine exchange (SuFEx) chemistry has enabled the development of an enantiopure bifunctional S(VI) transfer reagent (t-BuSF) to overcome current synthetic limitations. Here, this reagent platform serves as a chiral SuFEx template for the rapid asymmetric synthesis of over seventy different sulfoximines, sulfonimidoyl fluorides and sulfonimidamides with excellent enantiopurity and good overall yields. Furthermore, the practical utility of t-BuSF was demonstrated in the syntheses of enantiopure pharmaceutical intermediates and analogs

Enantioselective Total Synthesis of CannabinoidsA Route for Analogue Development

A practical synthetic approach to Δ⁹-tetrahydrocannabinol (<b>1</b>) and cannabidiol (<b>2</b>) that provides scalable access to these natural products and should enable the generation of novel synthetic analogues is reported