Design and synthesis of C3-symmetric molecules bearing propellane moieties via cyclotrimerization and a ring-closing metathesis sequence

We have developed an efficient synthetic strategy to assemble C3-symmetric molecules containing propellane moieties as end groups and a benzene ring as a central core. The synthesis of these C3-symmetric molecules involves simple starting materials. Our approach to C3-symmetric compounds relies on a Diels–Alder reaction, cyclotrimerization and ring-closing metathesis as key steps

Target Specific Tactics in Olefin Metathesis: Synthetic Approach to <i>cis</i>-<i>syn</i>-<i>cis</i>-Triquinanes and -Propellanes

A concise and simple synthetic approach to <i>cis</i>-<i>syn</i>-<i>cis</i>-triquinanes and -propellanes has been demonstrated via olefin metathesis starting with <i>exo</i>-nadic anhydride. This approach involves a ring-opening and ring-closing metathesis sequence of norbornene derivatives using Grubb’s catalyst. Early-stage diallylation of norbornene derivatives is demonstrated followed by ring-closing metathesis that delivers propellanes exclusively. Surprisingly, ring-opening metathesis, late-stage diallylation, followed by ring-closing metathesis delivers triquinane as well as propellane derivatives

Molecular Signatures of the Different Types of Hyperlipidemia According to the Fredrickson Classification

Hyperlipidemia, characterized by abnormally high levels of lipoproteins in the plasma, is one of the biggest epidemics facing our healthcare system today. The Center for Disease Control and Prevention (CDC) estimates that about one-third of American adults have some form of hyperlipidemia and that of those, only one-third are well-managed. With the growing obesity problem in America and the significant, detrimental health effects that hyperlipidemia can cause, developing new, more effective tools to help prevent, diagnose and treat hyperlipidemias is an urgent matter of public health. Hyperlipidemias can be classified into three main categories: Primary (familial) caused by specific genetic abnormalities, secondary (acquired) abnormal plasma lipoprotein concentrations due to another underlying disorder, or idiopathic elevated lipoprotein. All three forms can almost double the risk of developing cardiovascular disease, the leading cause of death in the United States, and thus for decades scientists have sought to research, organize and understand how the chronic elevation of these lipoproteins in the blood circulation influence the human body. However, recently, researchers have begun to question the clinical usefulness of one of the most widely used hyperlipidemia classification models which first originated in 1967 and adopted by the World Health Organization, the Fredrickson familial hyperlipidemia classification. This classification is based on the pattern of lipoproteins in the plasma, which was resolved by physical analytic techniques, and includes five categories. Although Fredrickson’s model was instrumental in the original understanding of familial hyperlipidemias, this classification is not based on molecular causes of hyperlipidemias and therefore it has limitations in its clinical use, especially in the era of precision medicine. Thus, the objective of this project was to conduct a comprehensive literature review of the published biomedical literature for molecular defects in patients with different types of familial hyperlipidemias. Using this knowledge, we sought to better understand how molecular mechanisms govern elevated lipoproteins and then to subsequently integrate this information into the previously established Fredrickson classification. Our hope is that with this project, along with further research in the future, we are one day able to produce a more useful clinical tool which will provide a better explanation for hyperlipidemias and lead to better patient treatments

An Alternative Measurement of Central Obesity: Abdominobesity Index (ABI)

Obesity has reached epidemic proportions in the developed world. Approximately 35.0% of men and 40.4% of women in the United States were considered obese in 2013-2014. Obesity, and more specifically central obesity, is associated with a myriad of health problems. Central obesity, also known as abdominal obesity, refers to an excess fat deposit around and within the abdominal cavity. Central obesity has been linked to hypercholesterolemia, high blood pressure, type 2 diabetes, coronary artery disease, and other health concerns. We have established the concept of Abdominobesity Index (ABI), a new measurement to be used in quantifying a person’s central obesity. We propose such a new measurement because obesity rates continue to rise in our country and various places around the world. To best solve a problem, one must understand it, in this case by measuring it as accurately as possible. Therefore, we propose this new measurement as a supplement to those that already exist for measuring obesity, such as Body Mass Index (BMI) and Waist to Hip Ratio (WHR). Our measurement is an important supplement because it specifically focuses on quantifying a person’s degree of central obesity. ABI departs from previous measurements in that it specifically targets the abdominal fat by comparing abdominal circumference with chest circumference. We set forth the formula for our new ABI measurement along with a discussion of the preliminary data analysis that demonstrates the utility of ABI as a measurement distinct from BMI. In the future, we hope to conduct further studies that also track patient outcomes. In conjunction with other obesity measurements, we believe ABI will help advance further obesity research and improve risk stratification in obese patients