Installing the "magic methyl" - C-H methylation in synthesis

The selective and efficient C-H methylation of sp2 and sp3 carbon centres has become a powerful transformation in the synthetic toolbox. Due to the potential for profound changes to physicochemical properties attributed to the installation of a "Magic Methyl" group at a strategic site in a lead compound, such techniques have become highly desirable in modern drug discovery and synthesis programmes. This review will cover the diverse techniques that have been employed to enable the selective installation of the C-Me bond in a wide range of chemical structures, from simple building blocks to complex drug-like architectures

HFIP promoted carbo-lactonisation as a new route to functionalised lactones

We have been able to induce a series of lactonisation reactions of unsaturated acids using a carbocationic intermediate formed in situ. The transformation generates five and six membered lactone rings AND forms a new exocyclic C-C bond at the same time, thus removing the need for further derivatisation of typical lactonisation products (such as from iodo lactonisation). The reaction is operationally straightforward, does not employ any metals and utilises readily accessible alcohol and unsaturated acid substrates

Double antiplatelet therapy in patients with acute coronary syndrome

The paper presents the evolution in the modern approaches towards antiplatelet therapy (aspirin, clopidogrel) in acute coronary syndrome, as well as the results of the studies on effectiveness and safety of such new antiaggregant medications as prasugrel and ticagrelor

RESISTANCE TO ANTIPLATELET DRUGS IN PATIENTS WITH ISCHEMIC HEART DISEASE

The clinical, cell and genetic factors are distinguished among reasons for resistance to antiplatelet drugs. There are many methods to detect sensitivity to antiplatelet drugs, but they all have disadvantages. Moreover, there is no unified approach for interpretation of received results, and no recommendations for their practical use. It is necessary to work out unified procedure to assess platelet function, to define indications for its usage and to work out unified criteria of resistance. Individualized approach and each patient’s peculiarities consideration are essential when prescribing antiplatelet therapy.</p

A vicinal diol approach for the total synthesis of molestin E ent-sinulacembranolide A and ent-sinumaximol A

In this work an approach for the synthesis of furanocembranoid natural products containing the C-7,8-diol moiety is disclosed. This culminated in the first total synthesis of the natural product molestin E, together with ent-sinulacembranolide A and entsinumaximol A as well as a thorough exploration of their chemistry. Late-stage ring-closure of the C-7,8-diols to the corresponding epoxides was also demonstrated. Key features of this synthetic strategy include a stereoselective Baylis-Hillman reaction, ringclosing metathesis and Shiina macrolactonisation. Chiral-pool materials were deployed to ensure the desired absolute stereochemistry which was confirmed by late-stage single crystal Xray diffraction

Lethal necrotizing granulomatous vasculitis after bariatric surgery and bilateral mammaplasty

The aim of case presentation. To present a typical case of systemic autoimmune disease related to extremely aggressive medical alterations of the immune status which were carried out not only for life-saving indications, but for cosmetic reasons as well. Summary. The patient (32-year-old female) had a history of persistent irregular febrile fever for two years, renal disease (tubulointerstitial nephritis with papillary necrosis), hemorrhagic vasculitis-like skin involvement and mediastinal lymphadenopathy. Patient underwent multiple investigations aimed for ruling out infectious causes of the disease that yielded negative result, repetitive courses of antibiotics provided transient positive effect at onset of disease. Five years before the origin of symptoms patients underwent sleeve gastrectomy with biliopancreatic shunting for obesity (body weight - 130 kg, BMI - 43.4 kg/m2), cholecystectomy and appendectomy. After that within a year patient lost 55 kg of body weight and developed severe symptoms of malabsorption. In 1.5 years after the fever onset bilateral mammaplasty with silicone implants was carried following which the fever became constant. At transthoracic biopsy of mediastinal lymph nodes demonstrated the pattern of Wegener-type ANCA-negative necrotizing granulomatous vasculitis of small arteries (PCR for mycobacteria and acid fast stain were negative). Despite provided corticosteroid and cyclophosphan treatment, the disease progressed (focal affection of the lungs) and the patient died of brain stem hemorrhage. Autopsy revealed the signs of vasculitis with involvement of the brain, skin, mediastinal lymphnodes, lungs, as well as the signs of chronic inflammation, atrophy of breast gland lobules, embolization of the focal lymphatics by the implant substance, ulceronecrotic enteritis of defunctioning bowel, severe liver steatosis with the chronic vitamin deficiency. Conclusion. The relation of atypical necrotizing vasculitis with yet undescribed clinical presentation with previous bariatric surgery and long-standing malabsorption is highly probable; application of silicone implants with adjuvant-associated immune response were additional resolving factors. Incomplete effect of immunosuppressive therapy indicates the dominant role of autoinflammation in the course of disease. Selection of patients for bariatric and cosmetic surgery should be more careful and involve estimation of the general and immune status of the body