Towards Antibiotic Synthesis in Continuous-Flow Processes

Continuous-flow chemistry has become a mainstream process and a notable trend among emerging technologies for drug synthesis. It is routinely used in academic and industrial laboratories to generate a wide variety of molecules and building blocks. The advantages it provides, in terms of safety, speed, cost efficiency and small-equipment footprint compared to analog batch processes, have been known for some time. What has become even more important in recent years is its compliance with the quality objectives that are required by drug-development protocols that integrate inline analysis and purification tools. There can be no doubt that worldwide government agencies have strongly encouraged the study and implementation of this innovative, sustainable and environmentally friendly technology. In this brief review, we list and evaluate the development and applications of continuous-flow processes for antibiotic synthesis. This work spans the period of 2012–2022 and highlights the main cases in which either active ingredients or their intermediates were produced under continuous flow. We hope that this manuscript will provide an overview of the field and a starting point for a deeper understanding of the impact of flow chemistry on the broad panorama of antibiotic synthesis

Efficient pilot-scale synthesis of the key cefonicid intermediate at room temperature

Abstract Cefonicid is a common second-generation cephalosporin, and the 7-amino-3-[sulphomethyl-1-H-tetrazol-5-yl-thiomethyl]-3-cephem-4-carboxylate monosodium salt is a key synthetic intermediate in its preparation. Despite the considerable international demand for this antibiotic, its preparation is hampered by low synthetic yield, long reaction time, and time-consuming industrial filtration over charcoal after the purification step. In the context of the industrial production of pharmaceutical intermediates, in which the balance between streamlining and enhancing productivity is necessary in order to compete in the global active pharmaceutical ingredients (API) market, we have investigated an efficient and practical procedure for the synthesis of a key cefonicid intermediate that features a telescopic route whose synthetic steps are all performed at room temperature; from the displacement of the acetoxy group with boron trifluoride to crystallization without treatment with charcoal. In other words, a simpler, scalable, cost-effective and energy-saving protocol is herein reported as a means of moving towards commercial manufacturing. The optimization of the process parameters and the industrial-scale impact assessment should pave the way for industrialization

Indications for upper gastrointestinal endoscopy before bariatric surgery: a multicenter study

The role of preoperative upper gastrointestinal endoscopy before bariatric surgery is still debated, and a consensus among the international scientific community is lacking. The aims of this study, conducted in three different geographic areas, were to analyze data regarding the pathological endoscopic findings and report their impact on the decision-making process and surgical management, in terms of delay in surgical operation, modification of the intended bariatric procedure, or contraindication to surgery

Reduced Plasma Levels of sCD14 and I-FABP in HIV-infected Patients with Mesalazine-treated Ulcerative Colitis

BACKGROUND: Microbial translocation (MT) is a shared feature of HIV infection and inflammatory bowel disease (IBD). AIMS: This study was conducted to assess the impact of IBD (and particularly ulcerative colitis, UC) on plasma markers of MT and immune activation in HIV+ subjects. METHODS: A cross-sectional study was conducted in 3 groups of patients: HIV+/UC+(group HIV/UC); HIV+/UC- (group HIV); HIV-/UC+(group UC). Plasma levels of soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), and endotoxin core antibodies (endoCAB) were measured as plasma markers of MT. Inflammation and immune activation were evaluated by measuring plasma levels of IL-6, IL-21, TNF-alpha, and high-sensitivity C-reactive protein (hs-CRP). T- and B-cells subpopulations were characterized by FACS analysis. RESULTS: Seven patients were enrolled in group HIV/UC, 9 in HIV, and 10 in UC. All HIV-positive patients had plasma values of HIV-1 RNA < 37 copies/mL for at least 12 months and good immunological recovery. All patients with UC were treated with oral mesalazine. Markers of MT, immune activation, and inflammation were not increased in subjects with HIV/UC. In fact, they had lower levels of I-FABP (p = 0.001) and sCD14 (p = 0.007) when compared to other patients groups. Positive correlations were found between I-FABP and sCD14 (r = .355, p = 0.076). Frequency of T- and B-cell subsets did not differ among groups. CONCLUSIONS: Our results suggest that UC does not worsen MT, inflammation, or immune activation in HIV-infected subjects. The anti-inflammatory activity of chronic mesalazine administration on intestinal mucosa may contribute to this finding

SCL-90 empirical factors predict post-surgery weight loss in bariatric patients over longer time periods

This longitudinal study examined how pre-intervention psychological health helps predict bariatric surgery (BS) success as percentage of expected body mass index loss (ëMIL) over shorter to longer periods

Occult hepatitis B virus infection predicts non-alcoholic steatohepatitis in severely obese individuals from Italy

Obesity is associated with\ua0non-alcoholic fatty liver (NAFL), which may progress towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B virus infection (OBI) may contribute to hepatic damage in patients with\ua0chronic liver disease\ua0of different aetiologies (eg\ua0HCV, alcohol). However, information on the prevalence and clinical impact of OBI in obese individuals is lacking. The aims of this study were to investigate NASH prevalence and risk factors in obese people who underwent bariatric surgery

Significant coronary stenosis detected by coronary computed angiography in asymptomatic HIV infected subjects

Objectives: increased incidence of acute coronary events, high rate of abnormal surrogate markers of atherosclerosis and increased amount of coronary calcium have been described in HIV infected population. To expand knowledge on coronary artery disease (CAD) in HIV patients, cardiac CT scan was performed in asymptomatic subjects with low cardiovascular (CV) risk. Methods: A cross-sectional study using dual-source CT (MDCT) coronary angiography. was conducted in HIV-infected subjects with the following characteristics: Framingham Risk Score (FRS) <= 10, absence of metabolic syndrome, negative echocardiographic and ECG stress-test. A luminal narrowing exceeding 50% was defined as a clinically significant coronary stenosis. Calcium score was quantified using the Agatston Calcium Score method. Results: Fifty-five subjects were enrolled. Significant coronary stenoses, requiring coronary angiography, were found in 16/55 (29.1%). At multivariate analysis older age was the only variable independently associated with the presence of significant luminal narrowing (p = 0.011). Conclusions: MDCT showed an unexpected, age-associated high rate of significant coronary stenosis in asymptomatic HIV positive subjects with low CV risk. These findings suggest that aggressive screening programs for coronary artery disease may be appropriate in this population; further studies are recommended to assess the appropriateness of MDCT for this purpose. (C) 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved