Gliflozins are an important class of prescription drugs used to treat type II diabetes. They reduce blood sugar levels by targeting the sodium-glucose transport protein 2 (SGLT2) and consequently inhibit glucose reabsorption in the kidney. There are currently several FDA-approved gliflozins as well as others in the pipeline to be launched in the next few years. This review describes the synthetic strategies used for manufacturing SGLT2 inhibitors on both bench and industrial scales. Moreover, the drawbacks to the strategies and the improvements made to obtain selected gliflozins and their glucose derivatives over the years are highlighted.

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We have investigated the synthesis of p-mentha-2,8-dien-1-ol (1) as a cannabidiol precursor by photochemical oxidation of (R)-limonene (2) with singlet oxygen (1O2) using meso-tetraphenyl­porphyrin (TPP) as a photosensitizer. Different home-made engineered set-ups were used for reaction intensification. Under optimized conditions, the target compound was obtained at up to 580.8 μmol·min–1 (66.7 g·day–1) using a low concentration of TPP (0.1 mM) and requiring 20 min for total conversion. Low-temperature photoreactor approaches made it possible to raise the level of selectivity of the desired limonene derivative up to 66%, with 55% conversion.

Figure 3. Chemical structure of (À)-2. Scheme3.Natural intermediates in the biosynthesiso f(À)-4. Scheme1.The CBD ((À)-2)i solation protocolestablished by Adams and co-workers.

The discovery and development of approaches toward the synthesis of cannabidiol (CBD), which has an increasing meaning as a medicine, have arisen from the successful extraction of Cannabis plants for cannabinoid fermentation in brewer's yeast. To understand different contributions to the design and enhancement of the synthesis of CBD and its key intermediates, a detailed analysis of the history behind cannabinoid compounds and their optimization is given in the Review by R.O.M.A. de Souza et al. on page 5577.

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Orally available antivirals against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary because of the continuous circulation of new variants that challenge immunized individuals. Because severe COVID-19 is a virus-triggered immune and inflammatory dysfunction, molecules endowed with both antiviral and anti-inflammatory activity are highly desirable. We identified here that kinetin (MB-905) inhibits the in vitro replication of SARS-CoV-2 in human hepatic and pulmonary cell lines. On infected monocytes, MB-905 reduced virus replication, IL-6 and TNFα levels. MB-905 is converted into its triphosphate nucleotide to inhibit viral RNA synthesis and induce error-prone virus replication. Coinhibition of SARS-CoV-2 exonuclease, a proofreading enzyme that corrects erroneously incorporated nucleotides during viral RNA replication, potentiated the inhibitory effect of MB-905. MB-905 shows good oral absorption, its metabolites are stable, achieving long-lasting plasma and lung concentrations, and this drug is not mutagenic nor cardiotoxic in acute and chronic treatments. SARS-CoV-2-infected hACE-mice and hamsters treated with MB-905 show decreased viral replication, lung necrosis, hemorrhage and inflammation. Because kinetin is clinically investigated for a rare genetic disease at regimens beyond the predicted concentrations of antiviral/anti-inflammatory inhibition, our investigation suggests the opportunity for the rapid clinical development of a new antiviral substance for the treatment of COVID-19.

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