Dihydronaphthofurans: synthetic strategies and applications

Dihydronaphthofurans (DHNs) are an important class of arene ring-fused furans which are widely found in many natural and non-natural products and drug candidates with relevant biological and pharmacological activities. Furthermore, vinylidene-naphthofurans exhibit photochromic properties when exposed to UV or sun light at room temperature. For these reasons, a vast array of synthetic procedures for the preparation of dihydronaphthofurans including annulation of naphthols with various reagents, cycloaddition reactions ([3 + 2], [4 + 1] and Diels–Alder), intramolecular transannulation, Friedel–Crafts, Wittig, Claisen rearrangement, neophyl rearrangement and other reactions under various conditions have been developed over the past decades. This review aims to describe the different strategies developed so far for the synthesis of dihydronaphthofurans and their applications. After a brief introduction to the types of dihydronaphthofurans and their biological activities, the different synthetic approaches such as chemical, photochemical, and electrochemical, methods are described and organized on the basis of the catalysts and the other reagents employed in the syntheses. The subsequent section focuses on biological and pharmacological applications and photochromic properties of the target compounds.

Dihydronaphthofurans (DHNs) are an important class of arene ring-fused furans which are widely found in many natural and non-natural products and drug candidates with relevant biological and pharmacological activities.     

Echocardiographic characteristics including tissue Doppler imaging after enhanced external counterpulsation therapy

This study assessed the effects of a course of enhanced external counterpulsation (EECP) therapy on systolic and diastolic cardiac function using echocardiography to measure left ventricular ejection fraction (LVEF), end-systolic volume (ESV), end-diastolic volume (EDV), systolic wave (Sm), early diastolic wave (Ea), Vp, E/Ea, E/Vp, and diastolic function grade in 25 patients before and after 35 hours of EECP. EECP reduced ESV and EDV and increased ejection fraction significantly in patients with baseline LVEF < or = 50% (P=.018, .013, .002), baseline E/Ea > or = 14 (P=.032, .038, .007), baseline grade II or III diastolic dysfunction (decreased compliance) (P=.014, .032, .027), baseline Ea <7 cm/s (P=.015, .024, .001), and baseline Sm <7 cm/s (P=.017, .016, .006), but not in patients with baseline LVEF >50%, baseline E/Ea <14, baseline normal diastolic function or grade I diastolic dysfunction (impaired relaxation), baseline Ea > or = 7 cm/s, and Sm > or = 7 cm/s. These results demonstrate improved systolic and diastolic function in selected patients and provide new insight into potential clinical applications of EECP.     

COVID‐19 reinfection or reactivation in a renal transplant patient

Recurrences of COVID‐19 infection may occur in immunocompromised patients. Reinfection or reactivation of COVID‐19 virus is a challenging issue in these patients.     

CSGALNACT1‐congenital disorder of glycosylation: A mild skeletal dysplasia with advanced bone age

Congenital disorders of glycosylation (CDGs) comprise a large number of inherited metabolic defects that affect the biosynthesis and attachment of glycans. CDGs manifest as a broad spectrum of disease, most often including neurodevelopmental and skeletal abnormalities and skin laxity. Two patients with biallelic CSGALNACT1 variants and a mild skeletal dysplasia have been described previously. We investigated two unrelated patients presenting with short stature with advanced bone age, facial dysmorphism, and mild language delay, in whom trio‐exome sequencing identified novel biallelic CSGALNACT1 variants: compound heterozygosity for c.1294G>T (p.Asp432Tyr) and the deletion of exon 4 that includes the start codon in one patient, and homozygosity for c.791A>G (p.Asn264Ser) in the other patient. CSGALNACT1 encodes CSGalNAcT‐1, a key enzyme in the biosynthesis of sulfated glycosaminoglycans chondroitin and dermatan sulfate. Biochemical studies demonstrated significantly reduced CSGalNAcT‐1 activity of the novel missense variants, as reported previously for the p.Pro384Arg variant. Altered levels of chondroitin, dermatan, and heparan sulfate moieties were observed in patients’ fibroblasts compared to controls. Our data indicate that biallelic loss‐of‐function mutations in CSGALNACT1 disturb glycosaminoglycan synthesis and cause a mild skeletal dysplasia with advanced bone age, CSGALNACT1‐CDG.     

Recent advances in the synthesis and synthetic applications of Betti base (aminoalkylnaphthol) and bis-Betti base derivatives

The multicomponent reaction between 2-naphthol, arylaldehydes and ammonia yields aminobenzylnaphthols in a process known as the Betti reaction, which was first uncovered at the beginning of the 20th century. Various methods have been reported for the synthesis of aminobenzylnaphthol (Betti base) and bis-Betti base derivatives using various types of naphthols, aromatic amines, heteroaromatic amines, and aliphatic and cyclic amines instead of ammonia or diamines and aliphatic and aromatic aldehydes or dialdehyde compounds under various conditions in recent years. The Betti reaction produces racemic and non-racemic aminobenzylnaphthol ligands. It is also clear that the most important area of application of the non-racemic aminonaphthols prepared in this manner is their use in asymmetric synthesis, either as chiral ligands or as chiral auxiliaries. The functional groups in these Mannich products offer many ring closure possibilities. Some of these products or the starting bifunctional compounds possess biological activity. Herein, we present a selection of the relevant studies on this topic.

The multicomponent reaction between 2-naphthol, arylaldehydes and ammonia yields aminobenzylnaphthols in a process known as the Betti reaction, which was first uncovered at the beginning of the 20th century.     

Doppler Echocardiographic Assessment of Pulmonary Prostheses: A Comprehensive Assessment Including Velocity Time Integral Ratio and Prosthesis Effective Orifice Area

Objective. Few reports have been published on the Doppler‐derived echocardiographic data for pulmonary valve prostheses (PVPs). The aim of this study was to provide a comprehensive Doppler echocardiographic assessment of PVPs. Methods. We studied 40 patients (mean age 24.2) with PVPs: 13 (32.5%) mechanical and 27 (67.5%) bioprosthetic valves. After clinical evaluation, all patients underwent complete, two‐dimensional and Doppler studies. Results. In 30 patients with normally functioning PVPs, the mean (SD) peak velocity was 2.33 (0.36) m/s with an average peak pressure gradient of 22.69 (6.7) mm Hg and an average mean pressure gradient of 12.5 (4.1) mm Hg. The mean PVPs velocity time integral (VTI) was 47.49 (12.78) cm with mean right ventricle outflow tract/peak velocity (PV) VTI ratio 0.43 (0.14), mean PVPs effective orifice area was 1.63 (0.36) cm². Metallic PVPs had significantly better hemodynamic Doppler study compared with biologic PVPs. In 9 patients with PVP malfunction, average peak PVPs velocity, average peak pressure gradient, mean pressure gradient, PV VTI, PV/left ventricle outflow tract VTI ratio was significantly increased (P < 0.05). Conclusion. This study contributes to establishing the normal range for Doppler hemodynamics in various PVPs.     

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), physicochemical and physiological properties of a new fluorinated bile acid that prevents 17alpha-ethynyl-estradiol-induced cholestasis in rats

3alpha-6alpha-Dihydroxy-7alpha-fluoro-5beta-cholanoate (UPF-680), the 7alpha-fluorine analog of hyodeoxycholic acid (HDCA), was synthesized to improve bioavailability and stability of ursodeoxycholic acid (UDCA). Acute rat biliary fistula and chronic cholestasis induced by 17alpha-ethynyl-estradiol (17EE) models were used to study and compare the effects of UPF-680 (dose range 0.6-6.0 micromol/kg min) with UDCA on bile flow, biliary bicarbonate (HCO(3)(-)), lipid output, biliary bile acid composition, hepatic enzymes and organic anion pumps. In acute infusion, UPF-680 increased bile flow in a dose-related manner, by up to 40.9%. Biliary HCO(3)(-) output was similarly increased. Changes were observed in phospholipid secretion only at the highest doses. Treatment with UDCA and UPF-680 reversed chronic cholestasis induced by 17EE; in this model, UDCA had no effect on bile flow in contrast to UPF-680, which significantly increased bile flow. With acute administration of UPF-680, the biliary bile acid pool became enriched with unconjugated and conjugated UPF-680 (71.7%) at the expense of endogenous cholic acid and muricholic isomers. With chronic administration of UPF-680 or UDCA, the main biliary bile acids were tauro conjugates, but modification of biliary bile acid pool was greater with UPF-680. UPF-680 increased the mRNA for cytochrome P450 7A1 (CYP7A1) and cytochrome P450 8B (CYP8B). Both UDCA and UPF-680 increased the mRNA for Na(+) taurocholate co-transporting polypeptide (NCTP). In conclusion, UPF-680 prevented 17EE-induced cholestasis and enriched the biliary bile acid pool with less detergent and cytotoxic bile acids. This novel fluorinated bile acid may have potential in the treatment of cholestatic liver disease.     

Late occurrence of fatal aortitis: a complication of Aspergillus endocarditis following coronary artery bypass graft surgery

The most common fungal organism to cause endocarditis is Candidawhich is followed by Aspergillus. Aspergillus endocarditis canoccur in either the native or prosthetic heart valves, usuallyoccurs post-operative after cardiac valve surgery. This caseis illustrative of a 49-year-old man with previous history ofcoronary artery bypass grafting presenting with aortic valveendocarditis which was diagnosed as Aspergillus endocarditis.Unfortunately, despite medical and surgical therapy, progressivefatal aortic invasion occurred.