Study of Aryl Triazoles for Absolute Configuration Determination

A variety of chiral mono- and di-1,4-disubstituted 1,2,3-triazoles were synthesized by CuAAC 'click chemistry' as model compounds and their spectroscopic properties characterized. The UV and CD study of these compounds showed that 4-substituted aryl triazoles give rise to moderate exciton CD curves, under either homo- or hetero-coupling. The direction of the electric transition moment of the non-symmetric chromophores was determined by conformational analysis and supported by NMR data. The signs of the Cotton effects of the CD spectra were in complete agreement with the determined directions of the electric transition moments of the chromophores. Therefore, 4-substituted aryl triazoles can be used for the determination of the absolute configuration of organic compounds. In addition, the 4–(4-bromo-phenyl)-1,2,3-triazole allows red-shifted chromophores to be obtained via Suzuki reactions, thus avoiding overlap with the substrate absorption

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study

COVID-19; Artritis psoriásica; VacunaciónCOVID 19; Artritis psoriàsica; VacunacióCOVID-19; Psoriatic arthritis; VaccinationObjective: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. Patients and methods: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. Results: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. Conclusion: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation

Triphenylbismuth dibromide-iodine: An efficient reagent for the dehydration of alcohols

4 pages, 1 table, 2 schemes.Tertiary and secondary alcohols react under mild conditions with triphenylbismuth dibromide and iodine under an inert atmosphere to give the corresponding most stable alkenes in good yields.This work was supported by Investigation Programme no. PB90-0083 of the Dirección General de Investigación Científica y Técnica. We thank the Dirección General de Universidades e Investigación del Gobierno de Canarias for a fellowship granted to R.L. Dorta

Organoselenium reagents in the tandem β-fragmentation-cyclization of carbohydrate anomeric alkoxy radicals

4 pages, 1 table, 1 scheme.Carbohydrates possessing a suitably positioned hydroxyl group in the presence of organoselenium reagents and iodine under an argon atmosphere undergo intramolecular β-fragmentation-cyclization reaction to give aldofuranose and aldopyranose forms of carbohydrates, specifically.This work was supported by Investigation Programme No. PB90-0083 of the Dirección General de Investigación Científica y Técnica. We thank the Dirección General de Universidades e Investigación de Canarias for a fellowship granted to R.L. Dorta

A selenurane derivative promotes β-fragmentation of carbinolamides leading to cyclic imides

4 pages, 1 table, 2 schemes.The alkoxy radical intermediates generated by reaction of carbinolamides with diphenylselenium hydroxyacetate (1) in the presence of iodine and under irradiation with visible light undergo β-fragmentation to afford 3,4-substituted cyclic imides in good yields.This work was supported by Investigation Programme No. PB90-0083 of the Dirección General de Investigación Científica y Técnica. We thank the Dirección General de Universidades e Investigación de1 Gobiemo de Canarias for a fellowship to R.L. Dorta

Hypervalent organoiodine reagents in the transannular functionalisation of medium-sized lactams: synthesis of 1-azabicyclo compounds

2 pages, 1 table, 1 scheme.The amidyl radical intermediates, produced by photolysis of medium-sized lactams 7-heptanelactam (1), 8-octanelactam (3), and 9-nonanelactam (6) in the presence of (diacetoxyiodo)benzene (DIB) and iodine, undergo transannular hydrogen abstraction to afford intermolecularly functionalised compounds such as oxoindolizidines (4) and (5) and the 1-azabicyclo[5.3.0]decan-2-one (7) that are obtained in high yield from lactams (3) and (6), respectively.This work was supported by the Investigation Programme No. PB0406 of the Dirección General de Investigación Científica y Técnica. R.L.D. thanks the Ministerio de Educación y Ciencia for a fellowship

Serendipitous acid-catalyzed rearrangement of 13-Methoxy-1,6,8-trioxidaspiro(4.1.5.3)pentadecane to 3-Choroman-5-ylpropan-1-ol

2 pages, 1 scheme, 1 chart.-- PMID: 11671542 [PubMed].The molecular arrangement of trioxadispiroacetals appears in nature in a small number of polyether ionophores. The formation of this three-ring system linked in a spiro fashion at two ketal carbons represents a synthetic challenge. Thus, only a few natural products and simpler models possessing this structure have been synthesized so far. Not surprisingly, the field of the trioxadispiroacetal reactions has not been fully explored. For the less complex dioxaspiro compounds, only a few reactions have been studied, the most noteworthy being the acid-catalyzed spiroisomerization, the opening of spiroacetals to thermodynamically less favored ketones by treatment with mineral acids, and the reductive ring opening to monocyclic compounds or to a 1,6-dioxadecalin system.We report here on the unexpected rearrangement undergone by the trioxadispiroacetals of type 1-4 in the presence of acid to produce a chroman derivative 5 (Chart 1). The removal of the methoxyl group and the aldol condensation reaction play a decisive role in the displacement of the equilibria from the tricyclic structures to the new bicyclic aromatic arrangement.This work was supported by the Investigation Programme no. PB93-0171 of the Dirección General de Investigación Científica y Técnica and Programmes nos. 93/030 and 93/014 of the Dirección General de Universidades e Investigación del Gobierno de Canarias. A.M. thanks the Ministerio de Educación y Ciencia, Spain, for a fellowship

Synthesis of (5R, 7S, 13S)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane

4 pages, 1 figure, 2 schemes.The synthesis of (5R, 7S, 13S)- and (5S, 7S, 13S)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3] pentadecane from tri-O-acetyl-d-glucal, by a convenient homologation of C-1 and C-6 atoms which led to an appropriate dihydroxyl intermediate 7, is reported. The key steps for the construction of the two spiroacetal systems involved a double, step by step, radical abstraction promoted by (diacetoxyiodo)benzene and iodine.This work was supported by the Investigation Programme no. B93-0171 of the Dirección General de Investigación Científica y Técnica and Programmes nos. 93/030 and 93/014 of the Dirección General de Universidades e Investigaci6n del Gobierno de Canarias. A. M. thanks the Ministerio de Educación y Ciencia, Spain, for a fellowship

Intramolecular hydrogen abstraction. The use of organoselenium reagents for the generation of alkoxy radicals

4 pages, 1 table, 1 scheme.The alkoxy radical intermediates, produced by photolysis of several hydroxy compounds in the presence of diphenylselenuranes (1) and iodine, undergo intramolecular hydrogen abstraction to afford cyclic ethers in good yield.This work was supported by the Investigation Programme of the Comisión Asesora de Investigación Científica y Técnica

Syntesis of Chiral Dispiroacetals from Carbohydrates

11 pages, 7 schemes.-- Printed version published Apr 3, 1998.-- Supporting information available at: http://pubs.acs.org/doi/suppl/10.1021/jo972023aThe syntheses of trioxadispiroacetals from carbohydrates are described. (5R,7S,13R)-13-Methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane (23) and (5S,7S,13R)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane (24) were prepared starting from d-galactose. The construction of the lateral tetrahydrofuran and tetrahydropyran rings was realized by homologation at C1 and C6 by appropriate tethers possessing a terminal primary alcohol. The cyclization of these alcohols at C1 and C5, respectively, was performed with (diacetoxyiodo)benzene and iodine in order to generate the alkoxy radicals which undergo an intramolecular hydrogen abstraction reaction. The diastereoisomers (5R,7S,13S)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane (37) and (5S,7S,13S)-13-methoxy-1,6,8-trioxadispiro[4.1.5.3]pentadecane (38) were prepared starting from tri-O-acetyl-d-glucal using a suitable methodology in which homologation and intramolecular hydrogen abstraction were again the key steps. We believe that this protocol could be easily extended to other tricyclic dispiroacetal ring systems.This work was supported by the Investigation Programme PB96-1461 of the Dirección General de Investigación Científica y Técnica. A.M. thanks the Ministerio de Educación y Cultura, Spain, for a fellowship