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Gold-catalyzed 5- exo-dig hydroamination on O -homopropargylic hydroxylamine gave expeditious access to methylene isoxazolidine. Excess catalyst loading led to facile 1,3-sulfonyl migration in a cascade fashion to furnish the isoxazoline. Mechanistic studies using react-IR and NMR as well as crossover experiments indicated that 1,3-sulfonyl group migration is an intramolecular concerted process. The ene-hydroxylamine moiety also underwent dipolar cycloaddition reactions with nitrile oxide and nitrones leading to the first examples of spirocyclic bis -isoxazolidine derivatives.

Acid catalysed reductive etherification of N -propargyl amino alcohols for the stereoselective synthesis of cis -2,5/2,6-disubstituted morpholines and cis -2,6/2,7-disubstituted oxazepanes has been developed. Mechanistic studies revealed that terminal alkynols gave morpholines via a 6- exo-dig hydroalkoxylation-isomerization-reduction cascade. Interestingly, an alkyne hydration-cyclization-reduction sequence is found to be involved in the formation of oxazepanes from alkyl substituted internal alkynols. The strategy was used as a key step in the total synthesis of fungicides tridemorph and fenpropimorph.

A TMSOTf-mediated highly diastereoselective synthesis of isoxazolidine bearing three contiguous stereocenters is described. This method utilizes O -propargyl hydroxylamines as a novel building block for the rapid assembly of the isoxazolidines via alkyne-oximium cyclization. The strategy could be used in the synthesis of enantiomerically enriched isoxazolidines. Reductive cleavage of the N-O bond efficiently gives the corresponding 1,3-aminodiols with precise control over all stereocenters formed.

Aim: To develop an accurate lab score based on in-hospital patients' potent clinical and biological parameters for predicting COVID-19 patient severity during hospital admission., Methods: To conduct this retrospective analysis, a derivation cohort was constructed by including all the available biological and clinical parameters of 355 COVID positive patients (recovered = 285, deceased = 70), collected in November 2020-September 2021. For identifying potent biomarkers and clinical parameters to determine hospital admitted patient severity or mortality, the receiver operating characteristics (ROC) curve and Fischer's test analysis was performed. Relative risk regression was estimated to develop laboratory scores for each clinical and routine biological parameter. Lab score was further validated by ROC curve analysis of the validation cohort which was built with 50 COVID positive hospital patients, admitted during October 2021-January 2022., Results: Sensitivity vs. 1-specificity ROC curve (>0.7 Area Under the Curve, 95% CI) and univariate analysis (p<0.0001) of the derivation cohort identified five routine biomarkers (neutrophil, lymphocytes, neutrophil: lymphocytes, WBC count, ferritin) and three clinical parameters (patient age, pre-existing comorbidities, admitted with pneumonia) for the novel lab score development. Depending on the relative risk (p values and 95% CI) these clinical parameters were scored and attributed to both the derivation cohort (n = 355) and the validation cohort (n = 50). ROC curve analysis estimated the Area Under the Curve (AUC) of the derivation and validation cohort which was 0.914 (0.883-0.945, 95% CI) and 0.873 (0.778-0.969, 95% CI) respectively., Conclusion: The development of proper lab scores, based on patients' clinical parameters and routine biomarkers, would help physicians to predict patient risk at the time of their hospital admission and may improve hospital-admitted COVID-19 patients' survivability., Competing Interests: No. The authors have declared that no competing interests exist.