Unexpected Racemization in the Course of the Acetalization of (+)-(S)-5-Methyl-Wieland-Miescher Ketone with 1,2-Ethanediol and TsOH under Classical Experimental Conditions.

(+)-(S) and (-)-(R)-5-methyl-Wieland-Miescher ketone (+)-1 and (-)-1, are important synthons in the diastereo and enantioselective syntheses of biological and/or pharmacological interesting compounds. A key step in these syntheses is the chemoselective C(1)O acetalization to (+)-5 and (-)-5, respectively. Various procedures for this transformation have been described in the literature. Among them, the classical procedure based on the use of 1,2-ethanediol and TsOH in refluxing benzene in the presence of a Dean-Stark apparatus. Within our work on bioactive natural products, it occurred to us to observe the partial racemization of (+)-5 in the course of the acetalization of (+)-1 by means of the latter methodology. Aiming to investigate this drawback, which, to our best knowledge, has no precedents in the literature, we acetalized with 1,2-ethanediol and TsOH in refluxing benzene and in the presence of a Dean-Stark apparatus under various experimental conditions, enantiomerically pure (+)-1. It was found that the extent of racemization depends on the TsOH/(+)-1 and 1,2-ethanediol/(+)-1 ratios. Mechanism hypotheses for this partial and unexpected racemization are provided.

Analysis of screening and confirmatory tests in the diagnosis of primary aldosteronism: need for a standardized protocol.

BACKGROUND: The upright serum aldosterone/upright plasma renin activity ratio (ARR) has been recommended as a screening tool for the diagnosis of primary aldosteronism. OBJECTIVE: We reviewed the data collected from hypertensive patients in order to define retrospectively the cut-off values and evaluate the reliability of the ARR and of the saline infusion test in the diagnosis of primary aldosteronism. PATIENTS: In 157 patients referred to our unit with a suspicion of primary aldosteronism, 61 of whom had confirmed primary aldosteronism [26 aldosterone-producing adenoma (APA); 35 idiopathic hyperaldosteronism], the supine and upright ARR, and the ARR after the administration of captopril and losartan were calculated, and the results of the saline infusion test were analysed. RESULTS: Choosing 40 as the cut-off value, the upright ARR had 100% sensitivity and 84.4% specificity. The post-captopril and post-losartan ARR were slightly more specific, but at the cost of a lower sensitivity. A cut-off value of 7 ng/dl for serum aldosterone at the end of the saline infusion in patients with an upright ARR of 40, gave 100% specificity and a positive predictive value. Furthermore, APA patients showed increased mean levels of aldosterone/cortisol ratio after the saline infusion test. CONCLUSION: Our data reinforce the superiority of a standardized upright ARR as a screening test in the diagnosis of primary aldosteronism, identifying 40 as an ideal cut-off value. Saline infusion represents a useful test to confirm such a diagnosis, with a serum aldosterone level of 7 ng/dl as a satisfactory cut-off value. Some more information is obtained when the aldosterone/cortisol ratio is considered.