Stereoselective Chemoenzymatic Synthesis of Optically Active Aryl-Substituted Oxygen-Containing Heterocycles

A two-step stereoselective chemoenzymatic synthesis of optically active α-aryl-substituted oxygen heterocycles was developed, exploiting a whole-cell mediated asymmetric reduction of α-, β-, and γ-chloroalkyl arylketones followed by a stereospecific cyclization of the corresponding chlorohydrins into the target heterocycles. Among the various whole cells screened (baker’s yeast, Kluyveromyces marxianus CBS 6556, Saccharomyces cerevisiae CBS 7336, Lactobacillus reuteri DSM 20016), baker’s yeast was the one providing the best yields and the highest enantiomeric ratios (up to 95:5 er) in the bioreduction of the above ketones. The obtained optically active chlorohydrins could be almost quantitatively cyclized in a basic medium into the corresponding α-aryl-substituted cyclic ethers without any erosion of their enantiomeric integrity. In this respect, valuable, chiral non-racemic functionalized oxygen containing heterocycles (e.g., (S)-styrene oxide, (S)-2-phenyloxetane, (S)-2-phenyltetrahydrofuran), amenable to be further elaborated on, can be smoothly and successfully generated from their prochiral precursors

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality

Correction: Capozzi, M.A.M.; Cardellicchio, C. (<i>S</i>,<i>S</i>)-2-(((Hydroxynaphth-1-yl)(4′-nitrophenyl)methyl)amino)-3-methylbutanoic Acid Methyl Ester. <i>Molbank</i> 2022, <i>2022</i>, M1528

In the original publication [...

(<i>S</i>,<i>S</i>)-1-(Phenyl((1′-4-nitrophenyl-ethyl)amino)methyl)-2-naphthol

The Betti reaction of 2-naphthol, benzaldehyde and (S)-1-(4-nitrophenyl)ethylamine without any solvent gave the corresponding aminobenzylnaphthol, that is the (S,S)-1-(phenyl((1′-4-nitrophenyl-ethyl)amino)methyl)-2-naphthol, in good yield (56%). The absolute configuration of the title compound was attributed by NMR analysis, a procedure that is reliable if compared with the data obtained by X-ray diffraction experiments

(<i>S</i>,<i>S</i>)-2-(((Hydroxynaphth-1-yl)(4′-nitrophenyl)methyl)amino)-3-methylbutanoic Acid Methyl Ester

The solvent-free Betti reaction of 2-naphthol, 4-nitrobenzaldehyde and (S)-valine methyl ester gave the corresponding aminobenzylnaphthol of the (S,S)-2-(((hydroxynaphth-1-yl)(4′-nitrophenyl)methyl)amino)-3-methylbutanoic acid methyl ester in good yield (59%). This product was fully characterized. We observed that the racemization that occurs in some Betti reactions with (S)-valine methyl ester was absent in this reaction, and thus the predominant (S,S)-product was obtained

Organosulfur Compounds as Chiral Building Blocks

“Organosulfur compounds in asymmetric synthesis” is an excellent 2008 Wiley book [1] that covers the main results within this chemistry. Two chapters of this book are relevant for the reader of the present work [2, 3]. This book has been accompanied by highly reputed recent review articles published in journals, among which three are mentioned [4–6]. The present work aims to update the Wiley book with the most recent results. However, the present work is not exhaustive but selective due to the editorial limitations. In this selection, meaningful reviews were preferred to many original papers. Within these constraints, it was decided to write a guide to extri- cate the vast literature on this topic by focusing on the most successful sulfur chiral building blocks and briefly analyzing their merits. To this end, a short introduction to past work is needed to understand the recent progress fully

1-[(1<i>S</i>)-(4-Fluorophenyl)-((1′<i>S</i>)-1′-naphthalen-1-yl-ethylamino)-methyl]-naphthalen-2-trifluoromethanesulfonate

The complex structure of aminobenzylnaphthols can be easily obtained with the useful Betti reaction. These valuable compounds can give rise to chiral intermediates, that found wide application in asymmetric synthesis. 1-[(1S)-(4-Fluorophenyl)-((1′S)-1′-naphthalen-1-yl-ethylamino)-methyl]-naphthalen-2-ol 1 was treated with triflic anhydride to yield the corresponding (S,S)-triflate 2, which is a valuable intermediate in the future synthesis of aminophosphine, to be used in asymmetric catalysis. Preliminarily structural considerations based upon H(1)-NMR spectroscopy are also reported

Stereoselection in the Betti reaction of valine methyl esters

The multi-component Betti reaction of 2-naphthol, benzaldehyde and (S)-amines, that usually provides highly valuable aminobenzylnaphthol bearing two stereogenic centers, yielded a completely racemic product, when (S)-valine methyl ester was employed as the amine in the usual reaction protocol. The cause of this drawback, that appears to be overlooked in the literature, was investigated. As a result, new reaction conditions were set up, that were able to yield the expected useful product, having two fully resolved stereogenic centers. Furthermore, when the effect of substituents on the phenyl ring was preliminarily studied, we found that 4-fluoro- and 4-chlorobenzaldeyde gave stereoisomerically pure compounds also in the original reaction protocol