Revisiting the bromination of 3ß-hydroxycholest-5-ene with CBr4/PPh3 and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior.

Cholesterol reacts under Appel conditions (CBr4/PPh3) to give 3,5-cholestadiene (elimination) and 3ß-bromocholest-5-ene (substitution with retention of configuration). Thus, the bromination of cholesterol deviates from the stereochemistry of the standard Appel mechanism due to participation of the Δ5 π-electrons. In contrast, the subsequent azidolysis (NaN3/DMF) of 3ß-bromocholest-5-ene proceeds predominantly by Walden inversion (SN2) affording 3α-azidocholest-5-ene. The structures of all relevant products were revealed by X-ray single crystal structure analyses, and the NMR data are in agreement to the reported ones. In light of these findings, we herein correct the previous stereochemical assignments reported by one of us in the Beilstein J. Org. Chem. 2015, 11, 1922-1932 and the Monatsh. Chem. 2018, 149, 505-517.

Recent Advances Toward Robust N-Protecting Groups for Glucosamine as Required for Glycosylation Strategies.

2-Amino-2-deoxy-d-glucose (d-glucosamine) is among the most abundant monosaccharides found in natural products. This constituent, recognized for its ubiquity, is presented in most instances as its N-acetyl derivative 2-acetamido-2-deoxy-d-glucopyranose (N-acetylglucosamine, GlcNAc, NAG). It occurs as the ß-linked pyranosyl group in polysaccharides and oligosaccharides, and sometimes as the monosaccharide itself, either in its native state or as a glycoconjugate. The compound's acylation profile and other aspects of its structure are important elements in determining the variety of reactivities and functions of the molecule as a whole. Methods elaborated to investigate these challenges have been intensively reviewed; however, a relatively more comprehensive reviewing of this subject is introduced here to cover some aspects that have not been sufficiently covered. This might enable those who are beginners in this field to be aware of the subject in a more comprehensive context. 2-Amino-2-deoxy-d-glucosylation strategies demand robust amino-protecting groups that survive under a variety of chemical conditions, yet provide groups that can be deprotected under relatively mild conditions. At the end of this review, a table that includes all the N-protecting groups that have been used for glucosamine is provided to introduce them at a glance to aid in constructing building blocks that will act as useful 2-amino-2-deoxy-d-glucosyl donors.

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners.

3ß-Azidocholest-5-ene (3) and (3ß)-3-(prop-2-yn-1-yloxy)cholest-5-ene (10) were prepared as substrates to synthesize a variety of three-motif pharmacophoric conjugates through CuAAC. Basically, these conjugates included cholesterol and 1,2,3-triazole moieties, while the third, the pharmacophore, was either a chalcone, a lipophilic residue or a carbohydrate tag. These compounds were successfully prepared in good yields and characterized by NMR, MS and IR spectroscopic techniques. Chalcone conjugate 6c showed the best antimicrobial activity, while the lactoside conjugate 27 showed the best cytotoxic effect in vitro.