Abdul Rouf

Synthesis of Single‐enantiomer Bioactive Molecules: A Brief Overview

Chiral-center enantiomers have been shown to differ significantly in biological activity, pharmacodynamics, pharmacokinetics and toxicity. New developments in the stereoselective organic synthesis have enriched the vast literature of synthetic methodologies applicable to access natural products as well as bioactive molecules. These compounds also include new drugs, drug candidates and reagents used to explore biological processes. The article reviews the synthesis of optically pure drugs, biologically active intermediates and amino alcohols by using different methods.

2,3-Unsaturated Allyl Glycosides as Glycosyl Donors for Selective α-Glycosylation

In the presence of NBS and a catalytic amount of a Lewis acid, 2,3-unsaturated allyl glycosides [6-(allyloxy)-3,6-dihydro-2-(hydroxymethyl)-2H-pyran-3-ol] have been successfully used as versatile glycosyl donors for the stereoselective α-glycosylation of a variety of alcohols comprising sensitive functions such as acetonide, keto, nitro, and ester in 50-90% yields. The methodology offers an equally facile alternative to 4-pentenyl replacement in unsaturated sugars.

Tetrahydropyranyl ether (THPE) formation in hydroxyl group protection and conversion to other useful functionalities

This short review highlights the various methods of formation of tetrahydropyranyl ethers (THPEs) as a method for the protection of simple alcohols as well as a diverse range of complex molecules using a variety of reagents and reaction conditions, i.e., acid catalyst, heterogeneous catalyst and neutral reagent mediated reactions. We also discuss their direct conversion to other useful functionalities.

Efficient Preparation of Biologically Important 1,2-Amino Alcohols

Abstract An efficient three-step methodology developed for the preparation of 1,2-amino alcohols. In the first step a rapid coupling between bromoketones and potassium phthalimide in ionic liquid produced α-phthalimido ketones in quantitative yields, which is followed by a facile reduction using NaCNBH3 in acetic acid to give corresponding phthalimido alcohols and finally effecting hydrazinolysis in water at 60 °C to yield biologically important 1,2-amino alcohols. GRAPHICAL ABSTRACT

Common precursor strategy for the synthesis of bestatin, amprenavir intermediate and syn-4-hydroxy-5-phenyl-γ-lactam

A common precursor strategy for the synthesis of bestatin hydrochloride, an anticancer agent, 1,3-diaminoalcohol, an amprenavir intermediate, and a syn-4-hydroxy-5-phenyl-γ-lactam intermediate of various bioactive molecules using an α,β-unsaturated ester as a common precursor is described. The protocol offers mild reaction conditions, good yields and excellent stereoselectivity.

Exploring Derivatives of Quinazoline Alkaloid l-Vasicine as Cap Groups in the Design and Biological Mechanistic Evaluation of Novel Antitumor Histone Deacetylase Inhibitors

l-Vasicine is a quinazoline alkaloid with an electron dense ring and additional functionalities in its structure. Employing target oriented synthesis (TOS) based on in silico studies, molecules with significant docking scores containing different derivatives of l-vasicine as caps were synthesized. Interestingly, one molecule, i.e., 4a, which contained 3-hyroxypyrrolidine as a cap group and a six carbon long aliphatic chain as a linker was found to inhibit HDACs. 4a showed more specificity toward class I HDAC isoforms. Also 4a was found to be less cytotoxic toward normal cell lines as compared to cancer cell lines. 4a inhibited cancer cell growth and induced cell death by various mechanisms. However, 4a was found to induce cell death independent of ROS generation, and unlike many natural product based HDAC inhibitors, 4a was found to be nontoxic under in vivo conditions. Importantly, we for the first time report the possibility of using a 3-hydroxypyrrolidine cap for the synthesis of HDAC inhibitors with good potency.