Santosh Rudrawar

“On water” organic synthesis: a highly efficient and clean synthesis of 2-aryl/heteroaryl/styryl benzothiazoles and 2-alkyl/aryl alkyl benzothiazolines

A convenient and clean “on water”-mediated synthesis of benzothiazoles/benzothiazolines is reported. Aromatic, heteroaromatic, and styryl aldehydes are converted to 2-substituted benzothiazoles in high yields in a one-pot reaction with 2-aminothiophenol in water at 110 °C (oil-bath). Alkyl and aryl alkyl aldehydes afforded the benzothiazolines. The reaction is highly chemoselective with no competitive thia-Michael addition, O-dealkylation/debenzoylation, reduction of the nitro or the α,β-unsaturated carbonyl groups, and substitution of the halogen atom or the nitro group. The reaction is found to be general with respect to the 2-aminothiophenol substrate through the reaction of a few substituted 2-aminothiophenols with a few representative aromatic and aliphatic aldehydes. The procedure does not involve the use of any additional reagent/catalyst, produces no waste, and represents a green synthetic protocol.

An efficient synthesis of 2-amino alcohols by silica gel catalysed opening of epoxide rings by amines

Silica gel (60-120 mesh) efficiently catalyses the opening of epoxide rings by amines at rt under solvent-free conditions providing an easy method for the synthesis of 2-amino alcohols. Aromatic and aliphatic amines react with cyclohexene oxide with exclusive formation of the trans-2-aryl/alkylaminocyclohexanols in high yields. A complementary regioselectivity is exhibited by aromatic and aliphatic amines during the reaction with styrene oxide. The epoxide ring of non-styrenoidal unsymmetrical alkene oxide undergoes selective nucleophilic attack at the sterically less hindered carbon by aniline.

One-Pot Synthesis of 2-Substituted Benzoxazoles Directly from Carboxylic Acids

Methanesulfonic acid has been found to be a highly effective catalyst for a convenient and one-pot synthesis of 2-substituted benzoxazoles by the reaction of 2-aminophenol with acid chlorides, generated in situ from carboxylic acids. Aryl, heteroaryl, and arylalkyl carboxylic acids provided excellent yields of the corresponding benzoxazoles. The reaction conditions were compatible with various substituents such as chloro, bromo, nitro, methoxy, cyclopentyloxy, phenoxy, thiophenoxy, and conjugated double bonds. Benzoxazole formation was found to be general with respect to substituted 2-aminophenols.

Protection against radiotherapy-induced toxicity

Radiation therapy is a highly utilized therapy in the treatment of malignancies with up to 60% of cancer patients receiving radiation therapy as a part of their treatment regimen. Radiation therapy does, however, cause a wide range of adverse effects that can be severe and cause permanent damage to the patient. In an attempt to minimize these effects, a small number of compounds have been identified and are in use clinically for the prevention and treatment of radiation associated toxicities. Furthermore, there are a number of emerging therapies being developed for use as agents that protect against radiation-induced toxicities. The aim of this review was to evaluate and summarise the evidence that exists for both the known radioprotectant agents and the agents that show promise as future radioprotectant agents.

Novel 3,4-disubstituted-Neu5Ac2en derivatives as probes to investigate flexibility of the influenza virus sialidase 150-loop

Novel 3,4-disubstituted-Neu5Ac2en derivatives have been synthesised to probe the open 150-loop conformation of influenza virus sialidases. Both equatorially and axially (epi) substituted C4 amino and guanidino 3-(p-tolyl)allyl-Neu5Ac2en derivatives were prepared, via the 4-epi-hydroxy derivative. The equatorially-substituted 4-amino derivative showed low micromolar inhibition of both group-1 (pdm09 H1N1) and group-2 (pdm57 H2N2) sialidases, and provides the first in vitro evidence that a group-2 sialidase may exhibit 150-loop flexibility.

Solid-Phase O-Glycosylation with a Glucosamine Derivative for the Synthesis of a Glycopeptide

An efficient synthesis of the O-linked glycosylamino acid Fmoc–l-Ser((Ac)3–β-d-GlcNAc)-OH building block is described. The utility of the method was demonstrated with direct solid-phase O-glycosylation of the hydroxyl group on the amino acid (Ser) side chain of a human α-A crystallin-derived peptide (AIPVSREEK) in nearly quantitative glycosylation yield.

Correction: Menaquinone biosynthesis inhibition: a review of advancements toward a new antibiotic mechanism

Correction for ‘Menaquinone biosynthesis inhibition: a review of advancements toward a new antibiotic mechanism’ by M. Boersch et al., RSC Adv., 2018, 8, 5099–5105.

Mechanisms underlying select chemotherapeutic-agent-induced neuroinflammation and subsequent neurodegeneration

Abstract This review demonstrates the importance of uncovering the mechanisms that underlie chemotherapy‐induced neuroinflammation. It builds upon the well‐established connection between chemotherapeutic‐agents and neurotoxicity along with widespread peripheral toxicities. This article summarises the major studies which have linked chemotherapy‐induced neurodegeneration with direct evidence of neuroinflammation. Cancer and chemotherapy‐related adverse effects impact a large proportion of the population. A better understanding of the link between chemotherapy, neurotoxicity and specifically the mechanisms of neuroinflammation, will allow the development of strategies to improve the management of side effects, and overall to reduce the burden on cancer patients receiving chemotherapy. This review has developed a summary schematic of the relationship between different chemotherapeutic agents and inflammatory markers within the central nervous system and links this correlation with some major ailments associated with chemotherapy use.

Peptides, Peptidomimetics, and Carbohydrate–Peptide Conjugates as Amyloidogenic Aggregation Inhibitors for Alzheimer’s Disease

Alzheimers disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted toward the aggregation of the tau protein as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed. Diagnosis of AD has shifted from measuring late stage senile plaques to early stage biomarkers, amyloid-β and tau monomers and oligomeric assemblies. Synthetic peptides and some derivative structures are being explored for use as theranostic tools as they possess the capacity both to bind the biomarkers and to inhibit their pathological self-assembly. Several studies have demonstrated that O-linked glycoside addition can significantly alter amyloid aggregation kinetics. Furthermore, natural O-glycosylation of amyloid-forming proteins, including amyloid precursor protein (APP), tau, and α-synuclein, promotes alternative nonamyloidogenic processing pathways. As such, glycopeptides and related peptidomimetics are being investigated within the AD field. Here we review advancements made in the last 5 years, as well as the arrival of sugar-based derivatives.

Quinoline, Coumarin and Other Heterocyclic analogues Based HIV-1 Integrase Inhibitors

Human Immunodeficiency Virus Type 1 Integrase or HIV-1 integrase (IN) is a 288 amino acid protein that incorporates the retrotranscribed viral DNA into the host chromosomal DNA. Over the past 30 years, large number of derivatives have been evaluated for their inhibitory potential against IN. There is vast literature available which need to be collated to help scientists plan the future drug design. This review discusses the reports of past 25 years on analogs of quinoline, coumarin and other related heterocycles, which exhibit low micromolar inhibitory potency against IN.