DMSO-KSO mediated iodine-free conversion of glycal C-3 ether to 3-enopyranones: synthesis of furo[3,2-] pyrans.

A straightforward, highly efficient, and regioselective method for directly converting 3--benzylated and silylated glycals into their corresponding enones has been developed using a DMSO-KSO reagent system. This reaction is scalable to gram quantities under mild conditions, achieving up to 80% yields. The resulting enones are valuable intermediates for the synthesis of furo[3,2-] pyrans, which are integral components of various biologically significant scaffolds.

Anomeric oxyacetamide assisted site-selective C-2 arylation and its application in / glycosylation of 2,3 eno-pyranoside.

Herein we developed a palladium-catalyzed coupling of 2,3-enopyranose with arylboronic acid using a removable oxyacetamide directing group, which provides an efficient method for the synthesis of C-2 aryl sugars. The synthesized products were subsequently utilized as glycosyl donors in / glycosylation, enabling regio- and stereoselective production of 1,2-disubstituted branched sugars.

Synthesis of aryl enopyranones directly from glycals and aromatic halides to access 2-deoxy-β-C-aryl glycosides.

An efficient synthesis of aryl enopyranones an oxidative Heck-type coupling reaction between ether protected D/L-glycals and different aryl halides is developed. This one-step method attaches an aryl group at the C-1 position keeping the C-1/C-2 double bond intact the Saegusa-Ito type oxidation, thus facilitating the synthesis of medicinally important 2-deoxy-β-aryl-C-glycosides after Pd/C reduction.

Peroxodisulfate-assisted synthesis of 2-thiocyanato glycals and their transformation to C-2-thio acrylo/aryl nitrile-substituted glycals.

An efficient regioselective method to attach thiocyanato groups at the β-position of enol double bonds in sugar enol ethers using KSCN and potassium persulfate has been developed. The highly regioselective addition of the resulting sugar thiocyanate to electron rich species like terminal alkynes and benzynes under Pd catalysis generated C-2-thio acrylo/aryl nitrile glycals simultaneous introduction of thio and cyano groups into carbon-carbon triple bonds.

Discovery of colchicine aryne cycloadduct as a potent molecule for the abrogation of epithelial to mesenchymal transition via modulating cell cycle regulatory CDK-2 and CDK-4 kinases in breast cancer cells.

In this study, we synthesized a new-generation library of colchicine derivatives via cycloaddition of colchicine utilizing position C-8 and C-12 diene system regioselectivity with aryne precursor to generate a small, focused library of derivatives. We assessed their anticancer activity against various cancer cell lines like MCF-7, MDA-MB-231, MDA-MB-453, and PC-3. Normal human embryonic kidney cell line HEK-293 was used to determine the toxicity.

A path from synthesis to emergency use authorization of molnupiravir as a COVID-19 therapy.

Coronaviruses are a group of enveloped viruses with non-segmented, single-stranded, and positive-sense RNA genomes. It belongs to the 'Coronaviridae family', responsible for various diseases, including the common cold, SARS, and MERS. The COVID-19 pandemic, which began in March 2020, has affected 209 countries, infected over a million people, and claimed over 50,000 lives.

EIDD-1931 Treatment Tweaks CYP3A4 and CYP2C8 in Arthritic Rats to Expedite Drug Interaction: Implication in Oral Therapy of Molnupiravir.

EIDD-1931 is the active form of molnupiravir, an orally effective drug approved by the United States Food and Drug Administration (USFDA) against COVID-19. Pharmacokinetic alteration can cause untoward drug interaction (drug-drug/disease-drug), but hardly any information is known about this recently approved drug. Therefore, we first investigated the impact of the arthritis state on the oral pharmacokinetics of EIDD-1931 using a widely accepted complete Freund's adjuvant (CFA)-induced rat model of rheumatoid arthritis (RA) after ascertaining the disease occurrence by paw swelling measurement and X-ray examination.

C-30 analogues of betulinic acid as potent cytotoxic agents: design, synthesis, biological evaluation and studies.

In an endeavour to improve the anti-cancer activity of betulinic acid (BA), a series of C-30 derivatives were envisaged and synthesized with a novel synthetic approach. All the derivatives were evaluated for cytotoxic activity by MTT assay against six different human cancer cell lines: prostate (PC3), lung (A549), human hepatocellular carcinoma (HepG2), human leukemia (Molt-4), pancreatic (Panc-1) and breast (MCF-7). The data revealed that compound was observed most promising cytotoxic agent with IC values of μM, μM, and μM against A549, MCF-7, and PC3 cancer cell lines respectively.

Design, synthesis, and biological evaluation of 3,3'-diindolylmethane -linked glycoconjugate as a leishmanial topoisomerase IB inhibitor with reduced cytotoxicity.

Leishmaniasis, one of the neglected diseases, ranks second to malaria in the cause of parasitic mortality and morbidity. The present chemotherapeutic regimen faces the limitations of drug resistance and toxicity concerns, raising a great need to develop new chemotherapeutic leads that are orally administrable, potent, non-toxic, and cost-effective. Several research groups came forward to fill this therapeutic gap with new classes of active compounds against leishmaniasis, one such being 3,3'-diindolylmethane (DIM) derivatives.

Switchable reactivity of 2-benzoyl glycals towards stereoselective access of 1-3 and 1-1 / linked disaccharides.

We have developed a synthesis of 1-3 and 1-1 disaccharides from 2-benzoyl glycal and anomeric thiol and/or hydroxy sugar acceptors under mild conditions at room temperature. The regio and stereo-selectivity of the newly formed inter-glycosidic linkages are dependent on the nature of the glycal donor (D or L) and anomeric acceptor.

Impact of Disease States on the Oral Pharmacokinetics of EIDD-1931 (an Active Form of Molnupiravir) in Rats for Implication in the Dose Adjustment.

The pharmacokinetic alteration of an antimicrobial medication leading to sub-therapeutic plasma level can aid in the emergence of resistance, a global threat nowadays. In this context, molnupiravir (prodrug of EIDD-1931) is the most efficacious orally against corona virus disease (COVID-19). In addition to drug-drug interaction, the pharmacokinetics of a drug can significantly vary during any disease state, leading to disease-drug interaction.

Pd-catalyzed synthesis of hetero 1,2-interlinked -disaccharides by coupling of glycals with glycals.

A facile synthesis of C1-C2 interlinked disaccharides is achieved from readily available -glycals and unsubstituted glycals. Ester-protected donors reacted with ether-protected acceptors under Pd-Ag catalysis to access -disaccharides bearing C-3 vinyl ether, which upon ring opening by Lewis acid furnished pi-extended conjugated orthogonally protected chiral ketones. Benzyl deprotection and reduction of the double bonds resulted in a fully saturated disaccharide stable toward acid hydrolysis.

Base-Mediated Transformation of Glycals to Their Corresponding Vinyl Iodides and Their Application in the Synthesis of C-3 Enofuranose and Bicyclic 3,4-Pyran-Fused Furanose.

A simple method for the iodination of unsaturated sugars to form sugar vinyl iodides was developed under oxidant-free conditions using NaH/DMF/iodine as a reagent system at ambient temperature. 2-Iodoglycals bearing ester, ether, silicon, and acetonide protection were synthesized in good to excellent yield. 3-Vinyl iodides derived from 1,2:5,6-diacetonide glucofuranose were transformed to C-3 enofuranose and bicyclic 3,4-pyran-fused furanose via Pd-catalyzed C-3 carbonylation and intramolecular Heck reaction, respectively, as the key step.

Regio and Stereoselective One-Pot Synthesis of 2-Deoxy-3-thio Pyranoses and Their -Glycosides from Glycals.

A reaction of glycals with two different types of nucleophiles in the presence of SnCl enabled one-pot rapid access to 2-deoxy-3-thio pyranoses and their -glycosides. The process involves thioaryl substitution at C-3 with stereoretention and α-selective -glycosylation at C-1 from d-glycals, thus combining two reactions with three interventions. The present methodology features an attractive three-component coupling (1:1.

Identification and characterization of forced degradation products of sertraline hydrochloride using UPLC, ultra-high-performance liquid Chromatography-Quadrupole-Time of flight mass spectrometry (UHPLC-Q-TOF/MS/MS) and NMR.

The present study focused on the forced degradation behavior of sertraline hydrochloride (SRT), selective serotonin reuptake inhibitor (SSRI). The drug was exposed to different stressed conditions (hydrolytic, oxidative, thermal and photolytic) according to ICH Q1A (R2) guidelines. The study revealed that SRT was stable in hydrolytic (acidic, basic and neutral) and thermal degradation conditions.

Isolation and anticancer activity evaluation of rare Bisaryl anthraquinone antibiotics from novel Streptomyces sp. strain of NW Himalayan region.

Biosynthesis of bisaryl preanthraquinone antibiotics by various microorganisms differs in monomeric subunits as well as their dimerization positions leading to different configurations. The present study relates to the production of rare bisaryl anthraquinone antibiotics by a new Streptomyces strain isolated from Shivalik region of NW Himalayas. In vitro anticancer and anti-migratory effects of Setomimycin (9,9' bisanthraquinone antibiotic) was seen with a significant reduction in the expression of both MEK as well as ERK pathways in a dose dependent manner at 6.

Ni-catalyzed domino transformation of enopyranoses and 2-iodo phenols/anilines to pyrano fused dihydro-benzofurans/indoles.

A Ni-catalyzed direct access to various pyrano -fused dihydro benzofurans and indoles from unsaturated enopyranoses and phenols/anilines is developed. The domino synthesis of pyrano C2-C1 and C3-C2 -fused heteroarynes were achieved both from glycals and pseudo glycals in which heteroatoms are linked at C2 and C3 positions, respectively, with excellent chemo-selectivity.

Setomimycin as a potential molecule for COVID‑19 target: in silico approach and in vitro validation.

COVID-19 pandemic caused by the SARS-CoV-2 virus has led to a worldwide crisis. In view of emerging variants time to time, there is a pressing need of effective COVID-19 therapeutics. Setomimycin, a rare tetrahydroanthracene antibiotic, remained unexplored for its therapeutic uses.

Conversion of acyl amidines to amidoximes: a convenient synthetic approach to molnupiravir (EIDD-2801) from ribose.

An efficient method is described for the preparation of molnupiravir (EIDD-2801) an antiviral agent regioselective conversion of an acyl-nucleoside intermediate, generated through stereo and regioselective glycosylation of protected ribose and -acetyl cytosine, to an amidoxime. This method avoids use of expensive starting materials, enzymes, complex reagents, and cumbersome purification procedures.

Conversion of Glycals to 2,3-Di-Substituted-3-Deoxy-Glycals by N-(Glycosyloxy) Acetamides-assisted C-2-Alkenylation and C-3-Nucleophilic Substitution.

Transformation of glycals to 2,3-di-substituted-3-dexoy-glycals were achieved by sequential C2 alkenylation of pseudoglycals followed by capture of nucleophiles at C3 position. Anomeric linked N-(glycosyloxy) acetamides group assisted innate C2-H activation of pseudoglycals under palladium catalysis is achieved. The synthesized C2 alkenylated products were further attacked by thio/amino nucleophiles at C3 position under basic conditions in stereo-selective fashion to generate 2,3-branched glycals with the elimination of directing groups and translocation of double bond.

Correction: Conversion of -acyl amidines to amidoximes: a convenient synthetic approach to molnupiravir (EIDD-2801) from ribose.

[This corrects the article DOI: 10.1039/D1RA06912H.].

Correction: Diastereoselective synthesis of glycopyrans 1,2-annulated with dioxazinanes from 1,2-anhydrosugars and -substituted nitrones.

Correction for 'Diastereoselective synthesis of glycopyrans 1,2-annulated with dioxazinanes from 1,2-anhydrosugars and -substituted nitrones' by Ajaz Ahmed , , 2022, , 1436-1443, DOI: 10.1039/d1ob02310a.

Stereoselective Construction of Orthogonally Protected, N-O Interlinked Disaccharide Mimetics Using N-Substituted β-Aminooxy Donors.

Orthogonally protected N-substituted β-aminooxy sugars can be stereoselectively synthesized from sugar epoxides and nitrones derived from aromatic aldehydes. Both the ether- and ester-protected sugar epoxides can be employed. The synthesized aminooxy sugars could be reacted with aldehyde bearing/free reducing sugars under the heating condition to afford N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in a good yield.

Diastereoselective synthesis of glycopyrans 1,2-annulated with dioxazinanes from 1,2-anhydrosugars and -substituted nitrones.

1,2-Annulated pyranose sugars fused with six membered rings have emerged as an important class of carbohydrates with wide biological and synthetic utility. We now describe zinc chloride catalyzed one pot diastereoselective synthesis of sugar fused dioxazinanes from 1,2-anhydro sugars and -substituted aromatic nitrones. Various aromatic nitrones with different substituents undergo the reaction smoothly.