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Prof Henok Kinfe

Prof Henok Kinfe
Department of Chemistry
Professor (Deputy HOD: Reasearch)

Contact Details
C2-Lab 232
+27 (0) 11 559 3918
APK

Prof H Kinfe's Research Group  

 

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In the picture from left to right: Prof H Kinfe, Pfanelo Mulokwe (MSc student), Tommy Mabasa (MSc student) Dr PT Moshapo (former PhD student), Munashe Chizema (MSc Student) and Bruce Marakalala (MSc Student).  Picture taken at the 2016 Frank Warren Conference hosted by Rhodes University.


Research Profile: 

Prof H Kinfe's research group focuses on the synthesis of bioactive molecules that are aimed at treating diseases such as malaria, cancer and HIV. The research group exploits readily available carbohydrate monomers, more precisely, glycals as building blocks to achieve asymmetric synthesis as well as chirality in the target molecules. Furthermore, the group exploits multicomponent reactions in the synthesis of new compounds with potential medicinal applications.  

Below are some of the representative research contributions by the group:

  • Alphonse Fiebor, Richard Tia, Banothile C. E. Makhubela and Henok H. Kinfe, Water-soluble SNS cationic palladium(II) complexes and their Suzuki–  Miyaura cross-coupling reactions in aqueous medium. Beilstein J. Org. Chem. 2018, 14, 1859–1870.

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Unlike their SCS analogues, SNS pincer complexes are poorly studied for their use in coupling reactions. Accordingly, a series of water soluble cationic    Pd(II) SNS pincer complexes have been successfully synthesised and investigated in detail for their catalytic activity in Suzuki–Miyaura coupling reactions.    By using only 0.5 mol % loading of the complexes, the coupling of inactivated aryl bromides and activated aryl chlorides with various boronic acids in water was achieved in excellent yields and the catalysts were found to be reusable for three cycles without a significant loss of activity. The investigation of the mechanism of the reaction revealed that a Pd(II) to Pd(IV) route is the more likely pathway which was further supported by computational studies. Click on the link to read the article. Line image.jpg

  • Mokgethwa B. Marakalala, Edwin M. Mmutlane and Henok H. Kinfe. β-Hydroxy sulfides and their syntheses. Beilstein J. Org. Chem. 2018, 14, 1668.

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Sulfur-containing natural products are ubiquitous in nature, their most abundant source being marine organisms since sulfur, in the form of the sulfate ion, is the second most abundant anion in sea water after chloride. As part of natural products, sulfur can appear in a multitude of combinations and oxidation states: thiol, sulfide (acyclic or heterocyclic), disulfide, sulfoxide, sulfonate, thioaminal, hemithioacetal, various thioesters, thiocarbamate and isothiocyanate. This review article focuses on β-hydroxy sulfides and analogs; their presence in natural products, general protocols for their synthesis, and examples of their application in target oriented synthesis. Click to access the article

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  • Kagiso G. Madumo, Paseka T. Moshapo and Henok H. Kinfe. Effects of lipophilicity, protecting group and stereochemistry on the antimalarial activity of carbohydrate-derived thiochromans. Med Chem Res. 2018, 27, 817.

 

Med Chem Res - Madumo.pngA series of novel carbohydrate-derived thiochromans has been successfully synthesised in order to investigate the influence of alkyl substituents on the aromatic ring of the thiophenol moiety in addition to the effect of protecting groups and stereochemistry on the sugar component of the target molecules. Results from the evaluation of the thiochromans for their antimalarial activity against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum suggest that the presence of short chain alkyl substituents, a benzyl ether protecting group and equatorial orientation of the C-4 substituent on the sugar moiety are crucial structural features that impart high antimalarial activity.



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Polyhedron- C Adokoh.jpgThe synthesis of novel phosphinogold(I) thiocarbohydrate complexes and their excellent anticancer activities (lower nanomolar IC50 values) against MCF7, HCT116 and PC3 cell lines with tumor specificity of more than 700 are some of the highlights of our current report.   
Click to view the article 

 

                  

 

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  • Mokgethwa B. Marakalala, Henok H. Kinfe, Iodine- and PhI(OAc)2-mediated multicomponent synthesis of (E)-1,3-diphenyl-1-butene derivatives. Eur. J. Org. Chem. 2017, 2017, 3311.

Eur JOC - Marakalala Cover page.pngA regio- and stereoselective three-component reaction towards 1,3-diphenyl-1-butene derivatives has been developed. The reaction proceeds in the presence of iodine and PhI(OAc)2; addition of metals or strong acids is not needed. Unlike previously developed protocols, the current methodology allows the incorporation of a sulfur heteroatom as well as two different styrene derivatives in the dimer.

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                                                                                                                      Click to view the article

 


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Org Biomol Chem - Paseka Cover page 2.jpgWe hereby report a one-pot cyclization sequence involving the Ferrier and Povarov-like reactions in the synthesis of novel pentacyclic N-heterocycles: benzopyran-fused pyranoquinolines. The reaction entails three component condensation of a glycal with a variety of anilines and 2-hydroxybenzaldehydes under Lewis acid catalysis to yield the title compounds in 4–24 hours of reaction time, in moderate to high yields and excellent diastereoselectivity. CAN-mediated oxidative ring opening of the pentacyclic N-heterocycle gave the corresponding enantiometrically pure chromenoquinoline bearing a pendant sugar moiety. Click to view the article

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New J Org Chem - Chris.gifSeveral bio-friendly carbohydrate disulfides and thiocarbohydrates have been synthesized via the reaction of D-(+)-gluconic acid δ-lactone with aminoalkylthiols, leading to n-gluconamidoalkyldisulfides {di-(2-gluconamidoethyl)disulfide (L1), di(3-gluconamidopropyl)-disulfide (L2), di(4-gluconamidobutyl) disulfide (L3) and (2-gluconamidoethyl)thiol (L4)}. Acetylation of hydroxy groups in L1–L3 and subsequent reduction produced the following disulfides and thiols: acetylated di(2-gluconamidoethyl)disulfide (L5), acetylated di(3-gluconamidopropyl)disulfide (L6), acetylated di(4-gluconamidobutyl)disulfide (L7), acetylated di(2-gluconamidoethyl)thiol (L8), acetylated di(3-gluconamidopropyl)thiol (L9) and acetylated di(4-gluconamidobutyl)thiol (L10). Compounds L1–L10 were characterized by combination of NMR and infrared spectroscopy, microanalysis, mass spectrometry and in a selected case X-ray crystallographic data. These thiocarbohydrate compounds were used to stabilize gold nanoparticles to gold glyconanoparticles (AuNPs) of sizes in the range of ca. 2–9 nm. The thiocrabohydrates are non-toxic toward both cancer and normal cell lines and have IC50 values generally ≥200 μM. Click to view article


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  • Henok H. Kinfe,  Fanuel M. Mebrahtu,  Mandlenkosi M. Manana,  Kagiso Madumo, Mokela S. Sokamisa, Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals. Beilstein J. Org. Chem. 201511, 583.

 

Beilstein_J_Org_Chem-Fano.jpg1-C and 2-C-branched carbohydrates are present as substructures in a number of biologically important compounds.  In this article a synthetic strategy for the synthesis of 1,2-cis-2-C-branched-aryl-C-glucosides is reported via a hydrogenolytic desulfurization of suitably orientated carbohydrate based hemithioacetals. 1,2-cis-2-Hydroxymethyl and 2-carbaldehyde of aryl-C-glucosides have been synthesized using the current strategy in very good yields. The 2-carbaldehyde-aryl-C-glucosides have been identified as suitable substrates for the stereospecific preparation of 2,3-unsaturated-aryl-C-glycosides (Ferrier products).  Click to view the article

 

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  • Paseka T Moshapo, Henok H Kinfe, Diastereoselective synthesis of novel and enantiopure tetrahydropyrano [3, 2-c] quinolones. Synthesis 2015, 47, 3673.

 

Synthesis - Moshapo PT.pngDiastereoselective synthesis of novel and enantiopure N-alkylated tetrahydropyrano[3,2-c]quinolines is described via intramolecular Friedel–Crafts alkylation using a 1-O-acetylglucosyl derivative as the key intermediate. Unprecedented formation of new glycal derivatives and α,β-unsaturated carbaldehyde products is also discussed. Click to view the article




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Eur J Med Chem Paseka.jpgA novel class of fused thiochroman derivatives has been prepared by an efficient and versatile synthetic procedure involving nucleophilic displacement of the side-chain iodo substituent in 2-deoxy-2-C-iodomethyl glucosides by thiophenolate ions, and subsequent intramolecular C-glycoside formation. A range of aromatic substituents is tolerated, and the subsequent facile selective oxidation of the sulfur to the sulfoxide or sulfone level expands the range and molecular diversity of the series of compounds. A selection of the sulfoxide and sulfone derivatives bearing lipophilic substituents on the aromatic portion were found to have antimalarial activities in the low micromolar range. Click to view the article

 


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  • Sandile B Simelane, Henok H Kinfe, Alfred Muller, D Bradley G Williams, Aluminum triflate catalyzed tandem reactions of d-Galactal: Toward chiral benzopyrans, chromenes, and chromans. Org. Lett. 2014, 16, 4543.

 

Org Lett - Simelane.gif3,4,6-Tri-O-acetyl-d-galactal is selectively converted into 1-O-aryl-2-deoxy derivatives or chiral bridged benzopyrans under Al(OTf)3 catalysis, depending on reaction conditions. The benzopyrans react with Al(OTf)3/acetic anhydride in ring-opening reactions in the absence or presence of acetic acid to selectively produce chiral chromenes or chromans, respectively, in high yields. Click to view the article



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JOC - Makolo1.pngA regiospecific synthetic strategy for the synthesis of 2-chloro-3-substituted benzo[b]thiophenes is developed via a dichlorocarbene insertion and sigmatropic rearrangement of an in situ generated ylide. The current protocol provides a reversed regiochemistry to the commonly employed electrophilic cyclization reaction for the synthesis of benzo[b]thiophenes and access to their hitherto under-represented chlorinated derivatives.  Click to view the article 

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JOC-Fano1.pngAn efficient and highly stereoselective strategy for the synthesis of 2,3-substituted thiochromenes having a complex and easily transformable group at the stereogenic center has been developed via a tandem thio-Michael addition reaction of an in situ generated α,β-unsaturated aldehyde sugar derivative. The protocol is superior to reported protocols in that the carbohydrate-derived substituent at the stereogenic center of the thiochromene is versatile and is amenable for further transformation.      Click to view the article 


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  • Henok H Kinfe, Yonas H Belay, Jitcy S Joseph, Emmanuel Mukwevho, Evaluation of the Influence of thiosemicarbazone–triazole hybrids on genes implicated in lipid oxidation and accumulation as potential anti-obesity agents. Bioorg. Med. Chem. Lett. 2013, 23, 5275.


Jonas.pngA series of thiosemicarbazone–triazole hybrids are efficiently synthesised and evaluated for their influence on the expression of genes, 
cpt-1, acc-1 and pgc-1, which are essential in lipid metabolism. The test results show that the hybrids exhibited relatively high influence on the expression of cpt-1 and pgc-1 and suppression of acc-1 as desired.  Click to view the article








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OBC - Simelane.pngA temperature-controlled mechanism switch between the Al(OTf)3-catalysed direct addition of alcohols or the Ferrier rearrangement reactions in some glycals is presented. The scope and limitations are investigated as are the influence of the stereochemistry and nature of the protecting groups on the glycal substrate.      Click to view the article





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  • Henok H Kinfe, Fanuel M Mebrahtu, Khuphukile Sithole, NaHSO4 supported on silica gel: an alternative catalyst for Ferrier rearrangement of glycals. Carbohydr. Res. 2011, 346, 2528.

Carbohydr Res - Khuphu.pngNaHSO4 supported on silica gel catalyses the Ferrier rearrangement reaction of 3,4,6-tri-O-acetyl-d-glucal with alcohols and thiols to give the corresponding 2,3-unsaturated glycosides in high anomeric selectivity and good to excellent yield in short reaction time. Click to view the article

 


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To view more research publications by the group please click the links provided below:

Google Scholar

Research Gate


Financial assistance from the research funders below is acknowleged

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