Skip Navigation LinksProf-Henok-Kinfe Prof Henok Kinfe


Skip Navigation LinksHome Contact Prof Henok Kinfe


Prof Henok Kinfe

Prof Henok Kinfe
Department of Chemistry
Professor

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

 

Prof H Kinfe's Research Group  

 

Group Picture.jpg

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:


Abstract:

This review documents all the new homoisoflavonoids (HIFs) that have been reported since 2007, whose total number has grown from 159 in 2007 to 295 at the present time. This review contains their structures, biological sources, plant parts they are obtained from, and, if reported, their optical rotations and melting points. The same classification is followed as an earlier review to ease reference to both reviews. This review takes note of the recent revision of plant families that were known to contain HIFs that have now been merged into one big family, Asparagaceae. Homoisoflavonoids also occur in Fabaceae and others. Two taxa, Ophiopogoan japonicus (Asparagaceae) and Caesalpinia sappan (Fabaceae), have been the source of many HIFs. These are briefly summarized. The biological properties of HIFs are also reviewed under the topics such as antioxidant, anti-inflammatory, antimicrobial, antidiabetic, and cytotoxic. The review also surveys the total synthesis of natural HIFs. All new compounds are classified and tabulated following the same style as the previous review           

Line image.jpg

                                                                                    Application of glycals.png

 Abstract:

Glycals, 1,2-unsaturated sugar derivatives, are versatile starting materials for the synthesis of natural products and the generation of novel structural features in Diversity Oriented Synthesis (DOS). The versatility of glycals in synthesis emanates, among others, from the presence of the ring oxygen and the enol-ether type unsaturation, the different types of stable conformations they can adopt depending on the nature of the protecting groups present and the ease with which the protecting groups of the three hydroxy groups could be tailored to suite for a desired manipulation. This review summarizes the literature on the different transformations of the endoglycals into biologically relevant compounds such as chromans, thiochromans, chromenes, thiochromenes, peptidomimetics, bridged benzopyrans etc., as well as on the use of glycals as chiral building blocks for the synthesis of various natural products such as aspicilin, reblastatin, diospongins, decytospolides, osmundalactones, paclitaxel, isatisine, D-fagomine, and spliceostatin, reported post 2014.

Line image.jpg

  • Munashe Chizema, Tommy F. Mabasa, Heinrich C. Hoppe, Henok H. Kinfe,  Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate- based thiochromans.  Chem Biol Drug Des. 2018;1–8.
                                                    cover page.jpg


 
Abstract
Sulfone/sulfoxide–containing carbohydrate derived thiochromans were found to be highly active antiplasmodial agents. However, the inability of the sulfone/sulfoxide functional groups for further derivatization and manipulation limited the potential for further exploration. In this study, based on the interesting and important physicochemical properties, as well as amenability of sulfoximines (isosters of sulfones) for further derivatization, a series of novel sulfoximine–type carbohydrate–derived thiochroman derivatives have been successfully synthesized, characterised and evaluated for their antiplasmodial activity. Although the replacement of the sulfone functional group with a sulfoximine unit improved the antiplasmodial activity of the scaffolds, the activity was highly dependent on the configuration of the stereogenic centre at the sulfur atom. Moreover, analysis of the crystal structures of the sulfoximine analogues revealed that the bond between the sulfur and nitrogen atoms of the sulfoximine functional group is not a true double bond but rather a polarized single bond. Click on the link to read the full article. 

Line image.jpg


  • 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.

                                                             1860-5397-14-160-presentation.png 

Abstract

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.

                                                                HH Kinfe Beilentein abstract.jpg

Abstract

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

Line image.jpg

  • 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.pngAbstract

A 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.



Line image.jpg


Polyhedron- C Adokoh.jpgAbstract

The 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 

 

                  

 

   Line image.jpg

  • 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.pngAbstract

A 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.

                      Eur JOC - Marakalala Abstract.png 

                                                                                                                      Click to view the article

 


Line image.jpg

 

Org Biomol Chem - Paseka Cover page 2.jpgAbstract

We 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

                      OBC - paseka 1.png

 

Line image.jpg

New J Org Chem - Chris.gifAbstract

Several 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


Line image.jpg
  • 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.jpgAbstract

1-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

 

Line image.jpg

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

 

Synthesis - Moshapo PT.pngAbstract

Diastereoselective 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




Line image.jpg

Eur J Med Chem Paseka.jpgAbstract

A 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

 


Line image.jpg 

  • 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.gifAbstract

3,4,6-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



Line image.jpg

JOC - Makolo1.pngAbstract

A 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 

 Line image.jpg

JOC-Fano1.pngAbstract

An 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 


Line image.jpg

  • 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.pngAbstract

A 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








Line image.jpg

 

OBC - Simelane.pngAbstract

A 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





Line image.jpg

  • 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.pngAbstract

NaHSO4 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

 


Line image.jpg

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

funders 2.png