University of Cape Town, Rondebosch, 7701
Tel: +27 21 6502544
Personal web page: http://www.chemistry.uct.ac.za/?page_id=221
Principal areas of expertise: Synthetic organic chemistry; Medicinal chemistry
♦ Application of synthetic organic chemistry to a broad range of problems in synthesis methodology, medicinal chemistry and total synthesis, including asymmetric catalysis
Total synthesis, methodology and catalysis – A number of bioactive alkaloids (Castanospermine, Tacamonine, Lepadiformine) are being pursued via total synthesis, with the emphasis on new synthetic methodology. Recently, a new ephedrine-based auxiliary-controlled methodology has been developed for accessing a key chiral, non-racemic azaquaternary synthon relevant to Lepadiformine synthesis. Organocatalysis is also being used to access azaquaternary centres, in which a novel hydrazide catalysis is being developed. Finally there is a longstanding interest in my group around new synthesis methodology, eg for preparing unsymmetrical disulfides.
Novel Bifunctional HIV-1 Reverse-Transcriptase Inhibitorsand HIV-1 NCp7 Inhibitors – The one objective is to design, synthesize and develop HIV reverse-transcriptase bifunctional inhibitorscontaining a NNRTI and a NRTI separated by a tether so as to bind to each target site (a pocket and the polymerisation substrate-binding site respectively) simultaneously on RT.
New Antimalarials – Medicinal chemistry leads against malaria are being pursued, an example being new chloroquine-based antimalarial hybrids incorporating a dibemethin grouping, which have been shown to be active against KI, the chloroquine–resistant strain of Plasmodium falciparum responsible for Malaria infection.
Garlic mimics – Compounds resembling allicin and ajoene from garlic are being synthesized and developed as stable mimics with potent antimicrobial and anti–cancer properties. A structure–activity profile has been developed for the anti–cancer agent ajoene. Chemical biology studies regarding mode-of-action are underway.
Bailey CM, Sullivan TJ, Iyidogan P, Tirado-Rives J, Chung R, Ruiz-Caro J, Mohamed E, Jorgensen W, Hunter R, AndersonKS (2013) Bifunctional inhibition of HIV-1 reverse transcriptase: mechanism and proof-of-concept as a novel therapeutic design strategy. J Med Chem 56: 3959−3968
Kaschula CH, Hunter R, Stellenboom N, Caira MR, Winks S, Ogunleye T, Richards P, Cotton J, Kilbeyaz K, Wang Y, Siyo V, Ngarande E, Parker MI (2012) Structure-activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells. Eur J Med Chem 50: 236-254
Zishiri VK, Hunter R, Smith PJ, Taylor D, Summers R, Kirk K, Martin RE, Egan TJ (2011) A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRT. Eur J Med Chem 46: 1729-1742
Zishiri VK, Joshi MC, Hunter R, Chibale K, Smith PJ, Summers RL, Martin RE, Egan TJ (2011) Quinoline antimalarials containing a dibemethin group are active against chloroquinone-resistant Plasmodium falciparum and inhibit chloroquine transport via the P. falciparum chloroquine-resistance transporter (PfCRT). J Med Chem 54: 6956-6968
Kaschula CH, Hunter R, Hassan HT, Stellenboom N, Cotton J, Zhai XQ, Parker MI (2011) Anti-proliferative activity of synthetic ajoene analogues on cancer cell-lines. Anticancer Agents Med Chem 11: 260-266
Younis Y, Hunter R, Muhanji CI, Hale I, Singh R, Bailey CM, Sullivan TS, Anderson KS (2010) [d4U]-spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase. BioorgMed Chem 18: 4661‑4673
Smith MW, Hunter R, Patten D, Hinz W (2009) A new approach to indolo[2,3-a]quinolizidines through radical cyclization of 2-acyl-1-phenylthiotetrahydro-b-carbolines bearing pendent a,b-unsaturated esters. Tetrahedron Lett 50: 6342-6346
Hunter R, Rees-Jones SCM, H Su (2007) Vinylogous Mukaiyama aldol reactions with 4-oxy-2-trimethylsilyloxypyrroles: relevance to castanospermine synthesis. Beilstein J Org Chem 3: 38-43
Hunter R, Caira MR, Stellenboom N (2006) Inexpensive, one-pot synthesis of unsymmetrical disulfides using 1-chlorobenzotriazole. J Org Chem 71: 8268-8271