Research Projects (Current and Past)
Total Organic and Bioorganic Synthesis
The focus of my research would be on the design, development and total synthesis of natural and non-natural products targeting disease areas of anti-cancer, anti-HIV, anti-viral, microbial, pain, inflammation, anti-malaria, tuberculosis and anti-diabetic molecules.
Previous problems currently being or to be addressed include:
- The synthesis of the AB, EF and IJ subunits of adriatoxin (an analogue of yessotoxin a polyether natural product which had been shown to exhibit exceptional cytotoxic activity against human cancer cell lines, inducing caspase activation, causing apoptotic changes, and induces a two-fold increase in cytosolic calcium as published in Angew. Chem. Int. Ed. 2008, 47, 8055-8058.
- The synthetic efforts of pectenotoxin 1 and 6 (an anticancer agent which depolymerizes actin and induces apoptosis in p53 deficient tumor cells).
- Synthesized a series of mono and per-substituted amino cyclodextrin derivatives as inserts into α-hemolysin ion channels – a collaborative work with Prof. Henry White at University of Utah.
- Fully synthesized and characterization of quinazolinone hit compounds as inhibitors of PARP-1, poly(ADP-ribose)polymerase exhibiting ~60-80 nM activity.
- Fully synthesized and characterization of korormicin derivatives which has an inhibitory activity towards the growth of marine Gram-negative bacteria.
- Fully synthesized and characterization of hundreds of novel hit compounds of phenyl-indeno-pyrimidin derivatives as optimized adenosine A2A/A1 receptor antagonists targeting the treatment of Parkinson’s disease.
- Designed and synthesized new perphenylated cross-conjugated iso-polydiacetylenes (iso-PDAs) using an iterative divergent route as potential candidates for optical and material applications as published in Chem. Eur. J., 2005, 11, 321-329.
- Assembled a series of polyenyne oligomers, thus tert-butyldimethylsilyl (TBDMS) end-capped iso-polydiacetylenes (iso-PDAs) and 7,7,8,8-tetraethynyl-dihydro-p-quinodimethane (TEQ) derivatives for optical and material applications.
- Synthetic efforts of alkaloids, heterocyclics, anti-viral, antibiotics, anti-fungi, antitumor agents of biological interests.
- Design and synthesis of novel libraries of spirocyclic natural and non-natural products of small organic molecules of broad structural diversity for binding to and modulating the function of biological targets.
Medicinal and Pharmaceutical Chemistry
The focus of our medicinal and pharmaceutical chemistry research field would be on the interplay between structure-activity relationship/structure-property relationship (SAR/SPR) of biological, organic and organometallic molecules targeting various disease areas of oncology, anti-HIV, anti-viral, pain, inflammation, anti-malaria, tuberculosis, anti-diabetic, hepatitis and neurodegenerative diseases and also in collaboration and partnership with other departments particularly the pharmacy, agriculture and medicine; training, teaching and researching together to benefit the university, the country and if possible expand globally. Animal studies (including in-vitro and in-vivo pharmacology), pharmacodynamics/pharmacokinetics (PD/PK) to ascertain the safety and efficacy of our biologically active hit to lead compounds and if possible we file an Investigational New Drug (IND) Application with FDA for onward clinical studies/trials.
Previous problems currently being or to be addressed include:
- SAR/SPR evaluation of polyether natural and non-natural products and their ability to bind to ion channels.
- SAR/SPR evaluation of quinazolinone hit compounds as inhibitors of PARP-1 and other biological receptors.
- SAR/SPR evaluation of korormicin derivatives which has an inhibitory activity towards the growth of marine Gram-negative bacteria.
- SAR/SPR evaluation of novel hit compounds of phenyl-indeno-pyrimidin derivatives as optimized adenosine A2A/A1 receptor antagonists targeting the treatment of neurodegenerative diseases.
- SAR/SPR evaluation of novel libraries of spirocyclic natural and non-natural products of small organic molecules of broad structural diversity for binding to and modulating the function of biological targets.
- SAR/SPR evaluation of proprietary ChemKits and ChemCores in the target areas of GPCR, Kinase, and Ion channel based research.
- SAR/SPR evaluation of imidazole and benzimidazole motifs and their interactions with biological receptors.
- SAR/SPR evaluations of thieno-pyrimidine lactam, carbamate and urea as well as pyrazole-triazine lactam, carbamate and urea scaffolds and their interactions with biological receptors.
- SAR/SPR evaluations of indole motifs, tryptophan-cycloaromatic motifs and amidine derivatives, their binding and interactions with biological receptors.
Organometallic Chemistry
Our organometallic chemistry research group projects would be focused on the discovery, development and synthesis of various compounds of medicinal significance, utilizing Pd-type coupling area of focus (Suzuki, Stille, Sonogashira and Buchwald couplings), Negishi-organozinc couplings, Olefin Metathesis Reactions (Grubbs and Schrock catalysts) and other plans e.g Takai, Tebbe, Peterson, Wittig olefinations etc,.
Previous problems currently being or to be addressed include:
- The synthesis of hundreds of medicinally significant molecules utilizing palladium-catalyzed Suzuki cross-coupling protocol for ChemRoutes and CanAm Bioresearch Inc.
- The synthesis of hundreds of bioactive molecules utilizing palladium-catalyzed Buchwald cross-coupling protocol for ChemRoutes Corporation.
- The synthesis of cross-conjugated (iso-PDA) oligomers ranging from monomer to pentadecamer, using a palladium-catalyzed Sonogashira cross-coupling protocol as published in Chem. Eur. J., 2005, 11, 321-329. .
- The use of ring-opening/cross-metathesis (ROCM) reactions between unsymmetrical norbornene derivatives and electron-rich olefins in the presence of the second-generation Grubbs’ catalyst to generate highly substituted furans and pyrroles.
- Utilization of the ring-closing metathesis (RCM) reactions into the formation of the first generation E-ring and second generation I-ring of adriatoxin.
- The use of the Wilkinson’s catalyst for the isomerisation of the 7-membered E-ring of the first generation synthesis of adriatoxin.
- The synthesis of the AB, EF and IJ subunits of adriatoxin, utilizing our olefin metathesis, carbonyl olefination protocol (variant of Takai olefination) as published in Angew. Chem. Int. Ed. 2008, 47, 8055-8058. .
- Expansion of our stereoselective 1,2-hydride migration protocol to iterative C-glycoside technology.
- The synthesis of 7,7,8,8-tetraethynyl-dihydro-p-quinodimethane (TEQ) derivatives for optical and material applications using a palladium-catalyzed Sonogashira cross-coupling protocol.
- Application of palladium-catalyzed Suzuki cross-coupling protocol into synthesizing and characterization of korormicin derivatives which has an inhibitory activity towards the growth of marine Gram-negative bacteria.
Proteins-Peptides and Amino Acids
Our proteins, peptides and amino acids research group would be focused on design, synthesis and development of biologically active target molecules of natural and non-natural origin. Students would be exposed to the various formations of amide bonds from less to more hindered targets, and most importantly NMR (1H, 13C, DEPT, COSY, HMQC/HMBC, nOe, and Coupling Constant Calculations studies or other 2D experiments) interpretation.
Previous problems currently being or to be addressed include:
- The synthesis of hundreds of medicinally significant molecules utilizing amide bond formation protocol for ChemRoutes and CanAm Bioresearch Inc.
- Synthesis of the Tripeptide Boc-Gln(Trt)-Ala-Arg(Mtr)-OH for MET Inhibition.
- Synthesis of Boc-Gln(Trt)-Ala-OH and Arg(Mtr)-OH Motifs for biological targets.
- Critical amide bond coupling for the synthesis and characterization of korormicin derivatives which has an inhibitory activity towards the growth of marine Gram-negative bacteria.
- Synthesis of Tryptophan-cycloalkane/aromatic motifs and their binding and interactions with biological receptors.
- Synthesis of D-serine-alanine, cysteine-alanine and other motifs and their binding and interactions with biological receptors.
Reaction Development and Methodology
This program would be focused on developing a general synthetic plan, scheme or methodology for the various target molecules. The emphasis would be to use these strategies as building blocks to design our target molecules and other natural and non-natural products of medicinal significance.
Previous problems currently being or to be addressed include:
- To specifically and selectively deliver a hydride via syn-facial [1,2]-hydride migration in a pinacol-type rearrangement reaction and the results published in Angew. Chem. Int. Ed. 2008, 47, 8055-8058.
- Exploring the scope of a Glycal [3,3] Claisen Rearrangement. To generate the fused EF-ring bicyclic ethers of Adriatoxin (an analog of Yessotoxin), a unique glycal [3,3] Claisen rearrangement was applied to stereoselectively generate the syn 1,3-diaxial angular methyl groups as published in Angew. Chem. Int. Ed. 2008, 47, 8055-8058.
- Exploring and expanding the scope of the novel amide bond formation.
Phytochemistry
The genesis of my phytochemistry research group would be from extraction, to isolation, purification, identification and characterization of medicinal and pharmaceutically significant plant materials as well as of marine and soil natural resources. Students would be exposed to the general extraction and isolation techniques, and most importantly NMR (1H, 13C, DEPT, COSY, HMQC/HMBC, nOe, and Coupling Constant Calculations studies or other 2D experiments) interpretation.
Previous problems currently being or to be addressed include:
- UNDER CONSTRUCTION
Spectroscopy
Our planned studies will impart extensive practical laboratory knowledge and skills to the students with whom I work and broaden their understanding in spectroscopy and exposed them to various analytical techniques like ESI-MS, GC-MS, LC-MS, FT-IR, X-RAY analysis, UV-VIS analysis, TLC Techniques, HPLC (analytical and preparative), EA, Optical Rotation Measurements and NMR (1H, 13C, DEPT, COSY, HMQC/HMBC, nOe, and Coupling Constant Calculations studies or other 2D experiments) interpretation.
Previous problems currently being or to be addressed include:
- The relative stereochemistry of the AB subunit of adriatoxin (an analogue of yessotoxin) was established via NMR coupling constant calculation studies and other 2D experiments like COSY and nOe as published in Angew. Chem. Int. Ed. 2008, 47, 8055-8058.
- The relative stereochemistry of the EF ring system of adriatoxin and the angular methyl groups were established using NMR coupling constant calculation studies and other 2D experiments like COSY and nOe and the results published in Angew. Chem. Int. Ed. 2008, 47, 8055-8058.
- The relative stereochemistry of the IJ subunit of adriatoxin was established via NMR coupling constant calculation studies and other 2D experiments like COSY and nOe as published in Angew.Chem. Int. Ed. 2008, 47, 8055-8058.
- The absolute stereochemistry of the perphenylated cross-conjugated iso-polydiacetylenes (iso-PDAs) were fully characterized using X-ray crystallographic analysis, NMR interpretation and UV-VIS analysis, as published in Chem. Eur. J., 2005, 11, 321-329.
- The quinazolinone hit compounds as PARP I inhibitors and korormicinderivatives which has an inhibitory activity towards the growth of marine Gram-negative bacteria were fully characterized via NMR interpretation, ESI-MS, GC-MS, LC-MS, FT-IR and HPLC analysis.
- The hundreds of novel hit compounds of phenyl-indeno-pyrimidin derivatives as optimized adenosine A2A/A1 receptor antagonists targeting the treatment of Parkinson’s disease were fully characterized using NMR interpretation, ESI-MS, LC-MS, FT-IR and HPLC analysis.