Organic chemistry of marine natural products, synthesis, NMR, and biomedical applications
Ph.D., , Australian National University, Canberra, Australia
B.S., , Monash University, Melbourne
Awards and Academic Honors
President, American Society of Pharmacognosy
Albert Hofmann Centennial Prize, University of Zürich
Chair, Gordon Conference, Marine Natural Products
Marine natural products (MNP's) are chemically-diverse compounds found in marine organisms, such as marine sponges, ascidians, algae and molluscs. Many MNP's have complex molecular structures with multiple elements stereocenters, the presence of halogen (Cl, Br, I) and exotic functional groups. Our group investigates the structure, synthesis and biological properties of novel MNP's. Recent results include discovery of compounds that inhibit cancer cell growth or survival pathways that render cancer cells prone to programmed cell death (apoptosis) and may be useful as drug leads for treatment of human disease.
Fungal infections in individuals with with weakened immune systems such as AIDS patients or those undergoing chemotherapy including are caused by Candida and Cryptococcus and other species. We have discovered compounds that may prove useful in understanding the progression of fungal disease and its treatment.
An outstanding challenge in modern natural products is development of spectroscopic tools that push the limits of detection with vanishingly small quantities of organic compounds. In our nanomole-scale natural products program, we are developing tools which integrate analysis using micro-NMR (e.g. 1.7 mm cryoprobe), chiroptical spectroscopy, particularly circular dichroism (CD), and mass spectrometry for determining absolute configuration of natural products available in amounts <10 nanomole. Funded for our research is from the National Institutes of Health.
Primary Research Area
- Dalisay DS, Molinski TF, "Structure elucidation at the nanomole scale. 2. Hemi-phorboxazole A from Phorbas sp.", Org Lett, 2009, 9, 1967-70
- Dalisay DS, Morinaka BI, Skepper CK, Molinski TF, "A tetrachloro polyketide hexahydro-1H-isoindolone, muironolide A, from the marine sponge Phorbas sp. natural products at the nanomole scale.", J Am Chem Soc, 2009, 22, 7552-3
- Dalisay DS, Quach T, Nicholas GN, Molinski TF, "Amplification of the Cotton effect of a single chromophore through liposomal ordering-stereochemical assignment of plakinic acids I and J.", Angew Chem Int Ed Engl, 2009, 24, 4367-71
- Molinski TF, Dalisay DS, Lievens SL, Saludes JP, "Drug development from marine natural products.", Nat Rev Drug Discov, 2009, 1, 69-85
- Morinaka BI, Pawlik JR, Molinski TF, "Amaroxocanes A and B: sulfated dimeric sterols defend the Caribbean coral reef sponge Phorbas amaranthus from fish predators.", J Nat Prod, 2009, 2, 259-64
- Mulder RJ, Shafer CM, Dalisay DS, Molinski TF, "Synthesis and structure-activity relationships of bengazole A analogs.", Bioorg Med Chem Lett, 2009, 11, 2928-30
- Pigza JA, Quach T, Molinski TF, "Oxazoline-oxazinone oxidative rearrangement. divergent syntheses of (2S,3S)-4,4,4-trifluorovaline and (2S,4S)-5,5,5-Trifluoroleucine.", J Org Chem, 2009, 15, 5510-5
- Rogers EW, Dalisay DS, Molinski TF, "(+)-Zwittermicin A: assignment of its complete configuration by total synthesis of the enantiomer and implication of D-serine in its biosynthesis.", Angew Chem Int Ed Engl, 2008, 42, 8086-9
- Skepper CK, Macmillan JB, Zhou GX, Masuno MN, Molinski TF, "Chlorocyclopropane macrolides from the marine sponge Phorbas sp. assignment of the configurations of phorbasides A and B by quantitative CD.", J Am Chem Soc, 2007, 14, 4150-1
- Masuno MN, Pessah IN, Olmstead MM, Molinski TF, "Simplified cyclic analogues of bastadin-5. Structure-activity relationships for modulation of the RyR1/FKBP12 Ca2+ channel complex.", J Med Chem, 2006, 15, 4497-511