Maya I. Mitova

Evolving Trends in the Dereplication of Natural Product Extracts: New Methodology for Rapid, Small-Scale Investigation of Natural Product Extracts

The use of an HPLC bioactivity profiling/microtiter plate technique in conjunction with capillary probe NMR instrumentation and access to appropriate databases effectively short-circuits conventional dereplication procedures, necessarily based on multimilligram extracts, to a single, more rapid submilligram operation. This approach to dereplication is illustrated using fungal or bacterial extracts that contain known compounds. In each case the dereplication steps were carried out on microgram quantities of extract and demonstrate the discriminating power of (1)H NMR spectroscopy as a definitive dereplication tool.

Evolving Trends in the Dereplication of Natural Product Extracts. 2. The Isolation of Chrysaibol, an Antibiotic Peptaibol from a New Zealand Sample of the Mycoparasitic Fungus Sepedonium chrysospermum

By the application of an HPLC bioactivity profiling/microtiter technique in conjunction with capillary NMR instrumentation and access to the AntiMarin database the conventional evaluation/isolation dereplication/characterization procedures can be dramatically truncated. This approach is illustrated using the isolation of a new peptaibol, chrysaibol (1), from a New Zealand isolate of the mycoparasitic fungus Sepedonium chrysospermum. The unique nature of chrysaibol was recognized by bioactivity-guided fractionation using HPLC bioactivity profiling/microtiter plate analysis in conjunction with capillary NMR instrumentation and the AntiMarin database. 2D NMR techniques, in combination with MS fragmentation experiments, determined the planar structure of chrysaibol (1), while the absolute configurations of the amino acid residues were defined by Marfeys method. Chrysaibol (1) was cytotoxic against the P388 murine leukemia cell line (IC50 6.61 microM) and showed notable activity against Bacillus subtilis (IC50 1.54 microM).

Isolation of 2-pyridone alkaloids from a New Zealand marine-derived penicillium species.

Fermentation of a Penicillium sp. isolated from a surface-sterilized thallus segment of the brown alga Xiphophora gladiata, collected from Macrocarpa Point, Otago, New Zealand, in half-strength potato dextrose broth led to the isolation and characterization of three alkaloids: the known N-hydroxy-2-pyridone, PF1140 (1), and two new 2-pyridones, 2 and 3.

Concise, Stereoselective Route to the Four Diastereoisomers of 4-Methylproline

The full stereochemical characterization of 4-methylproline, a rare amino acid found in a number of peptidic secondary metabolites, has often been hindered by long reaction sequences or low stereoselectivity in the synthesis leading to reference samples. The preparation of the four diastereoisomers of 4-methylproline by a concise and stereoselective route is presented and features a six-step route with late-stage stereodivergence, good stereoselectivity for both cis- and trans-series (75% and 88% de, respectively), and good overall yields (cumulative yields of 30-40%). Additional data on the Marfeys derivatives of the stereoisomers are also presented.

Biosynthesis of spiro-mamakone A, a structurally unprecedented fungal metabolite.

Biosynthetic studies on spiro-mamakone A (1), a potently cytotoxic and antimicrobial compound from an endophytic fungus isolated from the New Zealand native tree Knightia excelsa (rewarewa), confirm the polyketide origins of this unique compound belonging to the spirobisnaphthalene class of compounds. The biosynthesis proceeds via an unprecedented symmetric enedione with the two halves of the molecule being formed from two separate pentaketide units connected by oxidative coupling.