Natural Product-Derived Chiral Pyrrolidine-2,5-diones, Their Molecular Structures and Conversion to Pharmacologically Important Skeletons.

The versatility of the natural products (2S,3S)- and (2S,3R)-3-hydroxy-5-oxotetrahydrofuran-2,3-dicarboxylic acids (1 and 2), isolated in large amounts from tropical plant sources, has been demonstrated by the construction of 3-substituted and 3,4-disubstituted chiral pyrrolidine-2,5-diones. The absolute configurations of chiral pyrrolidine-2,5-diones have been ascertained using chiroptical spectroscopic methods and/or single-crystal XRD data. A combination of different reaction strategies delivering a diverse matrix of fused heterocyclic ring systems is presented. The pyrrolo[2,1-a]isoquinoline alkaloid (+)-crispine A possesses a wide range of pharmacological activities including antidepressant, antiplatelet, antileukemic, and anticancer activities. The analogues of indolizino[8,7-b]indole alkaloids (+)- and (-)-harmicine show strong antileishmanial, antinociceptive, PDE5-inhibitory, antimalarial, and antiviral activities. The bicyclic furo[2,3-b]pyrrolo skeleton is present in many natural products. Thus, the uniqueness of relatively cheap, naturally occurring chiral 2-hydroxycitric acid lactones as chirons has been demonstrated by the construction of some important molecular skeletons that are otherwise difficult to synthesize.

A highly sensitive GC-MS method for simultaneous determination of anacardic acids in cashew (Anacardium occidentale) nut shell oil in the presence of other phenolic lipid derivatives.

The commercial value of cashew nut shell liquid (CNSL) has become a cornerstone of the agrowaste industry. It is the by-product of the cashew industry and has an 1/8 inch thickness of soft honeycomb structure. CNSL contains phenolic lipids with aliphatic chains such as anacardic acid, cardanol, cardol and methyl cardol, and their derivatives. The developed GC-MS method is rapid, accurate and selective using a selected derivatizing reagent, namely N-methyl-N-(trimethylsilyl)-trifluoroacetamide that was previously diluted 1:1% with anhydrous pyridine. The proposed GC-MS method was applied for the analysis of different CNSL samples. The results showed that all classes of CNSL compounds were detected. The four alkyl phenols were detected with their different alkyl sidechains without any interference. This method is also specified for the detection of fatty acids of saturated and unsaturated chains. Silylation did not cause any alteration in the chemical structure of CNSL compounds regardless of esterification action. Silylation is considered a safe derivatizing agent compatible with GC chromatography and specific for all volatile and nonvolatile polar and nonpolar CNSL compounds that could be detected in CNSL samples.

Chiroptical spectroscopy of natural products: avoiding the aggregation effects of chiral carboxylic acids.

Determination of the absolute configurations and predominant conformations of chiral natural products, occurring as carboxylic acids, using chiroptical spectroscopic methods becomes challenging due to the formation of solute aggregates (in the form of dimers, etc.) and/or solute-solvent complexes resulting from intermolecular hydrogen bonding with solvent. A hypothesis that such aggregation effects can be avoided by using corresponding sodium salts or acid anhydrides for chiroptical spectroscopic measurements has been tested. For this purpose, vibrational circular dichroism, electronic circular dichroism, and optical rotatory dispersion spectra for disodium salts of two natural products, hibiscus acid and garcinia acid, and the anhydride of acetylated garcinia acid have been measured. These experimental spectra are analyzed in combination with quantum chemical calculations of corresponding spectra. The spectral analysis for sodium salts and anhydride turned out to be simpler, suggesting that the conversion of carboxylic acids to corresponding salts or anhydride can be advantageous for the application of chiroptical spectroscopy.