Current Organic Chemistry - Volume 24, Issue 7, 2020

Semi-synthesis, the way of preparing novel bioactive molecules via modification of compounds isolated from natural sources is very much useful nowadays in the drug discovery process. The modification is based on the reaction of functional group(s) present in a natural compound. Among the examples of functional group transformation, double bond modification is also common in the literature. Several reactions like hydrogenation, cyclopropanation, epoxidation, addition reaction (halogenations, hydroxylation), Michael addition, Heck reaction, cycloaddition, dipolar cycloaddition, etc. are employed for this purpose. In this review, we have tried to gather the reactions performed with several double bond containing classes of natural products like diterpenes, xanthones, sesquiterpene exomethylene lactones, diaryl heptanoids, steroidal lactones, triterpenoids, limonoids, and alkamides. Where available, the effects of transformations on the biological activities of the molecules are also mentioned.

Many catalysts were tested in asymmetric Michael additions in order to synthesize enantioenriched products. One of the most common reaction types among the Michael reactions is the conjugated addition of malonates to enones making it possible to investigate the structure–activity relationship of the catalysts. The most commonly used Michael acceptors are chalcone, substituted chalcones, chalcone derivatives, cyclic enones, while typical donors may be dimethyl, diethyl, dipropyl, diisopropyl, dibutyl, di-tert-butyl and dibenzyl malonates. This review summarizes the most important enantioselective catalysts applied in these types of reactions.

In this review, we examined the possibility that some halogenated organic derivatives were used in the primitive ocean at the beginning of life on Earth. Firstly, we described the existence of extraterrestrial halogenated molecules, then we studied their nonbiological syntheses on the present Earth, especially in volcanic environments. In order to demonstrate the diversity of today’s halogenated biomolecules, representative examples are given and the biosynthesis of some of them is summarized. Finally, we proposed two aspects of the chemistry of halogenated compounds that may have been useful en route to biomolecules, firstly the use of methyl chloride as the first methylation reagent, secondly the synthesis and use of α-chloro-carbonyl derivatives.

Five metabolites were isolated by chromatographic methods from the fruit stems of P. vera and their chemical structures were characterized as masticadienonic acid (1), tirucallol (2), masticadienolic acid (3), pistachionic acid (4) and inulobiose (5) via FT-IR, 1H-NMR, 13C-NMR, 1D-NMR and 2D-NMR. Pistachionic acid (4), a new shikimic acid derivative, was isolated from the ethanol extract for the first time. The hexane, chloroform, ethanol extracts and pure metabolites exhibited antidiabetic properties by inhibiting α- glycosidase and α-amylase enzymes at different rates. Their inhibitory effects against the α- glycosidase enzyme were also higher than that of the acarbose (IC50=10.30 mg/mL). Masticadienolic acid (3) (IC50=0.03 mg/mL), masticadienonic acid (1) (IC50=0.13 mg/mL) and hexane extract (IC50=0.09 mg/mL) with the lowest IC50 values were found to be most active substances. Nevertheless, the inhibitory effect of acarbose against the α-amylase enzyme was determined to be higher than the inhibition effects of the extracts and pure metabolites. According to the IC50 values, the best inhibitors against the α-amylase were ethanol extract (IC50=5.17 mg/mL), pistachionic acid (4) (IC50=7.35 mg/mL), tirucallol (2) (IC50=7.58 mg/mL) and masticadienolic acid (3) (IC50=8.22 mg/mL), respectively among the applications. In addition, anticholinesterase properties of the extracts and pure metabolites were investigated by testing the inhibitory properties against acetylcholine esterase (AChE) and butrylcholine esterase (BChE) enzymes activities. The results showed that the anticholinesterase properties of all extracts and pure metabolites were weaker than those of the commercial cholinesterase inhibitors, neostigmine and galantamine, and all applications reduced the activity of these enzymes at very high concentrations.

Lipases in the native or immobilized form have commonly been used as catalysts in the chemical and pharmaceutical industry. One of the widely available enzyme catalysts on the market is lipase from Burkholderia cepacia (BCLs), previously called Pseudomonas cepacia (PCLs). This enzyme is applied, among others, in the stereoselective acylation of molecules to achieve chiral pure enantiomers of drugs or their building blocks. In this study, Amano lipase PS (APS-BCL), which is a commercial lipase from Burkholderia cepacia (BC) was tested. The lipolytic activity of APS-BCL by hydrolysis of vegetable oils and enantioselective activity of APS-BCL by the kinetic resolution of (R,S)-1-phenylethanol with using isopropenyl acetate as an acyl donor were evaluated. An effect of reaction media with different logP values (t-butyl methyl ether, dichloromethane, diisopropyl ether, toluene, cyclohexane, n-hexane, isooctane and n-heptane) on the enantioselective activity of lipase was also studied. The high value of the enantiomeric ratio (E =308.5) with the utilization of isopropenyl acetate was achieved. Whereas, the best reaction medium turned out to be diisopropyl ether, C =47.9%, eep =98%, ees =90%, after 24 h of incubation. Moreover, the influence of ω6/ω9 polyunsaturated fatty acids (PUFAs) ratio in commercial (peanut, camelina, rape, pumpkin seed, walnut, sesame, avocado, rice, corn, black cumin, hemp, safflower, grape seed) oils was investigated for the lipase activity. For the first time, the cut-off limit of ω6/ω9 ratio was proposed. The ratio equal to or higher than 2.3 allows achieving higher lipolytic activity.