Acylation of lycoctonine: Semi-synthesis of inuline, delsemine analogues and methyllycaconitine

Bioactive Alkaloids from Plants Poisonous to Livestock in North America

“…For example, it can block acetylcholine evoked currents in rat fetal hippocampal neurons at picomolar concentrations providing pharmacological evidence that the neuronal depolarization is mediated by alpha‐7 nAChR,, and some norditerpenoid alkaloids isolated from D. denudatum have been reported to act as acetylcholinesterase inhibitors . Structure‐function studies of norditerpenoid alkaloids have shown that the aromatic ester functional group on MLA is a significant haptophore, and that the succinimide group imparts significant toxicity to the alkaloids ,. Current research interest in larkspur alkaloids includes the identification of new alkaloids, [24,25], species alkaloid composition, risk assessment, and the study of biological activities in rats and insects ,…”

“…[20] Structure-function studies of norditerpenoid alkaloids have shown that the aromatic ester functional group on MLA is a significant haptophore, [21] and that the succinimide group imparts significant toxicity to the alkaloids. [22,23] Current research interest in larkspur alkaloids includes the identification of new alkaloids, [24,25], species alkaloid composition, risk assessment, [26][27][28] and the study of biological activities in rats and insects. [29,30]…”

A Review of Advances in the Synthesis of Analogues of the Delphinium ­Alkaloid Methyllycaconitine

“…Subsequent reaction of the half-acid amide mixture with carbonyl diimidazole (CDI) in dicholoromethane achieved closure of the succinimide ring and formation of MLA (4), in 55% yield from inuline (8), which was found to be identical to the natural product. 36 At this time, Blagborough and co-workers 37 also determined the absolute stereochemistry of the methylsuccin- imide moiety to be S. This was accomplished by isolating MLA (4) from garden hybrid Delphiniums, purification by vacuum liquid chromatography then saponification with sodium hydroxide to produce lycoctonine (5) and isomeric N-(methylsuccinyl)anthranilic acids. Acid-catalysed hydrolysis of the half-acid amides with aqueous sulfuric acid afforded methyl succinic acid 13 with little detectable racemisation.…”

Asymmetric reduction of 2-substituted 2-butenolides with reductase from Marchantia polymorpha

“…On the other hand, no reduction occurred in the case of 3-substituted 2-butenolide 4, indicating that the p68 reductase isolated from M. polymorpha is a novel enzyme apparently different from the reductase in yeast with respect to the substrate specificity. A challenging substrate for the asymmetric reduction, citraconic anhydride 5, was reduced to give enantiomerically pure (R)-methylsuccinic anhydride 9 (100% ee) 10,11 which is a potentially useful chiral building block for organic and polymer syntheses. 11,12 These results demonstrate that the p68 reductase from M. polymorpha is able to catalyze the enantiofacediscriminating hydrogenation of the C-C double bond of 2-substituted 2-butenolides to give (R)-butanolides and capable of reducing citraconic anhydride to give (R)-methylsuccinic anhydride.…”