Crystallographic and NMR Investigation of Ergometrine and Methylergometrine, Two Alkaloids from Claviceps purpurea.

Ergometrine and methylergometrine are two alkaloids that are used as maleate salts for the prevention and control of postpartum hemorrhage. Although the two molecules have been known for a long time, few and discordant crystallographic and NMR spectroscopic data are available in the literature. With the aim of providing more conclusive data, we performed a careful NMR study for the complete assignment of the 1H, 13C, and 15N NMR signals of ergometrine, methylergometrine, and their maleate salts. This information allowed for a better definition of their conformational equilibria. In addition, the stereochemistry and the intermolecular interactions in the solid state of the two maleate salts were deeply investigated by means of single-crystal X-ray diffraction, showing the capability of these derivatives to act as both hydrogen-bond donors and acceptors, and evidencing a correlation between the number of intermolecular interactions and their different solubility.

A New Chemoenzymatic Synthesis of the Chiral Key Intermediate of the Antiepileptic Brivaracetam.

Brivaracetam is a new anticonvulsant compound, recently approved as an antiepileptic drug. This drug substance presents a 4-substituted pyrrolidone structure: the (4R)-configuration of the stereocenter present on the heterocyclic ring is the main target of the synthesis. The described method allows to prepare the suitable optically pure 2-substituted primary alcohol by means of a Pseudomonas fluorescens lipase-catalyzed transesterification. The obtained (2R)-alcohol was easily transformed into the (3R)-3-propylbutyrolactone, an advanced intermediate of brivaracetam. The described synthetic pathway is completed with the chromatographic methods and the NMR analyses necessary to establish the chemical and the optical purity of the intermediates and of the final lactone.

Inhibitory effect of stabilized analogues of glycoglycerolipids on Epstein-Barr virus activation and mouse skin tumor promotion.

Nine new synthetic compounds, structurally related to the most active glycoglycerolipid analogues carrying a hexanoyl chain, were tested for their anti-tumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus (EBV) activation. All these compounds, in which the ester function is replaced by different metabolically more stable groups, were almost as active as their ester reference compounds in inhibiting the EBV activation promoted by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Two of these, devoid of any functionality on the lipophilic chain, when tested in an in vivo two-stage carcinogenesis test, exhibited marked inhibitory effects on mouse skin tumor promotion.