Chemical structures, production and enzymatic transformations of sapogenins and saponins from Centella asiatica (L.) Urban.

Centella asiatica (L.) Urban is a medicinal herb traditionally used in Asiatic countries for its multiple therapeutic properties, essentially due to its accumulation of specific pentacylic triterpenoid saponins, mainly asiaticoside and madecassoside and the corresponding sapogenins. This review summarizes the updated knowledge about the chemical structures of about forty centelloids, found as minor metabolites in Centella, and all derived from ursane and oleane ring patterns.

A new derivative detected in accelerated ageing of artesunate-amodiaquine fixed dose combination tablets.

An unknown impurity detected in small amounts during the heat treatment of artesunate-amodiaquine bilayer tablets was purified by semipreparative HPLC and identified by MS and NMR as the tetrahydrofuranyl acetate-rearranged derivative of anhydrodihydroartemisinin. When anhydrodihydroartemisinin was treated with a Fe(II) salt in acetonitrile-water solution, the same product was generated, together with an isomeric 2-deoxy-4α-hydroxy-anhydrodihydroartemisinin derivative, as expected from the usual homolytic radical opening of the endoperoxide bond previously described for other artemisinin derivatives.

Microbial production of phase I and phase II metabolites of midazolam.

Midazolam, a potent benzodiazepine derivative and a typical substrate of CYP3A4/3A5, is essentially metabolized in human into 1'-hydroxymidazolam, then eliminated as the corresponding phase II metabolite, the 1'-O-β-D-glucuronide derivative. A high yield alternative to the current multistep synthesis of 1'-hydroxymidazolam is described, using a biotransformation of midazolam by a fungal microorganism, Beauveria bassiana. The corresponding phase II metabolite, 1'-hydroxymidazolam-1'-O-β-D-glucuronide, has been then prepared by chemical synthesis (3 steps, 20% yield), or by microbial glucuronidation (one step, 20% yield) using a Streptomyces sp.

Microbial production of phase I and phase II metabolites of propranolol.

1. The production in multimilligram amounts of 4- and 5-hydroxylated metabolites of (R)- or (S)-propranolol by biotransformation with two fungal strains, an Absidia sp. M50002 and a Cunninghamella sp.

Parameters and mechanistic studies on the oxidative ring cleavage of synthetic heterocyclic naphthoquinones by Streptomyces strains.

Screening of fungal and bacterial strains allowed selection of two Streptomyces strains ( S. platensis and S. cinnamonensis) that oxidatively cleave, in moderate to high yields (up to 65% in 24 h), the quinonic ring of a thiazole fused 1,4-naphthoquinone compound, INO5042, used as a model compound for a series of homologous substituted heterocyclic naphthoquinones.