Stereoselective Synthesis of Chiral Isatin Containing Bisphosphonates as Potential Anti-Resorption Bone Drugs

Bisphosphonates are currently the major class of drugs used for the treatment of osteoporosis, a disease that leads to bone fragility and increase in fracture risk that affects hundreds of million elderly individual worldwide. All commercially available bisphosphonates are achiral albeit their activity is demonstrated to be related to inactivation of specific enzymes. Cinchona alkaloid urea derivatives are efficient organocatalysts for the asymmetric aldol reaction of ketones to an isatin containing bisphosphonate precursor to provide a class of new chiral enantioenriched potentially anti-resorption bone drugs. High chemical yields were generally achieved in a wide array of substrates tested an

Enantioselective Catalytic Desymmetrization of Maleimides by Temporary Removal of an Internal Mirror Plane and Stereoablative Over-reduction: Synthesis of (R)-Pyrrolam A

A highly enantioselective (>95% ee) strategy to affect the desymmetrization of a maleimide has been performed by temporary attachment to an anthracene template followed by asymmetric reduction with an oxazaborolidine catalyst. A stereoablative over-reduction process was partially responsible for the high levels of enantioselectivity. Exemplification of the strategy by stereoselective functionalization and retro-Diels−Alder reaction provided the natural product pyrrolam A

Quick Identification of Piperidine Alkaloid from Roots of Grewia nervosa and Their Glucosidase Inhibitory Activity

Grewia nervosa is a herbal plant used in traditional medicine for different purposes. Bioassay-guided chemical fractionation of G. nervosa roots resulted in an identification of two known and one new compound, namely microgrewiapine A, homomicrogrewiapine, and N-methylmicrocosamine, respectively. Their structures were determined using combination of LC/HR-MS, 1H-NMR, and IR spectral analyses and followed by comparison with those reported in the literature. The problematic separation of these alkaloids on traditional column chromatography (Silica gel, Octadecyl silane, Sephadex) was resolved by using HPLC. Structurally similar compounds from the piperidine family have been characterized by using HR-MS analysis in combination with NMR data of crude samples. The major constituent i.e. N-methylmicrocosamine isolated from the butanol fraction of methanol root extract (MRE) was found to possess the dose dependent α-glucosidase inhibition activity with an IC50 value of 53.40 μm. Furthermore, N-methylmicrocosamine showed maximum α-glucosidase inhibition of 97.48 ± 0.7% at 107.5 μm, which is approximately 1.3 × 103 fold higher than the activity shown by acarbose (97.72% inhibition at 61.95 mm), a standard anti-diabetic drug available commercially. This work also reports the in vitro α-glucosidase inhibitory activity of the major alkaloids isolated from G. nervosa for the first time. © 2017 Wiley-VHCA AG, Zurich, Switzerlan