Concise synthesis of (+)-conduritol F and inositol analogues from naturally available (+)-proto-quercitol and their glucosidase inhibitory activity
An effective synthesis of (+)-conduritol F, (+)-chiro- and (+)-epi-inositols from naturally available (+)- proto-quercitol is described. This synthetic method provides a concise synthesis of cyclitols in enantiomerically pure form. Of the synthesized cyclitols, (+)-conduritol F potently inhibits type I α-glucosidase with an IC50 value of 86.1 lM, which is five times greater than the standard antidiabetic drug, acarbose.
Potent chemical chaperone compounds for GM1-gangliosidosis: N-substituted (+)-conduramine F-4 derivatives
The development of second-generation valienamine-type chemical chaperones for GM1-gangliosidosis is described. Several N-substituted (+)-conduramine F-4 derivatives were designed as novel chemical chaperones based on a lead chaperone compound, N-octyl-4-epi-β-valienamine, to decrease the inhibitory activity while increasing the enzyme enhancement activity. Among the derivatives synthesized during this study, a conduramine derivative with an N-cyclohexylmethyl group has demonstrated significant enhancement of R201C mutated β-galactosidase activity. This journal is