Work has continued on the syntheses of glycolipid analogues of sphingolipids that yield a chromogenic moiety on enzymatic hydrolysis. These compounds are used for the diagnosis and studies of Niemann-Pick, Gaucher's and Krabbe's and Krabbe's disease. Conduritol B epoxide, a saccharide that strongly inhibits Beta-glucosidases, was synthesized by a method developed by this section that provides the product in greater yield than previously available and permits the preparation of this compound containing a tracer with extraordinarily high specific radioactivity. Administration of conduritol B-epoxide to animals produces a syndrome that resembles Gaucher's disease in humans by inhibiting the enzyme glucocerebrosidase. Radioactive conduritol B-epoxide reacts with the active site of glucocerebrosidase isolated from normal human tissues and from patients with Gaucher's disease. This use of the radioactive conduritol Beta-epoxide will materially accelerate the identification of the amino acid substitutions (or deletions) that occur in the glucocerebrosidase moledule in patients with Gaucher's disease. Also fluorescent and cytotoxic substrates were prepared which can be used for the separation of affected and normal cells.
