Synthesis of protein conjugates and analogues of N-acetylneuraminic acid

N-Acetylneuraminic acid (1) was prepared from the salivary gland mucins of the Chinese swiftlet by an improved procedure using acidic resin hydrolysis. Compound 1 was transformed into the known acetochloroneuraminic acid (3) by a new two-step procedure. Koenigs–Knorr glycosylation of 3 followed by subsequent reductive ozonolysis of the 2-propenyl α-glycoside afforded the key aldehyde precursors 7 and 8, which were coupled to bovine serum albumin or tetanus toxoid by reductive amination. The factors influencing the extent of incorporation were investigated. A series of N-acetylneuraminic acid analogues modified at strategic functionalities were also synthesized. Keywords: sialic acid, N-acetylneuraminic acid, neoglycoproteins, bovine serum albumin, tetanus toxoid.

Lack of specificity of current anti-digoxin antibodies, and preparation of a new, specific polyclonal antibody that recognizes the carbohydrate moiety of digoxin.

Current immunoassays for digoxin do not distinguish digoxin from its glycosidic metabolites. We have synthesized a novel digoxin/bovine serum albumin conjugate via reductive ozonolysis of the lactone ring such that the carbohydrate moiety of digoxin remains intact. Antibodies raised against this conjugate show minimal cross reactivity to digoxigenin, bisdigitoxide, monodigitoxide, digoxigenin, and digitoxin. With this antibody, digoxin can be measured in the presence of these metabolites.

Synthesis of ring A of ambruticin and proof of its absolute stereochemistry

Appropriately derivatized ambruticin was converted by reductive ozonolysis to tetrahydropyran 9c and cyclopropane 12a, which were synthesized from L-arabinose and (R)-Feist's acid in an unambiguous manner.