title: Synthesis of stable analogues of thiamine di- and triphosphate as tools for probing a new phosphorylation pathway.
abstract: Thiamine (vitamin B1) is an essential nutritional factor metabolized inside the body in its mono-, di-, and triphosphate forms. Although the action of thiamine and thiamine diphosphate have been intensely investigated, many questions remain unanswered and the role of thiamine triphosphate is still especially unknown. To probe recent hypotheses on the implication of thiamine triphosphate in a new phosphorylation pathway involving synaptic proteins, we synthesized a series of thiamine di- and triphosphate analogues that are resistant to both enzymatic and chemical hydrolyses. The key step in the preparation of the title compounds is the coupling of thiamine propyl disulfide with adequately protected methylenebis-phosphonic acid, the corresponding triphosphate analogue, and difluoromethylenebisphosphonic acid.
authors.affiliation: Laboratoire de Chimie Bioorganique associé au CNRS Faculté de Pharmacie Université Louis Pasteur de Strasbourg, 74, route du Rhin, B.P.24, 67401 Illkirch, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Klein
authors.forename: Hoàng-Oanh
authors.initials: HO
authors.lastname: Nghiêm
authors.forename: Alain
authors.initials: A
authors.lastname: Valleix
authors.forename: Charles
authors.initials: C
authors.lastname: Mioskowski
authors.forename: Luc
authors.initials: L
authors.lastname: Lebeau