title: Stereoselective convergent synthesis of 24-substituted metabolites and analogues of vitamin D.
abstract: The synthesis of vitamin D(3) active metabolites [24R,25-(OH)(2)-D(3), 24S,25-(OH)(2)-D(3) and 1alpha,24R,25-(OH)(3)-D(3)] and the first 24-aminovitamin D(3) derivatives [24S-benzoylamino-25-OH-D(3) and 24S-benzoylamino-1alpha,25-(OH)(2)-D(3)] are reported. The stereogenic center at C-24 was generated through ultrasonically induced aqueous conjugate addition of iodide 8 to dioxolanone 6 or oxazolidinone 7. The vitamin D triene system was constructed using the Lythgoe approach. The synthetic route, which is both short (6 or 7 steps from iodide 8) and efficient (32-45% overall yield), constitutes a practical method for the preparation of 24-functionalized metabolites and analogues of vitamin D(3). The ultrasonically induced conjugate addition in the key step provides a novel example of a highly stereoselective reaction promoted by the zinc-copper couple in aqueous media.
authors.affiliation: Departamento de Química Fundamental, Universidade da Coruña, E-15071 A Coruña, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Cornella
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Suárez
authors.forename: Antonio
authors.initials: A
authors.lastname: Mouriño
authors.forename: José Pérez
authors.initials: JP
authors.lastname: Sestelo
authors.forename: Luis A
authors.initials: LA
authors.lastname: Sarandeses
mesh_terms: D013237:Stereoisomerism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D014807:Vitamin D