Stereoselective convergent synthesis of 24-substituted metabolites and analogues of vitamin D.
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.
Cornella
Iván
I
Departamento de Química Fundamental, Universidade da Coruña, E-15071 A Coruña, Spain.
Suárez
Rosa M
RM
Mouriño
Antonio
A
Sestelo
José Pérez
JP
Sarandeses
Luis A
LA
D013237:Stereoisomerism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
D014807:Vitamin D