Novel synthetic approach to 1alpha,25-dihydroxyvitamin D3 and analogues.
A mild and stereoconvergent synthesis of 1alpha,25-dihydroxyvitamin D(3) (calcitriol, 1a) is described. The key step is a cascade process consisting of two consecutive transformations: An initial palladium-catalyzed 6-exo-cyclocarbopalladation of vinyl triflate 4 followed by a Negishi cross-coupling reaction with alkenyl zinc 3. This approach is of interest for the rapid synthesis of a variety of new vitamin D(3) analogues of therapeutic potential, especially those modified at the triene and ring-A. The mildness of the method also allows the preparation of thermal sensitive vitamin D(3) analogues.
Maestro
Miguel
M
Departamento de Química Fundamental, Universidad de A Coruña, E-15071 A Coruña, Spain.
Gómez-Reino
Clara
C
Nicoletti
Daniel
D
Sigüeiro
Rita
R
Fraga
Ramón
R
Ghini
Alberto
A
Torneiro
Mercedes
M
Mouriño
Antonio
A
D015394:Molecular Structure; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
C118756:dihydroxy-vitamin D3; D014807:Vitamin D