Stereoselective synthesis of C24-hydroxylated vitamin D3 analogs: a practical and expeditius route to calcipotriol.
The synthesis of the clinically important drug calcipotriol (2, MC903) is described as an example of a new and efficient approach to C24-hydroxylated analogs and metabolites of vitamin D3 (1). The key step of the process is the generation of the C24 stereocenter by DAIB [(-)-3-exo-(dimethylamino)isoborneol]-catalyzed addition of the alkenylzinc derivative of alkyne 3 to cyclopropylcarboxaldehyde.
Rumbo
Antonio
A
Departamento de Química Orgánica y Unidad Asociada al C.S.I.C., Universidad de Santiago de Compostela, E-15706 Santiago de Compostela, Spain. antonio.rumbo@usc.es
Pérez-García
Xenxo
X
Mouriño
Antonio
A
D000438:Alcohols / Q000737:chemistry; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry; D002384:Catalysis; D002454:Cell Differentiation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004100:Dihydroxycholecalciferols / Q000138:chemical synthesis* / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D011565:Psoriasis / Q000188:drug therapy*; D013237:Stereoisomerism
D000438:Alcohols; D004100:Dihydroxycholecalciferols; C055085:calcipotriene; C023850:1 alpha,24-dihydroxyvitamin D3; D002117:Calcitriol