Ro-27-0574

Chemical Name: 26,26,26,27,27,27-Hexafluoro-1alpha,25-dihydroxy-20,21-methylene-23,24-didehydro-19-norvitamin D3
CAS No. 256459-48-0
项目整合开发状态: Preclinical
项目研究机构: Roche (Originator)
合成路线:The dimethylaluminium chloride-catalyzed addition of formaldehyde to the isopropenyl derivative (I) produced the homoallylic alcohol (II).The cyclopropane ring was then constructed over (II) by the Simmons-Smith procedure using diiodomethane and diethylzinc.The resulting cyclopropylethyl alcohol (III) was oxidized to aldehyde (IV) with pyridinium chlorochromate in CH2Cl2,and subsequent addition of diethyl azomethylphosphonate generated the terminal acetylene (V).The lithium acetylide of (V) was then added to hexafluoroacetone (VI),producing the propargylic alcohol (VII).Cleavage of the silyl protecting group with fluorosilicic acid liberated the secondary alcohol (VIII),which was further oxidized to ketone (IX) employing pyridinium dichromate.Condensation of this ketone (IX) with the ylide resulting from phosphine oxide (X) and n-butyllithium at low temperature produced the silylated cholecalciferol analogue (XI).Finally,desilylation with tetrabutylammonium fluoride gave the title compound.