【药物名称】Ro-27-0574
化学结构式(Chemical Structure):
参考文献No.38806
标题:1,3-Dihydroxy-20,20-dialkyl-vitamin D3 analogs
作者:Uskokovic, M.R.; Manchand, P.S. (F. Hoffmann-La Roche AG)
来源:EP 1015423; WO 9912894
合成路线图解说明:

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.

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