Vitamin D derivatives with cyclic substructures in the side chains, process and intermediate products for their production, and the use for the production of pharmaceutical agents

A process for the production of a compounds of formula IIa

• in which
• E is a side chain,
• E is a side chain,
• R7, R8, are each, independently of one another, a hydrogen atom or a methyl group, or together are an exocyclic methylene group or a cyclopropyl ring,
• Y2 is a hydrogen atom or a group —(CO)R5,
• Y3 is a hydrogen atom, a hydroxy group, a halogen atom, a group —O(CO)R5 or an OR5 group,
• R5 is an aromatic radical with 5 to 12 C atoms or an aliphatic C1-C12 alkyl radical, which optionally is interrupted by 1-2 oxygen atoms, 1-2 sulfur atoms and/or 1-2 NH groups and/or optionally is substituted by 1-2 hydroxy groups, 1-2 amino groups, 1-2 SH groups, 1-2 COOH groups and/or 1-2 phenyl groups,
• Y5 is a fluorine atom, a (CH2)n—OH group or a (CH2)n—O(CO)R5 group,
• n is 0 to 4,
• and optionally present hydroxy groups are each indpendently optionally present in protected form, said process comprising:
• converting a ketone of general formula XIIIc
• in which
• E is a side chain, and optionally present keto groups and/or hydroxy groups are present in protected form, by reaction with trimethylsilylacetic ester in the presence of a base or with a Wittig reagent in an aprotic solvent into a compound of formula XXXIVc
• in which
• Y6 is C1-C6 alkyl group, a benzyl group, or a phenyl group;
• converting the ester group by reaction with a reducing agent in hexane, toluene, tetrahydrofuran, diethyl ether or dioxane to form an allyl alcohol of formula XXXVc
• converting the allyl alcohol into a compound of formula XXXVc
• in which
• L is a leaving group, which is isolated or optionally produced in situ and immediatelly further reacted to form a Wittig reagent of formula XXXVIc,
• in which
• G is a C1-C10 alkyl group, a C1-C10 alkoxy group, a phenyl radical or a phenoxy radical;
• reacting the compound of formula XXXVIc with a ketone of formula XXXIIIc
• in which
• Y′3 is a hydrogen atom, a halogen atom, a protected hydroxy group, a group —O(CO)R5 or an OR5 group;
• and
• optionally cleaving protective groups.