Synthesis of 17-epi-calcitriol from a common androstane derivative, involving the ring B photochemical opening and the intermediate triene ozonolysis.
An efficient synthesis of 17-epi-calcitriol 2, an epimer of natural hormone, via 17-epi-cholesterol 5a is described. Synthesis of 5a includes palladium-catalyzed cyclopropanation of the common androstane derivative 7 with an alkyl diazoacetate, reductive fission of the less shielded side of cyclopropane carboxylic acid esters 6, oxidation of the products into acid 11a, and alkylation of ester 11b. Photolysis of 7,8-dedydro-17-epi-25-hydroxycholesterol 19b and consecutive thermal rearrangement gave a mixture of several products that was subjected to ozonolysis to provide, after chromatography, hydroxy ketone 3a. The silyl derivative 3b was coupled with the respective ring A building block.
Kurek-Tyrlik
Alicja
A
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, 01-224 Warsaw, Poland.
Michalak
Karol
K
Wicha
Jerzy
J
D000731:Androstanes / Q000737:chemistry*; D002117:Calcitriol / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D015525:Fatty Acids, Omega-3 / Q000737:chemistry*; D015394:Molecular Structure; D010126:Ozone / Q000737:chemistry*; D010777:Photochemistry; D013237:Stereoisomerism
D000731:Androstanes; D015525:Fatty Acids, Omega-3; C102870:trienyl; D010126:Ozone; D002117:Calcitriol; C033936:androstane