Expedient synthesis of 17α,21-dihydroxy-9β,11β-epoxy-16α-methylpregna-1,4-diene-3,20-dione 21-acetate from prednisolone utilising a novel Mattox rearrangement.
A six step transformation of prednisolone to 17α,21-dihydroxy-9β,11β-epoxy-16α-amethylpregna-1,4-diene-3,20-dione 21-acetate has been achieved in 13% unoptimised yield. Novel conditions for effecting a Mattox rearrangement and double dehydration of prednisolone were identified. Enhanced knowledge on the oxidation of silyl Δ(19,20)-enol ethers and structural factors that impact the success of the oxidation are also presented.
Second Generation API UK, Product Development, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.
David G
DG
Hulcoop
Peter D P
PD
Shapland
D005938:Glucocorticoids / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*
D005938:Glucocorticoids; D011239:Prednisolone
Conjugate addition; Mattox rearrangement; Oxidation of silyl enol ether