An Improved Synthesis of 3b-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate)

Abstract

Abstract:The oxidation of a borane intermediate by PFC provides a convenient synthesis of 24-ketolanosteryl acetate.

Synthesis of obtusifoliol and analogues as CYP51 substrates

“…Efficient synthetic routes to 1b , 2 and 4b from lanosterol have been reported, 14–19 and our success in synthesising obtusifoliol ( 3 ) is reported herein. The developed route to obtusifoliol ( 3 ) afforded several synthetically and biologically relevant compounds en route to the target, providing an excellent basis for future generation of CYP51 substrates/inhibitors to study emerging azole resistance in pathogens.…”

“…20 Heating of lanosterol-type compounds in the presence of strong acids is known to partially isomerise the generally inert C-8,9 double bond to the 7,8-olefin, 32,33 and significant effort has previously been spent attempting to find conditions for this ring-close reaction that avoid use of strong acids. 18,34 These conditions were applied regardless as Δ 7,8 -obtusifoliol (16) was of interest as a potential substrate of our CYP51.…”

“…This mixture contains mostly lanosterol (1a, ∼60%) along with 24,25-dihydrolano-sterol (1b, ∼40%) as well as other trace impurities including close analogues agnosterol and 24,25-dihydroagnosterol that feature a 7,9-diene. 13 Efficient synthetic routes to 1b, 2 and 4b from lanosterol have been reported, [14][15][16][17][18][19] and our success in synthesising obtusifoliol ( 3) is reported herein. The developed route to obtusifoliol (3) afforded several synthetically and biologically relevant compounds en route to the target, providing an excellent basis for future generation of CYP51 substrates/inhibitors to study emerging azole resistance in pathogens.…”

The Economic Synthesis of Pyridinium Fluorochromate(VI), C5H5NH[CrO3F] (PFC), and Solvent‐Free Oxidation of Organic Substrates with PFC

“…Thus, it very efficiently oxidizes primary, secondary, and allylic alcohols, fused ring hydrocarbons, benzylic systems, toluenes, sulfides, benzyl ethers, phosphorus compounds, arylalkanes, hydroxy acids, thio acids, benzaldehydes, and aromatic anils, for instance. [10 -14] PFC, owing to its controlled acidity (pk a , 2.7), [7,9] was successful in oxidizing acid sensitive substrates such as 5-andostene-3b,17b-diol to the corresponding 17-keto-steroid, [10] and was used in the synthesis of biochemically important S-( þ )-4-formyl-4-butanolide, chiral synthon (R)-1-benzoyloxy-3-buten-2-ol, derivatives of dimethyl penam and dimethyl penam-S,S-dioxide [14] and 3b-acetoxy-lanost-8-en-24-one (24-ketolanosteryl acetate). [14] It also permits oxidative deprotection of oximes and desilylative oxidations of alkyl trimethyl silyl ethers.…”

“…[10 -14] PFC, owing to its controlled acidity (pk a , 2.7), [7,9] was successful in oxidizing acid sensitive substrates such as 5-andostene-3b,17b-diol to the corresponding 17-keto-steroid, [10] and was used in the synthesis of biochemically important S-( þ )-4-formyl-4-butanolide, chiral synthon (R)-1-benzoyloxy-3-buten-2-ol, derivatives of dimethyl penam and dimethyl penam-S,S-dioxide [14] and 3b-acetoxy-lanost-8-en-24-one (24-ketolanosteryl acetate). [14] It also permits oxidative deprotection of oximes and desilylative oxidations of alkyl trimethyl silyl ethers. [15] This reagent has been used extensively in the studies of reaction dynamics of a variety of substrates.…”