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Retraction published on 10 August 2000, see Molecules 2000, 5(8), 992.
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An Improved Synthesis of 3b-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate)

Edward J. Parish
Hang Sun
Stephen Kizito
Terrence L. Boos
Department of Chemistry, Auburn University, Auburn, AL, 36849, USA
Author to whom correspondence should be addressed.
Molecules 2000, 5(2), 114-117;
Submission received: 29 November 1999 / Accepted: 10 January 2000 / Published: 11 February 2000


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


The C-24 of lanosterol is a major site of sterol metabolism in plants, fungi, and animals [1,2,3]. As a result of our continuing studies on sterol biosynthesis, we have devised a simplified chemical synthe-sis of 3β-acetoxy-lanost-8-en-24-one (2, 24-ketolanosteryl acetate), a key intermediate in the synthesis of C-24 alkylated metabolites and potential regulators of sterol biosynthesis.

Results and Discussion

We now report a rapid and convenient chemical synthesis of 2 utilizing commercial lanosterol as a starting material. Previous syntheses have required multiple step procedures resulting in poor yields [4,5,6,7]. In the present study, we have utilized the technique of hydroboration to form an organobo-rane intermediate. Oxidation of the resulting organoborane by pyridinium fluorochromate (PFC) in re-fluxing methylene chloride gave the ketone 2 directly, in high yield. PFC is a mild and selective oxi-dant and has been used in the oxidation of organic compounds [8,9,10].
Scheme 1. Synthesis of 24-ketolanosteryl acetate.
Scheme 1. Synthesis of 24-ketolanosteryl acetate.
Molecules 05 00114 sch001


The high yields, anhydrous reaction conditions and easy work-up procedure make this a highly convenient method for the synthesis of 2 and expands the scope and utility of using PFC in organic oxidations.



Commercial lanosterol was purified by multiple (4) recrystallizations from acetone/water and after recrystallization was found to be a mixture of lanosterol (61%) and 24,25-dihydrolanosterol (39%) upon GLC analysis. Acetylation of purified commercial lanosterol was accomplished by using acetic anhydride and pyridine, which yielded lanosteryl acetate. Lanosteryl acetate (1) (12.0 g, aprox. 15.6 mmol based on 61% purity) was dissolved in THF (75 mL) and cooled to 2°C in an ice-H2O bath. While maintaining a N2 atmosphere, 10 mL (10 mmol) of a 1M BH3⋅THF solution was added over a 10 min period. The reaction was stirred for 1h at 2°C under N2. Ice was cautiously added to decompose the excess hydride, H2O was added, and the reaction thoroughly extracted with ether. The extracts were dried over anhydrous MgSO4, evaporated at reduced pressure, toluene was added and the solvent evaporated at reduced pressure to remove traces of H2O (azeotrope). The residue was dried in a vac-uum desicator over P2O5 for 2h and dissolved in methylene chloride (100 mL), PFC (15 g) and mo-lecular sieves (100 mg, type 4Å) were added, and the reaction mixture refluxed for 3h. Saturated aque-ous NaCl was added and the mixture was extracted with methylene chloride. The solvent was removed under reduced pressure and the residue subjected to column chromatography. The solvent system used to perform the separation was toluene/hexane, the concentrations and amounts were varied as follows: 1:1 (500 mL), 3:1 (500 mL), and toluene (500 mL). The less polar component eluted first and after re-moval of the solvent, under reduced pressure, was recrystallized from acetone/water to yield 3.93 g (approx. 84% of the 24,25-dihydrolanosteryl acetate portion of commercial lanosteryl acetate), melting at 118-119°C.[11] Continued elution resulted in the isolation of the more polar component. After evaporation of the solvent, the dried residue was recrystallized from acetone/water (cooling to -15°C) to yield 6.65 g (approx. 88%) of 3β-acetoxy-lanost-8-en-3β-ol-24-one (2). m.p. 136-137°C (lit. 137°C)[5].

Spectral Data

1H NMR (CDCl3) [12] 0.682(s, 3H, C-18-CH3), 0.853-.903(m, 12H, C-14-CH3, 2 C-4-CH3, C-18-CH3), .972(s, 3H, C-19-CH3), 1.078(d, 3H, C27), 1.106(d, 6H, C-26), 2.050 (s, 3H, acetate), 4.486 (m, 1H, C-3-H).
13C NMR (CDCl3) [12,13] 15.970(C30), 16.729(C18), 18.309(C6), 18.519 & 18.578(C26,C27), 18.696(C21), 19.392(C19), 21.184(C11), 21.525(Acetate), 24.375(C2), 24.427(C28), 26.564(C7), 28.108(C29), 28.292(C16), 30.309(C23), 30.983 & 31.163(C12,C15), 35.468(C1), 36.292(C16), 37.097(C10), 37.682(C22), 38.002(C4), 41.023(C25), 44.692(C13), 50.004(C14), 50.561 & 50.693(C5,C17), 81.110(C3), 134.448 & 134.659(C8,C9), 171.199(Acetate), 215.659(C24).
MS (Electron Impact) 484 (M, 9%), 469 (M-CH3, 16%), 424 (M-acetic acid, 2%), 409 (M-CH3-acetic acid, 35%), 394 (M-2CH3-acetic acid, 2%), 379 (M-3CH3-acetic acid, 1%), 71 (98%), 43 (ace-toxy, 100%).
IR: vmax: 1729 (acetate), 1702 (ketone), 1240, 1025 cm-1.

References and Notes

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  • Samples Availability: Available from MDPI.

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MDPI and ACS Style

Parish, E.J.; Sun, H.; Kizito, S.; Boos, T.L. An Improved Synthesis of 3b-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate). Molecules 2000, 5, 114-117.

AMA Style

Parish EJ, Sun H, Kizito S, Boos TL. An Improved Synthesis of 3b-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate). Molecules. 2000; 5(2):114-117.

Chicago/Turabian Style

Parish, Edward J., Hang Sun, Stephen Kizito, and Terrence L. Boos. 2000. "An Improved Synthesis of 3b-Acetoxy-lanost-8-en-24-one (24-Ketolanosteryl Acetate)" Molecules 5, no. 2: 114-117.

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