224. The synthesis of lanosterol (lanostadienol)

Woodward, R. B.; Patchett, A. A.; Barton, D. H. R.; Ives, D. A. J.; Kelly, Robert C.

doi:10.1039/jr9570001131

Cited by 118 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lanosterol was purified according to the procedure of Bloch and Urech (8). 4,4-Dimethylcholesterol was prepared as described by Woodward et al (9). All sterols were checked for purity by thin-layer and gas chromatography and were found to be >97% pure.…”

Section: Methodsmentioning

confidence: 99%

Differential effects of cholesterol and lanosterol on artificial membranes.

Yèagle¹,

Martin²,

Lala³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

117

View full text Add to dashboard Cite

The effects of cholesterol, 4,4dimethylcho-lesterol, and lanosterol (4,4',14a-trimethyl-A8'4-cholestadiene-3,-ol) on some properties of lecithin vesicles have been compared. Unlike cholesterol, lanosterol retards the exit of trapped glucose from phospholipid vesicles only slightly. The 13C nuclear magnetic resonance spectrum of cholesterol/lecithin vesicles shows no resonances attributable to the sterol. By contrast, several resonances attributable to quaternary carbon atoms or methyl groups are seen in the 13C nuclear magnetic resonance spectrum of lanosterol/lecithin vesicles, indicating that lanosterol is much-less immobilized than cholesterol. Because the membrane behavior of 4,4-dimethylcholesterol is closely similar to that of cholesterol, it is concluded that the axial 14-a-methyl group is responsible for the lessened membrane immobilization of lanosterol. The results emphasize the importance of a planar sterol a-face for interaction with phospholipid acyl chains. A hypothesis on the evolution of sterols has recently been presented (1). Because the prebiotic atmosphere is assumed to have been essentially anaerobic and because oxygen is an obligatory electron acceptor in the contemporary biosynthesis of sterols, it was suggested that any chemical evolution of the sterol pathway, if it did indeed occur, must have stopped at the stage of squalene. Only when the terrestrial atmosphere turned aerobic and after the arrival of aerobic cells could squalene be oxidized to squalene oxide and then cyclized to lanosterol. However, intracellular lanosterol is rapidly metabolized to cholesterol, and cells that terminate sterol biosynthesis at the lanosterol stage are not known. We suggest that the apparently compulsory metabolic conversion of lanosterol to cholesterol can be explained on the basis of current models (1-6) for cholesterol-containing membranes. According to these models the planar a-face of cholesterol and related cholestane derivatives interacts hydrophobically with the phospholipid fatty acyl chains in the membrane bilayer. As space-filling models show, the axial methyl group at C14 of lanosterol obstructs these interactions (1). On the other hand, according to such models, the two methyl substituents at C4 of lanosterol do not interfere sterically with sterol-fatty acyl chain contacts. We provide here some evidence supporting the above hypothesis. Two types of experiments were performed. The effect of sterols on artificial membranes was examined by determining the exit of trapped glucose and independently by 13C nuclear magnetic resonance (NMR) spectroscopy. EXPERIMENTAL Phosphatidylcholine (PtdCho) was purified from egg yolk by a slight modification of the procedure of Singleton et al. (7). Cholesterol (Sigma) was dried at 560 at 0.5 mm Hg before use.[1-14C]Glucose (specific activity, 4.86 mCi/mmol) was from New England Nuclear. Lanosterol was purified according to the procedure of Bloch and Urech (8). 4,4-Dimethylcholesterol was prepared as described by Woodward et al. (9). All sterols were ...

show abstract

Section: Methodsmentioning

confidence: 99%

Differential effects of cholesterol and lanosterol on artificial membranes.

Yèagle¹,

Martin²,

Lala³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

117

View full text Add to dashboard Cite

show abstract

“…aromatic bromides instead of the desired otbromide. Also, the treatment of ^ with trimethylene thiotosylate, a reagent found to be excellent for oxidation of active methylene groups to the dithiane which can be oxidized by mercuric salts to the diketone(92), proved unsuccessful. Oxidation of 18 with lead tetracetate did not lead to OAc Pb(0Ac)4 normal product, the a-acetoxy ketone, but instead generated phenyl acetic acid^.…”

mentioning

confidence: 99%

Studies in valence isomerism of unsaturated paramagnetic species

Goettert

View full text Add to dashboard Cite

“…139-144". Crystallization from ether-ethanol yielded 610 mg (15. To a stirred suspetlsion of lithium aluminum hydride (2.5 g) in 200 ml of anhydrous ether was added 6.2 g (14.5 mmole) of lietone I1 in 300 ml of anhydrous ether (14). Excess hydride was destroyed by the dropwise addition of water and 10% sodium hydroxide solution.…”

Section: Sodium Borohydride Kedztctzon Of Ketone I Imentioning

confidence: 99%

Steroids: Vi. The Stereochemistry of 4-Ethyl-4-Methylcholest-5-en-3-One (Ii)

Just¹,

Richardson²

1964

Can. J. Chem.

View full text Add to dashboard Cite

The stereocheillistry of the title compou~ld was determined.In the course of the solvolysis of 4,4-dimethylcholesteryl tosylate, some 3,4-dimethylcholestane derivatives were isolated (1). I t was shown (2) that their formation was probably due to a I ,3-diaxial interaction of the C4-and Clo-methyl groups, resulting in deformation of the A-ring, since analogous 19-nor steroids give only the expected solvolysis products. .In order to establish whether the 4a or the @-methyl group migrated in this solvolysis, it was decided t o prepare a 4-ethyl-4-methylcholesteryl derivative of known stereochemistry a t C4. The object of this paper is to describe the preparation and structure proof of such a compound.Eth3-lation of 4-methylcholest-4-en-3-one (I) (3) with ethyl iodide and potassium t-butoxide in t-butanol resulted in the fornlation of a 70Yo yield of 4a-ethyl-@methyl-cholest-5-en-3-one (11), obtained by direct crystallization. In addition, small amounts of its isomer I11 were obtained with difficulty (see Experimental). Cltraviolet and infrared spectroscopy indicated the absence of conjugation in the two epimeric ketones. FLOWSHEET IIn order to prove the stereochemistry a t C4, a sample of 3a-hydroxy-4-ethyl-4-methylcholest-5-ene was required.Reduction of ketone I1 with sodium borohydride in aqueous dimethyl formamide (4),

show abstract

224. The synthesis of lanosterol (lanostadienol)

Cited by 118 publications

References 0 publications

Differential effects of cholesterol and lanosterol on artificial membranes.

Differential effects of cholesterol and lanosterol on artificial membranes.

Studies in valence isomerism of unsaturated paramagnetic species

Steroids: Vi. The Stereochemistry of 4-Ethyl-4-Methylcholest-5-en-3-One (Ii)

Contact Info

Product

Resources

About