The partial synthesis of ergosta-5,7,22,24(28)-tetraen-3β-ol

Barton, D. H. R.; Shioiri, Takayuki; Widdowson, David A.

doi:10.1039/c29700000939

Cited by 37 publications

(47 citation statements)

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“…1, compound I) and 24,25-dihydrolanosterol. Authentic I and 24,25-dihydrolanosterol were obtained from commercial lanosterol by using standard methods (12,13). Acetylation of each purified sample, using pyridine and acetic anhydride, yielded authentic lanosteryl acetate, (Fig.…”

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confidence: 99%

Pneumocysterol [(24 Z )-ethylidenelanost-8-en-3β-ol], a rare sterol detected in the opportunistic pathogen Pneumocystis carinii hominis : Structural identity and chemical synthesis

Kaneshiro

Amit

Swonger

et al. 1999

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

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Pneumocysterol [(24Z)-ethylidenelanost-8-en-3␤-ol], a rare sterol detected in the opportunistic pathogenCommunicated by William Trager, The Rockefeller University, New York, NY, November 2, 1998 (received for review February 4, 1998 ABSTRACTPneumocystis carinii pneumonia (PcP) remains among the most prevalent opportunistic infections among AIDS patients. Currently, drugs used clinically for deep mycosis act by binding ergosterol or disrupting its biosynthesis. Although classified as a fungus, P. carinii lacks ergosterol. Instead, the pathogen synthesizes a number of distinct ⌬ 7 , 24-alkylsterols, despite the abundance of cholesterol, which it can scavenge from the lung alveolus. Thus, the pathogen-specific sterols appear vital for organism survival and proliferation. In the present study, high concentrations of a C 32 sterol were found in humanderived P. carinii hominis. The definitive structural identities of two C-24 alkylated lanosterol compounds, previously not reported for rat-derived P. carinii carinii, were determined by using GLC, MS, and NMR spectroscopy together with the chemical syntheses of authentic standards. The C 31 and C 32 sterols were identified as euphorbol (24-methylenelanost-8-en-3␤-ol) and pneumocysterol [(24Z)-ethylidenelanost-8-en-3␤-ol], respectively. The identification of these and other 24-alkylsterols in P. carinii hominis suggests that (i) sterol C-24 methyltransferase activities are extraordinarily high in this organism, (ii) 24-alkylsterols are important components of the pathogen's membranes, because the addition of these side groups onto the sterol side chain requires substantial ATP equivalents, and (iii) the inefficacy of azole drugs against P. carinii can be explained by the ability of this organism to form 24-alkysterols before demethylation of the lanosterol nucleus. Because mammals cannot form 24-alkylsterols, their biosyntheses in P. carinii are attractive targets for the development of chemotherapeutic strategies against this opportunistic infection.Sterols and their biosyntheses are excellent targets for chemotherapeutic attack against infectious microbes, especially the fungi. Polyene antibiotics such as amphotericin B bind avidly to ergosterol in fungal cell membranes. After the sterol-drug complexes aggregate, large pores in the membranes are formed, dissipating ion gradients. Fluconazole and some other compounds routinely used clinically for systemic mycosis target ergosterol biosynthesis at nuclear demethylation steps. Ergosterol was not detected in Pneumocystis carinii carinii that was isolated and purified from the lungs of corticosteroid-immunosuppressed rats. In this respect, the pathogen appears to be unlike higher fungi. However, the organism synthesizes its own distinct sterols, e.g., fungisterol (24-methylcholest-7-en-3␤-ol and 24-ethylcholest-7-en-3␤-ol; refs. 1-4). Parasites generally scavenge sterols (e.g., cholesterol) from the host and utilize them for membrane formation and other cell functions. If host sterols do not fulfill the precise stereochemi...

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Pneumocysterol [(24 Z )-ethylidenelanost-8-en-3β-ol], a rare sterol detected in the opportunistic pathogen Pneumocystis carinii hominis : Structural identity and chemical synthesis

Kaneshiro

Amit

Swonger

et al. 1999

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

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“…Gases: carbon monoxide 3.7, hydrogen 4.3 (1:1, Messer-Griesheim). The following compounds were prepared according to literature procedures: 2-(bro-momethyl)-1-butene (5b), [13] 2-(bromomethyl)-3-methyl-1-butene (5c), [14] 1-bromo-2-phenyl-2-propene (5d), [15] 2-[(tert-butylsilyloxy)-methyl]-2-propen-1-ol, [16] and o-DPPFA (8).…”

Section: Methodsmentioning

confidence: 99%

Desymmetrizing Hydroformylation of Diallylcarbinols with the Aid of a Planar‐Chiral, Catalyst‐Directing Group

Breit

Breuninger

2005

Eur J Org Chem

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The desymmetrizing hydroformylation of diallylcarbinols has been achieved by employing a planar-chiral, substratebound catalyst-directing group − the ortho-(diphenylphosphanyl)ferrocenylcarbonyl group (o-DPPF). The method allows the simultaneous construction of two stereogenic centers in a 1,3-relative position with high levels of stereocontrol. The diastereoselectivity was investigated as a function of substrate structure. Determination of the relative and absolute configuration of the product aldehydes (chemical

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“…67, 5.50, 5.40 (all br d, J ca. 6 Hz,1 H;H6,7,11) Conversion from compound 9 to compound 11: A solution of compound 9 (4.8 g) in CH 2 Cl 2 (121 mL) was treated with 4-phenyl-1,2,4-triazoline-3,5-dione (1.53 g, 8.72 mmol) at room temperature for 1 h. Removal of the solvent from the reaction mixture under reduced pressure gave a crude product, which was purified by column chromatography (SiO 2 100 g, nhexane/EtOAc 5:1) to furnish a Diels ± Alder adduct (4.8 g, 71 % from compound 6). A solution of the Diels ± Alder adduct of compound 9 (4.6 g, 6.34 mmol) in CHCl 3 (127 mL) was treated with 3-chloro peroxybenzoic acid (mCPBA) (10.9 g, 63.4 mmol) at room temperature for 17 h. The reaction mixture was poured into 20 % aqueous K 2 CO 3 , then the whole mixture was extracted with EtOAc.…”

Section: Methodsmentioning

confidence: 99%