An integrated approach to the synthesis of contiguously substituted xanthopurpurins, pachybasins and purpurins.

Caron, Brigitte; Brassard, Paul

doi:10.1016/s0040-4020(01)80322-7

Cited by 14 publications

(13 citation statements)

References 54 publications

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“…Commercially available 2,4-dichloro-1,4-benzoquinone was treated with the Danishefsky diene derived from tiglic aldehyde 7 to form a Diels–Alder adduct, which on Jones oxidation yielded 2-chloro-8-hydroxy-7-methylnaphthaquinone 8 (60%). A subsequent Diels–Alder reaction with the Danishefsky diene derived from ethyl diacetoacetate 9 yielded oxanthroquinone ethyl ester ( 11 ) (58%) (ESI Fig. S6a–S6b † ), which on hydrolysis returned oxanthroquinone ( 9 ) (88%).…”

Section: Resultsmentioning

confidence: 99%

“…Bioassay-guided fractionation of a solid phase (cracked wheat) cultivation of MST-134270 resulted in the isolation and characterisation of five new polyketides, (+)-oxanthromicin (1), (±)-hemi-oxanthromicin A (2), (±)-hemi-oxanthromicin B (3), (±)-spiro-oxanthromicin A (4), and oxanthroquinone (9), as well as the detection and identification of four new metastable analogues, (±)-spiro-oxanthromicins B1/B2 (5/6), and (±)-spirooxanthromicins C1/C2 (7/8), and the isolation of the known indole alkaloid staurosporine (10) (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…In presenting a plausible mechanism for the biosynthetic/ chemical origins of 1-9 (Fig. 4), we speculate that the polyketide precursor, oxanthroquinone (9), undergoes stereospecific methylation to a single (10R) enantiomer of 2, which in turn undergoes dimerisation to (+)-oxanthromicin (1). Acidmediated dehydration of 2 could deliver an achiral carbocation intermediate that is reversibly quenched with either H 2 O or MeOH to yield (±)-hemi-oxanthromicin A (2) or B (3) respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Oxanthroquinone ethyl ester (11). A solution of 2-chloro-8hydroxy-7-methylnaphthaquinone (80 mg, 0.36 mmol) and the Danishefsky diene derived from ethyl diacetoacetate 9 (230 mg, 0.72 mmol) in toluene (5 mL) was refluxed for 3 days. After concentrating in vacuo the residue was extracted with CH 2 Cl 2 (5 mL) and stirred in the presence of silica gel (240 mg) at r.t. for 5 min.…”

Section: Synthetic Studiesmentioning

confidence: 99%

“…The reaction mixture was then concentrated in vacuo and the residue purified by silica gel chromatography (isocratic elution 1 : 10 EtOAc-light petroleum) to afford oxanthroquinone ethyl ester (11) , 339.0874). Oxanthroquinone (9). A solution of 11 (70 mg, 0.21 mmol) in aq.…”

Section: Synthetic Studiesmentioning

confidence: 99%

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Rare Streptomyces sp. polyketides as modulators of K-Ras localisation

et al. 2014

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Chemical investigations of a soil-derived Streptomyces sp. led to the isolation of five new polyketides, (+)-oxanthromicin, (±)-hemi-oxanthromicins A/B, (±)-spiro-oxanthromicin A and oxanthroquinone, and the known alkaloid staurosporine, and the detection of four new metastable analogues, (±)-spiro-oxanthromicins B1/B2/C1/C2. Among the compounds tested, SAR investigations established that the synthetic oxanthroquinone ethyl ester and 3-O-methyl-oxanthroquinone ethyl ester were optimal at mislocalising oncogenic mutant K-Ras from the plasma membrane of intact Madin-Darby canine kidney (MDCK) cells (IC50 4.6 and 1.2 μM), while a sub-EC50 dose of (±)-spiro-oxanthromicin A was optimal at potentiating (750%) the K-Ras inhibitory activity of staurosporine (IC50 60 pM). These studies demonstrate that a rare class of Streptomyces polyketide modulates K-Ras plasma membrane localisation, with implications for the future treatment of K-Ras dependent cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Synthetic Studiesmentioning

confidence: 99%

Section: Synthetic Studiesmentioning

confidence: 99%

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Rare Streptomyces sp. polyketides as modulators of K-Ras localisation

et al. 2014

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Methyl Cyanoformate

Mander¹,

Shing²,

Yeung³

2006

Encyclopedia of Reagents for Organic Synthesis

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Total Synthesis of cyclo‐Mumbaistatin Analogues through Anionic Homo‐Fries Rearrangement

Neufeind

Hülsken

Neudörfl

et al. 2011

Chemistry A European J

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The structurally unique polyketide mumbaistatin is the strongest naturally occurring inhibitor of glucose-6-phosphate translocase-1 (G6P-T1), which is a promising target for drugs against type-2 diabetes mellitus and angiogenic processes associated with brain tumor development. Despite its high relevance, mumbaistatin has so far withstood all attempts towards its total synthesis. In the present study an efficient total synthesis of a deoxy-mumbaistatin analogue containing the complete carbon skeleton and a spirolactone motif closely resembling the natural product in its cyclized form was elaborated. Key steps of the synthesis are a Diels-Alder cycloaddition for the construction of the fully functionalized anthraquinone moiety and an anionic homo-Fries rearrangement to build up the tetra-ortho-substituted benzophenone core motif, from which a spiroketal lactone forms in a spontaneous process. The elaborated strategy opens an entry to a variety of new analogs of mumbaistatin and cyclo-mumbaistatin and may be exploited for the total synthesis of the natural product itself in the future.

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An integrated approach to the synthesis of contiguously substituted xanthopurpurins, pachybasins and purpurins.

Cited by 14 publications

References 54 publications

Rare Streptomyces sp. polyketides as modulators of K-Ras localisation

Rare Streptomyces sp. polyketides as modulators of K-Ras localisation

Methyl Cyanoformate

Total Synthesis of cyclo‐Mumbaistatin Analogues through Anionic Homo‐Fries Rearrangement

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