Rhodium carbenoid O-H insertion reactions with phenols; A facile method for the synthesis of trialkyl 2-aryloxyphosphonoacetates and their use in the preparation of 2-aryloxy-3-phenylpropanoates.

Haigh, David

doi:10.1016/s0040-4020(01)81116-9

Cited by 39 publications

(19 citation statements)

References 28 publications

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“…Treatment of 8 with diazophosphonate 9 , resulted in the phenolic ether 10 , upon a rhodium carbenoid mediated O-H insertion 25. Regioselective nitration of 10 was accomplished under mild conditions enlisting ammonium nitrate and trifluoroacetic anhydride.…”

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confidence: 99%

Design, Synthesis, and Biological Evaluation of Conformationally Constrained cis-Amide Hsp90 Inhibitors

2009

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Conformationally constrained CIS-amide chimeric inhibitors of Hsp90 have been synthesized and evaluated for their Hsp90 inhibitory activity. These new compounds exhibited Hsp90 ATPase inhibition and induced Hsp90-dependent client protein degradation in a dose-dependent manner. Biological data reported herein suggests that amide bond isomerization of geldanamycin derivatives plays an important role in affinity for the heteroprotein complex present in cancer cells.The 90 kDa heat shock proteins (Hsp90) are ATP-dependent molecular chaperones overexpressed in response to cellular stress and necessary for the folding and rematuration of nascent and denatured polypeptides, respectively. 1,2,3,4 Two natural products, geldanamycin 5 (GDA, Figure 1) and radicicol 6 (RDC), bind the Hsp90 N-terminal binding pocket and competitively inhibit ATP binding resulting in degradation of Hsp90-dependent client proteins via the ubiquitin-proteasome pathway. 7 Hsp90 clientele play key roles in all six hallmarks of cancer 8 , therefore inhibition of the Hsp90 protein folding machinery results in simultaneous disruption of all six mechanisms of oncogenesis. 9,10 Consequently, not only has Hsp90 emerged as a promising anti-cancer target 11 , but GDA and RDC have proven to represent excellent models for which the development of new Hsp90 inhibitors can be pursued for drug development and mechanistic studies. 12Although RDC and GDA bind Hsp90 with high affinity, their modes of binding and inhibitory activities are different. Radicicol exists in the same bent conformation when bound and unbound to Hsp90 and produces a favorable entropy of 8.3 cal/mol upon binding. Not surprisingly, the predisposition of RDC to the bent conformation is believed to be responsible for its similar activity in both cellular and recombinant assays. 13 E-mail: bblagg@ku.edu. Supporting Information Available Experimental procedures and characterization for all compounds. This material is avalible free of charge via the internet at http://pubs.acs.org. NIH Public Access Author ManuscriptOrg Lett. Author manuscript; available in PMC 2010 June 4. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIn contrast to the bent, cis-amide conformation of GDA when bound to Hsp90, both solution and crystal structures have demonstrated that this natural product exists in an extended, trans-amide conformation when unbound to Hsp90 (Figure 2). 14 Multiple studies have demonstrated that prior to binding Hsp90, GDA must undergo two conformational changes; the ansa ring must rotate over the benzoquinone moiety and the amide bond must isomerize from trans to cis by rotation about C 1 -N 22 and C 20 -N 22 (Figure 2). The first event is reported to occur spontaneously; however isomerization of the amide bond is estimated to exceed 20 kcal/mol. 15 Accordingly, isothermal titration calorimetry (ITC) experiments have shown that GDA exhibits an entropic penalty of −6.4 cal/mol upon binding Hsp90. 16,17As a consequence of these thermodynamic data, Santi and co...

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confidence: 99%

Design, Synthesis, and Biological Evaluation of Conformationally Constrained cis-Amide Hsp90 Inhibitors

2009

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“…Flash chromatography was performed using Woelm 32-63 µm silica gel packing unless otherwise noted. Methods for the preparation of methanesulfonyloxyethanol (21), tert-butyldimethylsilyloxyethanol (22), methyl 2-phenoxydiethylphosphonoacetate (23), and methyl 2-diazodiethylphosphonoacetate (23) have been described in the cited literatures. 1 H NMR and 13 C NMR spectra were recorded on Varian U400 and U500 instruments.…”

Section: Methodsmentioning

confidence: 99%

“…(22). To synthesize compound 22, the fluorination precursor to the second PPARγ ligand, aldehyde 18 and the matched Horner-Emmons reagents 13-15 were prepared, as shown in Schemes 4 and 5, according to literature methods (21)(22)(23).…”

Section: Synthesis Of 3-[4-[2-[benzoxazol-2-yl-(2-fluoroethyl)amino]ementioning

confidence: 99%

Fluorine-Substituted Ligands for the Peroxisome Proliferator-Activated Receptor Gamma (PPARγ): Potential Imaging Agents for Metastatic Tumors

et al. 2001

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The peroxisome proliferator-activated receptor gamma (PPARgamma), a primary regulator of lipid metabolism, is present in many tumor cell lines and animal tumor systems and, in some cases, can mediate effective antitumor therapy with potent synthetic ligands. In an approach to image tumors with positron-emission tomography (PET) based on their content of PPARgamma, we have synthesized two fluorine-substituted analogues of a high affinity ligand from the phenylpropanoic acid class. The analogue having the highest affinity for PPARgamma was labeled with the positron-emitting radionuclide fluorine-18. In tissue distribution studies in normal rats and in SCID mice bearing human breast tumor xenografts, this compound did not show evidence of receptor-mediated uptake. The prospects for using PPARgamma as a target for imaging tumors may be limited by the low receptor concentrations in tumors and by the pharmacokinetic behavior of this class of ligands, which appears to be more favorable for therapy than for imaging.

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“…For rhodium carbenoid-mediated intermolecular O-H insertion reactions and their application to natural product synthesis, see: Paulissen et al (1973); Cox et al (1994); Haigh (1994); Aller et al (1995); Shi et al (1995); Bulugahapitiya et al (1997); Moody & Miller (1998); Nelson et al (2000); Medeiros & Wood (2010); Freeman et al (2010); Morton et al (2012). For rhodium-catalysed intramolecular O-H insertion reactions, see: Paulissen et al (1974); Moyer et al (1985); Moody & Taylor (1987); Heslin & Moody (1988); Davies et al (1990); Moody et al (1992); Sarabia-Garciá et al (1994); Padwa & Sá (1999); Im et al (2005).…”

Section: Related Literaturementioning

confidence: 99%

“…Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT; program(s) used to solve structure: SIR92 (Altomare et al, 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2009). (Paulissen, et al, 1973;Cox, et al 1994;Haigh, 1994;Aller et al, 1995;Shi et al, 1995;Bulugahapitiya et al, 1997;Moody & Miller, 1998;Morton et al, 2012). Hence the methodology has proven to be a useful stratagem in the synthetic acquisition of several natural products (Nelson et al, 2000;Medeiros & Wood, 2010;Freeman, et al 2010).…”

Section: Data Collectionmentioning

confidence: 99%

(2aR,5S,6aS,8aS,E)-Ethyl 5-hydroxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octahydro-1H-pentaleno[1,6-bc]oxepine-4-carboxylate

2012

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The title compound, C17H24O5, featuring a 2-carbethoxy-3-oxepanone unit in its intramolecularly O—H...O hydrogen-bonded enol form, was obtained via [(CF3CO2)2Rh]2-catalysed intramolecular O—H bond insertion in the α-diazo-ω-hydroxy-β-ketoester, ethyl 4-[(1S,3aS,6R,6aS)-6-hydroxy-2,2,3a-trimethyl-3-oxo-octahydropentalen-1-yl]-2-diazo-3-oxobutanoate. The seven-membered oxacyclic ring, thus constructed on a cis-fused diquinane platform, was found to adopt a distorted boat–sofa conformation

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Rhodium carbenoid O-H insertion reactions with phenols; A facile method for the synthesis of trialkyl 2-aryloxyphosphonoacetates and their use in the preparation of 2-aryloxy-3-phenylpropanoates.

Cited by 39 publications

References 28 publications

Design, Synthesis, and Biological Evaluation of Conformationally Constrained cis-Amide Hsp90 Inhibitors

Design, Synthesis, and Biological Evaluation of Conformationally Constrained cis-Amide Hsp90 Inhibitors

Fluorine-Substituted Ligands for the Peroxisome Proliferator-Activated Receptor Gamma (PPARγ): Potential Imaging Agents for Metastatic Tumors

(2aR,5S,6aS,8aS,E)-Ethyl 5-hydroxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octahydro-1H-pentaleno[1,6-bc]oxepine-4-carboxylate

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Rhodium carbenoid O-H insertion reactions with phenols; A facile method for the synthesis of trialkyl 2-aryloxyphosphonoacetates and their use in the preparation of 2-aryloxy-3-phenylpropanoates.

Cited by 39 publications

References 28 publications

Design, Synthesis, and Biological Evaluation of Conformationally Constrained cis-Amide Hsp90 Inhibitors

Design, Synthesis, and Biological Evaluation of Conformationally Constrained cis-Amide Hsp90 Inhibitors

Fluorine-Substituted Ligands for the Peroxisome Proliferator-Activated Receptor Gamma (PPARγ): Potential Imaging Agents for Metastatic Tumors

(2aR*,5S*,6aS*,8aS*,E)-Ethyl 5-hydroxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octahydro-1H-pentaleno[1,6-bc]oxepine-4-carboxylate

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(2aR,5S,6aS,8aS,E)-Ethyl 5-hydroxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octahydro-1H-pentaleno[1,6-bc]oxepine-4-carboxylate