Enantioselective Approaches to Potential MetAP-2 Reversible Inhibitors

Rodeschini, Vincent; Weghe, Pierre van de; Salomon, Emmanuel; Tarnus, Céline; Eustache, Jacques

doi:10.1021/jo047858h

Cited by 30 publications

(18 citation statements)

References 20 publications

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“…The palladium-catalyzed alkoxy-carbonylation of organic halides and triflates was used in synthetic applications toward fumagalone analogs [503], Uhle's ketone and the ergoline skeleton [337], pyrrolizidines [504], pilcadin (Eq. (57)) [505], 1,2-anhydro methyl rocaglate [506], (+)-8-epi-xanthin [507], carbasugars [508] and 261C [509].…”

Section: Carbon-carbon Bond Formation Via Insertion Of Carbon Monoxidementioning

confidence: 99%

“…(367) A number of synthetic applications of the palladiumcatalyzed formation of ␣,␤-unsaturated carbonyl compounds from silylenol ethers (Saegusa oxidation) were published. For example, applications toward kainoids [1515], gymnocin A [205], fumagalone analogs [503], guanacastepenes [1516], GKK1032s [138,1517], the ABCD ring system of manzamine [1176], xestobergsterol A [1518] and (+)-solanascone, (+)-dehydrosolanascone, and (+)-anhydro-␤-rotunol [1519] were described. Palladium hydroxide on carbon using tbutylhydrogen peroxide as the reoxidant was used in Saegusa-type oxidations [1520].…”

Section: Oxidationsmentioning

confidence: 99%

“…Michael additions of dimethylcuprate were used in synthesis of hamigeran B [202], (+)-allocyathine B 2 [128], umbrosone [85]. Stereoselective Michael additions of organocopper reagents were used in synthetic applications toward cylindramine [324], pumiliotoxin C [1613], fumagalone analogs [503], tridachiahydropyrone [1614], guanacastepenes [1516] and 5-epi-10-epi-vibsanin E [704].…”

Section: Reactions Of Isolated Transitionmetal Complexes and Copper-mentioning

confidence: 99%

See 2 more Smart Citations

Transition metals in organic synthesis: Highlights for the year 2005

Söderberg

2008

Coordination Chemistry Reviews

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Section: Carbon-carbon Bond Formation Via Insertion Of Carbon Monoxidementioning

confidence: 99%

Section: Oxidationsmentioning

confidence: 99%

Section: Reactions Of Isolated Transitionmetal Complexes and Copper-mentioning

confidence: 99%

See 1 more Smart Citation

Transition metals in organic synthesis: Highlights for the year 2005

Söderberg

2008

Coordination Chemistry Reviews

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“…Subsequent regioselective carboxymethylation with Mander's reagent16 in the presence of LHMDS at −78 °C afforded a β-ketomethylester; this was followed by methylation, thus methyl iodide in the presence of NaH granted the corresponding α-methyl-β-ketomethylester 17. Epoxidation of the enone moiety by TBHP in the presence of benzyltrimethylammonium hydroxide (triton B)18 furnished stereoselectively epoxide ( 14 ), in 65% yield for three steps from 13 19. The regioselective opening of the epoxide moiety20 found within 14 was established by PhSeNa (generated in situ from diphenyl diselenide and NaBH 4 ) in 86% yield followed by silylation of 15 with SEMCl, which led to disilyl ether ( 16 ) in 85% yield from 14 (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Toosendanin: Synthesis of the AB-ring and investigations of its anti-botulinum properties (Part II)

Nakai

Pellett

Tepp

et al. 2010

Bioorganic & Medicinal Chemistry

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Botulinum neurotoxins (BoNTs) are the etiological agents responsible for botulism, a disease characterized by peripheral neuromuscular blockade and a characteristic flaccid paralysis of humans. The natural product toosendanin, a limonoid, is a traditional Chinese medicine that has reported antibotulinum properties in animal models. Toosendanin effectively inhibits the biological activity of BoNT/A in neuronal cells at concentrations of 200 nM, and partial inhibition can be observed with concentrations as low as 8 nM. Mechanistically, toosendanin's inhibition is due to prevention of transduction of the BoNT LC through the HC channel. Intriguing questions as to the molecular architecture of toosendanin as related to its anti-botulinum properties have focused our attention on a synthesis of toosendanin's unusual AB-ring, containing a unique bridged hemi-acetal. Within the current work, a synthetic strategy allowing access to the AB-fragment of toosendanin was achieved from a trans-decalin system. In addition, this fragment was examined for its modulation of BoNT/A intoxication in a rat spinal cord cellular assay.

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“…The migration of the distal vinyl group to C 10 and C 11 weakened the inhibitory activity of compound aldehyde (73). The IC 50 for 73 against MetAP-2 inhibition is 281 M [90]. Introduction of a bulky t-butyl to the C3 position of the fumagillin while preserving the haloacetylcarbamoyl group, considered as an antiangiogenesis pharmacophore, gave TX-1898 (74).…”

Section: Methionine Aminopeptidasementioning

confidence: 99%

Antiangiogenesis Drug Design: Multiple Pathways Targeting Tumor Vasculature

Zhong¹,

Bowen²

2006

CMC

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The initiation, growth, and development of new blood vessels through angiogenesis are essential for tumor growth. Tumor masses require access to blood vessels for a sufficient supply of oxygen and nutrients to maintain growth and metastasis. Inhibiting tumor blood vessel formation as proposed by Judah Folkman in the early 1970s, therefore, offers promising therapeutic approaches for treating tumor afflicted patients. The blood vessel growth in normal tissues is regulated though a delicate and complex balance between the collective action of proangiogenic factors (e.g., vascular endothelial growth factor, VEGF) and the collective action of angiogenic inhibitors (e.g., thrombospondin-1). In pathological angiogenesis, the angiogenic switch is shifted toward the proangiogenic factors, and if the imbalance continues, irregular tumor vessel growth is the result. Despite intense research, the mechanism of the angiogenic switch is not fully understood. Many factors, however, have been shown to be involved in regulating the equilibrium between angiogenic stimulants and inhibitors. VEGFR tyrosine kinase, methionine aminopeptidase-2 (MetAP-2), p53, tubulin, cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) all directly and/or indirectly influence the angiogenic switch. This review will describe some of the advances in inhibitor design and the mechanisms of action for the aforementioned factors (targets) involved in angiogenesis regulation. Our discussion reveals that a diaryl group separated by various connecting modules is one of the most common features for antiangiogenesis drug design. This idea has been a working pharmacophore hypothesis for our own antiangiogenic drug design endeavors over the years. The recent advances of combination therapy (angiogenesis inhibitors with other chemotherapy/radiation) are also discussed.

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Enantioselective Approaches to Potential MetAP-2 Reversible Inhibitors

Cited by 30 publications

References 20 publications

Transition metals in organic synthesis: Highlights for the year 2005

Transition metals in organic synthesis: Highlights for the year 2005

Toosendanin: Synthesis of the AB-ring and investigations of its anti-botulinum properties (Part II)

Antiangiogenesis Drug Design: Multiple Pathways Targeting Tumor Vasculature

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