Aminohaloborane in organic synthesis. 2. Simple synthesis of indoles and 1-acyl-3-indolinones using specific ortho .alpha.-chloroacetylation of anilines

Sugasawa, Tsutomu; Adachi, Makoto; Sasakura, Kazuyuki; Kitagawa, Akiko

doi:10.1021/jo01318a021

Cited by 114 publications

(55 citation statements)

References 6 publications

(8 reference statements)

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“…Combustion microanalyses were performed at the Purdue University Microanalysis Laboratory using a Perkin-Elmer Series II CHNS/O model 2400 analyzer and all reported values are within 0.4% of calculated values. Precursor compounds 11 ,39 13 ,49 14 ,30 and 18 41–42 were prepared as previously described and as depicted in Scheme 1 and Scheme 2.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: Investigating the hypothesis of shared structure–activity relationships

Cinelli

Cordero

Dexheimer

et al. 2009

Bioorganic & Medicinal Chemistry

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The aromathecin topoisomerase I (top1) inhibitors offer promising scaffolds for the development of novel cancer chemotherapeutics. They are “composites” of the camptothecin and indenoisoquinoline top1 inhibitors. Interestingly, some structure-activity-relationship (SAR) overlap between the aromathecins and the indenoisoquinolines has been observed. For both classes, placement of certain polar groups in similar regions of the heteroaromatic system improves top1 inhibitory and antiproliferative activities. A series of water-soluble aromathecins substituted at position 14 with diaminoalkanes of various lengths has been prepared. These compounds all possess similar antiproliferative potency, but a general trend is observed: aromathecins with longer diaminoalkane substituents (> 6 carbons) possess lower anti-top1 activity than their smaller counterparts (2–4 carbons), presumably as a result of unfavorable hydrophobic interactions. This trend is also noted with the indenoisoquinolines, revealing additional SAR overlap that supports the hypothesis that there is a “universal” top1 inhibitor SAR.

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Section: Methodsmentioning

confidence: 99%

“…14-Chloromethylaromathecin ( 19 )30 was prepared by Friedlander condensation of ketone 16 with aminoacetophenone 18 (Scheme 2). Compound 18 was in turn prepared from aniline ( 17 ) and chloroacetonitrile using the Sugasawa modification of the Friedel-Crafts acylation 41–42…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: Investigating the hypothesis of shared structure–activity relationships

Cinelli

Cordero

Dexheimer

et al. 2009

Bioorganic & Medicinal Chemistry

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“…[27,28] AZ-2 was then treated under basic conditions with an appropriate benzaldehyde to yield the azaaurone of series 5. [29] The chalcones of series 8 were synthesized by a base-catalyzed aldol condensation of commercially available substituted acetophenones with suitably substituted benzaldehydes.…”

Section: Synthesismentioning

confidence: 99%

Aurones as Modulators of ABCG2 and ABCB1: Synthesis and Structure–Activity Relationships

et al. 2011

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The ability of aurones to modulate the efflux activities of ABCG2 and ABCB1 was investigated by quantifying their effects on the accumulation of pheophorbide A (PhA) in ABCG2-overexpressing MDA-MB-231/R cells and calcein AM in ABCB1-overexpressing MDCKII/MDR1 cells. Key structural features for interactions at both ABCG2 and ABCB1 are a methoxylated ring A, an intact exocyclic double bond, and the location of the carbonyl bond on ring C. Modifications on rings B and C were less critical and served primarily to moderate activity and selectivity for one or both transporters. These SAR trends were quantified by Free-Wilson analyses and are reflected in a pharmacophore model for PhA accumulation. Several compounds were found to be equipotent with fumitremorgin C (FTC) in promoting PhA accumulation, and they also demonstrated strong affinities for ABCB1. These compounds were disubstituted on ring B with methoxy or a combination of methoxy and hydroxy groups. Taken together, our findings highlight the versatility of the aurone template as a lead scaffold for the design of dual-targeting ABCG2 and ABCB1 modulators.

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“…Alternatively one may begin with an ortho-acylation of the aniline. The Sugasawa method [15] employs chloroacetonitrile as the reagent to obtain a 2-aminoaryl chloromethyl ketone, which after reduction with sodium borohydride undergoes smooth cyclization and dehydration. On the other hand, an ortho and N-doubly-acylated aniline affords also an indole when treated with McMurry low-valent titanium as demonstrated by A. Fürstner et al [16][17][18][19] N-Acyl-o-toluidines are the typical substrates for the Madelung cyclization which requires elevated temperatures (220-300°C) unless it is mediated by organometallic bases (e. g. butyllithium) rather than by sodium amide or potassium tert-butoxide.…”

Section: Introductionmentioning

confidence: 99%

In Search of Simplicity and Flexibility: A Rational Access to Twelve Fluoroindolecarboxylic Acids

2006

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All twelve indolecarboxylic acids 1-12 carrying both a fluorine substituent and a carboxy group at the benzo ring have been prepared either directly from the corresponding fluoroindoles 13-16 or from the chlorinated derivatives 22, 23 and 25 by hydrogen/metal permutation ("metalation"), or from the bromo-or iodofluoroindoles 17-20 and 26, 27, 29 and 30 by halogen/metal permutation, the organometallic intermediate being each time trapped with carbon dioxide. In most, though not all cases, the nitrogen atom in the fivemembered ring had to be protected by a trialkylsilyl group. Some of the bromo-or iodofluoroindoles (26 and 27) were successfully subjected to a basicity gradient-driven selective migration of the heavy halogen. An unexpected finding on the way to the target compounds were the rigorously site-

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Aminohaloborane in organic synthesis. 2. Simple synthesis of indoles and 1-acyl-3-indolinones using specific ortho .alpha.-chloroacetylation of anilines

Cited by 114 publications

References 6 publications

Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: Investigating the hypothesis of shared structure–activity relationships

Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: Investigating the hypothesis of shared structure–activity relationships

Aurones as Modulators of ABCG2 and ABCB1: Synthesis and Structure–Activity Relationships

In Search of Simplicity and Flexibility: A Rational Access to Twelve Fluoroindolecarboxylic Acids

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