A convenient synthesis of bisindolyl- and indolylaryl maleic anhydrides

Davis, Peter D.; Bit, Rino A.; Hurst, Stephen

doi:10.1016/0040-4039(90)80226-c

Cited by 40 publications

(13 citation statements)

References 6 publications

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“…Retrosynthetic Analysis. Acyclic bisindolylmaleimides can be prepared by reaction of indolyl-3-glyoxylyl chlorides with indole-3-acetic acids or indole-3-acetimidate esters . These methods, however, were not applicable to the synthesis of 1 − 4 due to the low yields and difficult chromatographic purifications required.…”

Section: Resultsmentioning

confidence: 99%

Macrocyclic Bisindolylmaleimides: Synthesis by Inter- and Intramolecular Alkylation

et al. 1998

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Macrocyclic bisindolylmaleimides 1−4 have been identified as competitive reversible inhibitors of PKC β1 and β2 and are being advanced to the clinic for evaluation as a treatment of retinopathy associated with diabetic complications. Highly convergent and stereoselective syntheses of 1−4 have been developed. The key synthetic step involves intermolecular alkylation of symmetrical bisindolylmaleimide 9 with chiral bisalkylating agent 8c and is amenable to the preparation of multikilogram quantities of these compounds. The synthetic sequence to 1, the most active compound, proceeds in 11 steps and 26% overall yield (>98% ee) from (R)-1-chloro-2,3-propanediol. No chromatographic purifications are required throughout the process and the final product is isolated in >97% purity after crystallization from DMF/MeOH. Synthesis of 1−4 by intramolecular alkylation proved less efficient, requiring 17 steps and affording 1−4 in lower overall yields of 6.0−8.5%.

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Section: Resultsmentioning

confidence: 99%

Macrocyclic Bisindolylmaleimides: Synthesis by Inter- and Intramolecular Alkylation

et al. 1998

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“…After acylation of 2-aminoacridone with maleic anhydride, the intermediate maleamic acid was cyclized to maleimide using PyBOP as condensing reagent [27]. During the development of the synthesis, we found that PyBOP is the superior reagent for ring closure over other tested "classical methods"-acidic dehydratation and DCCI cyclization [28,29]. Reaction with PyBOP is fast, with practical yield and free of isomaleimide isomer.…”

Section: Design Synthesis and Properties Of Miacmentioning

confidence: 99%

Determination of plasma aminothiols by high performance liquid chromatography after precolumn derivatization with N-(2-acridonyl)maleimide

Benkova

Lozanov

Ivanov

et al. 2008

Journal of Chromatography B

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“…Two alternative approaches to 7 have been developed that do not require maleimide protection. Perkin condensation of indole-3-acetic acid with indolyl-3-glyoxylyl chloride affords, in 24−64% yield, the bisindolylmaleic anhydrides, which are converted into the desired bisindolylmaleimides (R 1 , R 2 ≠ H), upon treatment with an ammonium source . Alternatively, direct access into 7 (R 1 = H, R 2 ≠ H) can be achieved, in 42−75% yield, by condensation of an indolyl-3-glyoxylyl chloride with indole-3-acetimidate ester .…”

Section: Introductionmentioning

confidence: 99%