Resolution of 4-cyano-4-(4-nitrophenyl)hexanoic acid: Synthesis of (R) and (S)-3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione (aminoglutethimide1)

Achmatowicz, O.; Malinowska, Iwona; Szechner, Barbara; Maurin, Jan K.

doi:10.1016/s0040-4020(97)00464-x

Cited by 15 publications

(10 citation statements)

References 8 publications

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“…They were used without additional purification. RS (+/−)AGT was supplied by Ampharm (Warsaw, Poland) and enantiomer R (+) was a gift of Prof. S. Achmatowicz21 from the Institute of Pharmacy (Warsaw, Poland). Buffer solutions of pH 9.0 (H 3 BO 3 –KCl–NaOH) were used.…”

Section: Methodsmentioning

confidence: 99%

Complexation of aminoglutethimide with native and modified cyclodextrins

Nowakowski

Długosz

Taraszewska

et al. 2009

J of Physical Organic Chem

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Complexations of R(R) and RS(R/S)aminoglutethimide (AGT), the drug used in a treatment of breast and prostate cancer with native and modified cyclodextrins (a-CD, b-CD, g-CD, 2,6-di-O-methyl-b-CD (DM-b-CD), 2,3,6-tri-O-methyl-b-CD (TM-b-CD) and carboxymethyl-b-CD (CM-b-CD)) were studied. The stability constants were determined with UV-Vis spectrophotometric method at pH 9.0. The NMR data obtained for TM-b-CD suggest that the complexation of AGT is possible from both sides of CD molecule. This was confirmed by molecular dynamic simulations. Figure 5. A part of {1H,13C}gHSQC spectrum of RS(þ/À)AGT/TM-b-CD complex (at ratio 0.120 mol dm À3 : 0.053 mol dm À3 ) in D 2 O at 25 8C. The arrows point the H1 00 /C1 00 cross-peaks of different AGT isomers 948-953 M. NOWAKOWSKI ET AL. a Up -averaged contact shorter than 5.5 Å between host and guest docked on the MeO(2 0 )/MeO(3 0 ) side in MD calculations; downsame on the MeO(6 0 ) side of TM-b-CD; NOE -contact observed in the NMR experiment.

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Section: Methodsmentioning

confidence: 99%

Complexation of aminoglutethimide with native and modified cyclodextrins

Nowakowski

Długosz

Taraszewska

et al. 2009

J of Physical Organic Chem

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“…204 [178], 205 [177] and 206 [179] (Figure 63) exist as simple R The remaining structure involves more complex bonding. Compound 202 [176] (Figure 62) displays primarily an imide NH to CO C(4) ribbon pattern of type B which is supplemented by an interaction of the same imide CO to an alcohol OH in a separate ribbon above or below the plane.…”

Section: 3-disubstituted Glutarimidesmentioning

confidence: 99%

“…Of the twelve reported structures for 3,3-disubstituted glutarimides, four compounds 203 [177], 204 [178], 205 [177] and 206 [179] (Figure 63) exist as simple R 2 2 (8) dimers of pattern A. It should be noted, however, that while 203 and 204 bond using the imide 6-CO away from the substituents, compound 205 uses the more hindered 2-CO, and for compound 206 one carbonyl of each type is involved, giving an unsymmetrical dimer.…”

Section: 3-disubstituted Glutarimidesmentioning

confidence: 99%

The Solid-State Structures of Cyclic NH Carboximides

Aitken

Sonecha

2020

Crystals

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“…Previous preparations of ( R )-aminoglutethimide have been reported utilising both biochemical and chemical , resolution technology as well as synthetic approaches to heteroaryl and fluoroaryl analogues . The key issues to be addressed in the prior art were:…”

Section: Synthetic Strategymentioning

confidence: 99%

Production of (R)-Aminoglutethimide: A New Route from 1-Chloro-4-nitrobenzene

Bunegar

Dyer

Evans

et al. 1999

Org. Process Res. Dev.

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The development of a short, safe and enantioselective route for the preparation of (R)-aminoglutethimide is described. The process was designed for economic large-scale manufacture of the bulk drug substance to acceptable quality standards, to allow clinical evaluation of the single enantiomer over the existing racemate. (R)-Aminoglutethimide was prepared from 1-chloro-4-nitrobenzene using a six-stage synthetic sequence, via chemoresolution of key intermediate racemic 4-cyano-4-(4-nitrophenyl)hexanoic acid using (−)-cinchonidine. The process allowed for preparation of several kilograms of the precursor (R)-nitroglutethimide, to cGMP at pilot-plant scale, along with demonstration of the final hydrogenation step to (R)-aminoglutethimide in the laboratory. This route avoids the problems of hazardous nitration technology, and therefore regio-isomer contamination of the product, associated with other procedures. The resolution chemistry described represents an improvement on literature procedures. Optimisation of the asymmetric Michael addition offers an attractive alternative approach.

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Resolution of 4-cyano-4-(4-nitrophenyl)hexanoic acid: Synthesis of (R) and (S)-3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione (aminoglutethimide1)

Cited by 15 publications

References 8 publications

Complexation of aminoglutethimide with native and modified cyclodextrins

Complexation of aminoglutethimide with native and modified cyclodextrins

The Solid-State Structures of Cyclic NH Carboximides

Production of (R)-Aminoglutethimide: A New Route from 1-Chloro-4-nitrobenzene

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