Search for radioprotectors in the series of glutamic acid derivatives

We report that phthalimides may be cyclized using a Mukaiyama-type aldol coupling to give variously substituted fused lactam (1,2,3,9b-tetrahydro-5H-pyrrolo[2,1-a]isoindol-5-one) systems. This novel process shows a high level of regioselectivity for o-substituted phthalimides, dictated by steric and electronic factors, but not for m-substituted phthalimides. The initial aldol adduct is prone to elimination, giving 2,3-dihydro-5H-pyrrolo[2,1-a]isoindol-5-ones, and the initial cyclisation can be conducted in such a way that aldol cyclisation-elimination is achievable in a one-pot approach. The 2,3-dihydro-5H-pyrrolo[2,1-a]isoindol-5-ones possess cross conjugation and steric effects which significantly influence the reactivity of several functional groups, but conditions suitable for epoxidation, ester hydrolysis and amide formation, and reduction, which provide for ring manipulation, were identified. Many of the derived lactam systems, and especially the eliminated systems, show low solubility, which compromises biological activity, although in some cases, antibacterial and cytotoxic activity was found, and this new class of small molecule provides a useful skeleton for further elaboration and study.

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“…File S1: Supporting Information (SI). References [88][89][90][91][92][93][94][95][96] occur only in the supplementary materials.…”

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confidence: 99%

Tricyclic Fused Lactams by Mukaiyama Cyclisation of Phthalimides and Evaluation of their Biological Activity

et al. 2022

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“…An interesting object for modification is Lglutamic acid which is known to play an important role in the organism. It was reported that some of the glutamic acid derivatives possess radioprotective activity [3,4].The purpose of this work was to synthesize a diethyl ester and salts of a dipeptide of L-glutamic acid with 4-bis(2-chloroethyl)amino]phenylalanine (sarcolysine) and study their radioprotective properties.Diesters were obtained by condensation of N-acetyl-4-[bis(2-chloroethyl)amino]-DL-phenylalanine (I) with the diethyl ester hydrochloride (I) of L-glutamic acid, followed by separation of the resulting diethyl ester of N-acetyl-4-[bis(2- …”

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confidence: 99%

Synthesis and radioprotective properties of 4-[bis(2-chloroethyl)amino]phenylalanyl-L-glutamic acid derivatives

et al. 1997

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A promising direction in the search for substances possessing radioprotective properties is the synthesis of compounds capable of inhibiting the metabolism of nucleic acids and proteins, in particular, on the basis of natural amino acid derivatives [1,2]. An interesting object for modification is Lglutamic acid which is known to play an important role in the organism. It was reported that some of the glutamic acid derivatives possess radioprotective activity [3,4].The purpose of this work was to synthesize a diethyl ester and salts of a dipeptide of L-glutamic acid with 4-bis(2-chloroethyl)amino]phenylalanine (sarcolysine) and study their radioprotective properties.Diesters were obtained by condensation of N-acetyl-4-[bis(2-chloroethyl)amino]-DL-phenylalanine (I) with the diethyl ester hydrochloride (I) of L-glutamic acid, followed by separation of the resulting diethyl ester of N-acetyl-4-[bis(2- chloroethyl)amino]-DL-phenylalanyl-L-glutamic acid (HI) into diastereomers: diethyl ester of N-acetyl-4-[bis(2-chloroethyl)amino]-L-phenylalanyl-L-glutamic acid (IV) and Nacetyl-4-[bis(2-chloroethyl)amino]-D-phenylalanyl-L-gluta mie acid (V). The corresponding salts (VI and VII) were ob-9 tained by saponification of the ester groups of compounds IV and V with an alkali solution.An important factor is the stereo-purity of the resulting disodium salts of N-acetyl-4-[bis(2-chloroethyl)amino]-Lphenylalanyl-L-glutarnic acid and N-acetyl-4-[bis(2-ehloroethyl)amino]-D-phenylalanyl-L-glutamic acid, which determines the activity of compounds VI and VII. The individual diastereomers IV and V were isolated in analytical amounts by chromatography on a silica gel eohmm.Due to the close chromatographic mobility of the two diastereomers, the method of column chromatography did not

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Lactam ring stability of stereoisomers of 4-amino-substituted pyroglutamic acids in acidic medium

et al. 2014

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Search for radioprotectors in the series of glutamic acid derivatives

Cited by 4 publications

References 1 publication

Tricyclic Fused Lactams by Mukaiyama Cyclisation of Phthalimides and Evaluation of their Biological Activity

Tricyclic Fused Lactams by Mukaiyama Cyclisation of Phthalimides and Evaluation of their Biological Activity

Synthesis and radioprotective properties of 4-[bis(2-chloroethyl)amino]phenylalanyl-L-glutamic acid derivatives

Lactam ring stability of stereoisomers of 4-amino-substituted pyroglutamic acids in acidic medium

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