Studies on pyrrolidinones. Synthesis of N-benzhydrylpyroglutamic acids and esters

Catalyzed N-alkylation of N,O-bistrimethylsilyl pyroglutamic acid with trimethylsilyl benzhydryl ethers yields trimethylsilyl N-benzhydrylpyroglutamates. Hydrolysis of these compounds or saponification of the methyl esters gives the corresponding acids.     

Studies on pyrrolidinones. Synthesis of some bioisosteres of 3,3,5-trimethylcyclohexyl pyroglutamate

The synthesis of new N-(4-chlorobenzyl) and N-(4-chlorobenzoyl)pyroglutamic esters and amids whose the structure conserves the main structural features of the cholesterol lowering agent crilvastatin is described.     

Studies on pyrrolidinones. Synthesis and reactivity of some n-protected pyroglutamic derivatives

The synthesis of pyroglutamoyl chloride N-protected by a methoxycarbonyl or a trifluoroacetyl group is described. Some aspects of the reactivity of these compounds and intermediates have been studied.     

Studies on pyrrolidinones. Synthesis of N-acylpyroglutamic acids having bactericide and fungicide properties

The best method to prepare N-acylpyroglutamic acids is to react N,O-bistrimethylsilylpyroglutamic acid with acid chlorides or a diketene. These acyl acids display bactericide and fungicide properties against several microorganisms.     

Studies on pyrrolidinones. On the carbamoylation of some pyroglutamic derivatives

The carbamoylation of some lactams derivatived from pyroglutamic acid as been studied; better yields were obtained starting from the unsubstitued lactam (toluene, 80°) rather than starting with the N-silyllactam (room temperature), although these latter reaction conditions could be interesting for heat sensitive compounds. Methyl and phenyl isothiocyanate react only with the sodium salt of methyl pyroglutamate, giving 1,5-diaddition products.     

Studies on pyrrolidinones. Synthesis of N-acylpyroglutamic esters with bactericide and fungicide properties

The best method to prepare N-acylpyroglutamic esters is to react N-trimethylsilylpyroglutamic esters with acid chlorides or diketene. These acylesters possess bactericide and fungicide properties against several microorganisms.     

Studies on pyrrolidinones. Synthesis of methyl N-(4-nitrobenzyl)pyroglutamate

Methyl N-trimethylsilylpyroglutamate is reacted with 4-nitrobenzyl chloride to yield methyl N-(4-nitrobenzyl)pyroglutamate.     

Studies on pyrrolidinones. Synthesis of 4,5-fused-3-hydroxypyridinyl-2-propionic acid derivatives

The synthesis of some condensed indolizinediones derived from pyroglutamic acid is described. Treatment of these ketones in HCl, HBr or MeONa/MeOH furnished aryl propionic acid derivatives. During the ketone transformations, two sequential processes could take place in competitive manner to provide heterocyclic systems bearing carboxylic acid or hydroxycarboxylic acid function. Easy synthesis of amides indicates that potential DNA-intercalating heterocyclic systems fused on γ-carboline and isoquinoline nucleus could be obtained from these series.     

Studies on pyrrolidinones. Synthesis of 1,2,3,5,11,11a-hexahydroindolizino[7,6-b]indole-3,11-dione

Condensation of N-trimethylsilylindole with methyl N-trimethylsilyloxymethylpyroglutamate is the best method to obtain methyl N-indolylmethylpyroglutamate. Friedel-Crafts cyclization of the corresponding acid yields a new ketone (1,2,3,5,11,11a-hexahydroindolizino[7,6-b] indole-3,11-dione).     

Studies on pyrrolidinones. synthesis of fused 1,5-naphthyridines

The synthesis of new condensed indolizinediones derived from pyroglutamic acid is described. The Semmler–Wolff transposition of the oxime of these ketones leads to fused dihydro-1,5-naphthyridinones. Easy introduction of side amino chains indicates that potential DNA-intercalating heterocyclic systems fused on 1,5-naphthyridine nucleus could be obtained in these series.     

Studies on pyrrolidinones. Synthesis of 1-[(N-acetylarylamino)methyl]pyroglutamic acid derivatives

Pyroglutamic acid was transformed into 1-[(N-Acetylarylamino)methyl]pyroglutamic acid derivatives by using trimethylsilyl variations of the Mannich reaction.     

Studies on pyrrolidinones. Michael reaction of glutamic acid and diethylglutamate

Starting from glutamic acid or diethyl glutamate, some derivatives of N-(2-carboxyethyl), N-(3-oxobutyl) and N-(2-cyanoethyl)pyroglutamic acid were synthesized.     

Studies on pyrrolidinones. Synthesis of new α‐pyridones derivatives

Dimethyl 7‐methoxycarbonylmethyl‐5‐oxo‐1,2,3,5‐tetrahydro‐indolizine‐3,8‐dicarboxylate was synthesized starting from methyl pyroglutamate. A study was made of the reactions of this highly functionalized pyridone with ethyl iodide, selenium oxide, isoamyl nitrite and formaldehyde. Literature reports that reaction of 4‐(1‐carbomethoxypropyl)‐5‐carbomethoxy‐1,6‐cyclopentano‐2‐pyridone with formaldehyde lead to a 95% yield of a monolactone (26) precursor of camptothecin. Our experiments resulted in 15 % of this monolactone and 40% of a new dilactone (27) .     

Studies on pyrrolidinones. synthesis of N-(2-nitrobenzyl)pyroglutamic acid

While methyl N-(4-nitrobenzyl)pyroglutamate can be obtained from methyl N-trimethylsilylpyroglutamate, the best way to obtain methyl N-(2-nitrobenzyl)pyroglutamate is to react 4-nitro benzyl bromide with the iminoether derived from methyl pyroglutamate.     

Exotic amino acids. 4. Synthesis of methyl esters of some N-heteroamino-methylenemalonic acids

Isopropylidene N-hetarylaminomethylenemalonates, obtained from isopropylidene ethoxymethylenemalonate and 2-aminopyridine, 2-amino-5-methylpyridine, 2-aminopyrimidine, 7-amino-4-methylcoumarin, and 2-amino-3,5-diethoxycarbonyl-4-methylthiophene, undergo methanolysis at room temperature to give methyl esters of the corresponding N-hetarylaminomalonic acids. Isopropylidene N-hetarylaminomethylenenemalonate, containing a 2-aminothiazole group as a heterocyclic substituent, does not react under analogous conditions, but cyclizes upon heating at reflux to give 5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid. 4-Oxo-9-R-4H-pyridino[1,2-a]pyrimidines are obtained upon the sublimation of isopropylidene N-pyridyl- and N-5-methylpyridylaminomethylenemalonates.Communication 3, see ref. [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 857–860, June, 2000.     

Studies on pyrrolidinones. A convenient synthesis of 5-cyano-2-pyrrolidinone derivatives

The reaction of 2-pyrrolidinone-5-carboxamide (pyroglutamide) with trimethylchlorosilane and zinc chloride as a catalyst afford in one step a 91% yield of N-trimethylsilylpyroglutamic acid nitrile whose acylation gives N-acyl compounds 2b,c .     

Studies on pyrrolidinones. Synthesis of 5-(5-oxo-2-pyrrolidinyl)-1,3,5-oxadiazole-2-thione derivatives

Starting from readily available pyroglutamic esters 1 , some new 1,3,4-oxadiazole-2-thione derivatives, bonded to a pyrrolidinone ring were synthesised and characterised by their spectral data.     

Studies on pyrrolidinones. Synthesis of 5-(5-oxo-2-pyrrolidinyl)-1,2,4-triazole-3-thione derivatives

Starting from readily available pyroglutamic esters 1 , some new 1,2,4-triazole-3-thione derivatives, bonded to a pyrrolidinone ring were synthesized and are characterized by their spectral data.