Hydroxy-pyrrolidinones

The vascular effects of the metabolites of levcromakalim (2) have been assessed [99]. Of the metabolites depicted in Figure 9.2, the only one to exhibit relaxant activity against noradrenaline-induced spasm in rabbit isolated mesenteric artery, or spontaneous tone in GPTS, was the 3 R-hydroxy-pyrrolidinone (50). Flowever, metabolite (50) was ten-fold less potent than levcromakalim (2), and because of its low occurrence, does not... 

Two different approaches to ( —)-statine (831), an unusual amino acid component of pepstatine, both employ 793c as their starting point. In the first synthesis (Scheme 120) [183], reduction of 793c with sodium borohydride produces a mixture of two isomeric 5-hydroxy-pyrrolidinones, from which the pure cis product 824 crystallizes in 85% yield. Conversion of bisacetate 825 to thioether 826 followed by removal of the acetate and silylation of the resulting alcohol affords 827. Radical cyclization of 827 produces a 3 2 mixture of isomers 828. Desilylation and debenzylation gives 829 as a single diastereomer. The Boc-protected intermediate 830 intersects with a known synthesis of ( —)-statine (831). 

A solution of 6.13 g (15.9nunol) of (3S.4R)-3,4-[cyclohexylidenebis(oxy)]-1-[4-(l,3-dithian-2-yli-dene)butyl]-5-hydroxy-2-pyrrolidinone and 4.4 mL (31.8 mmol) of triethylaminc (freshly distilled from CaH,) in 15 mL of Ch,C12, in a 100-mL flame-dried round-bottomed flask, is cooled to 0"C and then... 

In THF at -20°C the N-trimethylsilylated 2-pyrrolidinone 388 is converted by LDA into the a-anion which, on reaction with 1949 and subsequent acidification with AcOH, gives 43% 3-hydroxy-2-pyrrolidinone 1962 [150]. Lithium enolates of ketones such as camphor react with BTSP 1949 to give >95% of a mixture of exo-and mdo-2-hydroxycamphor [151]. Lithiated methyl heterocycles such as lithiated 2-methylpyridine 1963 are converted into mixtures of the 0-SiMe3 1964 and C-SiMe3 1965 compounds and C-methylated compounds such 1966 [152]. 2-Lithioto-luene 1967 is oxidized by 1949 into 1968 [140, 145] (Scheme 12.42). 

In intact cell systems or vivo, the primary products of a-hydroxylation, 22. have not been detected. The principal urinary metabolites of NNN resulting from a-hydroxylation are keto acid 21 from 2 -hydroxyl at ion and hydroxy acid 21 from 5 -hydroxylation. Trace amounts of 7 y 21> H ve also been detected as urinary metabolites (34). The interrelationships of these metabolites as shown in Figure 2 have been confirmed by administration of each metabolite to F-344 rats (37). The other metabolites which are routinely observed in the urine are NNN-1-N-oxide U1 and 5-(3-pyridyl)-2-pyrrolidinone [norcotinine, ]. The p-hydroxy derivatives 2. 1 were also detected in the urine of NNN treated rats, but at less than 0.1% of the dose (36). An HPLC trace of the urinary metabolites of NNN is shown in Figure 3. Urine is the major route of excretion (80-90% of the dose) of NNN and its metabolites in the F-344 rat in contrast to NPYR which appears primarily as CO2 (70%) after a dose of 16 mg/kg (17). This is because the major urinary metabolite of NNN, hydroxy acid 21> fs not metabolized further, in contrast to 4-hy-droxybutyric acid [2, Figure 1] which is converted to CO2. In addition, a significant portion of NNN is excreted as NNN-l-N-oxide U ], a pathway not open to NPYR. 

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

Dipolar cycloaddition reactions between three A-benzyl-C-glycosyl nitrones and methyl acrylate afforded key intermediates for the synthesis of glyco-syl pyrrolidines. It was found that furanosyl nitrones (574) and (575) reacted with methyl acrylate to give mixtures of all possible 3,5-disubstituted isoxazolidines (577) and (578). On the other hand, the reaction with pyranosyl nitrone (576) was much more selective and cycloaddition at ambient temperatures afforded only one of the possible Re-endo adducts (579a). The obtained isoxazolidines were transformed into the corresponding (V-benzyl-3-hydroxy-2-pyrrolidinones (580—582) on treatment with Zn in acetic acid (Scheme 2.264) (773). 

In connection with the enantioselective alkylation of Pro or 4-hydroxy-proline, the azabicyclo[3.3.0]octane system 81 was obtained after reaction with pivaldehyde (81HCA2704 85HCA155). In a more complex transformation A-protected L-Pro was transformed into the same bicyclic system (Scheme 49) (81JA1851 84JA4192). The product was prepared as a model substance in the total synthesis of pumiliotoxin. A related compound 82 was prepared from 5-(hydroxymethyl)-2-pyrrolidinone (prepared from L-pyroglutamic acid) by an acid-catalyzed condensation with benzaldehyde (86JOC3140). 

The formation of oxazolidines 54 or oxazolidinones 55 is currently utilized to assign the absolute stereochemistry of diastereomers of 1,2-amino alcohols, based on H NMR analysis of the H4 and H5 protons of these heterocycles. In the case of y-amino-p-hydroxy acids, the internally cyclized pyrrolidinone 56 is also suitable for determination of the relative configurations of the y-amino and p-hydroxy groups (Scheme 23). 

Chemical Name 2-Pyrrolidinone, l-(8-hydroxy-6-methyl-2,4,6-dodecatrienoyl)-, (E,E,E)-(R)-... 

The 5-chloro-2-(2-methyl-2-propenyloxy)benzoic acid, methyl ester was heated at reflux for 6 h in l-methyl-2-pyrrolidinone. The mixture was then vacuum distilled and the fraction collected and the desired 2-hydroxy-5-chloro-3-(2-methyl-2-propenyl)benzoic acid, methyl ester was obtained. 

N-[2(1-Hydroxy-2-phenethyl)]-5-heptyl-2-pyrrolidinone 2-Pyrrolidinone, 5-heptyl-1-(2-hydroxy-1 -phenylelhyl)-, [R-(R, R )]- (13) (139564-36-6)... 

BENZODIOXOLE, DIMETHYLBENZENE AND 1-METHYL 2-PYRROLIDINONE see BGD088 CYCLOPROPANECARBOXYUC ACID, 2,2-DIMETHYL-3-(2-METHYLPROPENYL)-, ESTER WITH 4-HYDROXY-3-METHYL-2-(2-PROPYNYL)-2-CYCLOPENTEN-l-ONE, trans-(+-)- see THI500 CYCLORYL 21 see SIB600... 

DP = dipolar aprotic solvent NMP = iV-methyl pyrrolidinone OAAT = 2-hydroxy-4,6-diamino-.s -triazine OIET = 2-hydroxy-4-(isopropylamino)-6-(ethylamino)-5-triazine OOAT = 2-hydroxy-4-hydroxy-6-amino-s-triazine PS = petroleum sulfide TBA = tetra-n-butylammonium TEA = tetraethylammonium TEOS = tetramethylorthosilicate TMA = tetramethylammonium TMU= tetramethylurea. c For reactions photoca-talyzed by POMs under anaerobic conditions, the reduced POM resulting from photooxidation of the substrate is reoxidized by reduction of protons generated in this initial substrate photooxidation step, forming H2. 

Hydroxy Ethyl Methacrylate N-vinyl Pyrrolidinone FIG. 1. Common graft monomers. 

Monomers, such as n-vinyl pyrrolidinone and hydroxy ethyl methacrylate, have been used to enhance the biocompatibility of films and to control the air permeation and hydrophilicity of microporous films and of non-woven polyolefin materials [10], Significant opportunities exist to pursue other uses in the bio-materials area [11, 12], Attempts to produce grafted films to control gas permeation for use in food packaging applications have not met with success [13], Co-extruded films have proven to be more acceptable in this food packaging area. The modification of films and non-woven materials rely upon low-voltage, self-shielded electron beams. The development of lower cost, low-voltage EB equipment reduces the economic barriers to further development in this area (Fig. 4) [14, 15],... 

Rearrangements arising by carbonyl hydrogen abstraction are frequently of value in the synthesis of nitrogen-containing heterocycles. The NN-disubstituted /S-keto-amides (133), on irradiation in benzene, are converted into the 4-hydroxy-2-pyrrolidinones (134), presumably by 8-hydrogen abstraction, in yields of up to 88%.107 Further reports of the cyclization of N-substituted phthalimides have been published. Irradiation of a series of TV-alicyclic phthalimides (135) provides a route to the benzazepines (136) via the cyclobutanols (137) 108 the cw-ring junction in the final product was confirmed by independent synthesis. The... 

It is prepared by treating 2-dimethyl-6-nitrile-3,4-epoxy coumarine first with sodium hydride in dimethylsulphoxide and secondly viith- 2-pyrrolidinone to obtain 2-dimethyl-3-hydroxy-6-nitrile-4 [T (2-pyrrolidinone)] eoumarine. The resolution of the resulting cromakalim is aehieved via the S-a-methylbenzyl carbamate to get the (-)-3S, 4R enantiomer. 

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