Piperazine dione

Stereoselective formation of 3-alkyl-6-methoxy-2,5-piperazine-dione derivatives by the addition of methanol in the presence of NBS to 3-alkyl-6-alkylidene-2,5-piperazinediones was recently reported by Shin et al. 232 The asymmetric induction in this reaction was accomplished by the chiral center of a derivative of the natural proteinogenic chiral amino acid threonine. 

The Kishi group developed a second synthesis of 3,6-epidithia-2,5-piperazine-diones that is particularly useful for the synthesis of simpler systems on a large scale [Scheme 5,41 ] 77 The route benefits from the stereochemistry of the double 5-alkylation of 41.1 to give the cis-product 41.2 A second double enolate alkylation was again stereoselective, giving 413 in 83% yield. Finally treatment of the bis(0,5-acetal) 413 with trichloroborane gave the 3,6-epidithia-2,5-piper-azinedione 41,4 in 77% yield. 

The authors reported that the Lewis-acid receptor ATPH and its congeners self-assemble with a dicarbonyl guest molecule in organic solvents to form a dimeric capsule the X-ray crystal structure of such a complex with l,4-dimethyl-2,5-piperazine-dione as a model guest is shown in Fig. 1 [166]. 

Conversion to the piperazine-2,5-dione with sorbitol/zinc sulphate [46] or diethanolamine/zinc sulphate [47], foUowed by measurement at 322nm in 1M NaOH, provided a stability indicating method for amoxicillin. Any piperazine dione present as impurity was corrected for by a sample blank and no interference was found from acid or alkali degradation products or from amoxicUlin oligomers. 

Spectral studies on 1,4-dioxopyrrolo[ 1,2-alpyrazines abound. Infrared absorption properties of a variety of derivatives of 168 have been com piled,48,147 and related to the conformations of the piperazine-dione ring. Gas-chromatographic techniques for separating diastereo-meric mixtures of derivatives of 168 have been described.150 Mass spectral fragmentation patterns for a series of dioxopiperazines, including derivatives of 168, has been reported.151 Numerous nuclear... 

Piperazine dione (52) reacts selectively with oxygen to yield bw-hydroperoxides 53... 

Covalent chlorinated impurities in MeSi(0Me)2 can be readily removed using Na and substantially reduce its rate of hydrolysis, while 3 amines accelerate the alcoholysis of Ph,SiCl, through silylated quaternary ammonium intermediates. The Bu (Ph)(MeO)Si group provides excellent protection to alcohols, its silyl acetal character providing for ready F cleavage, unlike Bu Ph2Si while analogues of the antibiotic bicyclomycin used bicyclic piperazine-diones as intermediates, and silylene protected dihydroxystyrene... 

CioHi6N2O2S, 3,6-Diethyl-1,4-dimethyl-3,6-epithio-2,5-piperazine-dione, 46B, 399 Cio i6 2C3S, Biotin, 20, 638... 

Linked piperazine-dione derivatives as heiicai mimetics for the disruption of bci-2-famiiy proteins... 

As the biosynthesis of cyclic peptide antibiotica proceeds independently of the normal RNA-controlled peptide synthesis, one may presume that their elaboration takes place by way of an enlargement of cyclopeptides by insertion of L-amino acids, starting with piperazine-diones. 

Elimination reactions have more often been carried out with piperazine-diones containing suitable leaving groups (OH, acetoxy, SCH3) in positions 3 and/or 6. In some cases 102, 168) the hydroxy compound is not isolated, but loses water in situ. Starting compounds for elimination reactions are summarized in Table 2. 

P. G. Sammes has dehydrogenated the iminoethers of piperazine-diones with 2,3-dichloro-5,6-dicyanobenzoquinone 243). Cyclo-L-Pro-L-Pro can be oxidized with this reagent directly to pyrocoll 243). The use of sulfur as oxidizing agent has been successful only with N-acetylated piperazinediones 242). 

Piperazine, I -diethyIcarbamyI-4-methyl-metabolism, 1, 227 Piperazine, N,JV-dimethyI-epoxy resin curative. 1, 406 Piperazine, 2,5-dioxo-occurrence, 3, 187 Piperazine-2,5-dione polymers, 1, 298... 

Several earlier methods (55,56) utilized a piperazinedione derivative in an Arbuzov-based sequence as a more stable source of the requisite iV-chloromethyl intermediate 51. Treatment of piperazine-1,4-dione with formaldehyde and phosphorus trichloride provided convenient access to this starting material. Subsequent reaction with either trimethyl or triethyl phosphite produced the iV-phosphonomethyl tetraester derivative 52, which has been hydrolyzed to GLYH3. 

Conjugate addition of azide ion to dihydropyran-2,5-diones affords the 3-amino derivative <96SL341>, whilst reaction with bisnucleophiles provides a route to piperazines, thiazines and diazepines <96JHC703>. 

Dicarboxylic acids were converted in a one-pot procedure with CDI (boiling THF, 15 min) into the bisimidazolides, and then by subsequent treatment with aliphatic, aromatic, or heteroaromatic primary amines into imides (piperazine-2,6-diones) in excellent yields [131]... 

The crystal structures of 4-phenyl-2- 4-[4-(2-pyrimidinyl)piperazin-l-yl]butyl -2,3,5,6,7,8-hexahydro-177-pyrido[l,2-c][l,3]oxazine-l,3-dione <1995ZK899>, 4-cyano-l-phenyl-l-trifluoromethyl-2,3-dihydro-l/7-pyrido[l,2-r-]pyrimidin-... 

The bromine atom of 4-aryl-2-(4-bromobutyl)-2,3,5,6,7,8-hexahydro-177- ancj -perhydropyrido[l,2-c]pyrimidine-l,3-diones was displaced with 4-substituted piperazines <2002FES959, 2004APH139, 2004PHA99>. Heating 3-hydroxymethyl derivatives of epimeric 6-methyl-l,3,4,6,7,llb-hexahydro-277-pyrimido[6,l-,2]isoquinolin-2-ones 152 resulted in the formation of the 3-unsubstituted derivatives 153 by loss of CH20 (Equation 26) <1997LA1165>. 

Amino-2-methoxyphenyl)perhydropyrido[l,2-tf]pyrazine was prepared from a 2-(5-nitro-2-methoxyphenyl)-3-one derivative by catalytic hydrogenation over Pd/C catalyst, followed by the reduction of the 3-oxo group by treatment with BH3-THF complex <1999WO99/042465>. A nitro group was reduced to an amino group in 2-[4-(3-nitrophenyl)piperazin-l-yl]butyl]perhydropyrido[l,2-tf]pyrazine-l,4-dione <2001JME186>, in 8-hydroxy-... 

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