The matrix photolysis of pyridine-2,3- and -3,4-dicarboxylic anhydrides

Photolysis of anhydrides ($\text{1}$) and ($\text{5}$) in low temperature matrices led to loss of CO and CO₂ in each case, but pyridynes were not detected, and if formed at all, underwent immediate further bond fission.     

The preparation of 7-substituted norbornadiene-2,3-dicarboxylic anhydrides and an experimental and theoretical study of their reactivity

Four new substituted methano-bridged or heteroatom-bridged norbornadienomaleic anhydrides have been prepared and converted to sesquinorbornadiene anhydrides by reaction with cyclic 1,3-dienes. The versatility of parity reversal, in conjunction with N-substituent steric effects, has been used to produce all three possible stereoisomers of the N,O-sesquinorbornadiene anhydrides in separate, stereoselective cycloadditions. The anhydrides have been synthesized by cyclization of their diacids (in situ production) or by flash vacuum pyrolysis of their furan adducts (yielding crystalline products); further fragmentation occurs at these or higher temperatures to produce five-membered carbocyclic or heterocyclic anhydrides. Activation energies have been evaluated for the fragmentation and cycloaddition processes using DFT calculations (B3LYP/6-31G∗) and these calculations correctly predict, which reaction can be intercepted at the norbornadienomaleic anhydride stage and preferred stereochemistry of cycloadducts.     

Novel thermolytic transformations of n-benzoyl 2-aza 3-oxa bicyclo(2.2.1)hept-5-ene and n-benzoyl 2-aza 3-oxa bicyclo(2.2.1)heptane

Novel thermolytic pathways were encountered in careful studies with N-benzoyl 2-aza 3-oxa bicyclo (2.2.1)heptene (1) and N-benzoyl 2-aza 3-oxa bicyclo(2.2.1)heptane (2). Compound 1 thermally fragments by four major pathways, namely, (3,3)-sigmatropic shift, (4 + 2) cycloreversion, N-O rupture and C-N homolysis. The (3,3)-sigmatropic shift provides a novel route to unusual, bicyclic heterocycles. Electron withdrawing aryl groupings tend to promote the (3,3)-sigmatropic shift pathway over others. The (4 + 2)-cycloreversion of 1 leads to nitroso carbonyl benzene and cyclopentadiene. The weak σ bonds of PhCONO undergo ready homolysis. The intermediate arising from N-O rupture leads to a cyclopentenone radical similar to that involved in the PG endoperoxide → PGE change. This radical either combines with benzoyl radical leading to 4-dibenzoylamino cyclopentenone or is transformed to an enamide by loss of hydrogen, which, in turn, undergoes (4 + 2)-cycloaddition with cyclopentadiene leading to a novel spiro adduct. The C-N rupture leads to the formation of benzanilide.Nitrosocarbonyl benzene is a powerful electrophile. With cyclohexene it forms a hydroximic ester, initiated by nucleophile acceptance at the CO oxygen. In contrast, it reacts with P(OMe)₃ leading to diphenylurea via nucleophile acceptance at NO oxygen. Thermolysis of 2 proceeds largely by N-O rupture, similar to that normally observed in the PG endoperoxide → PGE change.     

Synthesis of caulersin and its isomers by reaction of indole-2,3-dicarboxylic anhydrides with methyl indoleacetates

1-Benzenesulfonylindole-2,3-dicarboxylic anhydride was reacted with methyl 1-benzenesulfonylindole-2-acetate to give the corresponding 2-acylindole-3-carboxylic acid as the sole product in high yield, which could be converted to caulersin in four steps. In a similar manner, three isomers A, B, and C were synthesized by reaction of indole-2,3-dicarboxylic anhydrides with methyl indoleacetates.     

Synthesis of 2,3-dichlorobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid N-carboxyphenylimides

Russian Journal of Organic Chemistry -     

Synthesis of N-substituted 2,3-dichlorobicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic acid imides

Russian Journal of Organic Chemistry -     

Synthesis of benzo-γ-carboline alkaloid cryptosanginolentine by reaction of indole-2,3-dicarboxylic anhydrides with anilines

1-Benzenesulfonylindole-2,3-dicarboxylic anhydride was reacted with aniline to give the 2-carbamoylindole-3-carboxylic acid as the sole product, but with N-methylaniline, the 3-carbamoylindole-2-carboxylic acid was the major product, which could be transformed into the 1-benzenesulfonylbenzo-γ-carbolinone in the presence of Pd(OCOCF₃)₂. The reduction of the benzo-γ-carbolinone with LiAlH₄ gave the cryptosanginolentine in high yield.     

Preparation of a chiral azadiene for the synthesis of 5-aza analogues of angucyclinones

We have developed an efficient synthesis of both enantiomers of a key azadiene for the preparation of 5-aza analogues of angucyclinones through a hetero Diels-Alder reaction. These dienes were efficiently prepared via a 4-step procedure from known and readily available chiral diketoesters.     

抗肿瘤活性化合物去甲基斑蟊-5-烯酸的金属配位能力的研究

斑蟊类化合物是一种潜在的强有力的螯合剂, 本文研究了去甲斑蝥-5-烯酸(7-氧杂二环[2,2,1]-庚-5-烯-2,3-二羧酸)与一系列生命必需金属元素间结合能力, 与其它二元羧酸比较, 表现出很大的配位能力, 这是环氧原子参与配位所致, 它已由X射线分析证实. 研究了浓度, 酸度的影响, 这关系到一些配位体药物的抗癌活性.     

Synthesis of derivatives of pyrazine-2,3-dicarboxylic acids and pyrazine-2,3-dicarbonamides from 2,3-dichloroquinoxaline

The synthesis of dimethyl 2,3-dichloropyrazine-5,6-dicarboxylate from dichloroquinoxaline has been effected. The nucleophilic substitution reactions of the compound obtained have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1548–1551, November, 1973.     

7-氧杂双环[2.2.1]庚-2,3-二甲酸衍生物的合成及其抗HIV活性

以呋喃和顺丁烯二酸酐为原料,经环化反应制得7-氧杂双环[2.2.1]庚-5-烯-2,3-二甲酸酐(3);打开3的酸酐五元环,选择性地进行单酯化反应,合成了一系列7-氧杂双环[2.2.1]庚-3-烷氧羰基-2-甲酸(4a～4d),其结构经1H NMR和MS表征.初步探讨了4的抗HIV构效关系,其中4a的治疗指数与其先导化合物去甲基斑蝥素相当,毒性较之降低.     

Synthesis of pyridazinedione derivatives starting from anhydrides of 2,3-pyridine- and 2,3-quinolinedicarboxylic acids

A method was developed of preparation of heterocyclic compounds with pyridopyridazinoisoquinalinedione and isoquinopyridazinoquinalinedione structures formed regioselectively by intramolecular cyclization of phosphorus ylides containing pyridopyridazinedione and pyridazinoquinolinedione fragments.     

Synthesis of 1,9a-dihydro-9a-substituted fluorenones and their 4-aza analogues

Cyclization of 2,2-disubstituted indan-1,3-dione with CH₃COONH₄ yields 9a-substituted 1,9a-dihydrofluorenone and 9H-4a, 5-dihydroindeno(1,2-b)pyridine derivatives.     

Synthesis and application of chiral monoesters derived from cyclohex-4-ene-1,2-dicarboxylic acid and bicyclo[2.2.1]-hept-5-ene-2,3-dicarboxylic acid

Optically active alkyl and cycloalkyl hydrogen cyclohex-4-ene-1,2- and bicyclo[2.2.1]hept-5-ene- 2,3-dicarboxylates were synthesized by asymmetric Diels-Alder reactions in the presence of chiral catalyst. The cycloadducts were found to possess antimicrobial activity.     

Construction of quaternary carbon stereocentres: catalytic enantioselective allylation assisted by a bimetallic catalytic system

The asymmetric allylic alkylation of prochiral aryl cyano esters has been carried out in the presence of a bi-component catalytic system containing a palladium and a rhodium complex modified by phosphorus containing chiral auxiliaries. The allyl derivatives were isolated in up to 63% ee. The chiral pocket ligands of Trost appear the most appropriate to produce the desired chiral derivatives.     

Unconventional nucleotide analogues: Reaction of carbenes with uracil and uridine derivatives

Carbenes 2a-d (:CCl₂, :CBr₂, :CFC1, :CHCOOC₂H₅) add to the 5,6-double bond of uracil derivatives la-e to give adducts in modest to good yields The unsymmetrically substituted carbenes :CFC1 2c and CHCOOC₂H₅, 2d lead, as expected, to the formation of mixtures of endo and exo-isomers 3c-n which were separated and identified via their ¹H NMR spectra. Reaction of 2d with pyrimidine derivatives 5a,b resulted in products which can be rationalized in terms of addition at either the 5,6 or the 3,4 double bond. Addition of carbenes 2a-c to uridine derivatives gave diastereomeric adducts 12-16 which were isolated and identified. The two diastereomeric series, referred to as A and B, have been correlated and assigned the configurations 5S, 6S and 5R, 6R, respectively, on the basis of X-ray structure analysis of 12B The adducts of 2a,c and the uridine derivatives 11a,b have been deprotected to give 7,7-dihalocyclothymidines.     

Unconventional nucleotide analogues—XVII: Ring-transformations of uracil dihalocarbene adducts

Halocarbene adducts of 1,3-disubstituted uracil (3a, b, d) undergo ring-enlargement to yield 1,3-diazepine derivatives (4a–d). The ring-opening of the cyclopropane system is controlled by the stereochemical configuration of the halogen atom, which can be eliminated as a halide ion. Reduction of the adducts with n-Bu₃SnH leads to a variety of 1,3-diazepines. Details of the mechanism of formation of the diazepines and their further transformations are discussed.     

Synthesis and Properties of 6-Amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles

We have established that when 5-chloro-6-[cyano(2,3-dihydro-1-R-benzo[d]azol-2-yl)methyl]-2,3-pyrazinedicarbonitriles are reacted with nucleophilic reagents (aliphatic and aromatic amines, hydrogen sulfide), annelation of the five-membered ring occurs on the [b] face of the pyrazine with formation of 6-amino-7-hetaryl-5-R-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles and 6-amino-7-(1H-benzo[d]imidazol-2-yl)thieno[2,3-b]pyrazine-2,3-dicarbonitrile respectively. Further heating with excess of acylating reagent leads to formation of a novel heterocyclic system 1H-benzo[4,5]imidazo[1,2-c]pyrazino[2',3':4,5]pyrrolo[3,2-e]pyrimidine. Reaction of vicinal dinitriles with hydrazine hydrate leads to the novel system 1H-pyrrolo[2',3':5,6]pyrazino[2,3-d]pyridazine.