Oxindole structures

The mechanism of the rearrangement is explained as shown in Scheme 19. Protonation of the 9-hydroxy group followed by its elimination and subsequent chloride attack at the 4a-carbon generates a chloroindolenine 126. Addition of water to the 9a-imine carbon atom of 126 gives 127. Concerted elimination of the chloride with rearrangement of the alkyl side chain attached to the 9a carbon atom results in 3,3-disubstituted oxindole structure 120a. 

The oxindole structure (XXIX) of this alkaloid was established by consideration of a combination of spectral evidence. Thus, its mass spectrum confirmed the analytically found molecular formula of C23H30N2O6 bj showing a molecular ion at m/e 430. Further, it exhibited a strong peak at m/e 225 due to the fragment e, two mass units higher than the corresponding ion in the mass spectra of mitraphylline and carapanau-bine which have a C-16, C-17 double bond. Other peaks in the spectrum are also shifted by the appropriate number of mass units expected for... 

The library could in this study be generated in a dimethyl sulfoxide-rich solvent mixture, a prerequisite for not damaging the protein crystals, and the crystals were directly soaked with the DCL solution. By following the electron-density maps in the crystallography setup, the best binders could be identified and several oxindole structures with inhibitory activities in the nanomolar range were found. 

An asymmetric one-pot sequential Mannich/hydroamination sequence involves a three-catalyst system a chiral organocatalyst, BF3 and a gold complex. It converts an indole-imine into privileged spiro[pyrrolidin-3,2 -oxindole] structures in up to 91/97% yield/ee. 

Highly strained spirocyclic oxindole structures (less than five-manbered rings) represents one of the most important but less studied spirocyclic skeletons. In 2011,... 

Colegate and co-workers (98P437) isolated (-)-coerulescine (120b) from Phalaris coemlescens and determined that its structure has a 3,3-disubstituted oxindole nucleus (Scheme 18). The synthesis of ( )-coerulescine (120b) was... 

Only three examples of ibogan-type oxindole alkaloids are known, and two of them, crassanine (156) and tabemoxidine (155), were found in Tabernaemon-tana. Crassanine (C23H30N2O5, MP 191°C, [a]D +21°) was isolated in minute amounts by Cava et al. from T. crassa (79). Its IR spectrum indicated the presence of two carbonyl groupings (1739 and 1709 cm - ), while its UV spectrum was almost superimposable on that of known 10,11-dimethoxyoxindoles such as kisantine (200). In addition to the carbomethoxy methyl at 3.47 ppm and two aromatic methoxyls at 3.83 ppm (6H), the H-NMR spectrum of 156 exhibited two singlets (1H) at 6.50 and 7.01 ppm and the low-field oxindole NH at 9.30 ppm. The latter values are similar to those recorded for kisantine, and on this basis Cava et al. proposed the structure 102 for crassanine. To date, no evidence is available on the configuration at the C-7 spiro center. 

During the past two decades a great number of papers have been published on the isolation, structure elucidation, synthesis and transformation, biogenesis, chemotaxonomy, and pharmacology of indole alkaloids. In this chapter we summarize the new results that appeared from 1968 to mid 1984 for the cory-nantheine-yohimbine group of monoterpene indole alkaloids with greater emphasis on their chemistry, excluding the related oxindoles and heteroyohimbines. 

The amorphous alkaloid vincathicine (24), C46H56N4O9, initially isolated from C. rose us (37), was suspected to contain an oxindole chromophore. No further work was reported on the structure elucidation of 24 until it was observed that vincathicine (24) could be prepared from leurosine (11) by acid treatment (94,95). Efforts followed by the reisolation of vincathicine (24) from C. roseus led to the unambiguous structure elucidation of this alkaloid (94). 

Organometallic compounds asymmetric catalysis, 11, 255 chiral auxiliaries, 266 enantioselectivity, 255 see also specific compounds Organozinc chemistry, 260 amino alcohols, 261, 355 chirality amplification, 273 efficiency origins, 273 ligand acceleration, 260 molecular structures, 276 reaction mechanism, 269 transition state models, 264 turnover-limiting step, 271 Orthohydroxylation, naphthol, 230 Osmium, olefin dihydroxylation, 150 Oxametallacycle intermediates, 150, 152 Oxazaborolidines, 134 Oxazoline, 356 Oxidation amines, 155 olefins, 137, 150 reduction, 5 sulfides, 155 Oxidative addition, 5 amine isomerization, 111 hydrogen molecule, 16 Oxidative dimerization, chiral phenols, 287 Oximes, borane reduction, 135 Oxindole alkylation, 338 Oxiranes, enantioselective synthesis, 137, 289, 326, 333, 349, 361 Oxonium polymerization, 332 Oxo process, 162 Oxovanadium complexes, 220 Oxygenation, C—H bonds, 149... 

The C-2 and C-3 hydroxy derivatives of pyrrole are special in the sense that the tautomeric equilibria favor the pyrrolinone structures (see Section 3.04.6.2). Furthermore, the general synthetic methods are not usually applicable so that we will call attention in this section not only to the methods of directly introducing these substituents, which are rare, but also to those ring construction processes which specifically give the pyrrolinones and indolinones. The indole derivatives have widely used trivial names, oxindole (5) for indolin-2-one and indoxyl (6) for indolin-3-one, Carbocyclic hydroxy substituents in indole and carbazole, on the other hand, for the most part act as normal aromatic phenolic groups. These compounds are usually prepared by application of the standard ring syntheses. 

ABSTRACT The acid-catalysed epimerization reaction of bioactive indole alkaloids and their derivatives is reviewed. The three mechanisms, which have been proposed for the (J-carboline-type indole alkaloids, are discussed. Through recent developments, evidence for all three mechanisms has been obtained, which shows the complexity of the epimerization reaction. The epimerization seems to depend on structural features and reaction conditions making it difficult to define one universal mechanism. On the other hand, the isomerization mechanism of oxindole alkaloids has been widely accepted. The acid-catalysed epimerization reaction provides a powerful tool in selectively manipulating the stereochemistry at the epimeric centre and it can also have a marked effect on the pharmacology of any epimerizable compound. Therefore, examples of this reaction in die total synthesis of indole alkaloids are given and pharmacological activities of some C-3 epimeric diastereomers are compared. Finally, literature examples of acid-catalysed epimerization reactions are presented. 

An isomerization reaction closely similar to that observed with indole alkaloids has been noted with oxindole alkaloids. Due to their facile isomerization, it is pharmacologically difficult to test the individual oxindole isomers expected to have different activities. Instead of epimerization the term isomerization has been used with oxindole alkaloids since inversion of configuration can occur in more than one asymmetric centre. Isomerization was employed mainly to provide structural proof of different oxindole epimers isolated in nature. As early as 1959, Wenkert and co-workers [42] proposed a mechanism for the isomerization of oxindole alkaloids, Scheme (17). Almost simultaneously, Seaton et al. [43] reported analogous findings. 

The formation of cyclopropane derivatives by photolysis of diazoalkanes in the presence of alkenes is believed to occur by photolytic decomposition of the diazoalkane to yield the carbene, followed by addition of this carbene to the alkene. Cycloaddition of this type has been reported in furan, dihydrofuran, and thiophene.198 Thus, photolysis of ethyl diazoacetate in thiophene yields the bicyclic sulfur heterocycle (215). Alternatively, photolysis of 3-diazo-l-methyl-oxindole (216) in cyclohexene leads to the formation of two isomers which are thought to have the spirocyclopropyl structure (217) photolysis in ethanol yields 3-ethoxy-1-methyloxindole.194... 

Dimethyl acetylenedicarboxylate and the oxindole anion gave 295 (R = H), which was hydrogenated to 296,185 but oxindole with DMAD at 200° gave the furan 297,186 clearly derived by self-condensation of the ester, and the benzazepine 298 the structure and origin of which require further investigation. 

Gelsemicine (234) was the first naturally occuring l-methoxy-2-oxindole to be discovered in Gelsemium sempervirens roots (65MI3). Its structure... 

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