Decarboxylative transamination. A new route to spirocyclic and bridgehead-nitrogen compounds. Relevance to α-amino acid decarboxylases

Abstract

N-Substituted and a,&-disubstituted amino acids react with carbonyl compounds to generate 1,3-dipolar species under mild conditions mimicking a-amino acid decarboxylases; the 1,3-dipoles can be trapped both inter-and intra-molecularly to give bridgehead-nitrogen and spirocyclic products in good yield; pyridoxal is shown to react in an analogous fashion.

Construction of Spiro[pyrrolidine‐3,3′‐oxindoles] − Recent Applications to the Synthesis of Oxindole Alkaloids

“…Spiro[pyrrolidine-3,3Ј-oxindoles] are obtained from the reaction of azomethine ylides with oxindolylidene 3-ylidene acetate. [36] Azomethine ylides obtained from different precursors can also react with oxindolin-3-ylidene dipolarophiles leading to the spiro[pyrrolidine-3,3Ј-oxindole] ring system. (3) [Equation (1), Scheme 13].…”

Regioselective synthesis and anti-inflammatory activity of novel dispiro[pyrazolidine-4,3'-pyrrolidine-2',3"-indoline]-2",3,5-triones

“…The IR spectra were recorded on a Shimadzu 470 IR spectrometer (KBr) νmax /cm -1 . The 1 H-, and 13 C-NMR spectra were measured on Varian EM-200 ( 1 H, 200 MHz; 13 C, 50 MHz) spectrometer with TMS as internal standard and DMSO-d6 as solvent. Mass spectra were determined on a JEOL JMS-600 spectrometer.…”

“…Hence, only one set of regio-isomers 5a-j was formed. The structures of the isolated products were established to be dispiro[pyrazolidine-4,3'-pyrrolidine-2',3"-indoline]-2",3,5-triones, 5a-j, rather than the regio-isomeric form dispiro[pyrazolidine-4,4'-pyrrolidine-2',3''-indoline]-2",3,5-triones, 6a-j, based on spectroscopic (IR, 1 H-, 13 C-NMR, MS) and elemental analysis data. 1 H-NMR spectra of 5a-j reveal the presence of three triplet signal sets at δ = 3.54-3.63, 3.95-4.02 ppm (assignable for the magnetically non-equivalent pyrrolidinyl methylene protons H2C-5', coupled with each other and in turn with the vicinal methine proton HC-4') and 4.86-5.01 ppm (corresponding to the pyrrolidinyl methine proton HC-4'), excluding the formation of the other regio-isomeric form 6.…”

“…[3][4][5] N-Arylpyrazoles are a very interesting class of heterocyclic compounds that have remarkable pharmacological activities in areas such as antibacterialantifungal, 6 hypoglycemic, 7 tumor necrosis inhibition, 8 anti-thrombo-embolic disorders, as antiangiogenic-, 9 and anti-inflammatory effects. 10,11 In the present work, it is intended to utilize a natural product isatin scaffold for formation of non-stabilized azomethine ylides following the previously described and successful methods, [12][13][14][15] through decarboxylative condensation with α-amino acids and trapping the generated reactive intermediate via 1,3-dipolar cycloaddition reaction with the exocyclic olefinic linkage derived from 1-phenylpyrazolidine-3,5-dione. The anti-inflammatory properties of the prepared Reaction of the 4-arylidene-1-phenylpyrazolidine-3,5-diones 2a-e with non-stabilized azomethine ylides, generated in situ via decarboxylative condensation of sarcosine 4 and isatins 3a,b (Scheme 2) [12][13][14][15] in refluxing ethanol afforded only one product, as indicated by TLC, in a highly regio-and stereo-selective manner (Scheme 3).…”

“…10,11 In the present work, it is intended to utilize a natural product isatin scaffold for formation of non-stabilized azomethine ylides following the previously described and successful methods, [12][13][14][15] through decarboxylative condensation with α-amino acids and trapping the generated reactive intermediate via 1,3-dipolar cycloaddition reaction with the exocyclic olefinic linkage derived from 1-phenylpyrazolidine-3,5-dione. The anti-inflammatory properties of the prepared Reaction of the 4-arylidene-1-phenylpyrazolidine-3,5-diones 2a-e with non-stabilized azomethine ylides, generated in situ via decarboxylative condensation of sarcosine 4 and isatins 3a,b (Scheme 2) [12][13][14][15] in refluxing ethanol afforded only one product, as indicated by TLC, in a highly regio-and stereo-selective manner (Scheme 3). This cycloaddition is regioselective with the electron-rich carbon of the dipole adding to the β-carbon of the α,β-unsaturated moiety of 2a-e, and is stereoselective, affording only one diastereomer exclusively, despite the presence of three stereo-centers in the product as found in many similar cycloaddition studies.…”