Natürliche Pyrrolidinylspirooxindole als Vorlagen für die Entwicklung medizinischer Wirkstoffe

Galliford, Chris V.; Scheidt, Karl A.

doi:10.1002/ange.200701342

Cited by 514 publications

(69 citation statements)

References 148 publications

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“…[1] A range of compounds carrying the indole system exhibit antibacterial and antifungal activities. [2] The significant biological activity and recent synthetic advances of these natural products encouraged the development of biologically promising analogues that would be more efficacious and selective than the original natural products.…”

Section: Introductionmentioning

confidence: 99%

One‐Pot Synthesis of Spirooxindole Derivatives Catalyzed by Lipase in the Presence of Water

et al. 2011

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A facile one-pot synthesis route to spirooxindole derivatives was developed by combining the three types of catalytic activities of lipase from porcine pancreas (PPL) in the presence of water, i.e., the Knoevengel condensation, Michael addition and cyclization. PPL showed excellent catalytic activity and have a good adaptability to different substrates in the reaction. All the reactions go smoothly and provide spirooxindole derivatives with high yield under the mild conditions. This lipase-catalyzed multistep conversion method has provided a new strategy to synthesize spirooxindole derivatives and expanded the application of biocatalysts.

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Section: Introductionmentioning

confidence: 99%

One‐Pot Synthesis of Spirooxindole Derivatives Catalyzed by Lipase in the Presence of Water

et al. 2011

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“…As shown in Table 1, the use of 3.0 equivalents of d-diethyl tartrate in this reaction is essential to give 3a in good yields and high ee values ( Table 1, entries [1][2][3][4]. The combination of (DHQD) 2 PHAL (20 mol%) with l-diethyl tartrate (3.0 equiv.)…”

mentioning

confidence: 99%

“…[1] Encouraged by their unique structural features and significant biological activities, various effective synthetic methods for the construction of spirooxindoles and subsequent applications in natural product synthesis have been extensively explored over the last decade. [2] Previously, we reported that the nitrogen-containing Brønsted bases-mediated [4+2] annulations of isatins with but-3-yn-2-one could proceed smoothly to give the corresponding spiro[indoline-3,2'-pyran]-2,4'A C H T U N G T R E N N U N G (3'H)-diones in good to excellent yields under mild conditions.…”

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confidence: 99%

Asymmetric [4+2] Annulations of Isatins with But‐3‐yn‐2‐one

Wang

Lian

et al. 2013

Adv Synth Catal

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The catalytic asymmetric [4+2] annulations of isatins with but-3-yn-2-one catalyzed by the Cinchona alkaloids-derived oragnocatalyst (DHQD) 2 PHAL have been developed in the presence of 3.0 equivalents of d-diethyl tartrate in the mixed solvent (diphenyl ether/diethyl ether = 1/1) or a slightly modified one, affording the corresponding substituted spiro[indoline-3,2'-pyran]-2,4'-A C H T U N G T R E N N U N G (3'H)-diones in good to excellent yields with high enantioselectivities under mild conditions. Keywords: asymmetric [4+2] annulations; but-3-yn-2-one; Cinchona alkaloids; isatins; spiro[indoline-3,2'-pyran]s Spirooxindoles are privileged structural motifs found in many alkaloids such as gelsemine, mitraphylline or SR 121463 and unnatural biologically active compounds.[1] Encouraged by their unique structural features and significant biological activities, various effective synthetic methods for the construction of spirooxindoles and subsequent applications in natural product synthesis have been extensively explored over the last decade.[2] Previously, we reported that the nitrogen-containing Brønsted bases-mediated [4+2] annulations of isatins with but-3-yn-2-one could proceed smoothly to give the corresponding spiro[indoline-3,2'-pyran]-2,4'A C H T U N G T R E N N U N G (3'H)-diones in good to excellent yields under mild conditions. [3] In this paper, we wish to report the asymmetric variant to afford these products in good yields and good to high ee values with the Cinchona alkaloid-derived organo-A C H T U N G T R E N N U N G catalyst hydroquindine-1,4-phthalazinediyl diether [(DHQD) 2 PHAL] in the presence of d-diethyl tartrate. [4,5] We initially utilized isatin 1a (0.1 mmol, 1.0 equiv.) and but-3-yn-2-one 2a (0.3 mmol, 3.0 equiv.) as the substrates in the presence of several Cinchona alkaloids and 1R,2R-cyclohexanediamine derived organocatalysts (20 mol%) in THF at room temperature to examine the reaction outcomes and the results are shown in Scheme SI-1 in the Supporting Information. It was found that the corresponding cyclic product 3a was obtained in 65% yield along with 25% ee using (DHQD) 2 PHAL (20 mol%) as the catalyst (Scheme 1). In order to improve the reaction outcome, we screened various proton sources (1.0 equiv.) such as 732 cation exchange resin, (R)/(S)-binol, dcamphorsulfonic acid, 2-adamantanol, and d/l-diethyl tartrate or its derivatives for this reaction and the results are summarized in Table SI-1 in the Supporting Information. As can be seen from Table SI-1, we found that 3a could be obtained in 90% yield and 68% ee using (DHQD) 2 PHAL (20 mol%) as the catalyst in the presence of 3.0 equivalents of d-diethyl tartrate. Moreover, after further screening of the emScheme 1. Screening of the catalysts for the asymmetric [4+2] annulation of isatin 1a with but-3-yn-2-one 2a.

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“…[1] In addition to their medical and agricultural uses, non-natural heterocyclic spiro compounds have also been widely employed in industrial fields as fluorescent probes and electroluminescent devices because of their special rigid structures. [2] The spirooxazine motif (I) is the most popular group of photochromic materials and the best representative of heterocyclic spiro compounds with photochromic properties.…”

mentioning

confidence: 99%

One‐Pot Synthesis of Spirooxazino Derivatives via Enzyme‐ Initiated Multicomponent Reactions

Wang

Chen

et al. 2014

Adv Synth Catal

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A novel enzyme-initiated multicomponent reaction from readily available aldehyde, nitrostyrene, cyclohexanone and acetamide substrates was discovered, enabling the facile construction of six new C À C/ À N bonds and two rings in single step, one-pot operation, for the synthesis of spirooxazino derivatives in moderate to high yields. Several methods such as isotope labelling and enzyme mutation were used to probe the possible mechanism of this complex synthesis.

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Natürliche Pyrrolidinylspirooxindole als Vorlagen für die Entwicklung medizinischer Wirkstoffe

Cited by 514 publications

References 148 publications

One‐Pot Synthesis of Spirooxindole Derivatives Catalyzed by Lipase in the Presence of Water

One‐Pot Synthesis of Spirooxindole Derivatives Catalyzed by Lipase in the Presence of Water

Asymmetric [4+2] Annulations of Isatins with But‐3‐yn‐2‐one

One‐Pot Synthesis of Spirooxazino Derivatives via Enzyme‐ Initiated Multicomponent Reactions

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