Carbonylative synthesis and functionalization of indoles
- Alex De Salvo,
- Raffaella Mancuso and
- Xiao-Feng Wu
Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87
Graphical Abstract
Scheme 1: Pd(0)-catalyzed domino C,N-coupling/carbonylation/Suzuki coupling reaction for the synthesis of 2-a...
Scheme 2: Pd(0)-catalyzed single isonitrile insertion: synthesis of 1-(3-amino)-1H-indol-2-yl)-1-ketones.
Scheme 3: Pd(0)-catalyzed gas-free carbonylation of 2-alkynylanilines to 1-(1H-indol-1-yl)-2-arylethan-1-ones....
Scheme 4: Pd(II)-catalyzed heterocyclization/alkoxycarbonylation of 2-alkynylaniline imines.
Scheme 5: Pd(II)-catalyzed heterocyclization/alkoxycarbonylation of 2-alkynylanilines to N-substituted indole...
Scheme 6: Synthesis of indol-2-acetic esters by Pd(II)-catalyzed carbonylation of 1-(2-aminoaryl)-2-yn-1-ols.
Scheme 7: Pd(II)-catalyzed carbonylative double cyclization of suitably functionalized 2-alkynylanilines to 3...
Scheme 8: Indole synthesis by deoxygenation reactions of nitro compounds reported by Cenini et al. [21].
Scheme 9: Indole synthesis by reduction of nitro compounds: approach reported by Watanabe et al. [22].
Scheme 10: Indole synthesis from o-nitrostyrene compounds as reported by Söderberg and co-workers [23].
Scheme 11: Synthesis of fused indoles (top) and natural indoles present in two species of European Basidiomyce...
Scheme 12: Synthesis of 1,2-dihydro-4(3H)-carbazolones through N-heteroannulation of functionalized 2-nitrosty...
Scheme 13: Synthesis of indoles from o-nitrostyrenes by using Pd(OAc)2 and Pd(tfa)2 in conjunction with bident...
Scheme 14: Synthesis of substituted 3-alkoxyindoles via palladium-catalyzed reductive N-heteroannulation.
Scheme 15: Synthesis of 3-arylindoles by palladium-catalyzed C–H bond amination via reduction of nitroalkenes.
Scheme 16: Synthesis of 2,2′-bi-1H-indoles, 2,3′-bi-1H-indoles, 3,3′-bi-1H-indoles, indolo[3,2-b]indoles, indo...
Scheme 17: Pd-catalyzed reductive cyclization of 1,2-bis(2-nitrophenyl)ethene and 1,1-bis(2-nitrophenyl)ethene...
Scheme 18: Flow synthesis of 2-substituted indoles by reductive carbonylation.
Scheme 19: Pd-catalyzed synthesis of variously substituted 3H-indoles from nitrostyrenes by using Mo(CO)6 as C...
Scheme 20: Synthesis of indoles from substituted 2-nitrostyrenes (top) and ω-nitrostyrenes (bottom) via reduct...
Scheme 21: Synthesis of indoles from substituted 2-nitrostyrenes with formic acid as CO source.
Scheme 22: Ni-catalyzed carbonylative cyclization of 2-nitroalkynes and aryl iodides (top) and the Ni-catalyze...
Scheme 23: Mechanism of the Ni-catalyzed carbonylative cyclization of 2-nitroalkynes and aryl iodides (top) an...
Scheme 24: Route to indole derivatives through Rh-catalyzed benzannulation of heteroaryl propargylic esters fa...
Scheme 25: Pd-catalyzed cyclization of 2-(2-haloaryl)indoles reported by Yoo and co-workers [54], Guo and co-worke...
Scheme 26: Approach for the synthesis of 6H-isoindolo[2,1-a]indol-6-ones reported by Huang and co-workers [57].
Scheme 27: Zhou group’s method for the synthesis of 6H-isoindolo[2,1-a]indol-6-ones.
Scheme 28: Synthesis of 6H-isoindolo[2,1-a]indol-6-ones from o-1,2-dibromobenzene and indole derivatives by us...
Scheme 29: Pd(OAc)2-catalyzed Heck cyclization of 2-(2-bromophenyl)-1-alkyl-1H-indoles reported by Guo et al. [55]....
Scheme 30: Synthesis of indolo[1,2-a]quinoxalinone derivatives through Pd/Cu co-catalyzed carbonylative cycliz...
Scheme 31: Pd-catalyzed carbonylative cyclization of o-indolylarylamines and N-monosubstituted o-indolylarylam...
Scheme 32: Pd-catalyzed diasteroselective carbonylative cyclodearomatization of N-(2-bromobenzoyl)indoles with...
Scheme 33: Pd(0)-catalyzed synthesis of CO-linked heterocyclic scaffolds from alkene-indole derivatives and 2-...
Scheme 34: Proposed mechanism for the Pd(0)-catalyzed synthesis of CO-linked heterocyclic scaffolds.
Scheme 35: Pd-catalyzed C–H and N–H alkoxycarbonylation of indole derivatives to indole-3-carboxylates and ind...
Scheme 36: Rh-catalyzed C–H alcoxycarbonylation of indole derivatives to indole-3-carboxylates reported by Li ...
Scheme 37: Pd-catalyzed C–H alkoxycarbonylation of indole derivatives with alcohols and phenols to indole-3-ca...
Scheme 38: Synthesis of N-methylindole-3-carboxylates from N-methylindoles and phenols through metal-catalyst-...
Scheme 39: Synthesis of indol-3-α-ketoamides (top) and indol-3-amides (bottom) via direct double- and monoamin...
Scheme 40: The direct Sonogashira carbonylation coupling reaction of indoles and alkynes via Pd/CuI catalysis ...
Scheme 41: Synthesis of indole-3-yl aryl ketones reported by Zhao and co-workers [73] (path a) and Zhang and co-wo...
Scheme 42: Pd-catalyzed carbonylative synthesis of BIMs from aryl iodides and N-substituted and NH-free indole...
Scheme 43: Cu-catalyzed direct double-carbonylation and monocarbonylation of indoles and alcohols with hexaket...
Scheme 44: Rh-catalyzed direct C–H alkoxycarbonylation of indoles to indole-2-carboxylates [79] (top) and Co-catal...
Scheme 45: Pd-catalyzed carbonylation of NH free-haloindoles.
Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction
- Salvatore V. Giofrè,
- Santa Cirmi,
- Raffaella Mancuso,
- Francesco Nicolò,
- Giuseppe Lanza,
- Laura Legnani,
- Agata Campisi,
- Maria A. Chiacchio,
- Michele Navarra,
- Bartolo Gabriele and
- Roberto Romeo
Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278
Graphical Abstract
Figure 1: Some relevant MDM2-p53 interaction inhibitors.
Figure 2: Retrosynthetic route to spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones 3.
Scheme 1: Synthesis of compounds 2.
Scheme 2: Synthesis of 6a–f by 1,3-dipolar cycloaddition.
Figure 3: Selected NOESY observed for compounds 6a and 7a.
Figure 4: ORTEP drawing of the X-ray crystal structure of 7a showing the model atomic numbering scheme (C10 a...
Scheme 3: Reaction pathway.
Figure 5: Three-dimensional plots of TSs of reaction of dipolarophiles (Z)-8 and (E)-8 with nitrone 4. The la...
Figure 6: Free energy profiles for the cycloaddition reaction of the two isomers Z (A) or E (B) of dipolaroph...
Figure 7: Compound 6e reduces cancer cell proliferation. Treatment of SH-SY5Y, HT-29 and HepG2 cells with 6e ...
Figure 8: Cytotoxic effect of 6e. The cytotoxic activity of 6e was assessed in terms of both LDH release (a) ...
Figure 9: 6e modulate the levels of p53 in SH-SY5Y cells. (a) The SH-SY5Y cells were treated for 24 h with th...
Figure 10: (A) Representative Western Blots and (B) semiquantitative analyses of p53, MDM2, p21 expression lev...
Figure 11: (A) Representative Western Blots and (B) densitometric analysis of caspase-3 and PARP cleavage in t...
Figure 12: Compounds 6a (green) and 6c (blue) docked into MDM2 structure (PDB-ID: 3LBL) superimposed on the ke...
Figure 13: A) Compounds 6e (green) docked into MDM2 structure (PDB-ID: 3LBL); His96 and p53 residue (yellow st...
