15128-52-6Relevant articles and documents
Synthesis of β3 adrenergic receptor agonist LY377604 and its metabolite 4-hydroxycarbazole, labeled with carbon-14 and deuterium
Czeskis, Boris A.,Wheeler, William J.
, p. 407 - 419 (2005)
Synthesis of 14C-radiolabeled 4-hydroxycarbazole was accomplished starting from aniline-[U-14C], based on zinc chloride initiated Fischer cyclization of the phenylhydrazone prepared from phenylhydrazine-[U-14C] and cyclohexane-1,3-dione. The resulting tetrahydrooxocarbazole was subjected to dehydrogenation-aromatization using palladium on carbon. The aromatized 4-hydroxycarbazole-[4b,5,6,7,8,8a- 14C] was then used for the synthesis of 14C-labeled β3 adrenergic receptor agonist LY377604. The introduction of four deuteria in the carbazole fragment of LY377604 accomplished by its initial bromination and subsequent catalytic deuteration of the resulting tetrabromide. A similar approach was used for the conversion of 4-hydroxycarbazole into its tetradeutero-isotopomer. Copyright
Investigating 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole as scaffold of butyrylcholinesterase-selective inhibitors with additional neuroprotective activities for Alzheimer's disease
Purgatorio, Rosa,de Candia, Modesto,Catto, Marco,Carrieri, Antonio,Pisani, Leonardo,De Palma, Annalisa,Toma, Maddalena,Ivanova, Olga A.,Voskressensky, Leonid G.,Altomare, Cosimo D.
, p. 414 - 424 (2019)
Due to the role of butyrylcholinesterase (BChE)in acetylcholine hydrolysis in the late stages of the Alzheimer's disease (AD), inhibitors of butyrylcholinesterase (BChE)have been recently envisaged, besides acetylcholinesterase (AChE)inhibitors, as candidates for treating mild-to-moderate AD. Herein, synthesis and AChE/BChE inhibition activity of some twenty derivatives of 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole (HHAI)is reported. Most of the newly synthesized HHAI derivatives achieved the inhibition of both ChE isoforms with IC50s in the micromolar range, with a structure-dependent selectivity toward BChE. Apparently, molecular volume and lipophilicity do increase selectivity toward BChE, and indeed the N2-(4-phenylbutyl)HHAI derivative 15d, which behaves as a mixed-type inhibitor, resulted the most potent (IC50 0.17 μM)and selective (>100-fold)inhibitor toward either horse serum and human BChE. Moreover, 15d inhibited in vitro self-induced aggregation of neurotoxic amyloid-β (Aβ)peptide and displayed neuroprotective effects in neuroblastoma SH-SY5Y cell line, significantly recovering (P 1-42 and hydrogen peroxide insults. Overall, this study highlighted HHAI as useful and versatile scaffold for developing new small molecules targeting some enzymes and biochemical pathways involved in the pathogenesis of AD.
Divergent Coupling of 2-Carbonyl-anilines and Diazo-cyclopentanones: Asymmetric Total Synthesis of (+)-Leucomidine A
Yao, Xiaotong,Shan, Xiaosong,Zu, Liansuo
, p. 6498 - 6501 (2018)
The direct coupling of 2-carbonyl-anilines and diazo-cyclopentanones, promoted by a rhodium catalyst and diphenyl phosphate, is reported for the divergent generation of both carbazolones and indolones. The strategy allows for the successful transfer of the substituents/functionality and the chirality of the coupling partners into the functionalized heterocyclic products, thus serving as the strategic basis for natural product synthesis as demonstrated by the concise asymmetric total synthesis of (+)-leucomidine A.
Molecular structure and reactivity of the 1,2-dihydrocarbazol-4(3H)-one: X-ray crystal structure of N-methyl and N-(p-methylbenzenesulfonyl) derivatives
Rodriguez, Jose Gonzalo,Valle, Celestina del,Esteban-Calderon, Carmen,Martinez-Ripoll, Martin
, p. 249 - 258 (1995)
Synthesis and reactivity analysis of the 1,2-dihydrocarbazol-4(3H)-one, and the N-methyl, N-tosyl and 2,2-dimethyl derivatives have been carried out.Molecular structures of the N-methyl and N-tosyl derivatives have been analyzed by X-ray diffraction.Crystals of the N-methyl derivative are monoclinic, space group P21/c, a=8.868(1), b=16.652(1), c=7.5440(4) Angstroem, β=113.657(3).Crystals of the N-tosyl derivative are monoclinic, P21/c, a=12.0016(3), b=8.9178(2), c=16.0485(4) Angstroem, β=104.372(2).An extended conjugation from the carbonyl group to the nitrogen atom and an envelope conformation for the common cyclohexenone fragment are evident in both cases.Oximation and Beckmann rearrangement, and etherification of the carbonyl group is reported.KEY WORDS: Synthesis, reactivity, tetrahydrocarbazol-4-one.
A synthesis of calothrixin B
Sissouma, Drissa,Collet, Sylvain C.,Guingant, André Y.
, p. 2612 - 2614 (2004)
A new short and efficient synthesis of calothrixin B is reported. The key reaction is a hetero-Diels-Alder reaction between 3-bromo-9H-carbazole-1,4-dione and a 'push-pull' 2-aza-1,3-diene.
Tandem Ullmann-Goldberg Cross-Coupling/Cyclopalladation-Reductive Elimination Reactions and Related Sequences Leading to Polyfunctionalized Benzofurans, Indoles, and Phthalanes
Khan, Faiyaz,Fatima, Mehvish,Shirzaei, Moheb,Vo, Yen,Amarasiri, Madushani,Banwell, Martin G.,Ma, Chenxi,Ward, Jas S.,Gardiner, Michael G.
supporting information, p. 6342 - 6346 (2019/08/20)
On exposure to a combination of Cu[I]- and Pd[0]-based catalysts, compounds such as 1 and 7 engage in tandem Ullmann-Goldberg cross-coupling and cyclopalladation-reductive elimination reactions to give benzofurans such as 8. Related reactions involving hetero-Michael additions of o-halogenated phenols or anilines to propiolates and the Pd[0]-catalyzed cyclization of the resulting conjugates provide, in a one-pot process, alternately functionalized benzofurans, indoles, or phthalanes.
Enantioselective Synthesis of 1- and 4-Hydroxytetrahydrocarbazoles through Asymmetric Transfer Hydrogenation
Dilek, ?mer,Patir, Süleyman,Ertürk, Erkan
supporting information, p. 69 - 72 (2019/01/04)
Several 1- and 4-hydroxytetrahydrocarbazoles were prepared in high yields (up to 99%) and excellent enantiomeric excesses (up to >99% ee) from the corresponding 1- and 4-oxotetrahydrocarbazoles through asymmetric transfer hydrogenation by using the commercially available Noyori-Ikariya ruthenium catalyst. The immediate use of the freshly prepared catalyst and the use of a HCO 2 H-DABCO (11:6) mixture as the hydrogen source are crucial for achieving high activity and enantioselectivity. In this way, a tetrahydrocarbazole heterocycle fused to a lactone moiety was synthesized in 45% yield and 97% ee.
