Asymmetric oxidative coupling of hydroxycarbazoles: Facile synthesis of (+)-bi-2-hydroxy-3-methylcarbazole

Sako, M.; Sugizaki, Akimasa; Takizawa, Shinobu

doi:10.1016/j.bmcl.2018.02.033

Cited by 24 publications

(17 citation statements)

References 18 publications

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“…Of particular interest is the interaction with DNA or its metabolizing enzymes that induce programmed cell death, namely apoptosis . Several carbazole analogues structurally derived from ellipticine, an alkaloid from Ochrosia elliptica labill, introduced for the treatment of metastatic breast cancer, but later dismissed because of poor aqueous solubility and severe side effects, were synthesized …”

Section: Introductionmentioning

confidence: 99%

“…labill, [19] introduced for the treatment of metastatic breast cancer, [6,[20][21][22][23] but later dismissed because of poor aqueous solubility ands evere side effects, [24,25] were synthesized. [26][27][28][29][30] Trimethoxyphenylurea 1,4-dimethylcarbazoles, [31] N-thioalkylcarbazoles, [15] 1,4-dimethyl-N-alkylcarbazoles, [32] N-(1,4-dimethyl-9H-carbazol-3-yl)-N'-alkylguanidines, [33] benzofuro[2,3-f]quinazolin-1(2H)-ones, [34] and hydrazine-carbazole derivatives [20] were also prepared, and some of them showed interesting anti-proliferative activity against breast cancerc ells withouta ffecting the viability of non-tumor cell lines. Severals tudies have reported that carbazole derivatives, such as ellipticine and celiptium ( Figure 1), are inhibitors of human topoisomerases Ia nd II.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

et al. 2018

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Chemotherapy is used for the treatment of all stages of breast cancer, including the metastatic stage of the disease. Treatment regimens are generally tailored for each patient′s particular situation. However, chemotherapeutic agents are the leading cause of serious drug‐related adverse effects; moreover, drug resistance often occurs. In this study, we designed and synthesized a new series of N‐alkylcarbazoles derived from ellipticine, an alkaloid with a carbazole skeleton initially used in the treatment of metastatic breast cancer and later dismissed because of poor aqueous solubility and severe side effects. After evaluating the binding modes of our class of newly synthesized compounds with human topoisomerase II (hTopo II), we performed hTopo II decatenation assays, identifying compound 4 f (2‐(4‐((3‐chloro‐9H‐carbazol‐9‐yl)pentyl)piperazin‐1‐yl)‐N,N,N‐trimethylethanammonium iodide) as a good inhibitor. Moreover, 4 f and 4 g (2‐(4‐((3‐chloro‐9H‐carbazol‐9‐yl)hexyl)piperazin‐1‐yl)‐N,N,N‐trimethylethanammonium iodide) showed a good anti‐proliferative activity toward breast cancer cells, causing apoptosis by activation of the caspase pathway. Interestingly, the activity of these two compounds on triple‐negative MDA‐MB‐231 cells, which tend to be highly metastatic and aggressive, is strictly connected to the observed inhibition of hTopo II.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

et al. 2018

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“…Thus, the same authors extended the scope of their synthesis of sorazolon E2 [20]. As depicted in Scheme 12, the same catalyst 1 was applied to promote at the same catalyst loading (5 mol%…”

Section: (20 Mol%)mentioning

confidence: 99%

Enantioselective vanadium-catalyzed transformations. An update

Pellissier

2020

Coordination Chemistry Reviews

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“…α-Substituted α,β-unsaturated carbonyl compounds can be readily accessed by the Rauhut-Currier (RC) reaction, also called the vinylogous MBH reaction, through the coupling of two different α,β-unsaturated enones wherein one acts as a latent enolate. 85) As part of our research into the development of enantioselective domino reactions, [41][42][43][44][45][46][47][48][49][50][51][52][86][87][88][89][90] we became interested in designing sequences to address optically active α-methylidene-γ-lactams. We envisioned that the amidation of 28 with 27, followed by the BA-LB-catalyzed carbon-carbon bond-forming reaction of intermediary 29, would result in the generation of α-methylidene-γ-lactams 30 in high yield with high enantiocontrols (Chart 13).…”

Section: Stereoselective Synthesis Of α-Methylidene-γ-lactams By Amidmentioning

confidence: 99%

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita–Baylis–Hillman-Type Domino Reactions

Takizawa

2020

CHEMICAL & PHARMACEUTICAL BULLETIN

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Organocatalytic enantioselective domino reactions are an extremely attractive methodology, as their use enables the construction of complex chiral skeletons from readily available starting materials in two or more steps by a single operation under mild reaction conditions. Thus, these reactions can save both the quantity of chemicals and length of time typically required for the isolation and/or purification of synthetic intermediates. Additionally, no metal contamination of the products occurs, given that organocatalysts include no expensive or toxic metals. The aza-Morita-Baylis-Hillman (aza-MBH) reaction is an atom-economical carbon-carbon bond-forming reaction between α,β-unsaturated carbonyl compounds and imines mediated by Lewis base (LB) catalysts, such as nucleophilic phosphines and amines. aza-MBH products are functionalized chiral β-amino acid derivatives that are highly valuable as pharmaceutical raw materials. Although various enantioselective aza-MBH processes have been investigated, very few studies of aza-MBH-type domino reactions have been reported due to the complexity of the aza-MBH process, which involves a Michael/ Mannich/H-transfer/β-elimination sequence. Accordingly, in this review article, our recent efforts in the development of enantioselective domino reactions initiated by MBH processes are described. In the domino reactions, chiral organocatalysts bearing Brønsted acid (BA) and/or LB units impart synergistic activation to substrates, leading to the easy synthesis of highly functionalized heterocycles (some of which have tetrasubstituted and/or quaternary carbon stereocenters) in high yield and enantioselectivity.

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Asymmetric oxidative coupling of hydroxycarbazoles: Facile synthesis of (+)-bi-2-hydroxy-3-methylcarbazole

Cited by 24 publications

References 18 publications

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

Inhibition of Human Topoisomerase II by N,N,N‐Trimethylethanammonium Iodide Alkylcarbazole Derivatives

Enantioselective vanadium-catalyzed transformations. An update

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita–Baylis–Hillman-Type Domino Reactions

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