Lewis acid mediated highly regioselective intramolecular cyclization for the synthesis of β-lapachone

Bian, Jinlei; Deng, Bang; Zhang, Xiaojin; Hu, Tianhan; Wang, Nan; Wang, Wei; Pei, Haixiang; Yu, Xu; Chu, Hongxi; Li, Xiang; Sun, Haopeng; Qin, You

doi:10.1016/j.tetlet.2014.01.059

Cited by 17 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With the goal of broadening the toolbox for synthetic chemists, we set out to more deeply explore the reactivity of NbCl 5 as a catalyst for the intramolecular hydrofunctionalization of unactivated alkenes (C–O and C–N bonds formation, Scheme ). Such completely atom economic transformations promoted by either various and often precious transition metals (Au, Pt, Ru, Re, Zr, Ti, Al, Bi, Mg, ...) or Brønsted acids have been deeply studied showing contrasting results. Unfortunately, despite their great potential, only few transition-metal-based catalytic systems have shown suitable versatility regarding substrates and the direct use of strong organic acids often demonstrates inferior catalytic performance due to their inherent instability and difficulty to handle.…”

mentioning

confidence: 99%

Niobium-Catalyzed Intramolecular Addition of O–H and N–H Bonds to Alkenes: A Tool for Hydrofunctionalization

et al. 2017

View full text Add to dashboard Cite

A convenient, versatile and easy to handle intramolecular hydrofunctionalization of alkenes (C-O and C-N bonds formation) is reported using a novel niobium-based catalytic system. This atom economic and eco-friendly methodology provides an additional synthetic tool for the straightforward formation of valuable building blocks enabling molecular complexity. Various pyran, furan, pyrrolidine, piperidine, lactone, lactam derivatives as well as spirocyclic compounds are produced in high yields and selectivities.

show abstract

mentioning

confidence: 99%

Niobium-Catalyzed Intramolecular Addition of O–H and N–H Bonds to Alkenes: A Tool for Hydrofunctionalization

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The synthesis commenced with autoxidation of corresponding α-tetralone derivatives that have appropriate substituents on the aromatic ring . LiH-mediated C-prenylation followed by regioselective six-membered ring formation provided the desired β-lapachone derivatives (Scheme a). To install cyano or nitro groups at the C8 position, substrates bearing a bromo group at the C8 position were used for either palladium-catalyzed cyanation or copper-mediated nitration to furnish the desired compounds (Scheme b).…”

Section: Resultsmentioning

confidence: 96%

Identification of β-Lapachone Analogs as Novel MALT1 Inhibitors To Treat an Aggressive Subtype of Diffuse Large B-Cell Lymphoma

et al. 2015

View full text Add to dashboard Cite

The treatment of activated B cell-like DLBCL (ABC-DLBCL) is one of the urgent unmet medical needs because it is the most resistant DLBCL subtype to current therapies eagerly awaiting effective therapeutic strategies. Recently, the paracaspase MALT1 has emerged as a promising therapeutic target for the treatment of ABC-DLBCL. Herein, we report a new class of MALT1 inhibitors developed by high-throughput screening and structure-based drug design. The original hit, 4-amino-1,2-naphthoquinone series inhibited MALT1 activity but suffered from poor cellular activity. The extensive pharmacophore search led to the discovery of structurally similar β-lapachone that is a direct inhibitor of MALT1 and possesses favorable physicochemical properties. Molecular simulation studies suggested the possibility of the formation of a covalent bond between MALT1 and β-lapachone, which was corroborated by experimental wash-out studies. Inspired by this, we explored the structure-activity relationships by incorporating electron-withdrawing substituents at C8 position of β-lapachone. These MALT1 inhibitors exhibited potent antiproliferative activity to OCI-LY3 cell line and inhibited the cleavage of CYLD mediated MALT1.

show abstract

“…Since then, this switch of acid strength has been the standard methodology, with small adaptations, for the preparation of a large set of α‐ and β‐lapachone derivatives. Some interesting experimental variations include the use of 5‐substituted lapachol derivatives and Lewis acid catalysts ,…”

Section: Introductionmentioning

confidence: 99%

“…Some interesting experimental variations include the use of 5-substituted lapachol derivatives and Lewis acid catalysts. [11,12] Despite its simplicity, the prototypical mechanism ( Figure 1) is unable to explain the intriguing feature of the switchable regioselectivity of lapachol. Furthermore, based only on the relative stabilities of the αand β-isomers, it is impossible to correctly predict such behavior.…”

Section: Introductionmentioning

confidence: 99%

α‐ and β‐Lapachone Isomerization in Acidic Media: Insights from Experimental and Implicit/Explicit Solvation Approaches

et al. 2018

View full text Add to dashboard Cite

Combined experimental and mixed implicit/explicit solvation approaches were employed to gain insights into the origin of switchable regioselectivity of acid‐catalyzed lapachol cyclization and α‐/β‐lapachone isomerization. It was found that solvating species under distinct experimental conditions stabilized α‐ and β‐lapachone differently, thus altering the identity of the thermodynamic product. The energy profile for lapachol cyclization revealed that this process can occur with low free‐energy barriers (lower than 8.0 kcal mol−1). For α/β isomerization in a dilute medium, the computed enthalpic barriers are 15.1 kcal mol−1 (α→β) and 14.2 kcal mol−1 (β→α). These barriers are lowered in concentrated medium to 11.5 and 12.6 kcal mol−1, respectively. Experimental determination of isomers ratio was quantified by HPLC and NMR measurements. These findings provide insights into the chemical behavior of lapachol and lapachone derivatives in more complex environments.

show abstract

Lewis acid mediated highly regioselective intramolecular cyclization for the synthesis of β-lapachone

Cited by 17 publications

References 21 publications

Niobium-Catalyzed Intramolecular Addition of O–H and N–H Bonds to Alkenes: A Tool for Hydrofunctionalization

Niobium-Catalyzed Intramolecular Addition of O–H and N–H Bonds to Alkenes: A Tool for Hydrofunctionalization

Identification of β-Lapachone Analogs as Novel MALT1 Inhibitors To Treat an Aggressive Subtype of Diffuse Large B-Cell Lymphoma

α‐ and β‐Lapachone Isomerization in Acidic Media: Insights from Experimental and Implicit/Explicit Solvation Approaches

Contact Info

Product

Resources

About