(3 + 2) Cycloaddition of 1,3-Dipoles

Wei, Liang; Dong, Xiu‐Qin; Wang, Chun‐Jiang

doi:10.1016/b978-0-32-390644-9.00039-1

Cited by 2 publications

(2 citation statements)

References 339 publications

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“…Apparently, the development of an enantiomeric variant of 1,3-dipolar cycloaddition would circumvent the depletion of one enantiomer during kinetic resolution. [27,28] Continuous method developments in the context of natural product synthesis is currently underway and will be reported in due course.…”

Section: Discussionmentioning

confidence: 99%

Practical Synthesis of Valbenazine via 1,3-Dipolar Cycloaddition

Peng,

Lin,

Zhu

et al. 2023

Preprint

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Valbenazine (Ingrezza), a potent and highly selective inhibitor of vesicular monoamine transporter type 2 (VMAT2) through the active metabolite hydrotetrabenazine (HTBZ), has been approved for the treatment of tardive dyskinesia and, very recently, for chorea, which is associated with Huntington’s disease. Despite numerous synthetic efforts dedicated to the synthesis of HTBZ, the industrial preparation of valbenazine uses dihydroisoquinoline as a starting material and the chiral resolution of racemic HTBZ derived from ketone reduction. Herein, we present a practical synthesis of HTBZ and valbenazine featuring a highly stereoselective 1,3-dipolar cycloaddition and enzymatic kinetic resolution. The cascade process includes cycloaddition, N˗O bond cleavage, and lactamization, which proved to be operationally facile. The allure of the enzymatic resolution developed in this work offers a rapid access toward affording tetrahydroi-soquinoline (THIQ)-fused piperidine to access key frameworks in the production of medically significant compounds, such as yohimbine and reserpine.

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Section: Discussionmentioning

confidence: 99%

Practical Synthesis of Valbenazine via 1,3-Dipolar Cycloaddition

Peng,

Lin,

Zhu

et al. 2023

Preprint

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“…To improve the solubility of 15, several polar solvents were further screened using CAL-B (~1800 U/g). A substantial improvement was achieved when THF was introduced as solvent (E ~100 [26] ) (entry 9). Under the optimized conditions, the enzymatic kinetic resolution was upscaled using CAL-B.…”

Section: Chin J Chemmentioning

confidence: 99%

Practical Synthesis of Valbenazine via 1,3‐Dipolar Cycloaddition^†

Peng,

Lin,

Zhu

et al. 2024

Chin. J. Chem.

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Comprehensive SummaryValbenazine (Ingrezza), a potent and highly selective inhibitor of vesicular monoamine transporter type 2 (VMAT2) through the active metabolite hydrotetrabenazine (HTBZ), has been approved for the treatment of tardive dyskinesia and, very recently, for chorea, which is associated with Huntington's disease. Despite numerous synthetic efforts dedicated to the synthesis of HTBZ, the industrial preparation of valbenazine uses dihydroisoquinoline as a starting material and the chiral resolution of racemic HTBZ derived from ketone reduction. Herein, we present a practical synthesis of HTBZ and valbenazine featuring a highly stereoselective 1,3‐dipolar cycloaddition and enzymatic kinetic resolution. The cascade process includes cycloaddition, N˗O bond cleavage, and lactamization, which proved to be operationally simple. The allure of the enzymatic resolution developed in this work offers a rapid access toward affording tetrahydroisoquinoline (THIQ)‐fused piperidine to access key frameworks in the production of medically significant compounds, such as yohimbine and reserpine.This article is protected by copyright. All rights reserved.

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(3 + 2) Cycloaddition of 1,3-Dipoles

Cited by 2 publications

References 339 publications

Practical Synthesis of Valbenazine via 1,3-Dipolar Cycloaddition

Practical Synthesis of Valbenazine via 1,3-Dipolar Cycloaddition

Practical Synthesis of Valbenazine via 1,3‐Dipolar Cycloaddition^†

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(3 + 2) Cycloaddition of 1,3-Dipoles

Cited by 2 publications

References 339 publications

Practical Synthesis of Valbenazine via 1,3-Dipolar Cycloaddition

Practical Synthesis of Valbenazine via 1,3-Dipolar Cycloaddition

Practical Synthesis of Valbenazine via 1,3‐Dipolar Cycloaddition†

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Practical Synthesis of Valbenazine via 1,3‐Dipolar Cycloaddition^†