Synthetic route optimization of Sumepirin antiepileptic drug candidate

M. S. Dzyurkevich; N. V. Shtyrlin; Y. G. Shtyrlin

doi:10.15826/chimtech.2020.7.4.04

Synthetic route optimization of Sumepirin antiepileptic drug candidate

M. S. Dzyurkevich, N. V. Shtyrlin, Y. G. Shtyrlin

Abstract

In this work we describe the transformation of synthetic route of the antiepileptic drug candidate Sumepirin starting from discovery stage. Initial method included six step process requiring two steps of purification using colon chromatography and has poor overall yield of target compound. The process developed is convenient, scalable, technological and meet the most of conditions of green chemistry. The overall yield was increased up to 62.5% in four steps without colon chromatography purification which allows to obtain the target compound with purity of 99.5+% which is especially important for the active ingredient.

Keywords

pyridoxine; synthetic route optimization; scale-up; purification; antiepileptic drug; technology

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References

Janmohamed M, Brodie MJ, Kwan P. Pharmacoresistance – Epidemiology, mechanisms, and impact on epilepsy treatment. Neuropharmacology. 2020;168:107790 doi:10.1016/j.neuropharm.2019.107790

Štuhec M. Optimization of antiepileptic drug pharmacotherapy related to adverse drug effects: How to approach . Farm Vestn. 2015;66(1):28–34.

Korytnyk W. A seven-membered cyclic ketal of pyridoxol. J Org Chem. 1962;27(10):3724–6.

Shtyrlin NV, Strel’Nik AD, Sysoeva LP, Lodochnikova OA, Klimovitskii EN, Shtyrlin YG. New synthetic method for 2,3,4-tris(hydroxymethyl)- 6-methylpyridin-5-ol. Russ J Org Chem. 2009;45(8):1266–8. doi:10.1134/S1070428009080314

Pugachev MV, Shtyrlin NV, Sysoeva LP, Nikitina EV, Abdullin TI, Iksanova AG, Ilaeva AA, Berdnikov EA, Musin RZ, Shtyrlin YG. Synthesis and antibacterial activity of novel phosphonium salts on the basis of pyridoxine. Bioorg Med Chem. 2013;21(14):4388–95. doi:10.1016/j.bmc.2013.04.051

Shtyrlin NV, Dobrynin AB, Madzhidov TI, Pugachev MV, Sysoeva LP, Musin RZ, Litvinov IA, Klimovitskii EN, Shtyrlin YG. Experimental and theoretical study on 6-substituted pyridoxine derivatives. Synthesis of Cyclic 2,4,5,6-Tetrakis-(hydroxymethyl)pyridin-3-ol Acetonides. Russ J Org Chem. 2011;47(1):100–8. doi:10.1134/S107042801101012X

Lima CGS, Pauli FP, Costa DCS, de Souza AS, Forezi LSM, Ferreira VF, Da Silva F.C. para-Quinone Methides as Acceptors in 1,6-Nucleophilic Conjugate Addition Reactions for the Synthesis of Structurally Diverse Molecules. Eur J Org Chem. 2020;2020(18):2650–92. doi:10.1002/ejoc.201901796

Mukhopadhyay S, Gharui C, Pan SC. Applications of Bifunctional Organocatalysts on ortho-Quinone Methides. Asian J Org Chem. 2019;8(11):1970–84. doi:10.1002/ajoc.201900466

Loubinoux B, Miazimbakana J, Gerardin P. Reactivity of new precursors of quinone methides. Tetrahedron Lett. 1989;30(15):1939–42. doi:10.1016/S0040-4039(00)99619-9

Sanner MA, Stansberry M, Weigelt C, Michne WF. Quinone methide from 4-hydroxybenzyl alcohol diacetate: (P-acetoxy)benzylation of β-dicarbonyls. Tetrahedron Lett. 1992;33(37):5287–90. doi:10.1016/S0040-4039(00)79074-5

Khaziev R, Shtyrlin N, Pavelyev R, Nigmatullin R, Gabbasova R, Grishaev D, Shtro A, Galochkina A, Nikolaeva Y, Vinogradova T, Manicheva O, Dogonadze M, Gnezdilov O, Sokolovich E, Yablonskiy P, Balakin K, Shtyrlin Y. Synthesis and antimicrobial activity of adamantyl substituted pyridoxine derivatives. Lett Drug Des Discov. 2019;16(12):1360–9. doi:10.2174/1570180816666190911150705

Finley DR, Bell MG, Borel AG, Bloomquist WE, Cohen ML, Heiman ML, Kriauciunas A, Matthews DP, Miles T, Neel DA, Rito CJ, Sall DJ, Shuker AJ, Stephens TW, Tinsley FC, Winter MA, Jesudason CD. Potent benzimidazolone based human β3-adrenergic receptor agonists. Bioorg Med Chem Lett. 2006;16(21):5691–4. doi:10.1016/j.bmcl.2006.08.010

Murai M, Okamoto K, Miki K, Ohe K. Palladium-catalyzed three-component coupling reactions of 2-(cyanomethyl)phenol, aryl halides, and carbon monoxide. Tetrahedron. 2015;71(26):4432–7. doi:10.1016/j.tet.2015.04.049

Yazarians JA, Jiménez BL, Boyce GR. A regioselective etherification of pyridoxine via an ortho-pyridinone methide intermediate. Tetrahedron Lett. 2017;58(23):2258–60. doi:10.1016/j.tetlet.2017.04.082

Shearing EA, Smiles S. Derivatives of o-hydroxybenzylsulphonic acid. J Chem Soc. 1937;1348–51. doi:10.1039/jr9370001348

Jankowski P, Poterała M, Lindahl N, Wieczorek W, Johansson P. Chemically soft solid electrolyte interphase forming additives for lithium-ion batteries. J Mater Chem A. 2018;6(45):22609–18. doi:10.1039/c8ta07936f

DOI: https://doi.org/10.15826/chimtech.2020.7.4.04

Copyright (c) 2020 M. S. Dzyurkevich, N. V. Shtyrlin, Y. G. Shtyrlin

This work is licensed under a Creative Commons Attribution 4.0 International License.

Chimica Techno Acta, 2014-2024
ISSN 2411-1414 (Online)
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