vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8331-2018-54-1-80-86vestich-306Research ArticleБИООРГАНИЧЕСКАЯ ХИМИЯBIOORGANIC CHEMISTRYСИНТЕЗ 2-ХЛОРНИКОТИНАТОВ, НИКОТИНАТА И ПИРАЗИНОАТА 7-ЗАМЕЩЕННЫХ 19-НОРТЕСТОСТЕРОНОВSYNTHESIS OF 2-CHLORONICOTINATES, NICOTINATE AND PIRAZINOATE OF 7-SUBSTITUTED 19-NORTESTOSTERONESКовганкоН. В.KauhankaM. U.

д-р хим. наук

D. Sc. (Chemistry)

ДолгопалецВ. И.DolgopaletsV. I.

канд. хим. наук, вед. науч. сотрудник

ул. Купревича, 5/2, 220141, Минск

Ph. D. (Chemistry), Leading researcher

5/2, Kuprevich Str., 220141, Minsk

vid@iboch-bas.net.byЧерновЮ. Г.CharnouYu. G.

канд. хим. наук, вед. науч. сотрудник

ул. Купревича, 5/2, 220141, Минск

Ph. D. (Chemistry), Leading researcher

5/2, Kuprevich Str., 220141, Minsk

chernov@iboch.bas-net.byИнститут биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus2018050320185418086Copyright © Ковганко Н.В., Долгопалец В.И., Чернов Ю.Г., 20182018Ковганко Н.В., Долгопалец В.И., Чернов Ю.Г.Kauhanka M.U., Dolgopalets V.I., Charnou Y.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/306

Синтезированы новые сложные эфиры изомерных 7-метил-19-нортестостеронов и 2-хлорникоти- новой, никотиновой и пиразинкарбоновой кислот. В результате 1,6-присоединения метилмагнийиодида по 6(7)-двойной связи ацетата 19-нор-6-дегидротестостерона в присутствии ацетата меди (II) получены 17b-ацетокси-7a-метилэстр- 4-ен-3-он и его 7b-изомер. Метанолиз этих изомеров в присутствии карбоната калия и последующее ацилирование полученных 17b-гидрокси-7a-метилэстр-4-ен-3-она и 17b-гидрокси-7b-метилэстр-4-ен-3-она хлорангидридами 2-хлорникотиновой, никотиновой и пиразинкарбоновой кислот в присутствии 4-диметиламинопиридина (ДМАП) позволило синтезировать целевые 17b-(2-хлорникотиноилокси)-7a-метилэстр-4-ен-3-он, 17b-(2-хлорникотиноилокси)- 7b-метилэстр-4-ен-3-он, 17b-никотиноилокси-7a-метилэстр-4-ен-3-он и 17b-пиразинкарбонилокси-7a-метилэстр- 4-ен-3-он. 

New 7a- and 7b-methyl-19-nortestosterone derivatives bearing nicotinic, 2-chloronicotinic and pyrazinecarboxylic acids fragments at C-17 have been prepared. The key intermediate, 19-nor-6-dehydrotestosterone acetate, was synthesized from solasodine. A copper (II) acetate catalyzed 1,6-conjugate addition of methylmagnesium iodide to 19-nor6-dehydrotestosterone acetate led to a mixture of 17b-acetoxy-7a-methylestr-4-en-3-one as major product and its 7b-isomer. Methanolysis and subsequent acylation of the resulting compounds with 2-chloronicotinoyl chloride, nicotinoyl chloride and pyrazinecarbonyl chloride gave the corresponding target 17b-(2-chloronicotinoyloxy)-7a-methylestr-4-en-3-one, 17b-(2-chloronicotinoyloxy)-7b-methylestr-4-en-3-one, 17b-nicotinoyloxy-7a-methylestr-4-en-3-one, 17b-pyrazinecarbonyloxy-7a-methylestr-4-en-3-one. 

7-метил-19-нортестостерон2-хлорникотиноваяникотиновая и пиразинкарбоновая кислотыстероидыандрогеныхимический синтез7-methyl-19-nortestosteronenicotinic acid2-chloronicotinic acidpyrazinecarboxylic acidsteroidsandrogenschemical synthesisReferences7α-Methyl-19-nortesterone, a synthetic androgen with high potency: structure-activity comparisons with other androgens / N. Kumar [et al.] // J. Steroid Biochem. Mol. Biol. – 1999. – Vol. 71, N5–6. – P. 213–222.Kumar N., Crozat A., Li F., Catterall J. F., Bardin C. W., Sundaram K. 7α-Methyl-19-nortesterone, a synthetic androgen with high potency: structure-activity comparisons with other androgens. Journal of Steroid Biochemistry and Molecular Biology, 1999, vol. 71, no. 5–6, pp. 213–222. Doi: 10.1016/s0960-0760(99)00143-0Nieschlag, E. 7α-Methyl-19-nortesterone (MENT®): the Population Council’s contributions to research on male contraception and treatment of hypogonadism / E. Nieschlag, N. Kumar, R. Sitruk-Ware // Contraception. – 2013. – Vol. 87, N 3. – P. 288–295.Nieschlag E., Kumar N., Sitruk-Ware R. 7α-Methyl-19-nortesterone (MENT®): the Population Council’s contributions to research on male contraception and treatment of hypogonadism. Contraception, 2013, vol.87, no. 3, pp. 288–295. Doi: 10.1016/j.contraception.2012.08.036Distribution, metabolism and excretion of sythetic androgen 7α-methyl-19-nortesterone, a potential male-contraceptive / P. V. Prasad [et al.] // Steroids. – 2009. – Vol. 74, N 1. – P. 121–131.Prasad P. V., Arumugam R., Willman M., Ge R.-S., Sitruk-Ware R., Kumar N. Distribution, metabolism and excretion of sythetic androgen 7α-methyl-19-nortesterone, a potential male-contraceptive. Steroids, 2009, vol. 74, no. 1, pp. 121–131. Doi: 10.1016/j.steroids.2008.09.012Chao, J. Male contraception / J. Chao, S. T. Page, R. A. Anderson // Best Practice & Research Clinical Obstetrics & Gynaecology. – 2014. – Vol. 28, N 6. – P. 845–857.Chao J., Page S. T., Anderson R. A. Male contraception. Best Practice & Research Clinical Obstetrics & Gynaecology, 2014, vol. 28, no. 6, pp. 845–857. Doi: 10.1016/j.bpobgyn.2014.05.008Kogan, P. Male contraception: History and Development / P. Kogan, M. Wald // Urologic Clinics of North America. – 2014. – Vol. 41, N 1. – P. 145–161.Kogan P., Wald M. Male contraception: History and Development. Urologic Clinics of North America, 2014, vol. 41, no. 1, pp. 145–161. Doi: 10.1016/j.ucl.2013.08.012Nieschlag, E. Clinical trials in male hormonal contraception / E. Nieschlag // Contraception. – 2010. – Vol. 82, N 5. – P. 457–470.Nieschlag E. Clinical trials in male hormonal contraception. Contraception, 2010, vol. 82, no. 5, pp. 457–470. Doi: 10.1016/j.contraception.2010.03.020Sitruk-Ware, R. Contraception technology: past, present and future / R. Sitruk-Ware, A. Nath, D. R. Mishell // Contraception. – 2013. – Vol. 87, N. 3. – P. 319–330.Sitruk-Ware R., Nath A., Mishell D. R. Contraception technology: past, present and future. Contraception, 2013, vol. 87, no. 3, pp. 319–330. Doi: 10.1016/j.contraception.2012.08.002Tomizawa, M. Chapter Two – Chemical Biology of the Nicotinic Insecticide Receptor / M. Tomizawa // Adv. Insect Physiol. – 2013. – Vol. 44. – P. 63–99.Tomizawa M. Chapter Two – Chemical Biology of the Nicotinic Insecticide Receptor. Advances in Insect Physiology, 2013, vol. 44, pp. 63–99. Doi: 10.1016/B978-0-12-394389-7.00002-8Geng, C. Chapter Three – Nicotinic Acetylcholine Receptor as Spinosyn Targets for Insect Pest Management / C. Geng, G. B. Watson, T. C. Sparks // Adv. Insect Physiol. – 2013. – Vol. 44. – P. 101–210.Geng C., Watson G. B., Sparks T. C. Chapter Three – Nicotinic Acetylcholine Receptor as Spinosyn Targets for Insect Pest Management. Advances in Insect Physiology, 2013, vol. 44, pp. 101–210. Doi: 10.1016/b978-0-12-394389-7.00003-xPang, Y.-P. Insect Acetylcholinesterase as Target for Effective and Envirinmentally Safe Insecticides / Y.-P. Pang // Adv. Insect Physiol. – 2014. – Vol. 46. – P. 435–494.Pang Y.-P. Insect Acetylcholinesterase as Target for Effective and Envirinmentally Safe Insecticides. Advances in Insect Physiology, 2014, vol. 46, pp. 435–494. Doi: 10.1016/b978-0-12-417010-0.00006-9Sparks, T. C. Insecticide discovery: An evaluation and analysis / T. C. Sparks // Pesticide Biochem. Physiol. – 2013. – Vol. 107, N 1. – P. 8–17.Sparks T.C. Insecticide discovery: An evaluation and analysis Pesticide Biochemistry and Physiology, 2013, vol. 107, no. 1, pp. 8–17. Doi: 10.1016/j.pestbp.2013.05.012Kovganko, N. V. Synthesis of 19-hydroxysteroids I. New synthesis of 19-hydroxytestosterone / N. V. Kovganko, Zh. N. Kashkan, Yu. G. Chernov // Chem. Nat. Compd. – 1992. – Vol. 28, N 6. – P. 584–588.Kovganko N. V., Kashkan Zh. N., Chernov Yu. G. Synthesis of 19–hydroxysteroids I. New synthesis of 19-hydroxytestosterone. Chemistry of Natural Compounds, 1992, vol. 28, no. 6, pp. 584–588. Doi: 10.1007/bf00630434Ковганко, Н. В. Синтез 6-хлор(метокси)никотинатов 7a-метил-19-нортестостерона / Н. В. Ковганко, Ю. Г. Чернов, Ж. Н. Кашкан // Вес. Нац. акад. навук Беларусi. Сер. хiм. навук. – 2015. – № 4 – С. 50–54.Kauhanka N. V., Charnou Yu. G., Kashkan Zh. N. Synthesis of 7-α-methyl-19-nortestosterone 6-chloro(methoxy) nicotinates. Vescі Nacyanal’naj akademіі navuk Belarusі. Serya hіmіchnyh navuk = Proceedings of the National Academy of Sciences of Belarus. Chemical Series, 2015, no. 4, pp. 50–54 (in Russian).

The authors declare that there are no conflicts of interest present.