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"vestich-154Research ArticleОРГАНИЧЕСКАЯ ХИМИЯORGANIC CHEMISTRYСинтез 6-хлор(метокси)никотинатов 7α-метил-19-нортестостеронаSynthesis of 7α-methyl-19-nortestosterone 6-chloro(methoxy) nicotinatesКовганкоН. В.KauhankaM. N.kovganko@iboch.bas-net.byЧерновЮ. Г.CharnouJu. G.noemail@neicon.ruКашканЖ. Н.KashkanZh. N.noemail@neicon.ruИнститут биоорганической химии НАН БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus201508062016045155Copyright © Ковганко Н.В., Чернов Ю.Г., Кашкан Ж.Н., 20162016Ковганко Н.В., Чернов Ю.Г., Кашкан Ж.Н.Kauhanka M.N., Charnou J.G., Kashkan Z.N.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/154

Синтезированы новые сложные эфиры 7α-метил-19-нортестостерона, его 7β-изомера и 6-хлор- и 6-метоксинико-тиновых кислот. В результате 1,6-присоединения метилмагнийиодида по 6(7)-двойной связи ацетата 19-нор-6-дегидротестостерона в присутствии хлорида меди (I) получены 17β-ацетокси-7α-метилэстр-4-ен-3-он и его 7β-изомер. Метанолиз 17β-ацетокси-7α-метилэстр-4-ен-3-она и его 7β-изомера и последующее ацилирование 17β-гидрокси-7α-метилэстр-4-ен-3-она и 17β-гидрокси-7β-метилэстр-4-ен-3-она позволило синтезировать целевые 17β-(6-хлорникотиноилокси)-7α-метилэстр-4-ен-3-он, 17β-(6-хлорникотиноилокси)-7β-метилэстр-4-ен-3-он и 17β-(6-метоксиникотиноилокси)-7α-метилэстр-4-ен-3-он.

New 7α- and 7β-methyl-19-nortestosterone derivatives containing 6-chloro- or 6-methoxynicotinic acids fragments at C-17 have been prepared. The key intermediate, 19-nor-6-dehydrotestosterone acetate, was synthesized from diosgenin. A copper(I) chloride catalyzed 1,6-conjugate addition of methylmagnesium iodide to 19-nor-6-dehydrotestosterone acetate led to a mixture of 17β-acetoxy-7α-methylestr-4-еn-3-one as a major product and their 7β-isomer. Methanolysis and then acylation of made compounds with 6-chloronicotinoyl chloride or 6-methoxynicotinoyl chloride gave the corresponding target 17β-(6-chloronicotinoyloxy)-7α-methylestr-4-en-3-one, 17β-(6-chloronicotinoyloxy)-7β-methylestr-4-en-3-one and 17β-(6-methoxynicotinoyloxy)-7α-methylestr-4-en-3-one.

7-метил-19-нортестостерон6-хлор(метокси)никотиновые кислотыорганический синтезан-дрогены7-methyl-19-nortestosterone6-chloro(methoxy)nicotinic acidsorganic synthesisandrogensReferencesa-Methyl-19-nortestosterone, а synthetic androgen with high potency: structure-activity comparisons with other androgens / N. Kumar [et al.] // J. Steroid Biochem. Mol. Biol. - 1999. - Vol. 71, № 5-6. - P. 213-222.a-Methyl-19-nortestosterone, а synthetic androgen with high potency: structure-activity comparisons with other androgens / N. Kumar [et al.] // J. Steroid Biochem. Mol. Biol. - 1999. - Vol. 71, № 5-6. - P. 213-222.Nieschlag, E. 7a-Methyl-19-nortestosterone (MENTR): the Popukation Council's contribution to research on make contraception and treatment of hypogonadism / E. Nieschlag, N. Kumar, R. Sitruk-Ware // Contraception. - 2013. - Vol. 87, № 3. - P. 288-295.Nieschlag, E. 7a-Methyl-19-nortestosterone (MENTR): the Popukation Council's contribution to research on make contraception and treatment of hypogonadism / E. Nieschlag, N. Kumar, R. Sitruk-Ware // Contraception. - 2013. - Vol. 87, № 3. - P. 288-295.Distribution, metabolism and excretion of a synthetic androgen 7a-methyl-19-nortestosterone, a potential malecontraceptive / P. V. Prasad [et al.] // Steroids. - 2009. - Vol. 74, № 1. - P. 121-131.Distribution, metabolism and excretion of a synthetic androgen 7a-methyl-19-nortestosterone, a potential malecontraceptive / P. V. Prasad [et al.] // Steroids. - 2009. - Vol. 74, № 1. - P. 121-131.Chao, J. Make contraception / J. Chao, S. T. Page, R. A. Anderson // Best Practice & Research Clinical Obstetrics & Gynaecology. - 2014. - Vol. 28, № 6. - P. 845-857.Chao, J. Make contraception / J. Chao, S. T. Page, R. A. Anderson // Best Practice & Research Clinical Obstetrics & Gynaecology. - 2014. - Vol. 28, № 6. - P. 845-857.Kogan, P. Male Contraception: History and Development / P. Kogan, M. Wald // Urologic Clinics of North America. -2014. - Vol. 41, № 1. - P. 145-161.Kogan, P. Male Contraception: History and Development / P. Kogan, M. Wald // Urologic Clinics of North America. -2014. - Vol. 41, № 1. - P. 145-161.Nieschlag, E. Clinical trials in make hormonal contraception. / E. Nieschlag // Contraception. - 2010. - Vol. 82, № 5. - P. 457-470.Nieschlag, E. Clinical trials in make hormonal contraception. / E. Nieschlag // Contraception. - 2010. - Vol. 82, № 5. - P. 457-470.Sitruk-Ware, R. Contraception technology: past, present and future. Contraception / R. Sitruk-Ware, A. Nath, D. R. Mishell, Jr. // Contraception. - 2013. - Vol. 87, № 3. - P. 319-330.Sitruk-Ware, R. Contraception technology: past, present and future. Contraception / R. Sitruk-Ware, A. Nath, D. R. Mishell, Jr. // Contraception. - 2013. - Vol. 87, № 3. - P. 319-330.Tomizawa, 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 / M. Tomizawa // Adv. Insect Physiol. - 2013. - Vol. 44. - P. 63-99.Geng, C. Chapter Three - Nicotinic Acetylcholine Receptors 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. Chapter Three - Nicotinic Acetylcholine Receptors as Spinosyn Targets for Insect Pest Management / C. Geng, G. B. Watson, T. C. Sparks // Adv. Insect Physiol. - 2013. - Vol. 44. - P. 101-210.Pang, Y.-P. Insect Acetylcholinesterase as a Target for Effective and Environmentally Safe Insecticides / Y.-P. Pang // Adv. Insect Physiol. - 2014. - Vol. 46. - P. 435-494.Pang, Y.-P. Insect Acetylcholinesterase as a Target for Effective and Environmentally Safe Insecticides / Y.-P. Pang // Adv. Insect Physiol. - 2014. - Vol. 46. - P. 435-494.Sparks, T. C. Insecticide discovery: An evahiation and analysis / T. C. Sparks // Pesticide Biochem. Physiol. - 2013. -Vol. 107, № 1. - P. 8-17.Sparks, T. C. Insecticide discovery: An evahiation and analysis / T. C. Sparks // Pesticide Biochem. Physiol. - 2013. -Vol. 107, № 1. - P. 8-17.Kovganko, 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, № 6. - P. 584-588.Kovganko, 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, № 6. - P. 584-588.Синтез новых структурных аналогов имидаклоприда на основе 6-метоксиникотинового альдегида / Н. В. Ковганко [и др.] // Вес. Нац. акад. навук Беларусi Сер. хiм. навук. - 2009. - № 2. - С. 66-69.Синтез новых структурных аналогов имидаклоприда на основе 6-метоксиникотинового альдегида / Н. В. Ковганко [и др.] // Вес. Нац. акад. навук Беларусi Сер. хiм. навук. - 2009. - № 2. - С. 66-69.

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