RU2689131C1 - Sulfanilic and acetylsulfanyl derivatives of abietal type - Google Patents
Sulfanilic and acetylsulfanyl derivatives of abietal type Download PDFInfo
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- RU2689131C1 RU2689131C1 RU2018141961A RU2018141961A RU2689131C1 RU 2689131 C1 RU2689131 C1 RU 2689131C1 RU 2018141961 A RU2018141961 A RU 2018141961A RU 2018141961 A RU2018141961 A RU 2018141961A RU 2689131 C1 RU2689131 C1 RU 2689131C1
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- abiet
- thioacetate
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- -1 acetylsulfanyl derivatives of abietal Chemical class 0.000 title claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 abstract 1
- HOFSYSONRIGEAC-LWYYNNOASA-N abieta-7,13-dien-18-al Chemical compound O=C[C@]1(C)CCC[C@]2(C)[C@@H](CCC(C(C)C)=C3)C3=CC[C@H]21 HOFSYSONRIGEAC-LWYYNNOASA-N 0.000 abstract 1
- 229930001443 abietal Natural products 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 150000003464 sulfur compounds Chemical class 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 150000003573 thiols Chemical class 0.000 description 8
- 230000004071 biological effect Effects 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000002329 infrared spectrum Methods 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 4
- NFWKVWVWBFBAOV-MISYRCLQSA-N dehydroabietic acid Chemical compound OC(=O)[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 NFWKVWVWBFBAOV-MISYRCLQSA-N 0.000 description 4
- 229930004069 diterpene Natural products 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 4
- QUUCYKKMFLJLFS-UHFFFAOYSA-N Dehydroabietan Natural products CC1(C)CCCC2(C)C3=CC=C(C(C)C)C=C3CCC21 QUUCYKKMFLJLFS-UHFFFAOYSA-N 0.000 description 3
- NFWKVWVWBFBAOV-UHFFFAOYSA-N Dehydroabietic acid Natural products OC(=O)C1(C)CCCC2(C)C3=CC=C(C(C)C)C=C3CCC21 NFWKVWVWBFBAOV-UHFFFAOYSA-N 0.000 description 3
- 241000590002 Helicobacter pylori Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229930000074 abietane Natural products 0.000 description 3
- 229940118781 dehydroabietic acid Drugs 0.000 description 3
- 229940037467 helicobacter pylori Drugs 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 150000004694 iodide salts Chemical class 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 150000003460 sulfonic acids Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 108090001072 Gastricsin Proteins 0.000 description 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- 108010047320 Pepsinogen A Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- STIVVCHBLMGYSL-ZYNAIFEFSA-N abietane Chemical compound CC1(C)CCC[C@]2(C)[C@H]3CC[C@H](C(C)C)C[C@@H]3CC[C@H]21 STIVVCHBLMGYSL-ZYNAIFEFSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 150000002019 disulfides Chemical class 0.000 description 2
- 150000004141 diterpene derivatives Chemical class 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 230000008029 eradication Effects 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 description 1
- BTXXTMOWISPQSJ-UHFFFAOYSA-N 4,4,4-trifluorobutan-2-one Chemical compound CC(=O)CC(F)(F)F BTXXTMOWISPQSJ-UHFFFAOYSA-N 0.000 description 1
- BQACOLQNOUYJCE-FYZZASKESA-N Abietic acid Natural products CC(C)C1=CC2=CC[C@]3(C)[C@](C)(CCC[C@@]3(C)C(=O)O)[C@H]2CC1 BQACOLQNOUYJCE-FYZZASKESA-N 0.000 description 1
- 241000908198 Actinomucor Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000395107 Cladosporium cucumerinum Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 241000784329 Juniperus formosana Species 0.000 description 1
- 201000008225 Klebsiella pneumonia Diseases 0.000 description 1
- 241000588747 Klebsiella pneumoniae Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000235526 Mucor racemosus Species 0.000 description 1
- 239000004988 Nematic liquid crystal Substances 0.000 description 1
- 235000005205 Pinus Nutrition 0.000 description 1
- 241000218602 Pinus <genus> Species 0.000 description 1
- 206010035717 Pneumonia klebsiella Diseases 0.000 description 1
- 240000005384 Rhizopus oryzae Species 0.000 description 1
- 235000013752 Rhizopus oryzae Nutrition 0.000 description 1
- 241000235546 Rhizopus stolonifer Species 0.000 description 1
- 241001138418 Sequoia sempervirens Species 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000736854 Syncephalastrum Species 0.000 description 1
- 150000000150 abietanes Chemical class 0.000 description 1
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- SFLMUHDGSQZDOW-FAOXUISGSA-N coniferin Chemical compound COC1=CC(\C=C\CO)=CC=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 SFLMUHDGSQZDOW-FAOXUISGSA-N 0.000 description 1
- SFLMUHDGSQZDOW-IBEHDNSVSA-N coniferoside Natural products COC1=CC(C=CCO)=CC=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 SFLMUHDGSQZDOW-IBEHDNSVSA-N 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000007323 disproportionation reaction Methods 0.000 description 1
- 239000002019 doping agent Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical class CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 150000005217 methyl ethers Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 150000002898 organic sulfur compounds Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 150000004763 sulfides Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
- C07C321/02—Thiols having mercapto groups bound to acyclic carbon atoms
- C07C321/06—Thiols having mercapto groups bound to acyclic carbon atoms of a saturated carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C13/00—Cyclic hydrocarbons containing rings other than, or in addition to, six-membered aromatic rings
- C07C13/28—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof
- C07C13/32—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings
- C07C13/54—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings
- C07C13/573—Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with three condensed rings with three six-membered rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Изобретение относится к получению сульфанильных и ацетилсульфанильных производных абиетанового типа: абиета-7,13-диен-18-тиола, абиета-7,13-диен-18-тиоацетата, абиета-8,11,13-триен-18-тиола, абиета-8,11,13-триен-18-тиоацетата.The invention relates to the production of sulfanyl and acetylsulfanyl derivatives of abiethan type: abiet-7,13-diene-18-thiol, abiet-7,13-diene-18-thioacetate, abiet-8,11,13-triene-18-thiol, abiet -8,11,13-triene-18-thioacetate.
Тиолы используются в качестве реагентов в органическом синтезе для получения сульфидов, дисульфидов, тиолсульфинатов и тиолсульфонатов, сульфокислот, сульфохлоридов, сульфамидов, являющихся ценными полупродуктами для получения некоторых химико-фармацевтических препаратов, обладающих бактерицидной и фунгицидной активностью. Ацетилсульфанильные производные являются важными прекурсорами для получения тиолов.Thiols are used as reagents in organic synthesis to produce sulfides, disulfides, thiolsulfinates and thiolsulfonates, sulfonic acids, sulfonyl chlorides, sulfamides, which are valuable intermediates for the preparation of certain chemical-pharmaceutical preparations with bactericidal and fungicidal activity. Acetylsulfanyl derivatives are important precursors for the preparation of thiols.
В литературе серосодержащие производные абиетанового типа на сегодняшний день практически не описаны. Имеются сведения о получении и активности против Helicobacter Pylori натриевой соли 12-сульфоабиета-8,11,13-триен-18-овой кислоты [H. Osumi, J. Fujisaki, T. Suganuma, Y. Horiuchi, M. Omae, T. Yoshio, A. Ishiyama, T. Tsuchida, K. Miki. A significant increase in the pepsinogen I/II ratio is a reliable biomarker for successful Helicobacter pylori eradication // PLOS ONE. 2017, V.12, No. 8, p. 1–9]. Среди сульфанильных соединений по С18 описаны гидроксипропилсульфанильные и аминопропилсульфанильные производные, показывающие хорошую антигипертензивную активность. Данные алкилсульфанильные производные были получены по реакции соответствующих мезилатов с тиолами [A. Cerri, M. Gobbini, M. Torri, P. Ferrari, M. Ferrandi, G. Bianchi. Diterpenoid derivatives endowed of biological properties // Patent WO 2012/055894. 03 May 2012]. Описаны также дитиолановые производные, полученные по реакции 12-гидроксиабиета-8,11,13-триен-7-кето-18-аля, 12-гидроксиабиета-8,11,13-триен-7-она с 1,2-этандитиолом [Y.-H. Kuo, T.-R. Wu, M.-C. Cheng, Y. Wang. Five new compounds from the heartwood of Juniperus formosana Hayata // Chem. Pharm. Bull. 1990, V. 38, No. 12, p. 3195–3201].In the literature, sulfur-containing derivatives of the abietane type are practically not described today. There is information about the production and activity against Helicobacter pylori of sodium salt of 12-sulfobiet-8,11,13-triene-18-oic acid [H. Osumi, J. Fujisaki, T. Suganuma, Y. Horiuchi, M. Omae, T. Yoshio, A. Ishiyama, T. Tsuchida, K. Miki. A significant increase in the ratio of pepsinogen I / II is a reliable biomarker for Helicobacter pylori eradication // PLOS ONE. 2017, V.12, No. 8, p. 1–9]. Among sulfanyl compounds according to C 18 , hydroxypropylsulfanyl and aminopropylsulfanyl derivatives are described, showing good antihypertensive activity. These alkylsulfanyl derivatives were obtained by the reaction of the corresponding mesylates with thiols [A. Cerri, M. Gobbini, M. Torri, P. Ferrari, M. Ferrandi, G. Bianchi. Diterpenoid derivatives of biological properties // Patent WO 2012/055894. 03 May 2012]. Dithiolan derivatives obtained by the reaction of 12-hydroxyabiet-8,11,13-triene-7-keto-18-al, 12-hydroxyabiet-8,11,13-triene-7-one with 1,2-ethanedithiol [ Y.-H. Kuo, T.-R. Wu, M.-C. Cheng, Y. Wang. Juniperus formosana Hayata // Chem. Pharm. Bull. 1990, V. 38, No. 12, p. 3195-3201].
Дитерпеноиды абиетанового типа являются биологически активными соединениями природного происхождения, обладают широким спектром биологической активности, такой как противомикробная, противоязвенная, противораковая и противовоспалительная [A.S. Feliciano, M. Gordaliza, M.A. Salinero, M.J. Corral. Abietane acids: sources, biological activities, and therapeutic uses // Planta. Med. 1993, V. 59, No. 6, p. 485–490; M.A. González. Aromatic abietane diterpenoids: their biological activity and synthesis // Nat. Prod. Rep. 2015, V. 32, p. 684–704]. Наиболее изученными в плане биологической активности являются производные абиета-8,11,13-триен-18-овой (дегидроабиетиновой) кислоты. Так, продукты декарбоксилирования дегидроабиетиновой кислоты, как недавно было обнаружено, проявляют хорошую противораковую активность против рака толстой кишки, груди и легких [K.-H. Son, H.-M. Oh, S.-K. Choi, D.Ch. Han, B.-M. Kwon. Anti-tumor abietane diterpenes from the cones of Sequoia sempervirens // Bioorg. Med. Chem. Lett. 2005, V. 15, p. 2019–2021.]. Деизопропилированные метиловые эфиры 7- оксодегидроабиетиновой кислоты, отличающиеся конфигурацией С10, ингибируют рост нитевидных грибков (Actinomucor harzii, Cladosporium cucumerinum, Mucor racemosus, Rhizopus arrhizus, Rhizopus stolonifer и Syncephalastrum racemosum), а также грамположительных бактерий Staphylococcus aureus, но не эффективны по отношению к грамотрицательным бактериям Escherichia coli и Klebsiella pneumonia. Однако одновременное использование смеси изомеров благодаря возникновению синергического эффекта способствует проявлению ими высокой активности против грамотрицательных бактерий [S. Savluchinske Feio, B. Gigante, J.C. Roseiro, M.J. Marcelo Curto. Antimicrobial activity of diterpene resin acid derivatives // J. Microbiol. Methods. 1999, V. 35, No. 3, p. 201–206].Abiethan type diterpenoids are biologically active compounds of natural origin, possess a broad spectrum of biological activity, such as antimicrobial, antiulcer, anti-cancer and anti-inflammatory [AS Feliciano, M. Gordaliza, MA Salinero, MJ Corral. Abietane acids: sources, biological activities, and therapeutic uses // Planta. Med. 1993, V. 59, No. 6, p. 485–490; MA González. Aromatic abietane diterpenoids: their biological activity and synthesis // Nat. Prod. Rep. 2015, V. 32, p. 684-704]. The most studied in terms of biological activity are derivatives of abiet-8,11,13-triene-18-oic (dehydroabietic) acid. So, the products of decarboxylation of dehydroabietic acid, as it was recently discovered, show good anticancer activity against cancer of the colon, breast and lung [K.-H. Son, H.-M. Oh, S.-K. Choi, D.Ch. Han, B.-M. Kwon. Anti-tumor abietane diterpenes from the cones of Sequoia sempervirens // Bioorg. Med. Chem. Lett. 2005, V. 15, p. 2019–2021.]. The deisopropylated methyl ethers of 7-oxohydroabietic acid, differing in configuration C 10 , inhibit the growth of the bu-cure of the bu-pies, Actinomucor harzii, Cladosporium cucumerinum, Mucor racemosus, Rhizopus arrhizus, Rhizopus stolonifer, and Syncephalastrum, which is an exemplary of a sepulchroma, and Rucizopus rrhizus; Gram-negative bacteria Escherichia coli and Klebsiella pneumonia. However, the simultaneous use of a mixture of isomers due to the occurrence of a synergistic effect contributes to their high activity against gram-negative bacteria [S. Savluchinske Feio, B. Gigante, JC Roseiro, MJ Marcelo Curto. Antimicrobial activity of diterpene resin acid derivatives // J. Microbiol. Methods. 1999, V. 35, No. 3, p. 201–206].
Внедрение атома серы в структуру дитерпеновых соединений способно изменить спектр их биологической активности. Однако до этого момента удобных прекурсоров для получения сероорганических соединений с абиетановым углеродным скелетом, открывающих пути к получению разнообразных классов соединений: дисульфидов, сульфоксидов, сульфоновых кислот, сульфохлоридов, сульфамидов и др., – получено не было.The introduction of the sulfur atom into the structure of diterpene compounds can change the spectrum of their biological activity. However, up to this point, there were no convenient precursors for obtaining organosulfur compounds with abietan carbon skeleton, opening the way to obtaining various classes of compounds: disulfides, sulfoxides, sulfonic acids, sulfonyl chlorides, sulfamides, etc.
Задачей настоящего изобретения является синтез новых дитерпеновых тиолов абиетанового типа, полученных эффективным способом.The present invention is the synthesis of new diterpenic thiols of abiethan type, obtained in an effective way.
Технический результат заключается в расширении арсенала новых дитерпеновых сульфанильных производных заданной структуры, являющихся перспективными реагентами для получения сульфинил- и сульфонилсодержащих соединений абиетанового типа и полупродуктами в получении потенциальных биологически активных веществ.The technical result consists in expanding the arsenal of new diterpene sulfanyl derivatives of a given structure, which are promising reagents for producing sulfinyl and sulfonyl-containing compounds of abiethan type and intermediates in obtaining potential biologically active substances.
Технический результат достигается получением сульфанильных и ацетилсульфанильных производных абиетанового типа: абиета-7,13-диен-18-тиол, абиета-7,13-диен-18-тиоацетат, абиета-8,11,13-триен-18-тиол, абиета-8,11,13-триен-18-тиоацетат, – структурной формулы (I) The technical result is achieved by obtaining sulfanyl and acetylsulfanyl derivatives of abiethan type: abiet-7,13-diene-18-thiol, abiet-7,13-diene-18-thioacetate, abiet-8,11,13-triene-18-thiol, abiet -8,11,13-triene-18-thioacetate, - structural formula (I)
R1-CH2S-R2 (I)R 1 -CH 2 SR 2 (I)
где R1 – радикал абиетанового типа:where R 1 is a radical of abiethan type:
R2 – атом водорода H или ацетильная группа –COCH3, а звездочкой обозначена связь, через которую осуществляется присоединение к атому серы соединений формулы (I).R 2 is hydrogen atom H or acetyl group –COCH 3 , and the asterisk indicates the bond through which the compounds of formula (I) are attached to the sulfur atom.
Получение абиета-7,13-диен-18-тиоацетата 5а и абиета-8,11,13-триен-18-тиоацетата 5б (схема 1) осуществляется в четыре стадии из соответствующих смоляных кислот: абиетиновой 1а и дегидроабиетиновой 1б. Для повышения выхода конечных продуктов соответствующие кислоты количественно переводятся в эфиры 2a и 2б, восстановление которых протекает без образования побочных продуктов. Продукты восстановления – спирты – по реакции с системой иод-трифенилфосфин-бензимидазол при кипячении превращаются в иодиды 4а и 4б с выходами 73% и 80% соответственно [J.S. Yadav, G. Baishya, U. Dash. Synthesis of (+)-amberketal and ind its analog from L-abietic acid // Tetrahedron. 2007, V. 63, p. 9896–9902]. При кипячении полученных иодидов с полутораэквивалентным избытком CH3COSK образуются тиоацетаты абиетанового типа 5a и 5б с выходами обоих по 85%. Последующее восстановление тиоацетатов LiAlH4 протекает количественно до тиолов 6а и 6б. Таким образом, выходы сульфанильных производных по всем превращениям составляют 78% для 6а и 71% для 6б.The preparation of abiet-7,13-diene-18-thioacetate 5a and abiet-8,11,13-triene-18-thioacetate 5b (Scheme 1) is carried out in four stages from the corresponding resin acids: abietic 1a and dehydroabietic 1b. To increase the yield of the final products, the corresponding acids are quantitatively converted to esters 2a and 2b, the reduction of which proceeds without the formation of by-products. The reduction products — alcohols — upon reaction with the iodine-triphenylphosphine-benzimidazole system, when boiled, turn into iodides 4a and 4b with yields of 73% and 80%, respectively [JS Yadav, G. Baishya, U. Dash. Synthesis of (+) - amberketal and ind its analog from L-abietic acid // Tetrahedron. 2007, V. 63, p. 9896–9902]. When boiling the obtained iodides with a one and a half equivalent CH 3 COSK, abietane type thioacetates 5a and 5b are formed with the yields of both 85%. Subsequent reduction thioacetate LiAlH 4 proceeds quantitatively to thiols 6a and 6b. Thus, the yields of sulfanyl derivatives for all transformations are 78% for 6a and 71% for 6b.
Схема 1. Синтез абиета-7,13-диен-18-тиола, абиета-7,13-диен-18-тиоацетата, абиета-8,11,13-триен-18-тиола и абиета-8,11,13-триен-18-тиоацетатаScheme 1. Synthesis of abiet-7,13-diene-18-thiol, abiet-7,13-diene-18-thioacetate, abiet-8,11,13-triene-18-thiol and abiet-8,11,13- triene-18-thioacetate
В качестве исходных субстратов использовали абиетиновую кислоту 1а ([α]D 22 –103.5 (c 0.1, EtOH) (ср. лит.: [α]D 24 –106.0), содержащую 5% кислоты 1б, и дегидроабиетиновую кислоту 1б, полученную по методике [M. Zucolotto, E. Cidade da Rocha, M. Luiza A. Von Holleben. Disproportionation of rosin from Pinus Eliotti: obtention of emulsifier for polymerization // Quimica Nova. 1995, V. 18, No. 1, p. 78–79]. Разделение абиетиновой структуры от дегидроабиетиновой проводят на стадии образования иодидов. Иодид 4a имеет большую хроматографическую подвижность (Rf = 0.35) в отличие от иодида 4б (Rf = 0.25). Поэтому тиоацетат 5а и тиол 6а получают в виде оптически чистых продуктов. Дегидроабиетиновая кислота образуется с чистотой 98% и имеет угол оптического вращения [α]D 25 + 61.0 (c 0.1, EtOH) (ср. лит.: [α]D 20 + 62.5 (с 2.0, EtOH)) [H. Shitara, M. Aruga, E. Odagiri, K. Taniguchi, M. Yasutake, T. Hirose. Dehydroabietic acid esters as chiral dopants for nematic liquid crystals // Bull. Chem. Soc. Jpn. 2007, V. 80, No. 3, p. 589–593].Abietic acid 1a ([α] D 22 –103.5 (c 0.1, EtOH) (cf. lit. [α] D 24 –106.0) containing 5% acid 1b and dehydroabietic acid 1b obtained from method [M. Zucolotto, E. Cidade da Rocha, M. Luiza A. Von Holleben. Disproportionation of Pinus Eliotti: obtention of emulsifier for polymerization // Quimica Nova. 1995, V. 18, No. 1, p. 78 -79]. Separation abietic structure from dehydroabietic carried out at the stage of iodides. iodide 4a has a large chromatographic mobility (R f = 0.35) in contrast to iodide 4b (R f = 0.25). Therefore thioacetate 5a and 6a thiol obtained in the form of optically Num s products. dehydroabietic acid is produced with a purity of 98% and an angle of optical rotation [α] D 25 + 61.0 (c 0.1, EtOH) ( Wed lit .: [α] D 20 + 62.5 (c 2.0, EtOH)) [H Shitara, M. Aruga, E. Odagiri, K. Taniguchi, M. Yasutake, T. Hirose. Dehydroabietic acid esters as a chiral dopants for nematic liquid crystals // Bull. Chem. Soc. Jpn. 2007, V. 80, No. 3, p. 589-593].
ИК спектры регистрировали на ИК-Фурье-спектрометре Shimadzu IR Prestige 21 в тонком слое. Спектры ЯМР 1H и 13C регистрировали на спектрометре Bruker Avance-300 (300.17 МГц для 1Н и 75.48 МГц для 13С) в растворах CDCl3 (внутренний стандарт – сигнал хлороформа). Полное отнесение сигналов 1Н и 13С выполняли с помощью двумерных гомо- (1H–1H COSY, 1H–1H NOESY) и гетероядерных экспериментов (1H–13C HSQC, HMBC). Элементный анализ выполняли с использованием автоматического анализатора ЕА 1110 CHNS-O.IR spectra were recorded on a Shimadzu IR Prestige 21 FTIR spectrometer in a thin layer. The 1 H and 13 C NMR spectra were recorded on a Bruker Avance 300 spectrometer (300.17 MHz for 1 H and 75.48 MHz for 13 C) in CDCl 3 solutions (the internal standard is chloroform signal). The full assignment of 1 H and 13 C signals was performed using two-dimensional homo- ( 1 H – 1 H COZY, 1 H – 1 H NOESY) and heteronuclear experiments ( 1 H – 13 C HSQC, HMBC). Elemental analysis was performed using an automated analyzer EA 1110 CHNS-O.
Получение новых соединений показано на следующих примерах.Obtaining new compounds is shown in the following examples.
Пример 1. Абиета-7,13-диен-18-тиоацетат.Example 1. Abiet-7,13-diene-18-thioacetate.
Для получения абиета-7,13-диен-18-тиоацетата 5а растворяли иодид 4а и CH3COSK в диметилформамиде в эквивалентном соотношении 1 : 1.5. Кипятили реакционную смесь в течение 1 ч. По окончании реакции удаляли растворитель при пониженном давлении, к остатку прибавляли воду, экстрагировали продукт петролейным эфиром. Отделяли органический слой, сушили над Na2SO4, удаляли растворитель при пониженном давлении. Остаток делили методом колоночной хроматографии на SiO2, используя в качестве элюента смесь петролейного и диэтилового эфиров в соотношении 25:1 (Rf = 0.33). Выход 85%.[α]D 24 - 63.9° (c 0.37; CHCl3). ИК спектр (KBr, ν, см-1): 630, 954, 1105, 1134, 1381, 1450, 1694, 2924. Спектр ЯМР 1Н (CDCl3, δ, м.д.): 0.82 с (3H, H20), 1.01 с (3H, H19), 0,93–1.08 м (10H, H16, H17, H19, H3a), 1.14–1.30 м (2H, H11a, H1a), 1.37–1.61 м (4H, H1b, H2, H5), 1.73–1.97 м (3H, H3b, H9, H11b), 1.97–2.16 м (4H, H6, H12), 2.23 квн (1H, H15, J =7.0 Гц), 2.33 с (3H, COCH 3), 2.83 д (1H, H18a, J = 13.4 Гц), 2.96 д (1H, H18b, J = 13.4 Гц), 5.41 с (1H, H7), 5.79 с (1H, H14). Спектр ЯМР 13С (CDCl3, δ, м.д.): 13.89 (C20), 18.28 (C2), 20.22 (C19), 20.80 (C16), 21.36 (C17), 22.64 (C11), 23.78 (C6), 27.46 (C12), 30.73 (CH3CO), 34.84 (C15), 34.94 (C10), 36.63 (C4), 37.83 (C1), 38.71 (C3), 42.57 (C18), 47.23 (C5), 50.81 (C9), 120.79 (C7), 122.41 (C14), 135.35 (C8), 145.19 (C13), 195.68 (C=O). Найдено, %: С 76.30; Н 9.84; S 9.20. С22Н34OS. Вычислено, %: С 76.24; Н 9.89; S 9.25.Iodide 4a and CH are dissolved to obtain abiet-7,13-diene-18-thioacetate 5a3COSK in dimethylformamide in an equivalent ratio of 1: 1.5. The reaction mixture was boiled for 1 hour. At the end of the reaction, the solvent was removed under reduced pressure, water was added to the residue, and the product was extracted with petroleum ether. The organic layer was separated, dried over Na2SOfour, the solvent was removed under reduced pressure. The residue was divided by the method of column chromatography on SiO2, using as eluent a mixture of petroleum and diethyl ethers in a ratio of 25: 1 (Rf = 0.33). Output 85%. [Α]D 24 - 63.9 ° (c 0.37; CHCl3). IR spectrum (KBr, ν, cm-one): 630, 954, 1105, 1134, 1381, 1450, 1694, 2924. NMR spectrumoneH (CDCl3, δ, ppm): 0.82 s (3H, H20), 1.01 s (3H, Hnineteen), 0.93–1.08 m (10H, Hsixteen, H17, Hnineteen, H3a), 1.14–1.30 m (2H, H11a, H1a), 1.37–1.61 m (4H, H1b, H2, Hfive), 1.73–1.97 m (3H, H3b, H9, H11b), 1.97–2.16 m (4H, H6, H12), 2.23 kV (1H, H15J = 7.0 Hz), 2.33 s (3H, COCH 3), 2.83 d (1H, H18aJ = 13.4 Hz), 2.96 d (1H, H18bJ = 13.4 Hz), 5.41 s (1H, H7), 5.79 s (1H, H14). NMR spectrum13C (CDCl3, δ, ppm): 13.89 (C20), 18.28 (C2) 20.22 (Cnineteen) 20.80 (Csixteen) 21.36 (C17) 22.64 (Celeven) 23.78 (C6) 27.46 (C12), 30.73 (CH3CO), 34.84 (C15) 34.94 (Cten) 36.63 (Cfour), 37.83 (Cone) 38.71 (C3) 42.57 (C18) 47.23 (Cfive) 50.81 (C9) 120.79 (C7) 122.41 (C14), 135.35 (Ceight) 145.19 (C13), 195.68 (C = O). Found,%: C 76.30; H 9.84; S 9.20. WITH22H34OS. Calculated,%: C 76.24; H 9.89; S 9.25.
Пример 2. Абиета-8,11,13-триен-18-тиоацетат.Example 2. Abieta-8,11,13-triene-18-thioacetate.
Получение абиета-8,11,13-триен-18-тиоацетата 5б проводили аналогичным образом, как и тиоацетата 5а. Разделение проводили колоночной хроматографией на SiO2, используя элюент петролейный эфир: Et2O 25:1 (Rf = 0.33). Выход 85%. αD 24 +38.6 (с 0.4, CHCl3). ИК спектр (KBr, ν, см-1): 629, 820, 1105, 1134, 1382, 1455, 1688, 2955. Спектр ЯМР 1Н (CDCl3, δ, м.д.): 1.05 с (3H, H19), 1.23 с (3H, H20), 1.26 д (6H, H16, H17, J = 7.0 Гц), 1.32–1.55 м (3H, H1, H3a), 1.51–1.98 м (5H, H2, H5, H6), 2.24–2.37 м (1H, H3b), 2.34 с (3H, COCH3), 2.75–3.08 (5H, H7, H15, H18), 6.92 c (1H, H14), 7.02 c (1H, H12, J = 8.1 Гц), 7.19 c (1H, H11, J = 8.1 Гц). Спектр ЯМР 13С (CDCl3, δ, м.д.): 18.77 (C2), 19.02 (C6), 20.22 (C19), 23.95 (C16, C17), 25.11 (C20), 30.21 (C7), 30.69 (COCH3), 33.42 (C15), 37.18 (C10), 37.23 (C1), 37.58 (C4), 38.28 (C3), 42.54 (C18), 46.82 (C5), 123.83 (C12), 124.22 (C11), 126.84 (C14), 134.72 (C8), 145.54 (C13), 147.14 (C9), 195.56 (C=O). Найдено, %: С 76.64; Н 9.40; S 9.24. С22Н32OS. Вычислено, %: С 76.69; Н 9.36; S 9.30. The preparation of abiet-8,11,13-triene-18-thioacetate 5b was carried out in the same way as that of thioacetate 5a. The separation was performed by column chromatography on SiO 2 using eluent petroleum ether: Et 2 O 25: 1 (R f = 0.33). Yield 85%. α D 24 +38.6 (c 0.4, CHCl 3 ). IR spectrum (KBr, ν, cm -1 ): 629, 820, 1105, 1134, 1382, 1455, 1688, 2955. 1 H NMR spectrum (CDCl 3 , δ, ppm): 1.05 s (3H, H 19 ), 1.23 s (3H, H 20 ), 1.26 d (6H, H 16 , H 17 , J = 7.0 Hz), 1.32–1.55 m (3H, H 1 , H 3a ), 1.51–1.98 m (5H, H 2 , H 5 , H 6 ), 2.24–2.37 m (1H, H 3b ), 2.34 s (3H, COCH 3 ), 2.75–3.08 (5H, H 7 , H 15 , H 18 ), 6.92 c (1H , H 14 ), 7.02 c (1H, H 12 , J = 8.1 Hz), 7.19 c (1H, H 11 , J = 8.1 Hz). 13 C NMR spectrum (CDCl 3 , δ, ppm): 18.77 (C 2 ), 19.02 (C 6 ), 20.22 (C 19 ), 23.95 (C 16 , C 17 ), 25.11 (C 20 ), 30.21 (C 7 ), 30.69 (CO C H 3 ), 33.42 (C 15 ), 37.18 (C 10 ), 37.23 (C 1 ), 37.58 (C 4 ), 38.28 (C 3 ), 42.54 (C 18 ), 46.82 (C 5 ), 123.83 (C 12 ), 124.22 (C 11 ), 126.84 (C 14 ), 134.72 (C 8 ), 145.54 (C 13 ), 147.14 (C 9 ), 195.56 (C = O). Found,%: C 76.64; H 9.40; S 9.24. With 22 N 32 OS. Calculated,%: C 76.69; H 9.36; S 9.30.
Пример 3. Абиета-7,13-диен-18-тиол.Example 3. Abieta-7,13-diene-18-thiol.
Для получения абиета-7,13-диен-18-тиола 6а растворяли тиоацетат 5а в сухом эфире. Добавляли эквивалентное количество LiAlH4. Реакцию проводили в среде аргона. Перемешивали 0.5 ч, после чего добавляли воду. Выпавший осадок отфильтровывали, дважды промывали петролейным эфиром. Фильтрат переносили в делительную воронку, отделяли органическую фракцию от воды. Водный слой дополнительно экстрагировали петролейным эфиром. Объединенные органические фазы сушили над Na2SO4. Выпаривали растворитель при пониженном давлении. Остаток – бесцветное масло представляет собой чистый тиол. Выход 100%. αD 24 –63.1 (с 0.14, CHCl3). ИК спектр (KBr, ν, см–1): 885, 1020, 1381, 1462, 2926. Спектр ЯМР 1Н (CDCl3, δ, м.д.): 0.86 с (3H, H20), 1.03 с (3H, H19), 1.04 д (3H, H16, J = 6.8 Гц), 1.05 д (3H, H17, J = 6.8 Гц), 1.05–1.16 м (1H, H3a), 1.19–1.34 м (1H, H11a), 1.36–1.46 м (2H, H1), 1.51–1.67 м (3H, H2, H5), 1.78–2.03 м (6H, H3b, H6, H9, H11b, SH), 2.12 д (2H, H12, J = 6.8 Гц), 2.26 квн (1H, H15, J =7.0 Гц), 2.38 дд (1H, H18a, J = 13.6, 9.3 Гц), 2.55 дд (1H, H18b, J = 13.6, 8.1 Гц), 5.44 с (1H, H7), 5.82 с (1H, H14). Спектр ЯМР 13С (CDCl3, δ, м.д.): 13.95 (C20), 18.33 (C2), 20.12 (C19), 20.82 (C16), 21.39 (C17), 22.68 (C11), 23.53 (C6), 27.50 (C12), 34.79 (C10), 34.87 (C15), 36.27 (C4), 36.58 (C1), 38.60 (C18), 38.79 (C3), 45.71 (C5), 50.82 (C9), 120.68 (C7), 122.40 (C14), 135.57 (C8), 145.31 (C13). Найдено, %: С 78.94; Н 10.53; S 10.56. С20Н32S. Вычислено, %: С 78.88; Н 10.59; S 10.53. To obtain abiet-7,13-diene-18-thiol 6a, thioacetate 5a was dissolved in dry ether. An equivalent amount of LiAlH 4 was added. The reaction was carried out in argon. Stir for 0.5 h, then add water. The precipitate was filtered off, washed twice with petroleum ether. The filtrate was transferred to a separatory funnel, the organic fraction was separated from the water. The aqueous layer was further extracted with petroleum ether. The combined organic phases were dried over Na 2 SO 4 . The solvent evaporated under reduced pressure. The residue is a colorless oil is pure thiol. The yield is 100%. α D 24 –63.1 (with 0.14, CHCl 3 ). IR spectrum (KBr, ν, cm –1 ): 885, 1020, 1381, 1462, 2926. NMR spectrum 1 H (CDCl 3 , δ, ppm): 0.86 s (3H, H 20 ), 1.03 s ( 3H, H 19 ), 1.04 d (3H, H 16 , J = 6.8 Hz), 1.05 d (3H, H 17 , J = 6.8 Hz), 1.05–1.16 m (1H, H 3a ), 1.19–1.34 m ( 1H, H 11a ), 1.36–1.46 m (2H, H 1 ), 1.51–1.67 m (3H, H 2 , H 5 ), 1.78–2.03 m (6H, H 3b , H 6 , H 9 , H 11b , SH), 2.12 d (2H, H 12 , J = 6.8 Hz), 2.26 kV (1H, H 15 , J = 7.0 Hz), 2.38 dd (1H, H 18a , J = 13.6, 9.3 Hz), 2.55 dd ( 1H, H 18b , J = 13.6, 8.1 Hz), 5.44 s (1H, H 7 ), 5.82 s (1H, H 14 ). 13 C NMR spectrum (CDCl 3 , δ, ppm): 13.95 (C 20 ), 18.33 (C 2 ), 20.12 (C 19 ), 20.82 (C 16 ), 21.39 (C 17 ), 22.68 (C 11 ), 23.53 (C 6 ), 27.50 (C 12 ), 34.79 (C 10 ), 34.87 (C 15 ), 36.27 (C 4 ), 36.58 (C 1 ), 38.60 (C 18 ), 38.79 (C 3 ), 45.71 (C 5 ), 50.82 (C 9 ), 120.68 (C 7 ), 122.40 (C 14 ), 135.57 (C 8 ), 145.31 (C 13 ). Found,%: C 78.94; H 10.53; S 10.56. C 20 H 32 S. Calculated,%: C 78.88; H 10.59; S 10.53.
Пример 4. Абиета-8,11,13-триен-18-тиол.Example 4. Abieta-8,11,13-triene-18-thiol.
Получение абиета-8,11,13-триен-18-тиола 6б проводили аналогичным образом, как и тиола 6а. Выход 100%. αD 24 +27.9 (с 0.5, CHCl3). ИК спектр (KBr, ν, см-1): 756, 824, 1221, 1381, 1460, 1497, 2928. Спектр ЯМР 1Н (CDCl3, δ, м.д.): 1.03 с (3H, H19), 1.25 с (3H, H20), 1.26 д (6H, H16, H17, J = 7.0 Гц), 1.36–1.56 м (3H, H1, H3a), 1.67–1.86 м (6H, H2, H5, H6, SH), 2.26–2.36 м (1H, H3b), 2.44 дд (1H, H18a, J = 13.6, 9.4 Гц), 2.68 дд (1H, H18b, J = 13.6, 7.9 Гц), 2.77–2.97 (3H, H7, H15), 6.92 c (1H, H14), 7.03 c (1H, H12, J = 8.1 Гц), 7.22 c (1H, H11, J = 8.1 Гц). Спектр ЯМР 13С (CDCl3, δ, м.д.): 18.71 (C2), 18.78 (C6), 20.03 (C19), 23.95 (C16, C17), 25.11 (C20), 30.15 (C7), 33.43 (C15), 35.82 (C1), 36.71 (C10), 37.48 (C4), 38.38 (C3), 38.75 (C18), 45.65 (C5), 123.85 (C12), 124.32 (C11), 126.78 (C14), 134.66 (C8), 145.52 (C13), 147.27 (C9). Найдено, %: С 79.47; Н 9.94; S 10.65. С20Н30S. Вычислено, %: С 79.41; Н 10.00; S 10.60. The preparation of abiet-8,11,13-triene-18-thiol 6b was carried out in the same way as thiol 6a. The yield is 100%. α D 24 +27.9 (with 0.5, CHCl 3 ). IR spectrum (KBr, ν, cm -1 ): 756, 824, 1221, 1381, 1460, 1497, 2928. NMR spectrum 1 H (CDCl 3 , δ, ppm): 1.03 s (3H, H 19 ) , 1.25 s (3H, H 20 ), 1.26 d (6H, H 16 , H 17 , J = 7.0 Hz), 1.36–1.56 m (3H, H 1 , H 3a ), 1.67–1.86 m (6H, H 2 , H 5 , H 6 , SH), 2.26–2.36 m (1H, H 3b ), 2.44 dd (1H, H 18a , J = 13.6, 9.4 Hz), 2.68 dd (1H, H 18b , J = 13.6, 7.9 Hz), 2.77–2.97 (3H, H 7 , H 15 ), 6.92 c (1H, H 14 ), 7.03 c (1H, H 12 , J = 8.1 Hz), 7.22 c (1H, H 11 , J = 8.1 Hz). 13 C NMR spectrum (CDCl 3 , δ, ppm): 18.71 (C 2 ), 18.78 (C 6 ), 20.03 (C 19 ), 23.95 (C 16 , C 17 ), 25.11 (C 20 ), 30.15 (C 7 ), 33.43 (C 15 ), 35.82 (C 1 ), 36.71 (C 10 ), 37.48 (C 4 ), 38.38 (C 3 ), 38.75 (C 18 ), 45.65 (C 5 ), 123.85 (C 12 ), 124.32 (C 11 ), 126.78 (C 14 ), 134.66 (C 8 ), 145.52 (C 13 ), 147.27 (C 9 ). Found,%: C 79.47; H 9.94; S 10.65. C 20 H 30 S. Calculated,%: C 79.41; H 10.00; S 10.60.
Ниже приведены примеры использования новых химических соединений в синтезе сульфинильных (тиолсульфинаты, сульфинамиды) и сульфонильных (сульфоновые кислоты и их эфиры, сульфохлориды, сульфонамиды) производных. Below are examples of the use of new chemical compounds in the synthesis of sulfinyl (thiolsulfinates, sulfonamides) and sulfonyl (sulfonic acids and their esters, sulfonchlorides, sulfonamides) derivatives.
где R – радикал абиетинового типа:where R is a radical of abietin type:
R1, R2, R3 - алкил или арил; [O] – окислитель, NCS – N-хлорсукцинимид . R 1, R 2, R 3 is alkyl or aryl; [O] is an oxidizing agent; NCS is N-chlorosuccinimide.
Таким образом, сульфанильные и ацетилсульфанильные производные открывают пути к получению разнообразных классов органических соединений, которые помимо дальнейших модификаций в синтетических целях способны показать широкий спектр биологической активности [H. Osumi, J. Fujisaki, T. Suganuma, Y. Horiuchi, M. Omae, T. Yoshio, A. Ishiyama, T. Tsuchida, K. Miki. A significant increase in the pepsinogen I/II ratio is a reliable biomarker for successful Helicobacter pylori eradication // PLOS ONE. 2017, V.12, No. 8, p. 1–9; Q. Mo; L. Liu, W. Duan, B. Cen, G. Lin, N. Chen, Y. Huang, B. Liu. Synthesis and insecticidal activities of N-(5-dehydroabietyl-1,3,4-thiadiazol-2-yl)-N'-substituted thioureas // Linchan Huaxue Yu Gongye. 2015, V. 35, No. 2, p. 8–16]. Thus, sulfanyl and acetylsulfanyl derivatives open the way to obtaining various classes of organic compounds that, in addition to further modifications for synthetic purposes, can show a wide spectrum of biological activity [H. Osumi, J. Fujisaki, T. Suganuma, Y. Horiuchi, M. Omae, T. Yoshio, A. Ishiyama, T. Tsuchida, K. Miki. A significant increase in the ratio of pepsinogen I / II is a reliable biomarker for Helicobacter pylori eradication // PLOS ONE. 2017, V.12, No. 8, p. 1–9; Q. Mo; L. Liu, W. Duan, B. Cen, G. Lin, N. Chen, Y. Huang, B. Liu. Synthesis and insecticidal activities of N- (5- dehydroabietyl- 1, 3, 4- thiadiazol- 2- yl) - N'- substituted thioureas // Linchan Huaxue Yu Gongye. 2015, V. 35, No. 2, p. 8–16].
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| Title |
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| C. Tabacik et al. "Diterpenes de Juniperus Phoenicea: constituants mineurs" Phytochemistry, vol.10, 1971, 1639-1645. * |
| C. Tabacik et al. "Diterpenes de Juniperus Phoenicea: constituants mineurs" Phytochemistry, vol.10, 1971, 1639-1645. H.-J. Lee et al. "Synthesis and characterization of abietadiene, levopimaradiene, palustradiene, and neoabietadiene: hydrocarbon precursors of the abietane diterpene resin acids" Tetrahedron, 57, 2001, 6155-6167. * |
| H.-J. Lee et al. "Synthesis and characterization of abietadiene, levopimaradiene, palustradiene, and neoabietadiene: hydrocarbon precursors of the abietane diterpene resin acids" Tetrahedron, 57, 2001, 6155-6167. * |
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