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9N,O-Макроциклы
N,O-Macrocycles
Макрогетероциклы
Статья
Paper
http://macroheterocycles.isuct.ru
DOI: 10.6060/mhc141138s
Synthesis of Macroheterocyclic Compounds with a Furan Bridge Possessing Structural Fragments of 1,2,3-Triazoles and Natural Diterpenoids
Yuri V. Kharitonov,ab Makhmut M. Shakirov,a and Elvira E. Shultsab@
Novosibirsk Institute of Organic Chemistry, 630090 Novosibirsk, Russia Novosibirsk State University, 630090 Novosibirsk, Russia @Corresponding author E-mail: schultz@nioch.nsc.ru
Derivatives of natural diterpenoid lambertianic acid containing alkyne and dialkyne substituent in the furan ring were obtained. 1,2,3-Triazole-incarporated furan bridged macrocycles have been prepared by 1,3-dipolar cycloaddition of methyl 15,16-bis[(prop-2-yn-1-yloxy)methyl]lambertianate with various diazides in the presence of Cu(II)/sodium ascorbate in methylene chloride/water reaction medium.
Keywords: Lambertianic acid, labdanoid alkynes, azides, click chemistry, macroheterocycles.
Синтез макрогетероциклических соединений с фурановым мостиком, содержащих фрагменты 1,2,3-триазолов и природных дитерпеноидов
Ю. В. Харитонов,^ М. М. Шакиров^ Э. Э. Шульц3^
Новосибирский институт органической химии им. Н.Н. Ворожцова СО РАН, 630090 Новосибирск, Россия ьНовосибирский национальный исследовательский государственный университет, 630090 Новосибирск, Россия ®Е-шаИ: schultz@nioch.nsc.ru
Получены производные дитерпеноида ламбертиановой кислоты, содержащие ацетиленовые заместители в фурановом кольце. Реакцией 1,3-диполярного циклоприсоединения метил-15,16-бис[(проп-2-ин-1-илокси) метил]ламбертианата с различными диазидами в присутствии Си(11)/аскорбат натрия в системе хлористый метилен-вода синтезированы триазолсодержащие макрогетероциклы с фурановым мостиком.
Ключевые слова: Ламбертиановая кислота, лабданоидные алкины, азиды, СиААС реакция, макрогетероциклы.
Introduction
Natural and synthetic macrocyclic molecules are interesting compounds for various application in supramolecular chemistry,111 material science[2] and in the biological science. [3] Owing to the prominent characteristics, such as chiral rigid skeletons, multiplete chemical reaction sites and unique amphiphilicity steroidal compounds (especially bile acid and its derivatives) are increasingly used as building blocks in supramolecular chemistry, especially in recognition and assembly,[4] because their special characteristics offer a diversity of spacer, different sized cavities, varied binding sites, and unique spatial structure arrangement, as well as biological activity and biocompatibility.[5] With similar structural properties as the biogenic homologue of steroids, triterpenoids (18p-glycyrrhetinic acid, oleanolic acid) have also started to emerge in recognition and assembly systems, thus attracting more and more attention from organic and material scientists.[6-8] Among the synthesized macrocyclic steroidal dimers the compounds with good inverse recognition properties,[9] as well as cytotoxic hormone receptor modulating activities[10] were obtained. Glycyrrhetinic acid-tweezer receptors with excellent selectivity and affinity for Hg2+ ion,[11] and stable cyclic dimer based on oleanolic acid with remarkable binding ability to F- ion[7] were reported. In the series of macrocyclic diterpenoids from isosteviol[12,13] and steviol,[14] compounds with excellent antituberculosis activity were found.[14] Macrocyclic derivatives of diterpe-noid paclitaxel exhibited cytotoxicity against pancreatic cell lines expressing multidrug-resistant genes.[15]
In recent years, Cu1 catalyzed azide-alkyne cycloaddition (CuAAC) received much attention as a method for construction of steroid/triterpenoid-based functional molecules. In view of the specific chemical properties of the formed by this method 1,4-disubstituted 1,2,3-triazoles (stable to metabolic degradation, capable of hydrogen bonding, favorable in the solubility and binding of bimolecular targets because of its relative planarity and strong dipole characteristics[16]) tri-azole connecting macrocycles represent a challenging class of molecules with promising therapeutic potential.
During our previous investigation we demonstrated the possibility to synthesize the macrocyclic compounds based on labdane diterpenoids[17] using CuAAC reaction. In this work we describe the synthesis of compounds, possessing structural fragments of 1,2,3-triazoles and labdanoids with a furan bridge via the CuAAC reaction of a new diacetylenic derivatives - methyl-15,16-epoxy-15,16-bis(propinyloxymethyl)labdatriene with diazides.
The development of approaches to macroheterocyclic compounds with a furan bridge produce independent interest because of the high cytotoxicity of macrocyclic diterpenes and C4-norditerpenes of 14-membered cembranoids and polycyclic cembranoids.[18]
Experimental
NMR spectra were acquired on Bruker AV-400 ('H: 400.13 MHz, 13C: 100.78 MHz) or BrukerAV-600 ('H: 600.30 MHz, 13C: 150.95 MHz) (Bruker BioSpin GmbH, Rheinstetten, Germany) instruments, using tetramethylsilane (TMS) as an internal
standard. In the description of the 'H and 13C-NMR spectra, the labdane skeleton atoms numeration system given in structure 1 was used. The IR spectra were recorded by means of the KBr pellet technique on a Bruker Vector-22 spectrometer. The UV spectra were obtained on an HP 8453 UV-Vis spectrometer (Hewlett-Packard, Waldbronn, Germany). Mass spectra were recorded on a DFS spectrometer (Thermo Scientific, evaporator temperature 240-270 °C). The melting points were determined on a Stuart SMF-38 melting point apparatus (Bibby Scientific, Staffordshire, UK) and are uncorrected. Elemental analysis was carried out on a Carlo-Erba 1106 analysis instrument. Molecular weights were determined on a VP Osmometer K 7000 (Knauer, Germany). The optical rotation was measured on a polarimeter PolAAr3005 in ethanol at 20-25 °C. Elemental, spectral and analytical investigations were carried out at Collective Chemical Service center of Siberian Branch of the Russian Academy of Sciences.
Reaction products were isolated by column chromatography on silica gel 60 (0.063-0.200 mm, Merck KGaA) and eluted with chloroform and chloroform-ethanol (100:1; to 25:l). The reaction progress and the purity of the obtained compounds were monitored by TLC on Silufol UV-254 plates (detection under UV light or by spraying with a 10 % aqueous solution of H2SO4, followed by heating to 100 °C).
Lambertianic acid 1 was isolated from the soft resin of Siberian pine Pinus sibirica R. Mayr by known method.[19] Methyl-16-formyllabdatrienoate 2,[20] methyl 16-(propynyloxymethyl) lambertianate 3,[17] diazidopentane 4,[21] 1,10-diazidodecane 5,[22] 1-azido-2-(2-azidoethoxy)ethane 6,[23] and 1,2-bis(2- azidoethoxy) ethane 7[23] are known compounds and were prepared by the reported methods. Chemicals used - POCl3, NaBH4, NaH, 80 % solution of propargyl bromide in PhMe, CuSO4-5H2O - were purchased from Sigma-Aldrich (St. Louis, MO, USA) or Alfa Aesar (GmbH, Karlsruhe, Germany). Solvents (dichloromethane, acetonitrile, DMF, MeOH, i-propanol) were purified by standard methods and distilled in a stream of argon just before use.
(1S,4aR,5S,8aR)-Methyl-5-(2-{5-formyl-2-[(prop-2-yn-1-yloxy) methyl]furan-3-yl}ethyl)-1,4a-dimethyl-6-methylenedecahydro-naphthalene-1-carboxylate (8). Compound 3 (1.00 g, 2.51 mmol) was dissolved in 15 mL of dimethylformamide, phosphoryl chloride (0.45 mL, 5.02 mmol) was added dropwise under stirring at 20 °C, and the mixture was left to stand for 48 h at 20 °C. The mixture was then poured into ice water (40 mL), a saturated aqueous solution of sodium acetate (20 mL) was added, the organic phase was separated, and the aqueous phase was extracted with chloroform (3x30 mL). The combined extracts were washed with 5 % aqueous solution of sodium carbonate (3x30 mL), dried over MgSO4, filtered and evaporated under reduced pressure. The residue was subjected to chromatography on silica gel (petroleum ether-diethyl ether, 4:1) to isolate 0.98 g (100 %) of compound 8 as an oily substance. Mass spectrum, m/z (Irel, %): 426 (7.8), 358 (21), 357 (87), 325 (11), 311 (13), 310 (19), 297 (36), 189 (28), 187 (10), 181 (11), 175 (17), 161 (10), 149 (16), 133 (12), 123 (13), 122 (11), 121 (100), 199 (19), 109 (16), 107 (27), 105 (20), 95 (15), 93 (25), 91 (30), 81 (32), 79 (21), 77 (13), 67 (15), 55 (17), 41 (18). MS (EI, 70 eV) found: 426.2403. C26H34O5. calcd. 426.2401. UV (EtOH) Xmax nm (lge): 289 (4.04). IR v cm-1: 669 w, 756 m, 891 w, 988 w, 1028w, 1078 m, 1155 s, 1229 m, 1317 w, 1352 w, 1381 w, 1447 m, 1466 m, 1528 m, 1645 w, 1684 w, 1720 s, 2118 m, 2847 m, 2872 m, 2945 s, 3078 w, 3269 m, 3302 w, 3424 w. 1H NMR (CDCl3, 298 K) SH ppm: 9.55 (1H, s, CHO), 7.06 (1H, s, C14H), 4.87 (1H, s, C17H), 4.53 (1H, s, C17H), 4.50 (2H, s, CrH2), 4.13 (2H, d, J=2.4 Hz, C3H2), 3.55 (3H, s, OCH3), 2.57 (1H, m, C12H), 2.45 (1H, t, J=2.4 Hz, C5H), 2.37 (1H, t.d, J=12.4 Hz, J=3.1 Hz, C7H), 2.31 (1H, m, C12H), 2.10 (1H, d.m, J=12.9 Hz, C3H), 1.94 (1H, m, C6H), 1.67-1.85 (5H, m, CH, C2H, C6H, C7H, C"H), 1.57 (1H, m, C"H), 1.53 (1H, m, C9H), 1.44 (1H, m, C2H), 1.21 (1H, d.d, J=12.4 Hz, J=2.7 Hz, C5H), 1.12 (3H, s, C19H3), 0.96 (1H, d.t, J=13.3 Hz, J=4.0 Hz, C3H), 0.91 (1H, d.t, J=13.3 Hz, J=3.5 Hz, CH), 0.45 (3H, s, C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.9
(CHO), 177.6 (C18), 151.9 (C16)*, 151.8 (C15)*, 147.6 (C8), 127.3 (C13), 122.0 (C14), 106.5 (C17), 78.9 (C4'), 75.3 (C5'), 61.3 (C1'), 57.5 (C3'), 56.2 (C5), 54.9 (C9), 51.1 (OCH^, 44.2 (C4), 40.2 (C10), 39.0 (C1), 38.6 (C7), 38.1 (C3), 28.7 (C19), 26.2 (C6), 24.4 (C11), 22.9 (C12), 19.9 (C2), 12.6 (C20).
(1S,4aR,5S,8aR)-Methyl-5-(2-{5-(hydroxymethyl)-2-[(prop-2-yn-1-yloxy)methyl]furan-3-yl}ethyl)-1,4a-dimethyl-6-methylenedeca-hydronaphthalene-1-carboxylate (9). NaBH4 (0.89 g, 23.44 mmol) was added portion wise to a solution of aldehyde 8 (1.00 g, 2.34 mmol) in 15 mL of i-propanol under stirring at 20 °C. After stirring for 24 h at 20 °C the mixture was diluted with water, and extracted with chloroform (3x30 mL). The combined extract was washed with water (3x30 mL), dried over MgSO4, filtered and evaporated. The residue was subjected to column chromatography on silica gel (petroleum ether-diethyl ether, 2:1) to isolate 1.00 g (97 %) of compound 9 as an oily substance. [a] D + 40.39° (c 3.61; CHCl3). Mass spectrum, m/z (Irel, %): 428 (4), 372 (12), 357 (24), 341 (12), 249 (11), 193 (13), 189 (36)" 188 (10), 181 (15), 180 (14), 178 (22), 173 (15), 161 (13), 150 (24), 149 (19), 147 (10), 133 (16), 133 (11), 125 (15), 124 (45), 123 (10), 122 (13), 121 (100), 199 (22), 109 (22), 107 (31), 105 (27), 95 (20), 93 (32), 91 (32), 83 (10), 81 (44), 79 (27), 77 (17), 67 (21), 55 (27), 53 (12), 43 (15), 41 (26), 39 (15). MS (EI, 70 eV) found: 428.2551. C26H,6O5. calcd. 428.2557. UV (EtOH) Xmax nm (lge): 228 (3.84), 289 (3.31). IR (KBr) v cm-1: 667 w, 756 m, 889 w, 984 w, 1070 m, 1155 s, 1229 m, 1383 w, 1447 m, 1466 m, 1528 m, 1643 w, 1682 w, 1722 s, 1761 m, 2118 m, 2849 m, 2874 m, 2945 s, 3078 w, 3306 w, 3433 w. 1H NMR (CDCl3, 298 K) SH ppm: 6.14 (1H, s, C14H), 4.88 (1H, s, C17H), 4.56 (1H, s, C17H), 4.54 (2H, s, C1'H2), 4.44 (2H, s, C1"H2), 4.11 (2H, d, J=2.3 Hz, C3'H^), 3.59 (3H, s, OCH,), 2.52 (1H, m, C12H), 2.43 (1H, t, J=2.3 Hz, C5'H), 2.40 (1H, m, C7H), 2.25 (1H, m, C12H), 2.13 (1H, d.m, J=13.2 Hz, C3H), 1.96 (1H, m, C6H), 1.67, 1.76, 1.82, 1.88 (5H, all m, C1H, C2H, C6H, C7H, C11H), 1.57 (2H, m, C11H, C9H), 1.47 (1H, m, C2H), 1.26 (1H, d.d, J=12.4 Hz, J=2.8 Hz, C5H), 1.15 (3H, s, C19H^), 1.00 (1H, d.t, J=13.2 Hz, J=3.9 Hz, C3H), 0.96 (1H, d.t, J=14.2 Hz, J=2.7 Hz, C1H), 0.47 (3H, s, C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.6 (C18), 153.8 (C16), 147.7 (C8), 146.0 (C15), 125.9 (C13), 1095.4 (C14), 106.4 (C17), 79.4 (C4'), 74.7 (C5'), 61.1 (C1'), 57.5 (C1"), 56.6 (C3'), 56.1 (C5), 54.9 (C9), 51.0 (OCH3), 44.2 (C4), 40.1 (C10), 38.9 (C1), 38.6 (C7), 38.1 (C3), 28.7 (C19), 26.32 (C6), 24.5 (C11), 23.2 (C12), 19.8 (C2), 12.5 (C20).
By carrying out this reaction in methanol (1S,4aR,5S,8aR)-methyl 5-(2-{5-(dimethoxymethyl)-2-[(prop-2-yn-1-yloxy)methyl] furan-3-yl}ethyl)-1,4a-dimethyl-6-methylenedecahydronaphthalene-1-carboxylate (10) was obtained in the yield 98 %. Oily substance. 1H NMR (CDCl3, 298 K) SH ppm: 6.24 (1H, s, C14H), 5.32 (1H, s, CH(OCH3)2), 4.834 (1H, s, C17H), 4.53 (1H, s, C17H), 4.40 (2H, s, C1'H2), 4.05 (2H, d, J=2.2 Hz, C3 H2), 3.54 (3H, s, OCH3), 3.29 (6H, s, CH(OCH3)2), 2.49 (1H, m, C12H), 2.39 (1H, t, J=2.2 Hz, C5H), 2.35 (1H, m, C7H), 2.21 (1H, m. C12H), 2.09 (1H, d.m, J=12.6 Hz, C3H), 1.92 (1H, m, C6H), 1.65, 1.74, 1.85 (5H, all m, C1H, C2H, C6H, C7H, C11H), 1.53 (2H, m, C11H, C9H), 1.42 (1H, m, C2H), 1.21 (1H, d.d, J=12.2 Hz, J=2.7 Hz, C5H), 1.11 (3H, s, C19H3), 0.95 (1H, d.t, J=13.3 Hz, J=3.8 Hz, C3H), 0.91 (1H, d.t, J=14.2 Hz, J=3.5 Hz, C1H), 0.43 (3H, s, C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.4 (C18), 146.2 (C8), 150.3 (C16), 147.6 (C15), 125.5 (C13), 111.1 (C14), 106.3 (C17),
97.8 [CH(OCH3)2], 79.3 (C4'), 74.6 (C5'), 60.9 (C1'), 56.5 (C3'), 56.0 (C5), 54.8 (C9), 52.6, 52.7 (OCH3), 50.9 (OCH3), 44.0 (C4), 39.9 (C10),
38.9 (C1), 38.5 (C7), 37.9 (C3), 28.6 (C19), 26.1 (C6), 24.4 (C11), 23.2 (C12), 19.7 (C2), 12.4 (C20).
(1S,4aR,5S,8aR)-Methyl-5-(2-{2,5-bis[(prop-2-yn-1-yloxy) methyl]furan-3-yl}ethyl)-1,4a-dimethyl-6-methylenedecahydro-naphthalene-1-carboxylate (11). A) To a stirred solution of compound 9 (1.00 g, 2.2 mmol) in 10 mL of acetonitrile a dispersion of sodium hydride in mineral oil (0.17 g, 4.3 mmol) was added at 0 °C portion-wise. The mixture was stirred for 30 min, and a solution of propargyl bromide in toluene (0.48 mL, 4.3 mmol) was added. The reaction mixture was warmed to ambient temperature and stirred for additional 4 h, then poured on 50 g of ice, and extracted with chloroform (3x50 mL). The combined extracts were washed with water (3x50 mL), dried over
MgSO4, filtered and evaporated. The residue was subjected to column chromatography on silica gel. Eluting with a mixture of petroleum ether- diethyl ether, 10:1 gave 0.73 g (73 %) of compound 11 as an oily substance. B) To a stirred solution of compound 9 (1.00 g, 2.2 mmol) in 10 mL of DMF a dispersion of sodium hydride in mineral oil (0.17 g, 4.3 mmol) was added at 0 °C. The mixture was stirred for 30 min, and a solution of propargyl bromide in toluene (0.48 mL, 4.3 mmol) was added. The reaction mixture was warmed to ambient temperature and stirred for additional 4 h then poured on 50 g of ice, and extracted with chloroform (3x50 mL). The combined extracts were washed with water (7x50 mL), dried over MgSO4 and evaporated. By column chro-matography of the residue on silica gel (petroleum ether-diethyl ether, 10:1 as an eluent) compounds 11 (0.37 g, yield 34 %) and 12 (0.24 g, yield 23 %) were successively isolated.
Compound 11. [a]D + 16.00° (c 0.20; CHCl3). Mass spectrum, m/z (Irel, %): 466 (5), 411 (18), 397 (26), 341 (37), 231 (23), 218 (16), 216 (29), 189 (27), 181 (14), 173 (20), 162 (40), 161 (14), 149 (16), 133 (18), 131 (14), 121 (100), 119 (23), 117 (13), 109 (26), 107 (33), 105 (32), 97 (15), 95 (26), 93 (31), 91 (38), 85 (41), 83 (64), 81 (46), 79 (28), 77 (19), 71 (14), 69 (23), 67 (23), 57 (20), 55 (34), 53 (13), 46 (16), 43 (19), 41 (40), 39 (35). MS (EI, 70 eV) found: 466.2711. CTOH A. calcd. 466.2714. UV (EtOH) I nm
29 38 5 v ! max
(lge): 230 (4.00). IR (KBr) v cm-1: 635 w, 671 w, 822 m, 889 w, 988 w, 1030 w, 1074 m, 1155 s, 1229 m, 1352 w, 1383 w, 1445 m, 1464 m, 1643 w, 1684 w, 1722 s, 1761 m, 2116 m, 2849 m, 2945 s, 3078 w, 3292 w. 1H NMR (CDCl3, 298 K) SH ppm: 6.20 (1H, s, C14H), 4.86 (1H, s, C17H), 4.54 (1H, s, C17H), 4.47 (2H, s, C1'H2)*,
4.42 (2H, s, CrH2)*, 4.12 (2H, d, J=2.4 Hz, C3'H2)**, 4.08 (2H, d, J=2.4 Hz, C3"H2)**, 3.56 (3H, s, OCH3), 2.50 (1H, m, C12H),
2.43 (1H, t, J=2.4 Hz, C5H)*, 2.41 (1H, t, J=2.4 Hz, C5"H)*, 2.37 (1H, m, C7H), 2.24 (1H, m, C12H), 2.11 (1H, d.m, J=12.4 Hz, C3H), 1.93 (1H, m, C6H), 1.65, 1.74, 1.84 (5H, all m, C1H, C2H, C6H, C7H, C11H), 1.55 (2H, m, C11H, C9H), 1.45 (1H, m, C2H), 1.23 (1H, d.d, J=12.4 Hz, J=3.0 Hz, C5H), 1.13 (3H, s, C19H3), 0.98 (1H, d.t, J=13.2 Hz, J=4.0 Hz, C3H), 0.93 (1H, d.t, J=13.4 Hz, J=3.8 Hz, C1H), 0.45 (3H, s, C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.6 (C18), 150.4 (C16), 147.7 (C8), 146.8 (C15), 125.8 (C13), 111.8 (C14), 106.4 (C17), 79.4 (C4')*, 79.2 (C4")*, 74.8 (C5')**, 74.6 (C5")**, 63.2 (C1')*, 61.1 (C1")*, 56.8 (C3')**, 56.7 (C3')**, 56.1 (C5), 54.9 (C9), 51.0 (OCH3), 44.2 (C4), 40.0 (C10), 38.9 (C1), 38.6 (C7), 38.0 (C3), 28.7 (C19), 26.2 (C6), 24.5 (C11), 23.2 (C12), 19.8 (C2), 12.5 (C20).
(1S,4aR, 5S, 8aR) -Methyl-5-(2-{5-[(formyloxy)methyl)-2-((prop-2-yn-1-yloxy)methyl]furan-3-yl}ethyl)-1,4a-dimethyl-6-methylenedecahydronaphthalene-1-carboxylate (12). Mass spectrum, m/z (Irel, %): 456 (1), 357 (16), 189 (31), 181 (16), 173 (14), 161 (15), 133 (16), 121 (100), 119 (22), 109 (23), 107 (33), 105 (26), 95 (18), 93 (27), 91 (28), 81 (37), 79 (24), 67 (16), 55 (21), 41 (24), 39 (16). MS (EI, 70 eV) found: 456.2507. calcd. for C27H36O6. 456.2506. UV (EtOH) Xmax nm (lge): 228 (2.98), 284 (2.28). IR (KBr) v cm-1: 667 w, 756 m, "891 w, 934 w, 986 w, 1030 m, 1074 m, 1155 s, 1228 m, 1360 m, 1383 w, 1447 m, 1464 m, 1645 w, 1722 s, 1761 m, 2849 m, 2874 m, 2946 s, 3290 w, 3429 w. 1H NMR (CDCl3, 298 K) SH ppm: 8.06 (1H, s, CH2OCHO), 6.28 (1H, s, C14H), 5.07 (2H, s, CH2OCHO), 4.88 (1H, s, C17H), 4.55 (1H, s, C17H), 4.44 (2H, s, C1'H2), 4.12 (1H, d, J=2.3 Hz, C3 H), 4.10 (1H, d, J=2.3 Hz, C3 H), 3.58 (3H, s, OCH3), 2.51 (1H, m, C12H), 2.43 (1H, t, J=2.4 Hz, C5H), 2.40 (1H, m, C7H), 2.25 (1H, m, C12H), 2.13 (1H, d.m, J=12.6 Hz, C3H), 1.95 (1H, m, C6H), 1.67, 1.74, 1.78, 1.85 (5H, all m, C1H, C2H, C6H, C7H, C11H), 1.58 (2H, m, C11H, C9H), 1.49 (1H, m, C2H), 1.25 (1H, d.d, J=12.1 Hz, J=2.5 Hz, C5H), 1.15 (3H, s, C19H3), 0.99 (1H, d.t, J=13.4 Hz, J=4.3 Hz, C3H), 0.95 (1H, d.t, J=13.9 Hz, J=4.0 Hz, C1H), 0.47 (3H, s, C20H3). 13C NMR (CDCl3, 298 K) 5C ppm: 177.6 (C18), 160.4 (CHO), 148.2 (C16), 147.8 (C8), 147.3 (C15), 12(3.1 (C13), 112.8 (C14), 106.4 (C17), 79.3 (C4'), 74.8 (C5'), 61.1 (C1'), 57.5 (CH2), 56.9 (C3'), 56.1 (C5), 54.9 (C9), 51.1 (OCH3), 44.2 (C4), 40.1 (C10), 39.0 (C1), 38.6 (C7), 38.1 (C3), 28.7 (C19), 26.2 (C6), 24.6 (C11), 23.2 (C12), 19.9 (C2), 12.6 (C20).
Reaction of methyl ester (15,16-((prop-2-yn-1-yloxy) methyl)-15,16-epoxy-8(9),13(16),14-labdatrienoate (11) with 1,5-
diazidopentane (4). A) A solution of the diacetylene 11 (0.50 g, 1.07 mmol) in CH2Cl2 (20 mL) and a solution of CuSO4-5H2O (0.11 g, 0.43 mmol) in water (0.5 mL), and sodium ascorbate (0.21 g, 1.07 mmol) in water (0.5 mL) were mixed, and the 1,5-diazidopentane 4 (0.17 g, 1.07 mmol) was added with stirring at ambient temperature. The temperature was raised to 40 °C and stirring was continued for 10 h. The cooled mixture was diluted with water (10 mL), the organic phase was separated, washed with water (3x50 mL), dried over MgSO4 and filtered. The solvent was evaporated, the residue was subjected to column chromatography on silica gel (eluent chloroform-methanol, 50:1) to isolate 0.058 g (7 %) of diazide 13, 0.086 g (13 %) of macroheterocyclic compound 14, 0.279 g (42%) of cyclic dimer 15 and 0.133 g (20 %) of cyclic trimer 16. B) A solution of the diacetylene 11 (0.50 g, 1.07 mmol) in CH2Cl2 (107 ml) and a solution of CuSO4-5H2O (0.11 g, 0.43 mmol) in water (0.5 mL), and sodium ascorbate (0.21 g, 1.07 mmol) in water (0.5 mL) were mixed, and the 1,5-diazidopentane 4 (0.17 g, 1.07 mmol) was added with stirring at ambient temperature. The temperature was raised to 40 °C and stirring was continued for 90 h. The cooled mixture was diluted with water (10 mL), the organic phase was separated, washed with water (3x50 mL), dried over MgSO4, filtered and evaporated. Column chromatography on silica gel (eluent chloroform-methanol, 50:1) gave 0.452 g (68 %) of compound 14 and 0.08 g (12 %) of compound 15.
(1S,4aR,5S,8aR)-Methyl-5-{2-[2,5-bi{[(1-(5-azidopentyl)-1H-1,2,3-triazol-4-yl]methoxy}methyl)furan-3-yl]ethyl}-1,4a-dimethyl-6-methylenedecahydronaphthalene-1-carboxylate (13), oily substance. [a]D + 18.45° (c 1.03; CHCl3). Found: C 60.77, H 7.34, N 20.78%. C39H58N12O5. requires C 60.44, H 7.54, N 21.69 %. UV (EtOH) Xmax nm (lge): 216 (4.14), 283 (3.33). IR (KBr) v cm-1: 1049 m, 1093 m, 1136 s, 1155 m, 1229 m, 1333 m, 1358 m, 1379 w, 1452 m, 1464 m, 1645 w, 1681 w, 1720 s, 1759 m, 2097 s, 2849 m, 2870 s, 2943 s, 3140 s, 3327 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.54 (1H, s, C5"H)*, 7.52 (1H, s, C5'H)*, 6.21 (1H, s, C14H), 4.85 (1H, s, C17H), 4.65 (2H, s, C4"CH2)*, 4.61 (2H, s, C4'CH2)*, 4.53 (1H, s, C17H), 4.46 (2H, s, C16CH2)*, 4.42 (2H, s, C15CH2)*, 4.32 (2H, d.d, J=7.9 Hz, J=4.7 Hz, CH2№)**, 4.33 (2H, d.d, J=7.9 Hz, J=4.7 Hz, CH2№")**, 3.58 (3H, s, OCH3), 3.25 (4H, t, J=6.8 Hz, 2CH2N3), 2.60 (1H, m, C12H), 2.37 (1H, d.t, J=12.8 Hz, J=2.7 Hz, C7H), 2.21 (1H, m, C12H), 2.11 (1H, d.m, J=12.8 Hz, C3H), 1.91 (5H, m, CH2CH2Nr, CH2CH2N1-, C6H), 1.85 (1H, d.d, J=12.8 Hz, J=4.3 Hz, C7H), 1.75 (2H, m, C2H, C6H), 1.67 (1H, m, C1H), 1.60 (5H, m, 2CH2CH2N3, C11H), 1.56 (1H, m, C9H), 1.53 (1H, m, C11H), 1.45 (1H, m, C2H), 1.38 (4H, m, 2CH2), 1.24 (1H, d.d, J=12.8 Hz, J=3.2 Hz, C5H), 1.14 (3H, s, C19H3), 0.98 (1H, d.t, J=13.6 Hz, J=4.0 Hz, C3H), 0.95 (1H, d.t, J=13.3 Hz, J=4.7 Hz, C1H), 0.45 (3H, s, C20H3). 13C NMR (CDCl3, 298 K) 5C ppm: 177.6 (C18), 150.7 (C16), 147.9 (C8), 147.2 (C15), 145.0 (C4")*, 144.9 (C4')*, 125.5 (C13), 122.5 (C5")*, 122.4 (C5')*, 111.6 (C14), 106.3 (C17), 64.3 (CH2C16), 63.5 (CH2C4")*, 63.4 (CH2C4')*, 62.3 (CH2C15), 56.1 (C5), 55.0 (C9), 51.1 (OCH3), 51.0 (2CH2N3), 49.9 (CH2Nr, CH2№"), 44.2 (C4), 40.1 (C10), 338.9 (C1), 38.6 (C7), 38.1 (C3), 29.8 (CH2CH2Nr, CH2CH2Nr"), 28.7 (C19), 23.7 (2CH2CH2N3), 26.2 (C6), 24.6 (C11), 23.7 (2CH2), 23.3 (C12), 19.9 (C2), 12.6 (C20).
(1S, 4 aR, 5S, 8aR)-Methyl-5-(2-(3,10,25-trioxa-13,14,15, 21,22,23-hexaazatetracyclo[19.2.1.158.11215]hexacosa-1(24),5,7, 12(26),13,22-hexaen-6-yl)ethyl)-1,4a-dimethyl-6-methylenedeca-hydronaphthalene-1-carboxylate (14), oily substance. [a]D+31.25° (c 0.58; CHCl3). Found: C 65.51, H 7.62, N 12.99%. [M] 639. C34H48N6O5. requires C 65.78, H 7.79, N 13.54%. [M] 620. UV (EtOH) Xmax nm (lge): 216 (4.08), 282 (3.38). IR (KBr) v cm-1: 754 w, 77Tw, 822 w, 891 w, 986 w, 1049 m, 1067 m, 1092 m, 1155 m, 1229 m, 1333 w, 1362 w, 1383 w, 1449 m, 1464 m, 1531 w, 1547 w, 1654 w, 1720 s, 2870 m, 2945 s, 3080 s, 3140 s, 3400 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.38 (1H, s, C25H)*, 7.37 (1H, s, C24H)*, 6.23 (1H, s, C7H), 4.90 (1H, s, C11'H), 4.59 (2H, s, C11H2)*, 4.58 (1H, s, C11'H), 4.54 (2H, s, C2H2)*, 4.48 (2H, s, C9H2), 4.44 (2H, s, C4H2), 4.31 (4H, t, J=6.0 Hz, C16H2, C20H2), 3.59 (3H, s,
OCH3), 2.53 (1H, m, C10'H), 2.41 (1H, d.m, J=11.5 Hz, C7'H), 2.25 (1H, m, C10'H), 2.13 (1H, d.m, J=13.2 Hz, C2H), 1.68-1.98 (10H, m, C9'H, C4'H, C3'H, C8'H, C7'H, C8'H, C17H2, C19H2), 1.58 (1H, m, C5'H), 1.57 (1H, m, C9'H), 1.48 (1H, m, C3'H), 1.19, 1.22 (2H, all m, C18H2), 1.26 (1H, d.d, J=12.2 Hz, J=2.8 Hz, C8a'H), 1.15 (3H, s, C13H3), 0.99 (1H, d.t, J=13.3 Hz, J=4.0 Hz, C2H), 0.96 (1H, d.t, J=11.0 Hz, J=2.4 Hz, C4'H), 0.48 (3H, s, C14'H3). 13C NMR (CDCl3, 298 K) 5C ppm: 177.5 (C12), 150.4 (C8), 147.6 (C6), 146.8 (C53, 144.9 (C1)*, 144.9 (C12)*, 125.2 (C6), 122.5 (C24, C25), 111.5 (C7), 106.2 (C11'), 63.7 (C9), 62.5 (C11)*, 62.3 (C2)*, 61.4 (C4), 55.9 (C8a'), 54.8 (C5), 50.9 (OCH3), 49.9 (C16, C20), 44.0 (C1), 39.9 (C4a), 38.8 (C4'), 38.4 (C7'), 37.9 ( C2'), 28.7 (C19, C17), 28.5 (C13'), 26.0 (C8'), 24.4 (C9'), 23.0 (C18), 23.0 (C10'), 19.7 (C3'), 12.4 (C14').
Dimeric compound 15, oily substance. [a]D+26.41° (c 0.62; CHCL). Found: C 65.64, H 7.48, N 12.99%. [M] 1258. C^RNO,,,.
3 68 96 12 10
requires C 65.78, H 7.79, N 13.54%. [M] 1240. UV (EtOH) Xmax nm (lge): 216 (4.07), 282 (3.41). IR (KBr) v cm-1: 755 w, 777 w, 819 w,
891 w, 985 w, 1047 m, 1067 m, 1089 m, 1156 m, 1229 m, 1331 w, 1367 w, 1382 w, 1449 m, 1459 m, 1532 w, 1547 w, 1655 w, 1720 s, 2871 m, 2943 s, 3081 s, 3140 s, 3405 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.59, 7.59 (2H, all s, 2C5"H)*, 7.56, 7.57 (2H, all s, 2C5'H)*, 6.20 (2H, s, 2C14H), 4.88 (2H, s, 2C17H), 4.64 (4H, s, 2C4"CH2)*, 4.60 (4H, s, 2C4'CH2)*, 4.54 (2H, s, 2C17H), 4.47 (4H, s, 2C15CH2)*, 4.43 (4H, s, 2C16CH2)*, 4.29 (8H, t, J=7.0 Hz, 2CH2N1', 2CH2№")*, 3.59 (6H, s, 2OCH3), 2.51 (2H, m, 2C12H), 2.39 (2H, d.m, J=12.4 Hz, 2C7H), 2.23 (2H, m, 2C12H), 2.12 (2H, d.m, J=13.4 Hz, 2C3H), 1.94 (2H, m, 2C6H), 1.89 (8H, t, J=7.0 Hz, 2CH2CH2Nr, 2CH2CH2N1"), 1.84 (2H, m, 2C7H), 1.66, 1.73, 1.77 (8H, all m, 2C"H, 2CH, 2C2H, 2C6H), 1.56 (4H, m, 2C9H, 2C"H), 1.46 (2H, m, 2C2H), 1.30 (4H, m, 2CH2), 1.25 (2H, d.d, J=12.9 Hz, J=3.0 Hz, 2C5H), 1.14 (6H, s, 2C19H3), 0.99 (2H, d.t, J=13.4 Hz, J=4.0 Hz, 2C3H), 0.95 (2H, d.t, J=12.6 Hz, J=3.8 Hz, 2CH), 0.46 (6H, s, 2C20H3). 13C NMR (CDCl3, 298 K) 5C ppm: 177.5 (2C18), 150.6 (2C15), 147.7 (2C8), 146.9 (2C163, 144.8 (2C4')*, 144.6 (C4")*, 125.3 (s, 2C13), 122.6 (2C5")*, 122.4 (2C5')*, 111.5 (2C14), 106.2 (2C17), 64.2 (2CH2C15), 63.2 (2CH2C4')*, 63.1 (2CH2C4")*, 62.1 (2CH2C16), 55.9 (2C5), 54.8 (2C9), 50.9 (2OCH3), 49.6 (2CH2N1', 2CH2Nr"), 44.0 (2C4), 39.9 (2C10), 38.8 (2C1), 338.5 (2C7), 37.29 (2C3), 229.4 (6CH2), 28.6 (2C19), 26.0 (2C6), 24.4 (2C11), 23.1 (2C12), 19.7 (2C2), 12.4 (2C20).
Trimeric compound 16, oily substance. [a]D + 26.41° (c 0.62; CHCL). Found: C 65.63, H 7.85, N 13.28%. [M] 1774. C,„,H N O,<
3 102 144 18 15
requires C 65.78, H 7.79, N 13.54%. [M] 1860. UV (EtOH) Xmax nm (lge): 216 (4.07), 282 (3.41). IR (KBr) v cm-1: 756 w, 777 w, 821 w,
892 w, 985 w, 1049 m, 1066 m, 1089 m, 1155 m, 1228 m, 1332 w, 1366 w, 1382 w, 1449 m, 1459 m, 1533 w, 1548 w, 1654 w, 1720 s, 2871 m, 2942 s, 3082 s, 3139 s, 3405 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.55 (3H, s, 3C5"H)*, 7.52 (3H, s, 3C5'H)*, 6.21 (3H, s, 3C14H), 4.85 (3H, s, 3C17H), 4.63 (6H, s, 3C4"CH2)*, 4.59 (6H, s, 3C4'CH2)*, 4.52 (3H, s, 3C17H), 4.46 (6H, s, 3C15CH2)*, 4.42 (6H, s, 3C16CH2)*, 4.29 (12H, t, J=5.6 Hz, 3CH2Nr, 3CH2Nr)*, 3.57 (9H, s, 3OCH3), 2.50 (3H, m, 3C12H), 2.37 (3H, d.m, J=11.6 Hz, 3C7H), 2.21 (3H, m, 3C12H), 2.11 (3H, d.m, J=12.9 Hz, 3C3H), 1.90 (15H, m, 3CH2CH2Nr, 3CH2CH2№", 3C6H), 1.81 (3H, m, 3C7H), 1.68, 1.72, 1.75 (12H, all m, 3C"H, 3CH, 3C2H, 3C6H), 1.55 (3H, m, 3C9H), 1.52 (3H, m, 3C"H), 1.46 (3H, m, 3C2H), 1.32 (6H, m, 3CH2), 1.24 (3H, d.d, J=12.1 Hz, J=2.7 Hz, 3C5H), 1.13 (9H, s, 3C19H3), 0.98 (3H, d.t, J=13.4 Hz, J=3.8 Hz, 3C3H), 0.95 (3H, d.t, J=13.4 Hz, J=3.0 Hz, 3CH), 0.45 (9H, s, 3C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.7 (3C18), 150.8 (3C15), 147.9 (3C8), 147.2 (3C163, 145.0 (3C4')*, 144.9 (3C4")*, 125.5 (3C13), 122.2, 122.3 (3C5")*, 122.0, 122.1 (3C5')*, 111.7 (3C14), 106.4 (3C17), 64.4 (3CH2C15), 63.4 (3CH2C4")*, 63.3 (3CH2C4')*, 62.3 (3CH2C16), 56.1 (3C5), 55.0 (3C9), 51.1 (3OCH3), 49.8 (3CH2N1', 3CH2Nr), 4 4.2 (3C4), 40.1 (3C10), 39.0 ( 3C1), 38.6 (3C7), 38.1 (3C3), 29.6 (9CH2), 28.7 (3C19), 26.2 (3C6), 24.6 (3C11), 23.3 (3C12), 19.9 (3C2), 12.6 (3C20).
Reaction of dialkynyl labdatrienoate 11 with 1,10-diazido-decane (5). Diazide 5 (0.24 g, 1.07 mmol), was added to a mixture of a solution of compound 11 (0.50 g, 1.07 mmol) in dichloromethane
(107 mL), a solution of CuSO4-5H2O (0.11 g, 0.43 mmol) in H2O (0.5 mL) and a solution of sodium ascorbate (0.21 g, 1.07 mmol) in H2O (0.5 mL) with stirring. The temperature was raised to 40 °C and stirring was continued for 90 h. The cooled mixture was diluted with water (10 mL), the organic phase was separated, washed with water (3x50 mL), and dried over MgSO4. The solvent was evaporated, the residue was subjected to chromatography on silica gel (eluent chloroform-methanol, 100:2) to isolate 0.394 g (53 %) of compound 17 and 0.220 g (30 %) of dimeric compound 18.
(1S, 4aR, 5S, 8aR) -Methyl-5-(2-{3,10,30-trioxa-13,14,15,26, 27,28-hexaazatetracyclo[24.2.1.15-8.112- 15]heptriaconta-1 (29),5,7, 12(31),13,27-hexaen-6-yl}ethyl)-1,4a-dimethyl-6-methylenedeca-hydronaphthalene-1-carboxylate (17), oily substance. Found: C 67.48, H 8.54, N 11.78%. [M] 720. C39H58N6O5. requires C 67.80, H 8.46, N 12.16%. [M] 691. UV (EtOH) Xmx nm (lge): 221 (4.09), 285 (3.11). IR (KBr) v cm-1: 667 w, 754 w, 822 w, 891 w, 922 w, 964 w, 1051 m, 1072 m, 1153 m, 1229 m, 1333 w, 1360 w, 1449 m, 1464 m, 1558 m, 1643 w, 1682 w, 1720 s, 2855 m, 2930 m, 3078 s, 3136 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.55 (1H, s, C30H)*, 7.52 (1H, s, C29H)*, 6.21 (1H, s, C7H), 4.88 (1H, s, C11'H), 4.58 (2H, d, J=1.6 Hz, C2H2)*, 4.61 (2H, d, J=1.6 Hz, C11H2)*, 4.54 (1H, s, C11H), 4.46 (2H, s, C9H2), 4.42 (2H, s, C4H2), 4.30 (4H, t, J=6.4 Hz, C16H2, C25H2, J 6.4), 3.57 (3H, s, OCH3), 2.51 (1H, m, C10'H), 2.38 (1H, d.m, J=11.8 Hz, C7'H), 2.23 (1H, m, C10'H), 2.11 (1H, d.m, J=12.4 Hz, C2H), 1.94 (1H, m, C8'H), 1.86 (5H, m, C7'H, C17H2, C24H2), 1.76 (1H, m, C8'H), 1.73 (2H, m, C4'H, C3'H), 1.67 (1H, m, C9'H), 1.56 (1H, m, C5'H), 1.54 (1H, m, C9'H), 1.45 (1H, m, C3'H), 1.20 (13H, s, C8a'H, C18H2, C19H2, C20H2, C21H2, C22H2, C23H2), 1.13 (3H, s, C13'H3), 0.97 (2H, m, C4'H, C2'H), 0.46 (3H, s, C14 H3)2 13C NMR (CDCl3, 298 K) 5C ppm: 177.6 (C12'), 150.7 (C8), 147.8 (C6'), 147.2 (C5), 144.8, 144.6 (C1, C12), 125.4 (C6), 122.5 (C29, C30), 111.6 (C7), 106.3 (C11'), 64.5 (C9), 63.9, 63.8 (C2, C11), 62.3 (C4), 56.0 (C8a), 54.9 (C5'), 51.0 (OCH3), 50.2 (C16, C25), 44.2 (C1'), 40.1 (C4a'), 38.9 (C4'), 38.6 (C7'), 38.0 (C2'), 29.8 (C19, C22), 28.7 (C13'), 28.3 (C18, C23), 28.2 (C20, C21), 26.2 (C8'), 25.7 (C17, C24), 24.5 (C9'), 23.3 (C10'), 19.8 (C3'), 12.5 (C14').
Dimeric compound 18, oily substance. Found: C 67.91, H 8.54, N 13.22%. [M] 1450. C78H116N12O10. requires C 67.80, H 8.46, N 12.16%. [M] 1382. LTV (EtOH) Xmax nm (lge): 220 (4.33), 285 (3.35). IR (KBr) v cm-1: 665 w, 756™, 820 w, 891 w, 922 w, 988 w, 1051 m, 1074 m, 1092 m, 1136 m, 1153 m, 1229 m, 1333 w, 1362 w, 1450 m, 1464 m, 1549 m, 1643 w, 1682 w, 1722 s, 1765 w, 2855 m, 2930 m, 3076 s, 3136 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.54 (2H, s, 2C5"H)*, 7.51 (2H, s, 2C5'H)*, 6.21 (2H, s, 2C14H), 4.85 (2H, s, 2C17H), 4.65 (4H, s, 2C4"CH2)*, 4.61 (4H, s, 2C4'CH2)*, 4.53 (2H, s, 2C17H), 4.46 (4H, s, 2C15CH2), 4.42 (4H, s, 2C16CH2), 4.30 (4H, t, J=6.9 Hz, 2CH 2N1')*, 4.30 (4H, t, J=6.9 Hz, 2CH2№")*, 3.58 (6H, s, 2OCH3), 2.50 (2H, m, 2C12H), 2.38 (2H, d.m, J=10.4 Hz, 2C7H), 2.22 (2H, m, 2C12H), 2.12 (2H, d.m, J=12.9 Hz, 2C3H), 1.95 (2H, m, 2C6H), 1.85 (10H, m, 2C7H, 4CH2), 1.76, 1.72 (6H, all m, 2C1H, 2C2H, 2C6H), 1.65 (2H, m, 2C11H), 1.56 (4H, m, 2C9H, 2C11H), 1.46 (2H, m, 2C2H), 1.20 (26H, s, 12CH2, 2C5H), 1.14 (6H, s, 2C19H3), 0.98 (2H, d.t, J=13.2 Hz, J=4.0 Hz, 2C3H), 0.95 (2H, d.t, J=13.4 Hz, J=3.6 Hz, 2C1H), 0.45 (6H, s, 2C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.7 (2C18), 150.7 (2C15), 147.8 (2C8), 147.1 (2C16), 144.9, 144.7 (2C4', C4"), 125.4 (2C13), 122.4, 122.3 (2C5', 2C5"), 111.6 (2C14), 106.3 (2C17), 64.3 (2CH2C15), 63.5, 63.3 (2CH2C4', 2CH2C4"), 62.2 (2CH2C16), 56.0 (2C5), 54.9 (2C9), 51.1 (20CH3), 50.2 (2CH2N1', 2CH2Nr"), 44.2 (2C4), 40.1 (2C10), 38.9 (2C1), 38.6 (2C7), 38.0 (2C3), 28.8 (4CH2), 29.2 (4CH2), 30.2 (4CH2), 28.7 (2C19), 26.4 (4CH2), 26.2 (2C6), 24.5 (2C11), 23.2 (2C12), 19.8 (2C2), 12.6 (2C20).
Reaction of dialkynyl labdatrienoate 11 with 1-azido-2-(2-azidoethoxy)ethane (6). 1-azido-2-(2-azidoethoxy)ethane 5 (0.17 g, 1.07 mmol) was added to a mixture of compound 11 (0.50 g, 1.07 mmol) in dichloromethane (107 mL) and solutions of CuSO4-5H2O (0.11 g, 0.43 mmol) in H2O (0.5 mL) and sodium ascorbate (0.21 g, 1.07 mmol) in H2O (0.5 mL) with stirring. The temperature was raised to 40 °C and stirring was continued for 90 h. The cooled
mixture was diluted with water (10 mL), the organic phase was separated, washed with water (3x50 mL), dried over MgSO4 and filtered. The solvent was evaporated, the residue was subjected to chromatography on silica gel (eluent chloroform-methanol, 50:1) to isolate 0.255 g (38 %) of compound 19, 0.154 g (23 %) of dimeric compound 20 and 0.174 g (26 %) of trimeric compound 21.
(1S,4aR,5S,8aR)-Methyl-5-(2-{3,10,18,25-tetraoxa-13,14, 15,21,22,23-hexaazatetracyclo[19.2.1.158.11215]hexacosa-1(24), 5,7,12(26),13,22-hexaen-6-yl}ethyl)-1,4a-dimethyl-6-methylenedeca-hydronaphthalene-1-carboxylate (19), oily substance. [a]D +14.85° (c 3.07; CHCl3). Found: C 63.95, H 7.67, N 12.98%. [M] 624. C33H46N6O6. requires C 63.65, H 7.45, N 13.49%. [M] 622. UV (EtOH) J,maxnm (lge): 221 (4.04), 280 (2.61). IR (KBr) v cm-1: 754 w, 820 w, 891 w, 955 w, 988 w, 1049 m, 1072 m, 1109 m, 1134 m, 1153 m, 1229 m, 1333 w, 1360 w, 1450 m, 1464 m, 1558 w, 1643 w, 1720 s, 2855 m, 2870 m, 2945 s, 3078 s, 3142 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.47 (1H, s, C25H)*, 7.46 (1H, s, C24H)*, 6.23 (1H, s, C7H), 4.89 (1H, s, C11'H), 4.58 (2H, s, C11H2)*, 4.55 (1H, s, C11'H), 4.51 (2H, s, C2H2)*, 4.49 (2H, d, J=3.1 Hz, C9H2), 4.47 (4H, m, C16H2, C20H2), 4.44 (2H, s, C4H2), 3.78 (4H, q, J=4.7 Hz, C17H2, C19H2), 3.57 (3H, s, OCH3), 2.52 (1H, m, C10'H), 2.39 (1H, t.d, J=12.8 Hz, J=3.2 Hz, C7'H), 2.24 (1H, m, C10'H), 2.11 (1H, d.m, J=13.0 Hz, C2H), 1.95 (1H, d.m, J=13.0 Hz, C8'H), 1.86 (1H, d.t, J=12.8 Hz, J=4.7 Hz, C7'H), 1.76 (1H, m, C8 H), 1.74 (2H, m, C4'H, C3'H), 1.67 (1H, m, C9'H), 1.57 (1H, m, C5'H), 1.54 (1H, m, C9'H), 1.46 (1H, m, C3'H), 1.24 (1H, d.d, J=12.7 Hz, J=3.2 Hz, C8aH), 1.13 (3H, s, C13'H3), 0.98 (1H, d.t, J=13.0 Hz, J=3.8 Hz, C2'H), 0.95 (1H, d.t, J=13.0 Hz, J=3.0 Hz, C4'H), 0.46 (3H, s, C14 H3). 13C NMR (CDCl3, 298 K) 5C ppm: 177.6 (C12), 150.7 (C8), 147.7 (C6), 147.2 (C5), 144.9 (C12, C1), 125.4 (C6), 123.5 (C24)*, 123.6 (C25)*, 111.8 (C7), 106.4 (C11'), 69.5 (C19, C17), 63.8 (C9), 62.6 (C11)*, 62.3 (C2)*, 61.4 (C4), 56.1 (C8a'), 54.9 (C5'), 51.1 (OCH3), 50.3 (C16, C20), 44.2 (C1'), 40.1 (C4a'), 38.9 (C4'), 38.6 (C7'), 38.1 (C3'), 28.7 (C13'), 26.2 (C8'), 24.6 (C9'), 23.2 (C10), 19.8 (C3'), 12.6 (C14').
Dimeric compound 20, oily substance. [a]D +30.53° (c 0.57; CHCL). Found: C 63.81, H 7.67, N 13.58%. [M 1302. ^„HNO,.
3 66 92 12 12
requires C 63.65, H 7.45, N 13.49%. [M] 1244. UV (EtOH) Xmax nm (lge): 222 (4.45), 280 (3.31). IR (KBr) v cm-1: 754 w, 818 w, 8max1 w, 920 w, 988 w, 1049 m, 1069 m, 1134 m, 1151 m, 1227 m, 1333 w, 1360 w, 1449 m, 1462 m, 1547 m, 1558 w, 1643 w, 1720 s, 1763 w, 2855 m, 2870 m, 2932 m, 2945 s, 3078 s, 3144 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.42 (2H, s, 2C5"H)*, 7.41, 7.40 (2H, all s, 2C5'H)*,
6.18 (2H, s, 2C14H), 4.85 (2H, s, 2C17H), 4.58 (4H, d, J=5.4 Hz, 2C4"CH2)*, 4.56 (4H, d, J=3.8 Hz, 2C4 CH2)*, 4.51 (2H, s, 2C17H), 4.43 (4H, d, J=3.2 Hz, 2C15CH2)*, 4.40 (8H, m, 2CH2N1', 2CH2N1"), 4.39 (4H, s, 2C16CH2), 3.73 (8H, t, J=4.6 Hz, 4CH2O), 3.57 (6H, s, 2OCH3), 2.48 (2H, m, 2C12H), 2.37 (2H, d.m, J=11.8 Hz, 2C7H),
2.19 (2H, m, 2C12H), 2.10 (2H, d.m, J=13.4 Hz, 2C3H), 1.95 (2H, d.m, J=12.0 Hz, 2C6H), 1.81 (2H, d.t, J=14.0 Hz, J=3.2 Hz, 2C7H), 1.71, 1.75 (6H, all m, 2C1H, 2C2H, 2C6H), 1.63 (2H, m, 2C11H), 1.54 (4H, m, 2C9H, 2C11H), 1.46 (2H, m, 2C2H), 1.23 (2H, d.d, J=12.4 Hz, J=2.7 Hz, 2C5H), 1.13 (6H, s, 2C19H3), 0.97 (2H, d.t, J=13.4 Hz, J=4.3 Hz, 2C3H), 0.94 (2H, d.t, J=13.4 Hz, J=3.8 Hz, 2C1H), 0.44 (6H, s, 2C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.6 (2C18), 150.70, 150.72 (2C15), 147.7 (2C8), 147.08, 147.11 (2C16), 144.7 (2C4')*, 144.56, 144.59 (C4")*, 125.29, 125.32 (2C13), 123.90, 123.93 (2C5")*, 123.80, 123.83 (2C5')*, 111.53, 111.56 (2C14), 106.3 (2C17), 69.10, 69.12 (2CH2O), 69.1 (2CH2O), 64.26, 64.30 (2CH2C15), 63.3 (2CH2C4')*, 63.2 (2CH2C4")*, 62.1 (2CH2C16), 55.9 (2C5), 54.9 (2C9),
51.1 (2OCH3), 49.9 (2CH2N1', 2CH2№"),44.1 (2C4), 40.1 (2C10), 38.9 (2C1), 38.6 C2C7), 37.9 (2C3), 28.1 (2C19), 26.1 (2C6), 24.5 (2C11),
23.2 (2C12), 19.8 (2C2), 12.5 (2C20).
Trimeric compound 21, oily substance. [a]D+25.48° (c 2.74; CHCL). Found: C 63.48, H 7.75, N 13.66%. [M 1788. CH, N O .
3' L J 99 138 18 18
requires C 63.65, H 7.45, N 13.49%. [M] 1866. UV (EtOH) Xmax nm (lge): 221 (4.44), 280 (3.35). IR (KBr) v cm-1: 756 w, 820 w, 893^, 922 w, 988 w, 1051 m, 1069 m, 1134 m, 1151 m, 1229 m, 1335 w, 1360 w, 1450 m, 1464 m, 1643 w, 1664 w, 1720 s, 1761 w, 2856 m, 2870 m, 2930 m, 2947 s, 3078 s, 3142 s. 1H NMR (CDCl 298 K) 5„ ppm: 7.53
(6Н, s, 3С5'Н, 3С5"Н), 6.19 (3Н, s, 3С14Н), 4.83 (3Н, s, 3С17Н), 4.57 (6Н, d, J=3.8 Hz, 3C4"CH2)*, 4.55 (6Н, d, J=3.8 Hz, ЗС4'СН2)*, 4.50 (3Н, s, 3C17H), 4.42 (18Н2 s, 3СЩФ', 3CH2N1", 3СН2С15), 4.39 (6Н, s, ЗС16СН2), 3.74 (12Н, s, 6СН2О), 3.55 (9Н, s, 3OCH,), 2.47 (3Н, m, ЗС12Н), 2.35 (3Н, d.m, J=11.3 Hz, ЗС7Н), 2.19 (3Н, m, 3С12Н), 2.09 (3Н, d.m, J=12.9 Hz, ЗСЗН), 1.93 (3Н, d.m, J=11.8 Hz, ЗС6Н), 1.81 (3Н, d.t, J=14.5 Hz, J=3.2 Hz, ЗС7Н), 1.70, 1.73 (9Н, all m, 3C1H, ЗC2H, ЗC6H), 1.6З (3H, m, ЗС11Н), 1.53 (6Н, m, 3С11Н, 3C9H), 1.44 (3Н, m, 3С2Н), 1.23 (3Н, d.d, J=12.4 Hz, J=2.7 Hz, ЗС5Н), 1. 12 (9Н, s, 3С19Н,), 0.96 (3Н, d.t, J=12.9 Hz, J=3.2 Hz, ЗСЗН), 0.94 (3Н, d.t, J=11.8 Hz, J=3.8 Hz, ЗС1Н), 0.43 (9Н, s, 3С20Н,). 1ЗС NMR (CDCl3, 298 K) SC ppm: 177.6 (3С18), 150.6 (3С15), 147.8 (3С8), 147.0 (3С16), 144.71, 144.72, 144.6 (3С4', 3С4"), 125.4 (3С13), 12З.7, 12З.8, 12З.56, 123.59 (3С5', 3С5"), 111.6 (3С14), 106.3 (3С17), 69.2 (6СН2О), 64.2 (ЗС^С15), 6З.2, 6З.1 (ЗС^С4', ЗС^С4"), 62.1 (3СН2С16), 55.9 (3С5), 54.9 (3С9), 51.0 (3ОСНЗ), 4 9.8 (3CH2Nr, 3Œ2Nr), 44.1 (3С4), 40.0 (ЗС10), З8.9 (ЗС1), З8.6 (ЗС7), З7.9 (ЗСЗ), 28.6 (ЗС19), 26.1 (ЗС6), 24.5 (3С11), 23.2 (3С12), 19.8 (3С2), 12.5 (ЗС20).
Reaction of compound 11 with 1,2-bis(2-azidoethoxy)ethane (7). Diazide 7 (0.21 g, 1.07 mmol), was added to a mixture of a solution of compound 11 (0.50 g, 1.07 mmol) in dichloromethane (107 mL), a solution of CuSO4-5H2O (0.11 g, 0.4З mmol) in H2O (0.5 mL) and a solution of sodium ascorbate (0.21 g, 1.07 mmol) in H2O (0.5 mL) with stirring. The temperature was raised to 40 °C and stirring was continued for 90 h. The cooled mixture was diluted with water (10 mL), the organic phase was separated, washed with water (3x50 mL), dried over MgSO4 and filtered. The solvent was evaporated, the residue was subjected to column chromatography on silica gel (eluent chloroform-methanol, 50:1) to isolate 0.229 g (З2 %) of compound 22, 0.071 g (10 %) of dimeric compound 23, and 0.221 g (З1 %) of trimeric compound 24.
(1S,4aR,5S,8aR)-Methyl-5-(2-{3,10,18,21,28-pentaoxa-13,14,15,24,25,26-hexaazatetracyclo-[22.2.1.15-8.112- 15]nonacosa-1(27),5,7,12(29),13,25-hexaen-6-yl}ethyl)-1,4a-dimethyl-6-methylene decahydronaphthalene-1-carboxylate (22), oily substance. Found: С 6З.З2, H 7.88, N 13.02%. [M] 654. C)5H50N6O7. requires С 63.04, H 7.56, N 12.60. [M] 666. UV (EtOH) Xmax nm (lge): 221 (4.06), 285 (2.75). IR (KBr) v cm-1: 665 w, 754 w822 w, 89З w, 922 w, 988 w, 1051 m, 1072 m, 11З6 m, 1150 m, 1227 m, 1ЗЗЗ w, 1З58 w, 1450 m, 1464 m, 155З m, 164З w, 1682 w, 1720 s, 2870 m, 2945 m, З080 s, З142 s. 1H NMR (CDCl), 298 K) SH ppm: 7.67, 7.66 (both s, 1Н, С28Н and С27Н), 6.04 (1Н, s, С7Н), 4.87 (1Н, s, С11Н), 4.70 (2Н, s, С2Н2)*, 4.65 (2Н, s, С11Н2)*, 4.51 (1Н, s, С11'Н), 4.46 (4Н, m, С17Н2, С22Н2), 4.45 (2Н, s, С9Н2), 4.40 (2Н, s, С4Н2), З.76 (4Н, m, С16Н2, С2ЗН2), 3.57 (3Н, s, OCH3), 3.50 (4Н, s, С20Н2, С19Н2), 2.39 (2Н, m, С10'Н, С7'Н), 2.12 (2Н, m, С2'Н, С10'Н), 1.94 (1Н, d.m, J=12.1 Hz, С8Н), 1.86 (1H, d.t, J=12.1 Hz, J=4.0 Hz, С7'Н), 1.701.78 (3Н, m, С8'Н, С4'Н, СЗ'Н), 1.67 (1H, m, С9'Н), 1.60 (2Н, m, С5'Н, С9'Н), 1.45 (1Н, m, СЗ'Н), 1.21 (1Н, d.d, J=12.0 Hz, J=2.7 Hz, H8a'), 1.13 (3Н, s, С1ЗНЗ), 0.97 (1H, d.t, J=13.7 Hz, J=3.4 Hz, C2H), 0.91 (1H, d.t, J=13.7 Hz, J=4.0 Hz, C4'H), 0.44 (3Н, s, С14 Н)). 1ЗС NMR (CDCl3, 298 K) 5C ppm: 177.7 (С12'), 150.6 (С8), 147.7 (С6'), 147.1 (С5), 1444.9 (С1, С12), 125.2 (С6), 123.8, 123.7 (С28, С27), 111.4 (С7), 106.4 (С11'), 69.2 (С17, С22), 69.9 (С19, C20), 64.6 (С9), 64.1 (С11), 63.9 (С2), 62.3 (С4), 56.0 (С8!0, 54.9 (С5'), 51.1 (ОСН)), 50.0 (С16, С23), 44.2 (С1'), 40.1 (C4a'), З8.9 (С4'), З8.6 (С7'), З8.0 (С2'), 28.7 (С13'), 26.2 (С8'), 24.4 (С9'), 23.1 (С10), 19.8 (СЗ), 12.6 (С14').
Dimeric compound 23, oily substance. Found: С 62.98, H 7.82, N 12.67%. [M] 1267. C70H100N12O14. requires С 63.04, H 7.56, N 12.60%. [M] 1332. UV (EtOH) Jl^nm (lge): 221 (4.05), 285 (2.76). IR (KBr) v cm-1: 665 w, 755 w, 822 w, 894 w, 919 w, 987 w, 1052 m, 1072 m, 11З7 m, 1149 m, 1228 m, 1ЗЗ1 w, 1З54 w, 145З m, 1467 m, 155З m, 1645 w, 1720 s, 2870 m, 2946 m, З080 s, З14З s. 1H NMR (CDCl3, 298 K) SH ppm: 7.70, 7.70 (2Н, all s, 2С5"Н)*, 7.68, 7.68 (2Н, all s, 2С5'Н)*, 6.18 (2Н, s, 2С14Н), 4.87 (2Н, s, 2С17Н), 4.61 (4Н, d, J=2.0 Hz, 2С4СН2)*, 4.58 (4Н, d, J=2.0 Hz, 2С4'СН2)*, 4.53 (2Н, s, 2С17Н), 4.44 (8Н, m, 4СН20), 4.41 (4Н, s, 2С15СН2)*, 4.39 (4Н, s, 2С16СН2), 3.75 (8Н, m, 2СН2№', 2СН№"), 3.59 (6Н, s, 2OCH3), З.49
(8H, s, 20CH2CH20), 2.49 (2H, m, 2C12H), 2.39 (2H, d.m, J=11.6 Hz, 2C7H), 2.20 (2H, m, 2C12H), 2.12 (2H, d.m, J=13.2 Hz, 2C3H), 1.95 (2H, m, 2C6H), 1.82 (2H, m, J=3.2 Hz, 2C7H), 1.73-1.77 (6H, all m, 2CH, 2C2H, 2C6H), 1.67 (2H, m, 2C"H), 1.55 (4H, m, 2C9H, 2C"H), 1.49 (2H, m, 2C2H), 1.26 (2H, d.d, J=12.0 Hz, J=2.6 Hz, 2C5H), 1.15 (6H, s, 2C19H3), 0.99 (2H, d.t, J=13.0 Hz, J=3.6 Hz, 2C3H), 0.96 (2H, m, 2CH), 0.436 (6H, s, 2C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.7 (2C18), 150.7 (2C15), 147.7 (2C8), 147.13, 147.16 (2C16), 144.68, 144.72, 144.51, 144.56 (2C4', 2C4"), 125.4 (2C13), 123.9, 123.8 (2C5', 2C5"), 111.62, 111.64 (2C14), 106.4 (2C17), 70.2 (20CH2CH20), 69.3 (4CH20), 64.3, 64.4 (2CH2C15), 63.62, 63.65, 63.54, 63.57 (2CH2C4', 2CH2C4"), 62.2, 62.3 (2CH2C16), 56.1 (2C5), 55.1 (2C9), 51.1 (20CH3), 50.033, 50.05 (2CH2N1', 2CH2N1"), 44.2 (2C4), 40.2 (2C10), 39.0 (2C1), 38.7 (2C7), 38.1 (2C3), 28.8 (2C19), 26.2 (2C6), 24.6 (2C11), 23.3 (2C12), 19.9 (2C2), 12.6 (2C20).
Trimeric compound24, oily substance. Found: C 62.93, H 7.34, N 12.35%. [M] 1893. C105H150N18O21. requires C 63.04, H 7.56, N 12.60%. [M] 1998. UV (EtOH) Xmax nm (lge): 221 (4.03), 286 (2.74). IR (KBr) v cm-1: 667 w, 755 w, 822 w, 894 w, 920 w, 990 w, 1049 m, 1071 m, 1137 m, 1149 m, 1228 m, 1334 w, 1358 w, 1451 m, 1465 m, 1555 m, 1644 w, 1721 s, 2870 m, 2946 m, 3078 s, 3143 s. 1H NMR (CDCl3, 298 K) SH ppm: 7.55, 7.65, 7.67 (6H, all s, 3C5H, 3C5"H), 6.19 (3H, s, 3C14H), 4.84 (3H, s, 3C17H), 4.61 (6H, s, 3C4"CH2)*, 4.57 (6H, s, 3C4CH2)*, 4.51 (3H, s, 3C17H), 4.43 (18H, s, 3C15CH2, 6CH20), 4.39 (6H, s, 3C16CH2), 3.76 (12H, s, 3CH2N1', 3CH2№"), 3.58 (9H, s, 3OCH3), 3.49 (12H, s, 30CH2CH20), 2.47 (3H, m, 3C12H), 2.36 (3H, d.m, J=10.8 Hz, 3C7H), 2.19 (3H, m, 3C12H), 2.10 (3H, d.m, J=13.4 Hz, 3C3H), 1.94 (3H, m, 3C6H), 1.83 (3H, m, 3C7H), 1.711.78 (9H, m, 3CH, 3C2H, 3C6H), 1.65 (3H, m, 3C"H), 1.54 (6H, m, 3C9H, 3C"H), 1.45 (3H, m, 3C2H), 1.24 (3H, d.d, J=12.0 Hz, J=2.2 Hz, 3C5H), 1.13 (9H, s, 3C19H3), 0.97 (3H, d.t, J=12.9 Hz, J=3.2 Hz, 3C3H), 0.94 (3H, d.t, J=12.9 Hz, J=2.7 Hz, 3CH), 0.44 (9H, s, 3C20H3). 13C NMR (CDCl3, 298 K) SC ppm: 177.66, 177.68, 177.70 (3C18), 150.67, 150.69, 150.72 (3C15), 147.81, 147.84 (3C8), 147.05, 147.06, 147.09 (3C16), 144.7, 144.8, 144.6, 144.7 (3C4', 3C4"), 125.43, 125.45 (3C13), 123.8, 123.9, 123.6, 123.7 (3C5', 3C5"), 111.62, 111.64, 111.65 (3C14), 106.3 (3C17), 70.3 (30CH2CH20), 69.3 (6CH20), 64.26, 64.29 (3CH2C15), 63.39, 63.40, 63.42, 63.27, 63.29, 63.30 (3CH2C4', 3CH2C4"), 62.21, 62.24, 62.25 (3CH2C16), 56.0 (3C5), 55.0 (3C), 51.1 (30CH3), 50.1, 50.05 (t, 3CH2N1', 3CH2№"), 44.2 (3C4), 40.1 (3C10), 38.9 (3C1), 38.6 (3C7), 38.0 (3C3), 28.2 (3C19), 26.2 (3C6), 24.5 (3C11), 23.3 (3C12), 19.8 (3C2), 12.5 (3C20).
Results and Discussion
The synthetic route followed for the synthesis of the key compound - labdanoid diacetylenic derivatives 11 is outlined in Scheme 1. Vilsmeier-Haack formylation of compound 3 gave its 15-formyl derivative 8 which was converted to the compound 9 by treatment with sodium borohydride in i-propanol. By reduction of 8 in methanol the compound 10 was obtained exclusively. The reaction of 15-hydroxymethyl labdatrinoate 9 with propargyl bromide in DMF in the presence of sodium hydride resulted in formation of diacetylenic derivatives 11 (yield 34 %) and compound 12 (yield 23 %). Compound 11 was obtained in 75 % yield by reaction of compound 9 with propargyl bromide in acetonitrile.
The terpenoid dialkyne 11 was reacted with 1 equivalent of 1,5-diazidopentane 4 in CH2Cl2-water medium (20:1; 0.05 M solution of 11) in the presence of CuSO4 and sodium ascorbate in conditions used in our previous studies.[24] By performing the reaction at 40 °C over 10 h the full conversion of compound 11 was observed. After column chromatography on silica gel four compounds were isolated: diazide 13 (7 %), macroheterocyclic compound 14 (13 %), cyclic dimer 15 (42%) and cyclic trimer
Me02C
Me02C
10 R = CH(OCH3)2; 12 R = CH2OCHO.
Reagents and Reaction Conditions: (a): POCl3, DMF, AcONa, 20 °C, 48 h; (b): NaBH4, i-PrOH, 20 °C, 24 h; (c) BrCH2CsCH, NaH, CH.CN, 0 °C, then rt, 4 h.
Scheme 1.
16 (20 %) (Scheme 2). Dilution of the reaction mixture with methylene chloride (0.01 M solution) improved the yield of the target compound 14 to 68 %. Additionally, dimeric compound 15 was also isolated in the yield 12 %.
Reaction of dialkyne 11 (0.01 M solution in methylene chloride) with 1,10-diazidodecane (5) in the presence of CuSO, and sodium ascorbate resulted in the formation of a
mixture of compound 17 and dimeric compound 18 isolated in 53 % and 30 % yield after column chromatography.
By using of the mentioned CuAAC conditions for reacting of diterpenoid dialkyne 11 with 1-azido-2-(2-azidoethoxy)ethane 6 the compound 19 was isolated in the yield 38 % (Scheme 3). Cyclodimer 20 and cyclotrimer 21 were also isolated in the yield 22 % and 26 % respectivelly.
N=N
25(28)
X = C18H2 (4, 14, 15); CH2(19)CH2(20)CH2(21)CH2(22)CH2(23)CH2(24) (5, 17, 18)
Scheme 2.
11
X = O (6, 19, 20, 21); O(CH2)2O (7, 22, 23, 24); n = 2 (20, 23); 3 (21, 24). Scheme 3.
Comparable results were obtained in the reaction of dialkyne 11 with 1,2-bis(2-azidoethoxy)ethane (7); macro-cyclic derivatives 22, 23 and 24 were obtained in the yield of 32 %, 10 % and 31 % after column chromatography.
The composition and structure of the synthesized compounds were confirmed by IR, UV, 1H, and 13C spectroscopy, mass-spectrometry, elemental analysis data and mass-date for dimeric and trimeric compounds. The 1H and 13C NMR spectra of all synthesized compounds agree with their structure and contain the set of characteristic signals of labdanoid skeleton and the corresponding substituent. Formation of the 1,2,3-tri-azole ring in compounds 13-24 was confirmed by the NMR data. The H NMR spectra exhibited singlet signals for the H-5' proton (5=7.37-7.68 ppm). The 13C NMR signals of the C4-',5' carbon atoms were observed in the region of 144.6-145.9 ppm and 122.3-124.0 ppm, respectively. Macrocyclic 14, 19 and cyclodimeric compounds 15, 20 with a 5-membered linker between triazole rings possess greatly different in the shifts of the H-5 proton in the triazole ring. A shift around 0.2 ppm was observed for the signal of H-5 atom in the 1H NMR spectra of compound 15, 20 compared with compounds 14, 19.
Conclusions
As a result, we have elaborated bi-, tetra- and hexa-(1,2,3-triazol)containing furan bridged macrocyclic compounds using CuAAC reaction of diacetylenic derivatives of easily available methyl lambertianate with various diazides. The yield and composition of the target macrocyclic compounds were shown to be dependent on the nature of the starting diazides, better yield of bi(1,2,3-triazol)containing furan bridged macrocyclic compound being observed in the case of 1,5-diazidopentane and 1,10-diazidodecane.
Acknowledgements. This work was supported in part by the Grants Council of the president of the Russian Federation (NS-2625.2014.3) and Russian Science Foundation (Grant Nom 14-13-00822).
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Received 12.11.2014 Accepted 25.11.2014
