Note Cite This: J. Org. Chem. 2018, 83, 437−442
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Biomimetic Synthesis of Isorosmanol and Przewalskin A Zhongle Li, Xun Zhang, Zhenjie Yang, Yuhan Zhang, and Zhixiang Xie* State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. China S Supporting Information *
ABSTRACT: Przewalskin A, a novel C23 terpenoid with antiHIV-1 activity from Salvia przewalskii Maxim, was formed in 10 steps via isorosmanol from (+)-carnosic acid. The synthetic strategy was inspired primarily by the biogenetic hypothesis and was enabled by epoxidation, epoxide ring opening, and lactonization in one pot to prepare the 11,12-dimethoxy isorosmanol, and bismuthonium ylide-induced ring expansion of o-quinone to construct the 2-acyl-3-hydroxytropone.
activity with an EC50 of 40.74 μg/mL and a selectivity index (SI) of 2.19 and also exhibited cytotoxicity against C8166 with a CC50 of 89.13 μg/mL. As research continued, przewalskin B (3)6 was isolated from the acetone extract of S. przewalskii Maxim by Zhao and coworkers in 2007. Because of its specific structure with a spirocyclic enone system and α-hydroxy-β-ketone lactone moiety, and modest anti-HIV activity with an EC50 of 30.32 μg/mL, it has attracted the attention of various synthetic groups at our university. In 2011, She and Tu achieved the total synthesis of (−)- and (+)-przewalskin B, respectively.7 Three years ago, we also disclosed the total synthesis of przewalskin B.8 Herein, we report a biomimetic total synthesis of przewalskin A via isorosmanol from carnosic acid. Inspired by the structures and chemical activity of aromatic diterpenes, which had obtained previously from Salvia species, Luis and co-workers suggested a possible biogenetic pathway to this highly oxidized abietatriene diterpenes.9 As shown in Scheme 1, it may be proposed that carnosic acid (5) upon being treated with nicotinamide adenine dinucleotide (NAD+) generates 6,7-dehydrocarnosic acid (6) in vivo. The subsequent participation of singlet-state oxygen via the intermediate perepoxide (7) accounts for the products isorosmanol (8)10 and rosmanol (9)10 isolated from Salvia species.3,11 o-Quinone diterpenoids 10 and 11 could be formed from 8 and 9 by redox transformation. Zhao and co-workers postulated that przewalskin A might be biosynthetically constructed via a condensation reaction of 10 with acetoacetyl-CoA and a subsequent intramolecular aldol reaction along with an oxidation reaction.5 Similarly, salyunnanin A4h has the same subunit 2-acyl-3hydroxytropone compared to that of przewalskin A, and the same biogenetic pathway of salyunnanin A was proposed for 11.
T
he root of Salvia miltiorrhiza, one of the most commonly used traditional Chinese herbs with the Chinese name “Danshen”, has been used for the treatment of various cardiovascular diseases for hundreds of years in China.1 In recent years, Danshen has become widely accepted as a health product in the western countries because of its remarkable and reliable biological activities, especially in the treatment of cardiovascular disorders.2 Its genus, Salvia, is gaining interest in the medicinal chemistry and drug discovery community. As the characteristic components of the genus Salvia, diterpenes (mainly abietane and clerodane diterpenes) are rich and generally recognized as the active constituents with a potential ecological role.3 Specific diterpenes with 23 carbons in the skeleton derived from normal diterpenoids are rare in natural products and have been discovered in plants from the genus Salvia.3,4 Przewalskin A, a novel C23 terpenoid, was isolated by Zhao and co-workers in 2006 from Salvia przewalskii Maxim, which is a traditional Chinese herb used as the surrogate of Danshen for the treatment of various cardiovascular diseases5 (Figure 1).
Figure 1. Przewalskin A, its derivative (2), przewalskin B, and salyunnanin A.
Spectroscopic analyses revealed that its structure was featured by an unprecedented 6/6/7 carbon ring skeleton with a unique 2-acyl-3-hydroxytropone substituted with an isopropyl. The structure of 1 was confirmed by a single-crystal X-ray diffraction analysis of its PDC oxidation derivative (2).5 Bioactivity research showed that przewalskin A had moderate anti-HIV-1 © 2017 American Chemical Society
Received: September 19, 2017 Published: December 1, 2017 437
DOI: 10.1021/acs.joc.7b02369 J. Org. Chem. 2018, 83, 437−442
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reduction of an ester to a hemiacetal, followed by protection and oxidation from isorosmanol (8). The isorosmanol should be formed easily by lactonization of trans-diol 13, and subsequent deprotection. This strategy effectively avoids the formation of a five-membered ring. The key intermediate transdiol 13 would be synthesized from carnosic acid (5) via 6,7dehydrocarnosic acid derivatives 14, followed by epoxidation and epoxide ring opening. As shown in Scheme 3, we started our synthesis from the known 14 that was prepared from 5 by a literature method19,20
Scheme 1. Biogenetic Pathway Proposed for Przewalskin A and Salyunnanin A
Scheme 3. Synthesis of Isorosmanol (8)
Carnosic acid (5) is the most abundant abietane diterpene isolated from most Salvia species12 and has been increasingly exploited within the food, nutritional health, and cosmetics industries because of its antioxidative and antimicrobial properties.13 Alternatively, carnosic acid has been used as a naturally abundant chiral pool for semisynthesis or biomimetic synthesis of a complex optically active natural product.14 These important characteristics have been demanded for the chemical synthesis and biosynthesis of carnosic acid by the synthetic community.15 In our research, the naturally abundant carnosic acid was used as a starting material to synthesize przewalskin A via isorosmanol by employing the biogenetic approach mentioned above. On the basis of the literature,9,16,17 syntheses of 7,20epoxyabietanes have been found to be more difficult than syntheses of 6,20-epoxyabietanes because of the favored cyclization to five-membered rings as compared to the possible six-membered ring annulation.18 Inspired by the biogenetic pathway of przewalskin A, our retrosynthetic analysis of this natural product is shown in Scheme 2. We envisioned that the synthesis of przewalskin A could be achieved from compound 12 by ring expansion to deliver 2-acyl-3-hydroxytropones, followed by deprotection. o-Quinones 12 would be prepared by
in two steps on a gram scale with 45−63% yield. With compound 14 in hand, we attempted to transform compound 14 to 13 via 6,7-epoxy of abietane derivatives. Epoxidation of compound 14 with m-CPBA,21 to our surprise, gave no expected methyl 11,12-di-O-methyl-6,7-epoxycarnosate, but three epoxide opening products with a major complex mixture of 15a and 15b in 72%, and a minor product 13 in 11% yield, whose structure was confirmed after the next two transforms. Treated with 6 N NaOH in MeOH, trans-diol 13 was smoothly transformed to the desired six-membered ring lactone 16 in 85% yield. Removal of O-Me under BBr3 in 63% yield produced isorosmanol (8), which gave 1H NMR, 13C NMR, high-resolution mass spectrometric, and optical rotation results identical to those of the natural compound.10 The mixture of 15a and 15b contains hydroxy m-chlorobenzoates in a 1.5:1 ratio (calculated by 1H NMR). Then, this mixture was treated with 6 N NaOH in MeOH to produce the sole cis-diol 17 in 89% yield. To improve the yield of 13, we screened the reaction solvents and temperature. As shown in Table 1, using THF as a solvent, the yield of 13 was improved to 32% and the mixture of 15a and 15b was obtained in 37% yield accompanied by compound 17 in 5% yield (entry 1). We envisioned that epoxidation of the double bond of 14, generating a carbocation in the benzylic position via opening of the epoxide in an acidpromoted manner, and immediate attack of 3-chlorobenzoic acid from the less hindered face provided the observed 15b with a high level of diastereoselectivity. 15a must be obtained by intramolecular interesterification of 15b. Similarly, attack of less sterically hindered water provided 13 and 17. Thus, adding H2O to the reaction system and inhibiting electronic delocalization by solvent would increase the yield of compound
Scheme 2. Retrosynthetic Analysis of Przewalskin A
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DOI: 10.1021/acs.joc.7b02369 J. Org. Chem. 2018, 83, 437−442
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obtained. We postulated that the reaction produced the active p-methylene quinine intermediates leading to complex products.9,15,17 We thought that protection of the C-12 phenol hydroxyl group in the substrate would solve this problem. Under the TESCl/imidazole/DMAP condition, the C-12 phenolic hydroxyl group and the secondary hydroxyl group were protected by the TES group (Scheme 5). The
Table 1. . Optimization of the Conditions for the Synthesis of 13a
Scheme 5. Synthesis of Przewalskin A entry
solvent
T (°C)
13 (%)b
15a/15b (%)b
17 (%)b
1 2 3 4 5 6
THF 1:1 THF/H2O 1:1 THF/H2O Et2O/H2O CHCl3/H2O 1:1 MeCN/H2O
20 20 0 0 0 0
32 59 69 40 27 82
37 15 13 31 59 7
5 14 10 5 5 1
a
The reactions were performed, unless indicated otherwise, with 14 (0.099 mmol), m-CPBA (0.155 mmol), and solvents (0.1 M). b Isolated yield.
13.22 When a THF/H2O solvent [1:1 (v/v)] was used as a solvent, the yield of 13 was improved to 59% (entry 2). When the reaction temperature was decreased to 0 °C, the yield was further improved (entry 3). Using H2O-saturated Et2O or CHCl3 gave an unsatisfactory yield of 13 (entries 4 and 5). The possible pathway for the reaction is a partial SN1 or partial carbocation intermediate. Therefore, increasing the polarity of the solvent would be more effective for this reaction. Thus, using a MeCN/H2O solvent [1:1 (v/v)], the yield of 13 was further increased to 82% (entry 6). After optimization, lactone 16 was obtained in a one-pot procedure via epoxidation, epoxide opening, and lactonization from 14 (Scheme 4). Having constructed the lactone moiety,
maintenance of the C-11 phenolic hydroxy was due to the steric hindrance effect. The lactone group was successfully reduced to hemiacetal 21 with DIBAL-H in 60% yield. Hemiacetal 21 was oxidized smoothly to obtain the corresponding o-quinone with PIDA in 57% yield.27 As the active hemicactal would be a potential labile factor in the later reaction, the protection of hemiacetal by the TES gave oquinone 12. The next task was to expand o-quinone to install the tropone ring. Although a large variety of methods have been developed to construct the tropones, very little attention has been given to the utilization of ring expansion of o-quinone to obtain 2acyltropones.28 Acetonyltriphenylbismuthonium tetrafluoroborate was used in the key ring expansion reaction.28b Luckily, we obtained compound 22 successfully in 69% yield. To the best of our knowledge, it would be the first application of ring expansion of an o-quinone to the tropones in the total synthesis of a natural product.29 Finally, removal of the TES protecting groups with TBAF in THF afforded (+)-przewalskin A (1) in 73% yield. All spectral data for our synthetic sample are consistent with the literature data.5 In summary, we have developed a biomimetic route to produce (+)-przewalskin A (1) from carnosic acid via isorosmanol (8). The synthetic strategy was inspired primarily by the biogenetic hypothesis and was enabled by epoxidation, opening the epoxide, and lactonization in one pot to prepare the 11,12-dimethoxy isorosmanol, and bismuthonium ylideinduced ring expansion of o-quinone to construct the 2-acyl-3hydroxytropone. The biomimetic of other similar sesterterpenoids with 23 carbons in their skeletons derived from normal diterpenoids is in progress and will be reported in due course.
Scheme 4. Attempts To Prepare o-Quinone 12
we next focused on the synthesis of o-quinone, the precursor of the key ring expanding to achieve the 2-acyl-3-hydroxytropones. Lactone 16 was reduced by DIBAL-H to give hemiacetal 18 in 85% yield,23 which was protected by TES or Ac in 90 or 84% yield, respectively. A number of methods [HNO3,24 Ce(SO4)2/HClO4,25 PIDA,25 and CAN26] were used to oxidize 19a or 19b to o-quinone; however, deprotection compounds were obtained, or complete decomposition occurred. The attempt to remove the methyl protecting group also failed under the BBr3 or EtSNa conditions to give decomposition of 19a or 19b. Then we turned to isorosmanol (8), which would be easily transformed to o-quinone by oxidation. First, we tried to reduce isorosmanol by DIBAL-H directly, but a complex mixture was
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EXPERIMENTAL SECTION
General Experimental Details. Unless otherwise stated, all reactions were performed in oven-dried or flame-dried glassware under an atmosphere of dry Ar. Solvents were purified and dried by standard methods prior to use. All commercially available reagents were used without further purification unless otherwise noted. Column chromatography was performed on silica gel (200−300 mesh). NMR spectra were recorded on Varian Mercury 300M, Bruker 400 MHz, and Oxford 600 MHz spectrometers in CDCl3 or acetone-d6. Chemical shifts are reported as δ values relative to internal chloroform 439
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1733, 1572, 1457 cm−1; HRMS (ESIMS) calcd for C22H34O5N+ [M + NH4]+ 392.2437, found 392.2431. Methyl (4aR,9S,10R,10aS)-9,10-Dihydroxy-7-isopropyl-5,6-dimethoxy-1,1-dimethyl-1,3,4,9,10,10a-hexahydrophenanthrene-4a(2H)-carboxylate (17). To a stirred solution of compounds 15a and 15b (15 mg, 0.0276 mmol) in MeOH (1 mL) was added 6 M NaOH (aq) (0.018 mL, 0.110 mmol). The reaction mixture was stirred for 30 min and then diluted with ethyl acetate. The organic phase was washed, dried (Na2SO4), and filtered. Concentration of the filtrate gave a residue that was fractionated by column chromatography (petroleum ether/ethyl acetate, 4:1) to afford compound 17 (10 mg, 89%): [α]D20 = +80.7 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.00 (s, 1H), 4.70−4.66 (m, 2H), 3.74 (s, 3H), 3.67 (s, 3H), 3.60 (s, 3H), 3.48−3.41 (m, 1H), 3.28−3.21 (m, 1H), 2.63 (s, 1H), 2.31 (s, 1H),1.96 (d, J = 10 Hz, 1H), 1.78−1.39 (m, 4H), 1.22−1.19 (m, 10H), 0.97 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.0, 151.5, 150.8, 142.1, 133.4, 132.1, 122.1, 70.8, 69.0, 60.0, 59.4, 51.8, 50.6, 48.9, 40.0, 34.7, 33.7, 33.2, 26.8, 23.5, 23.1, 22.2, 19.1; IR (neat) ν 3444, 2957, 1733, 1601, 1450 cm−1; HRMS (ESIMS) calcd for C23H34O6Na + [M + Na]+ 429.2253, found 429.2248. One-Pot Synthesis of Compounds 16 and 17. To a stirred solution of compound 14 (37 mg, 0.0994 mmol) in a MeCN/H2O solvent [1:1 (v/v), 1 mL] was added m-CPBA (80%, 33 mg, 0.149 mmol). The reaction mixture was stirred for 10 h at 0 °C and then diluted with MeOH (1 mL) and 6 M NaOH (aq) (0.066 mL, 0.398 mmol). The reaction mixture was stirred for 10 min and then diluted with ethyl acetate. The organic phase was washed, dried (Na2SO4), and filtered. Concentration of the filtrate gave a residue that was fractionated by column chromatography (CH2Cl2/acetone, 400:1 to 50:1) to afford compound 16 (27 mg, 73%) and compound 17 (3.4 mg, 8%). Isorosmanol (8). To a stirred solution of 16 (364 mg, 0.97 mmol) in dry CH2Cl2 (10 mL) was added 1 M BBr3 in DCM (4.9 mL, 4.90 mmol) slowly at room temperature for 1.5 h. The reaction was quenched by the addition of water, and the whole was extracted with Et2O. The combined organic layers were washed with brine and dried over Na2SO4. Concentration of the filtrate gave a residue that was fractionated by column chromatography (petroleum ether/ethyl acetate, 2:1) to afford 8 (337 mg, 63%) as a gray solid: [α]D20 = −90.4 (c 1.00, CH3OH); mp 224−225 °C (lit.10 mp 227 °C); 1H NMR (400 MHz, acetone) δ 7.44 (br, 2H), 6.80 (s, 1H), 5.15 (d, J = 4.4 Hz, 1H), 4.35 (d, J = 2 Hz, 1H), 3.98 (s, 1H), 3.29 (sept, J = 6.8 Hz, 1H), 2.79 (d, J = 14 Hz, 1H), 2.59−2.51 (m, 1H), 1.92−1.82 (m, 1H), 1.59−1.28 (m, 4H), 1.20−1.18 (m, 6H), 1.04 (s, 3H), 0.91 (s, 3H); 13C NMR (100 MHz, acetone) δ 175.2, 143.8,143.6, 134.9, 129.9, 122.9, 116.0, 80.8, 69.0, 56.3, 48.7, 41.9, 34.8, 32.5, 29.8,27.5, 23.2, 22.9, 21.4, 19.6; IR (neat) ν 3385, 2925, 2371, 1721, 1594 cm−1; HRMS (ESIMS) calcd for C20H26O5Na+ [M + Na]+ 369.1678, found 369.1672. (4aR,9R,10R,10aS,12S)-7-Isopropyl-5,6-dimethoxy-1,1-dimethyl1,3,4,9,10,10a-hexahydro-2H-9,4a-(epoxymethano)phenanthrene10,12-diol (18). To a stirred solution of 16 (102 mg, 0.274 mmol) in dry CH2Cl2 (10 mL) was added 1.5 M DIBAL-H in toluene (0.4 mL, 0.630 mmol) slowly at −78 °C. The reaction was quenched by the addition of a saturated potassium tartrate solution, and the mixture was stirred overnight. Then, the whole was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over Na2SO4. Concentration of the filtrate gave a residue that was fractionated by column chromatography (petroleum ether/ethyl acetate, 6:1) to afford 18 (88 mg, 85%) as a colorless oil: [α]D20 = −60.0 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.97 (s, 1H), 5.38 (d, J = 10.4 Hz, 1H), 4.70 (d, J = 4.4 Hz, 1H), 4.10−4.06 (m, 1H), 3.85 (s, 3H), 3.81 (s, 3H), 3.35−3.28 (m, 1H), 2.52−2.48 (m, 2H), 1.67−1.56 (m, 4H), 1.36−1.29 (m, 1H), 1.22 (d, J = 4 Hz, 3H), 1.21 (d, J = 3.6 Hz, 3H), 1.10 (d, J = 3.6 Hz, 1H), 1.08 (s, 3H), 1.05 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 152.1, 152.0, 141.9, 132.4, 128.9, 120.0, 91.2, 73.6, 69.1, 61.1, 60.6, 56.7, 47.5, 41.0, 33.9, 33.4, 28.7, 26.8, 23.6, 23.3, 23.1, 18.4; IR (neat) ν 3424, 2961, 1454, 1370, 1017 cm−1; HRMS (ESIMS) calcd for C22H32O5Na+ [M + Na]+ 399.2147, found 399.2147.
(δ 7.26 for 1H NMR and δ 77.00 for 13C NMR) and acetone-d6 (δ 2.05 for 1H NMR and δ 29.84 for 13C NMR). High-resolution mass spectra (HRMS) were recorded on a 4G mass spectrometer by using electrospray ionization (ESI) analyzed by quadrupole time-of-flight (Q-TOF). Optical rotations were measured on a Rudolph Autoplo IV polarimeter. Methyl (4aR,9R,10R,10aS)-9,10-Dihydroxy-7-isopropyl-5,6-dimethoxy-1,1-dimethyl-1,3,4,9,10,10a-hexahydrophenanthrene-4a(2H)-carboxylate (13), Methyl (4aR,9S,10R,10aS)-10-[(3Chlorobenzoyl)oxy]-9-hydroxy-7-isopropyl-5,6-dimethoxy-1,1-dimethyl-1,3,4,9,10,10a-hexahydrophenanthrene-4a(2H)-carboxylate (15a), and Methyl (4aR,9S,10R,10aS)-9-[(3-Chlorobenzoyl)oxy]10-hydroxy-7-isopropyl-5,6-dimethoxy-1,1-dimethyl-1,3,4,9,10,10ahexahydrophenanthrene-4a(2H)-carboxylate (15b). To a stirred solution of compound 14 (37 mg, 0.0994 mmol) in CH2Cl2 (1 mL) was added m-CPBA (80%, 33 mg, 0.149 mmol). The reaction mixture was stirred for 30 min and then diluted with ethyl acetate. The organic phase was washed with saturated NaHCO3, dried over Na2SO4, and filtered. Concentration of the filtrate gave a residue that was fractionated by column chromatography (petroleum ether/ethyl acetate, 16:1 to 10:1 to 6:1) to afford compound 13 (4.6 mg, 11%) and a 1:1.5 mixture of compounds 15a and 15b (39 mg, 72%). Compound 13: [α]D20 = +140.0 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.18 (s, 1H), 4.51−4.41 (m, 2H), 3.72 (s, 3H), 3.64 (s, 3H), 3.61 (s, 3H), 3.38−3.31 (m, 1H), 3.23 (sept, J = 6.8 Hz, 1H), 2.87 (br, 2H), 1.83−1.75 (m, 3H), 1.52−1.49 (m, 1H), 1.35−1.29 (m, 1H), 1.22−1.11 (m, 10H), 0.94 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.9, 150.5, 149.8, 141.9, 133.7, 132.8, 118.8, 77.1, 72.3, 60.0, 59.1, 51.8, 51.4, 50.5, 39.2, 34.1, 33.5, 33.1, 26.9, 23.5, 23.2, 22.2, 18.4; IR (neat) ν 3387, 2960, 1733, 1449, 1315 cm−1; HRMS (ESIMS) calcd for C23H34O6Na+ [M + Na]+ 429.2253, found 429.2248. Compound 15a: 1H NMR (400 MHz, CDCl3) δ 8.07−8.04 (m, 1H), 7.99−7.94 (m, 1H), 7.56−7.52 (m, 1H), 7.42−7.38 (m, 1H), 6.96 (s, 1H), 6.42−6.30 (m, 1H), 4.96 (d, J = 3.6 Hz, 1H), 3.76 (s, 3H), 3.69 (s, 3H), 3.66 (s, 3H), 3.53−3.48 (m, 1H), 3.29−3.19 (m, 1H), 2.61 (d, J = 11.2 Hz, 1H), 1.90−1.50 (m, 4H), 1.30−1.28 (m, 1H), 1.25−1.13 (m, 9H), 0.84 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 175.6, 165.0, 151.5, 151.0, 142.4, 134.7, 133.2, 132.9, 132.1, 131.1, 129.9, 129.9, 127.9, 122.2, 73.5, 69.5, 60.1, 59.4, 51.9, 50.9, 46.5, 40.0, 34.5, 33.3, 33.0, 26.9, 23.5, 23.1, 22.2, 19.0; HRMS (ESIMS) calcd for C30H41O7NCl+ [M + NH4]+ 562.2572, found 562.2560. Compound 15b: [α]D20 = +120.0 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.93 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 8 Hz, 1H), 7.39−7.35 (m, 1H), 7.03 (s, 1H), 6.31 (d, J = 3.6 Hz, 1H), 5.08−5.02 (m, 1H), 3.75 (s, 3H), 3.68 (s, 3H), 3.65 (s, 3H), 3.50− 3.42 (m, 1H), 3.22−3.19 (m, 1H), 2.37 (d, J = 11.2 Hz, 1H), 2.02− 1.79 (m, 3H), 1.66−1.64 (m, 1H), 1.53−1.48 (m, 1H), 1.30−1.28 (m, 1H), 1.25 (s, 3H), 1.19 (d, J = 6.8 Hz, 3H), 1.14 (d, J = 6.8 Hz, 3H), 0.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 176.2, 165.6, 151.3, 151.3, 142.2, 134.9, 134.5, 133.0, 132.0, 129.8, 129.7, 128.2, 127.8, 123.4, 75.4, 68.3, 59.9, 59.2, 51.8, 50.6, 48.3, 39.6, 34.3, 33.7, 32.9, 26.8, 23.3, 23.0, 21.8, 18.8; IR (neat) ν 3515, 2961, 1719, 1475, 1257 cm−1; HRMS (ESIMS) calcd for C30H41O7NCl+ [M + NH4]+ 562.2572, found 562.2560. (4aR,9R,10R,10aS)-10-Hydroxy-7-isopropyl-5,6-dimethoxy-1,1-dimethyl-1,3,4,9,10,10a-hexahydro-2H-9,4a-(epoxymethano)phenanthren-12-one (16). To a stirred solution of compound 13 (36 mg, 0.0886 mmol) in MeOH (1 mL) was added 6 M NaOH (aq) (0.059 mL, 0.354 mmol). The reaction mixture was stirred for 10 min and then diluted with ethyl acetate. The organic phase was washed, dried (Na2SO4), and filtered. Concentration of the filtrate gave a residue that was fractionated by column chromatography (petroleum ether/ethyl acetate, 4:1) to afford compound 16 (28 mg, 85%): [α]D20 = −10.3 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.98 (s, 1H), 5.22 (d, J = 4.4 Hz, 1H), 4.37 (s, 1H), 3.82 (s, 3H), 3.79 (s, 3H), 3.33−3.26 (m, 1H), 2.77 (d, J = 14.0 Hz, 1H), 2.45−2.37 (m, 1H), 1.96−1.84 (m, 1H), 1.67−1.28 (m, 5H), 1.21−1.18 (m, 6H), 1.05 (s, 3H), 0.93 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 174.5, 152.4, 150.7, 142.5, 130.8, 128.8, 119.8, 79.2, 68.4, 61.0, 60.6, 56.9, 48.3, 40.8, 34.4, 32.1, 28.1, 26.8, 23.5, 23.2, 21.0, 18.8; IR (neat) ν 3443, 2960, 440
DOI: 10.1021/acs.joc.7b02369 J. Org. Chem. 2018, 83, 437−442
Note
The Journal of Organic Chemistry {[(4aR,9R,10R,10aS,12R)-7-Isopropyl-5,6-dimethoxy-1,1-dimethy l - 1 , 3 , 4 , 9 , 1 0 , 1 0 a - h e x a h y d ro - 2 H - 9 , 4a - ( e p ox ym e th an o) phenanthrene-10,12-diyl]bis(oxy)}bis(triethylsilane) (19a). To a magnetically stirred solution of 18 (45 mg, 0.118 mmol), imidazole (61 mg, 0.897 mmol), and DMAP (29 mg, 0.236 mmol) in CH2Cl2 (2 mL) was added TESCl (50 μL, 0.295 mmol). The reaction mixture was stirred for 30 min, and a saturated NH4Cl solution was added. The aqueous layer was extracted with CH2Cl2, and the combined organic phases were dried, filtered, and concentrated. Purification by column chromatography (petroleum ether/ethyl acetate, 50:1) afforded 19a (64 mg, 90%) as an oil: [α]D20 = −30.0 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.78 (s, 1H), 5.44 (s, 1H), 4.51 (d, J = 4.4 Hz, 1H), 4.10 (t, J = 4.0 Hz, 1H), 3.82 (s, 3H), 3.75 (s, 3H), 3.34−3.27 (m, 1H), 2.50−2.46 (m, 2H), 1.60−1.48 (m, 3H), 1.36−1.26 (m, 1H), 1.21 (d, J = 3.6 Hz, 1H), 1.17 (t, J = 7.2 Hz, 6H), 1.05 (s, 3H), 1.00 (s, 3H), 0.93−0.89 (m, 9H), 0.73−0.69 (m, 9H), 0.64−0.58 (m, 6H), 0.40−0.34 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 151.0, 151.0, 139.6, 133.0, 131.2, 119.3, 91.6, 74.2, 70.5, 60.7, 60.6, 55.0, 47.6, 41.5, 33.8, 33.8, 28.9, 26.5, 23.7, 23.7, 23.4, 18.6, 7.1, 6.5, 5.5, 5.0; IR (neat) ν 2960, 2877, 1754, 1456, 754 cm−1; HRMS (ESIMS) calcd for C34H60O5Si2Na+ [M + Na]+ 627.3877, found 627.3878. (4aR,9R,10R,10aS,12R)-7-Isopropyl-5,6-dimethoxy-1,1-dimethyl1,3,4,9,10,10a-hexahydro-2H-9,4a-(epoxymethano)phenanthrene10,12-diyl Diacetate (19b). To a magnetically stirred solution of 18 (140 mg, 0.37 mmol) and pyridine (1.2 mL, 1.49 mmol) in CH2Cl2 (3 mL) was added AcCl (84 μL, 1.12 mmol). The reaction mixture was stirred for 30 min, and a saturated NH4Cl solution was added. The aqueous layer was extracted with CH2Cl2, and the combined organic phases were dried, filtered, and concentrated. Purification by column chromatography (petroleum ether/ethyl acetate, 8:1) afforded 19b (144 mg, 84%) as an oil: [α]D20 = −30.0 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.78 (s, 1H), 6.51 (s, 1H), 5.16 (t, J = 4.0 Hz, 1H), 4.97 (d, J = 4.4 Hz, 1H), 3.86 (s, 3H), 3.78 (s, 3H), 3.36−3.29 (m, 1H), 2.59−2.51 (m, 1H), 2.27 (d, J = 14.4 Hz, 1H), 1.85 (s, 3H), 1.82 (s, 3H), 1.71−1.56 (m, 3H), 1.35−1.31 (m, 2H), 1.28−1.16 (m, 9H), 0.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 170.3, 151.7, 150.4, 141.2, 131.5, 129.6, 118.6, 91.1, 70.9, 70.6, 60.8, 60.7, 51.2, 44.9, 40.6, 33.8, 32.6,28.5, 26.6, 24.0, 23.2, 23.0, 21.2, 21.0, 18.4; IR (neat) ν 3401, 2962, 2371, 1739, 1239 cm−1; HRMS (ESIMS) calcd for C26H36O7Na+ [M + Na]+ 483.2359, found 483.2360. (4aR,9R,10aS,12S)-7-Isopropyl-1,1-dimethyl-6,10-bis[(triethylsilyl)oxy]-1,3,4,9,10,10a-hexahydro-2H-9,4a(epoxymethano)phenanthrene-5,12-diol (21). In step 1, to a magnetically stirred solution of 8 (15 mg, 0.043 mmol), imidazole (27 mg, 0.39 mmol), and DMAP (16 mg, 0.13 mmol) in CH2Cl2 (2 mL) was added TESCl (26 μL, 0.16 mmol). The reaction mixture was stirred for 30 min, and a saturated NH4Cl solution was added. The aqueous layer was extracted with CH2Cl2, and the combined organic phases were dried, filtered, and concentrated. Purification by column chromatography (petroleum ether/ethyl acetate, 30:1) afforded S1 (19 mg, 76%) as a slightly yellow oil: [α]D20 = −10.5 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.65 (s, 1H), 5.49 (s, 1H), 5.06 (d, J = 4.4 Hz, 1H), 4.40 (t, J = 4.0 Hz, 1H), 3.16−3.09 (m, 1H), 2.81 (d, J = 14 Hz, 1H), 2.48−2.40 (m, 1H), 1.92−1.88 (m, 1H), 1.63−1.60 (m, 1H), 1.48−1.25 (m, 3H), 1.17−1.15 (m, 6H), 1.00−0.90 (m, 24H), 0.79− 0.73 (m, 6H), 0.64−0.58 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 175.1, 144.2, 141.1, 136.8, 130.1, 120.5, 115.0, 79.8, 69.4, 56.1, 47.8, 41.1, 34.2, 32.4, 28.8, 27.1, 22.9, 22.7, 21.2, 18.7, 6.9, 6.6, 5.4, 5.3; IR (neat) ν 3397, 2957, 2373, 1736, 1594 cm−1; HRMS (ESIMS) calcd for C32H54O5Si2Na+ [M + Na]+ 597.3407, found 597.3407. In step 2, to a stirred solution of S1 (495 mg, 0.86 mmol) in dry CH2Cl2 (10 mL) was added 1 M DIBAL-H in toluene (1.9 mL, 1.90 mmol) slowly at −78 °C. The reaction was quenched by the addition of a saturated potassium tartrate solution, and the mixture was stirred overnight. The whole was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over Na2SO4. Concentration of the filtrate gave a residue that was fractionated by column chromatography (petroleum ether/ethyl acetate, 10:1) to afford 21 (298 mg, 60%) as a colorless oil: [α]D20 = −10.0 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.66 (s, 1H), 5.45 (s, 1H),
5.32 (d, J = 10.8 Hz, 1H), 4.56 (d, J = 4.4 Hz, 1H), 4.14−4.12 (m, 1H), 3.15 (sept, J = 6.8 Hz, 1H), 2.53−2.49 (m, 2H), 1.65−1.60 (m, 1H), 1.54 (br, 1H), 1.51−1.50 (m, 1H), 1.38−1.33 (m, 1H), 1.30 (d, J = 3.2 Hz, 1H), 1.25 (m, 1H), 1.19−1.16 (m, 6H), 1.06 (s, 3H), 1.00− 0.95 (m, 12H), 0.91−0.87 (m, 9H), 0.79−0.73 (m, 6H), 0.60−0.54 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 145.7, 140.8, 136.7, 131.9, 119.8, 115.5, 91.5, 74.0, 70.0, 55.7, 47.2, 41.3, 33.7, 33.6, 29.6, 27.1, 23.4, 23.0, 22.8, 18.4, 7.0, 6.6, 5.4; IR (neat) ν 3394, 2956, 2370, 1594, 1450 cm−1; HRMS (ESIMS) calcd for C32H56O5Si2Na+ [M + Na]+ 599.3564, found 599.3559. (4aR,10aS,12R)-7-Isopropyl-1,1-dimethyl-10,12-bis[(triethylsilyl)oxy]-1,3,4,9,10,10a-hexahydro-2H-9,4a-(epoxymethano)phenanthrene-5,6-dione (12). In step 1, to a stirred solution of acetate 21 (198 mg, 0.34 mmol) in a MeOH (4 mL)/H2O (0.4 mL) solvent was added PIDA (132 mg, 0.41 mmol). The reaction mixture was stirred at room temperature and then diluted with EtOAc. The organic phase was dried (Na2SO4) and filtered. Concentration of the filtrate gave a residue that was fractionated by column chromatography (petroleum ether/ethyl acetate, 4:1) to afford S2 (90 mg, 57%) as a yellow-green liquid: [α]D20 = +10.0 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.58 (d, J = 1.2 Hz, 1H), 5.40 (s, 1H), 4.40 (d, J = 4.4 Hz, 1H), 4.14−4.12 (m, 1H), 2.95 (sept, J = 6.8 Hz, 1H), 2.48−2.44 (m, 1H), 2.34−2.26 (m, 2H), 1.63−1.48 (m, 3H), 1.30−1.24 (m, 2H), 1.11−1.08 (m, 6H), 1.01−0.95 (m, 15H), 0.66−0.60 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 180.2, 177.8, 152.2, 148.7, 136.6, 132.7, 91.0, 73.3, 70.5, 54.9, 47.3, 40.7, 33.9, 33.5, 27.8, 27.3, 23.0, 21.3, 21.3, 17.9, 7.0, 5.3; IR (neat) ν 3404, 2925, 1720, 1598, 1460 cm−1; HRMS (ESIMS) calcd for C26H41O5Si+ [M + H]+ 461.2723, found 461.2718. In step 2, to a magnetically stirred solution of S2 (14 mg, 0.030 mmol), imidazole (6 mg, 0.091 mmol), and DMAP (4 mg, 0.030 mmol) in CH2Cl2 (1 mL) was added TESCl (6 μL, 0.036 mmol). The reaction mixture was stirred for 2 h, and a saturated NH4Cl solution was added. The aqueous layer was extracted with CH2Cl2, and the combined organic phases were dried, filtered, and concentrated. Purification by column chromatography (petroleum ether/ethyl acetate, 50:1) afforded 12 (12 mg, 71%) as a yellow-green liquid: [α]D20 = +60.5 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.57 (d, J = 1.2 Hz, 1H), 5.37 (s, 1H), 4.34 (d, J = 4.4 Hz, 1H), 4.09−4.07 (m, 1H), 2.98−2.92 (m, 1H), 2.41 (d, J = 12.8 Hz, 1H), 2.28−2.20 (m, 1H), 1.60−1.56 (m, 1H), 1.49−1.42 (m, 2H), 1.33−1.28 (m, 1H), 1.21 (d, J = 3.4 Hz, 1H), 1.09 (s, 3H), 1.07 (s, 3H), 0.99−0.94 (m, 15H), 0.86−0.82 (m, 9H), 0.66−0.59 (m, 6H), 0.52−0.46 (m, 6H); 13 C NMR (100 MHz, CDCl3) δ 180.5, 177.6, 150.7, 148.1, 138.2, 133.2, 91.5, 73.2, 70.5, 54.7, 48.0, 40.9, 33.8, 33.5, 27.9, 27.1, 23.1, 21.6, 21.2, 18.0, 7.0, 6.6, 5.3, 5.0; IR (neat) ν 3390, 2956, 2372, 1736, 1656 cm−1; HRMS (ESIMS) calcd for C32H55O5Si2+ [M + H]+ 575.3588, found 575.3583. (4aS,6R,11bR,12R)-10-Acetyl-9-hydroxy-8-isopropyl-4,4-dimethyl-5,12-bis[(triethylsilyl)oxy]-2,3,4,4a,5,6-hexahydro-6,11b(epoxymethano)cyclohepta[a]naphthalen-11(1H)-one (22). To a stirred suspension of acetonyltriphenylbismuthonium tetrafluoroborate (133 mg, 0.23 mmol) in dry THF (2.5 mL) was added 1 M t-BuOK in THF (190 μL, 0.19 mmol) slowly at −78 °C. After 15 min, o-quinone 12 (101 mg, 0.18 mmol) in dry THF (1 mL) was added and the resulting mixture was allowed to warm to room temperature. Evaporation of the solvent and purification by column chromatography (petroleum ether/ethyl acetate, 50:1) afforded 22 (77 mg, 69%) as a colorless oil: [α]D20 = +20.3 (c 1.00, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.66 (s, 1H), 5.39 (s, 1H), 4.38 (d, J = 4.4 Hz, 1H), 4.11−4.09 (m, 1H), 3.35−3.28 (m, 1H), 2.40 (s, 3H), 2.34−2.30 (m, 1H), 2.03 (d, J = 12.4 Hz, 1H), 1.57−1.25 (m, 5H), 1.19 (d, J = 6.8 Hz, 3H), 1.13 (d, J = 6.8 Hz, 3H), 1.02−1.00 (m, 6H), 0.95−0.91 (m, 9H), 0.79−0.75 (m, 9H), 0.64−0.59 (m, 6H), 0.44−0.38 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 204.5, 189.5, 173.2, 147.5, 145.9, 135.7, 131.9, 120.1, 90.9, 74.7, 70.5, 54.7, 48.1, 41.0, 33.8, 33.7, 29.7, 28.4, 26.9, 23.2, 22.8, 22.5, 18.1, 7.1, 6.5, 5.5, 5.0; IR (neat) ν 3374, 2958, 1594, 1414, 1261 cm−1; HRMS (ESIMS) calcd for C35H58O6Si2Na+ [M + Na]+ 653.3670, found 653.3666. Przewalskin A (1). To a stirred solution of compound 22 (77 mg, 0.12 mmol) in THF (4 mL) was added TBAF (128 mg, 0.49 mmol). 441
DOI: 10.1021/acs.joc.7b02369 J. Org. Chem. 2018, 83, 437−442
Note
The Journal of Organic Chemistry The reaction mixture was stirred at 50 °C and then diluted with EtOAc. The organic phase was washed, dried (Na2SO4), and filtered. Concentration of the filtrate gave a residue that was fractionated by column chromatography (petroleum ether/ethyl acetate, 4:1 to 2:1) to afford (+)-przewalskin A (1) (36 mg, 73%) as a colorless oil: [α]D20 = +88.2 (c 0.68, CHCl3); 1H NMR (400 MHz, acetone) δ 6.89 (s, 1H), 5.38 (d, J = 3.6 Hz, 1H), 4.54 (d, J = 4.4 Hz, 1H), 4.52 (s, 1H), 4.06− 4.03 (m, 1H), 3.97 (d, J = 5.2 Hz, 1H), 3.27 (sept, J = 6.8 Hz, 1H), 2.36 (s, 3H), 2.23−2.20 (m, 2H), 1.63−1.48 (m, 3H), 1.33−1.26 (m, 1H), 1.22 (d, J = 3.6 Hz, 1H), 1.17 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 6.8 Hz, 3H), 1.00 (s, 6H); 13C NMR (100 MHz, acetone) δ 205.6, 189.8, 173.8, 147.9, 146.2,138.8, 133.4, 121.0, 90.9, 75.4, 70.2, 55.4, 48.4, 41.8, 34.4, 34.1, 30.5, 28.6, 27.8, 23.2, 23.0, 22.8, 18.9; IR (neat) ν 3436, 2928, 1637, 1590, 1418 cm−1; HRMS (ESIMS) calcd for C23H31O6+ [M + H]+ 403.2121, found 403.2115.
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(5) Xu, G.; Hou, A. J.; Wang, R. R.; Liang, Y. G.; Zheng, Y. T.; Liu, Z. Y.; Li, X. L.; Zhao, Y.; Huang, S. X.; Peng, L. Y.; Zhao, Q. S. Org. Lett. 2006, 8, 4453−4456. (6) Xu, G.; Hou, A.-J.; Zheng, Y.-T.; Zhao, Y.; Li, X.-L.; Peng, L.-Y.; Zhao, Q.-S. Org. Lett. 2007, 9, 291−293. (7) (a) Zheng, J.; Xie, X.; Zhao, C.; He, Y.; Zheng, H.; Yang, Z.; She, X. Org. Lett. 2011, 13, 173−175. (b) Zhuo, X.; Xiang, K.; Zhang, F.M.; Tu, Y.-Q. J. Org. Chem. 2011, 76, 6918−6924. (8) Xiao, M. X.; Wei, L.; Li, L. Q.; Xie, Z. X. J. Org. Chem. 2014, 79, 2746−2750. (9) González, A. G.; Aguiar, Z. E.; Andrés, L. S.; Luis, J. G. Phytochemistry 1992, 31, 1297−1305. (10) Nakatani, N.; Inatani, R. Agric. Biol. Chem. 1984, 48, 2081− 2085. (11) (a) Miura, K.; Kikuzaki, H.; Nakatani, N. Phytochemistry 2001, 58, 1171−1175. (b) Zhu, L.-P.; Xiang, C.; Zhuang, W.-T.; He, J.; Li, P.; Li, B.-C. Tianran Chanwu Yanjiu Yu Kaifa 2013, 25, 785−788. (12) Abreu, M. E.; Müller, M.; Alegre, L.; Munné-Bosch, S. J. Sci. Food Agric. 2008, 88, 2648−2653. (13) Birtić, S.; Dussort, P.; Pierre, F.-X.; Bily, A. C.; Roller, M. Phytochemistry 2015, 115, 9−19. (14) For recent and representative examples, see: (a) Aoyagi, Y.; Takahashi, Y.; Satake, Y.; Takeya, K.; Aiyama, R.; Matsuzaki, T.; Hashimoto, S.; Kurihara, T. Bioorg. Med. Chem. 2006, 14, 5285−5291. (b) Li, F.-Z.; Li, S.; Zhang, P.-P.; Huang, Z.-H.; Zhang, W.-B.; Gong, J. X.; Yang, Z. Chem. Commun. 2016, 52, 12426−12429. (c) Thommen, C.; Neuburger, M.; Gademann, K. Chem. - Eur. J. 2017, 23, 120−127. (15) (a) Tada, M.; Ohkanda, T.; Kurabe, J. Chem. Pharm. Bull. 2010, 58, 27−29. (b) Scheler, U.; Brandt, W.; Porzel, A.; Rothe, K.; Manzano, D.; Božić, D.; Papaefthimiou, D.; Balcke, G. U.; Henning, A.; Lohse, S.; Marillonnet, S.; Kanellis, A. K.; Ferrer, A.; Tissier, A. Nat. Commun. 2016, 7, 12942−12952. (16) Luis, J. G.; Andrés, L. S.; Fletcher, W. Q. Tetrahedron Lett. 1994, 35, 179−182. (17) Marrero, J. G.; Andrés, L. S.; Luis, J. G. J. Nat. Prod. 2002, 65, 986−989. (18) Antoniotti, S.; Duñach, E. Tetrahedron Lett. 2009, 50, 2536− 2539. (19) (a) Wehrli, C. DSM IP Assets B.V. Appl. WO 2009/053026A2, 2009. (b) Kleefeldt, A. DSM IP Assets B.V. Appl. WO 2010/ 015617A1, 2010. (20) Luis, J. G.; Andrés, L. S.; Fletcher, W. Q.; Lahlou, E. H.; Perales, A. J. Chem. Soc., Perkin Trans. 1 1996, 2207−2211. (21) Geiwiz, J.; Haslinger, E. Helv. Chim. Acta 1995, 78, 818−832. (22) (a) Córdova-Guerrero, I.; Andrés, L. S.; Leal-Orozco, A. E.; Padrón, J. M.; Cornejo-Bravo, J. M.; León, F. Tetrahedron Lett. 2013, 54, 4479−4482. (b) Cambie, R. C.; Grimsdale, A. C.; Rutledge, P. S.; Walker, M. F.; Woodgate, P. D. Aust. J. Chem. 1991, 44, 1553−1573. (23) Fischer, M.; Harms, K.; Koert, U. Org. Lett. 2016, 18, 5692− 5695. (24) Zhao, J.-M.; Lu, H.-Y.; Cao, J.; Jiang, Y.; Chen, C.-F. Tetrahedron Lett. 2009, 50, 219−222. (25) Song, L.-Q.; Zhu, G.-L.; Liu, Y.-J.; Liu, B.; Qin, S. J. Am. Chem. Soc. 2015, 137, 13706−13714. (26) Lee, E.; Huang, Z.-G.; Ryu, J.-H.; Lee, M. Chem. - Eur. J. 2008, 14, 6957−6966. (27) Li, Q.-R.; Pan, Z.; Yin, H.; Wang, W. Chem. Res. Chin. Univ. 2007, 23, 421−425. (28) (a) Kogler, H.; Fehlhaber, H.-W.; Leube, K.; Dürckheimer, W. Chem. Ber. 1989, 122, 2205−2206. (b) Rahman, M. M.; Matano, Y.; Suzuki, H. J. Chem. Soc., Perkin Trans. 1 1999, 1533−1542. (c) Li, H. J.; Li, W. J.; Li, Z. P. Chem. Commun. 2009, 3264−3266. (29) Liu, N.; Song, W.-Z.; Schienebeck, C. M.; Zhang, M.; Tang, W.P. Tetrahedron 2014, 70, 9281−9305.
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02369. Copies of 1H and 13C NMR spectra for all new compounds (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Zhixiang Xie: 0000-0001-5809-3084 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The authors gratefully acknowledge financial support from the NSFC (Grants 21672088 and 21272104), the program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, IRT_15R28), the Fundamental Research Funds for the Central Universities (lzujbky-2016-ct02), and the Program for New Century Excellent Talents in University (NCET-12-0247 and lzujbky-2012-56).
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DOI: 10.1021/acs.joc.7b02369 J. Org. Chem. 2018, 83, 437−442
