Article pubs.acs.org/jnp
Skeleton Reassignment of Type C Polycyclic Polyprenylated Acylphloroglucinols Xing-Wei Yang, Jing Yang, and Gang Xu* State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, People’s Republic of China S Supporting Information *
ABSTRACT: The previous assignment of the type C skeleton of polycyclic polyprenylated acylphloroglucinols (PPAPs) was controversial and proved to be incorrect in this study. The structures of the type C PPAPs (3−6) were revised to corresponding type A structures (3a−6a) via 13C NMR spectroscopic analysis and a quantum computational chemistry method. Therefore, only types A and B PPAPs are likely present in plants of the family Clusiaceae.
T
or B structures.1,3 To date, only six compounds, nemorosone (1),4 hydroxynemorosone (2),4 garcinielliptones K−M (3−5),5 and 7-epi-nemorosone (6),6 were assigned to share the type C skeleton (Scheme 2 and Figure 1). However, the presence of type C PPAPs remains to be further confirmed. In 2001, nemorosone (1) and hydroxynemorosone (2) had been revised to type A structures (1a and 2a) by Cuesta-Rubio and Ciochina on the basis of methylation and NMR spectroscopic data analysis (Scheme 2).1,7 The positions of the bridgehead sub-
he structural assignments of complex natural products, especially those obtained as gums, by NMR spectroscopic data are problematic and sometimes lead to erroneous and ambiguous conclusions. Polycyclic polyprenylated acylphloroglucinols (PPAPs), featuring highly oxygenated and densely substituted acylphloroglucinol-derived cores decorated with prenyl or geranyl side chains, are such a class of structurally complex natural products and are usually isolated as gums.1 Biosynthetically, PPAPs are derived from hybrid biosynthetic pathways. Prenylation of the acylphloroglucinol core affords monocyclic polyprenylated acylphloroglucinols (MPAPs), which may be further cyclized to PPAPs with diverse carbon skeletons.1,2 Currently, the various PPAPs have been divided into types A, B, and C depending on the relative position of the acyl group on the phloroglucinol core (Scheme 1).1
Scheme 2. Skeleton Reassignment of 1 and 2 by Ciochina and Grossman
Scheme 1. Reported Biosynthetic Pathways to Types A, B, and C PPAPs
stituents (the benzoyl and isoprenyl groups) in 1a and 2a were switched from their originally assigned positions. In 2006, Ciochina and Grossman reviewed all the natural PPAPs and also challenged the structures of 3−5, but eventually retained their type C skeletons for lacking solid evidence.1 After this review, the concept of type C PPAPs was accepted by many researchers,8−20 notwithstanding the fact that some synthesis Over 400 natural PPAPs have been reported from plants of the Clusiaceae family thus far, almost all of which are type A © 2016 American Chemical Society and American Society of Pharmacognosy
Received: August 16, 2016 Published: December 29, 2016 108
DOI: 10.1021/acs.jnatprod.6b00754 J. Nat. Prod. 2017, 80, 108−113
Journal of Natural Products
Article
Figure 1. Structures of the remaining type C PPAPs (3−6) and corresponding revised structures (3a−6a).
Table 1. Reported 13C NMR Data for 3, 3a, and 7 in CDCl3
chemists only concerned about the types A and B PPAPs thus far.21−25 Our team has long been committed to investigation of PPAPs and reported a series of congeners with diverse structures and bioactivities.3,26 In this study, the remaining four type C PPAPs (3−6) were formally revised to type A structures (3a−6a), respectively, by 13C NMR spectroscopic analysis and a quantum computational chemistry method. As a result, the corrected structures of 3 and 6 were identical to those of propolone C (3a) and plukenetione D (6a), respectively,27,28 while the structures of 4 and 5 were changed to 4a and 5a. Two structurally well-defined PPAPs, hyperibrin C (7) and sampsonione M (11),29,30 were used to confirm the structures of 3a and 6a, respectively. In addition, furoadhyperforin isomer 2b (8),31 a PPAP whose structure was confirmed by X-ray diffraction data, isolated from Hypericum cohaerens,26d was utilized to further support the carbon skeletons of 4a and 5a.
■
RESULTS AND DISCUSSION Garcinielliptones K−M (3−5), isolated from Garcinia subelliptica in 2004, were reported to possess a type C PPAP skeleton.5 In fact, the original assignments of the 13C NMR data of C-1 and C-5 for 3−5 were interchanged,5 which cast some doubt on the structural assignments. Generally, when the acyl group of PPAPs change from benzoyl to isobutyryl (or 2-methylbutyryl), a 4 ppm downfield shift for the carbon (C-1) linked to the acyl group will be observed in their 13C NMR spectra.3,26 However, this change occurred at another bridgehead carbon (C-5) rather than C-1 for compounds 4 and 5 compared to 3, indicating the incorrect assignments for C-1 and C-5 of compounds 3−5. Furthermore, the 1H and 13C NMR spectroscopic data (Tables 1 and 2) of 3 are identical to those of propolone C (3a), which was isolated from Cuban propolis,27 indicating that one of the two structures must have been assigned incorrectly. However, the positional assignments of the acyl groups in 3 and 3a via NMR spectroscopic data were not sufficient. In order to clarify the structures of the two compounds, the 13C NMR spectroscopic data of 3 and 3a
no.
3
3a
7
1 2 3 4 5 6 7 8 9 10 11 12, 16 13, 15 14 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
70.3 171.9 118.5 190.3 65.3 41.7 43.1 47.0 206.9 192.6 137.1 128.5 128.2 132.8 26.5 93.5 70.6 26.4 23.7 29.3 119.5 134.7 25.9 18.2 27.7 122.3 133.5 26.0 17.9 15.7 24.1
70.6 171.9 118.3 188.1 65.3 41.8 43.2 47.0 206.9 193.2 137.2 128.5 128.2 132.8 26.5 93.5 70.6 26.4 23.7 29.3 119.5 134.7 26.0 18.1 27.7 122.3 133.5 25.9 17.9 15.7 24.1
70.2 172.9 118.2 190.7 64.8 41.5 43.0 46.9 206.5 192.7 137.1 128.1 128.0 132.4 26.2 93.4 71.3 26.7 24.5 29.2 119.6 134.4 26.0 18.1 27.6 122.3 133.5 25.9 17.9 15.8 24.8
were calculated by density functional theory (DFT) using Gaussian 09 (computational details, Figures S1−S4, Supporting Information).32 109
DOI: 10.1021/acs.jnatprod.6b00754 J. Nat. Prod. 2017, 80, 108−113
Journal of Natural Products
Article
Table 2. Reported 1H NMR Data for 3, 3a, and 7 in CDCl3 no.
3
6 7 12,16 13,15 14 17 18 20 21 22 23 25 26 27 28 30 31 32 33
3a
7
1.98, 1.43, 1.63, 7.57, 7.35, 7.50, 2.94,
dd (13.6, 4.0) m m m m m 2H, d (10.0)
2.00, 1.46, 1.67, 7.58, 7.35, 7.49, 2.96,
dd (13.6, 4.4) overlap overlap d (7.9) t (7.9) t (7.7) 2H, d (9.9)
4.65, 0.90, 0.90, 2.58, 2.47, 5.06, 1.70, 1.68, 2.11, 1.70, 4.94, 1.68, 1.56, 1.24, 1.34,
t (10.0) s s dd (14.0, 7.6) dd (14.0, 7.6) t (7.6) s s dd (13.6, 4.0) m t (7.6) s s s s
4.65, 0.90, 0.90, 2.57, 2.48, 5.06, 1.70, 1.67, 2.13, 1.65, 4.96, 1.67, 1.56, 1.24, 1.34,
t (9.9) s s m m m s s m overlap m s s s s
Table 3. Experimental and Calculated 13C NMR Data for 3 and 3a in CDCl3 (δ in ppm) 3 no.
exptl
calcd
Δδ
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
70.3 171.9 118.5 190.3 65.3 41.7 43.1 47.0 206.9 192.6 137.1 128.5 128.2 132.8 128.2 128.5 26.5 93.5 70.6 26.4 23.7 29.3 119.5 134.7 25.9 18.2 27.7 122.3 133.5 26.0 17.9 15.7
62.4 173.4 113.6 185.8 66.9 34.9 45.3 47.5 204.6 196.2 134.2 127.9 125.4 129.0 123.4 125.3 29.6 89.8 71.9 26.7 26.2 31.7 121.4 132.8 27.2 20.3 31.0 122.8 133.9 26.4 18.8 27.9
−7.9 1.5 −4.9 −4.5 1.6 −6.8 2.2 0.5 −2.3 3.6 −2.9 −0.6 −2.8 −3.8 −4.8 −3.2 3.1 −3.7 1.3 0.3 2.5 2.4 1.9 −1.9 1.3 2.1 3.3 0.5 0.4 0.4 0.9 12.2
Δδ
70.6 170.4 117.8 185.3 66.2 39.3 42.7 50.1 207.4 191.5 132.1 126.2 124.0 130.2 125.1 127.6 29.5 92.5 70.2 27.4 25.0 30.0 118.8 133.9 27.4 20.0 30.9 123.0 132.7 26.9 18.8 16.7
0.3 −1.5 −0.7 −5.0 0.9 −2.4 −0.4 3.1 0.5 −1.1 −5.0 −2.3 −4.2 −2.6 −3.1 −0.9 3.0 −1.0 −0.4 1.0 1.3 0.7 −0.7 −0.8 1.5 1.8 3.2 0.7 −0.8 0.9 0.9 1.0
4.0)
10.0) 10.0)
7.2) 7.2)
3 no.
calcd
dd (13.6, m m d (7.8) t (7.8) t (7.8) dd (14.8, dd (14.8, t (10.0) s s dd (14.0, dd (14.0, t (6.4) s s m m t (7.2) s s s s
Table 3. continued
3a a
1.97, 1.43, 1.58, 7.60, 7.30, 7.45, 3.00, 2.88, 4.20, 1.19, 1.16, 2.54, 2.46, 5.02, 1.67, 1.67, 2.11, 1.65, 4.94, 1.67, 1.54, 1.20, 1.43,
a
33 LADb MADc
exptl
calcd
24.1
30.0
3a Δδ
a
5.9 12.2 2.97
calcd 25.0 5.0 1.65
Δδa 0.9
a Δδ = |δcalcd − δexptl|. bLAD = largest absolute deviation. cMAD = mean absolute deviation, computed as (1/n) ∑ni |δcalcd − δexptl|.
A conformational search using molecular mechanics calculations was performed in Discovery Studio 3.5 Client. The corresponding minimum geometries were fully optimized at the mPW1PW9191/6-31G(d,p) level and subsequently at the mPW1PW9191/6-31G(d,p) level in the gas phase to get better optimized conformers of 3 and 3a. For all optimized structures, vibrational spectra were calculated to ensure that no imaginary frequencies for energy minimum were obtained. The 13C NMR shielding constants of each conformer were computed using the GIAO technique at the mPW1PW91-SCRF/6-31G(d,p) level of theory in the PCM solvent continuum model with chloroform as a solvent.33 As shown in Table 3, the largest absolute deviation (LAD) and average error (MAD) for 3 were 12.2 and 2.97 ppm, respectively, while the LAD and MAD were only 5.0 and 1.65 ppm for 3a, respectively. Especially, the experimental chemical shifts of C-1 (δC 70.3) and C-6 (δC 41.7) that were most probably influenced by the benzoyl did not match the calculated shifts (δC 62.4 and 34.9) of 3, but were closer to the calculated chemical shifts (δC 70.6 and 39.3) of 3a. In addition, the calculated GIAO 13C NMR chemical shifts for the optimized structures of 3 and 3a were plotted against the corresponding experimental 13C NMR chemical shifts. The calculated R2 value for 3 (0.9963) is lower than that for 3a (0.9993) in the linear correlations of the chemical shifts (Figure 2). Therefore, these results strongly suggest that the correct structure of garcinielliptone K is 3a rather than 3. The result also indicates that not only the positions of the bridgehead 110
DOI: 10.1021/acs.jnatprod.6b00754 J. Nat. Prod. 2017, 80, 108−113
Journal of Natural Products
Article
Figure 2. Linear correlations between the calculated and experimental 13C NMR data for 3 and 3a.
Table 4. 13C NMR Data for Compounds 4, 5, and 8 in CDCl3 no.
Figure 3. Structures of hyperibrin C (7) and furoadhyperforin isomer 2b (8).
substituents but also the enolic 1,3-diketo system in 3a were switched compared to their originally assigned positions.1,5 In addition, hyperibrin C (7), recently isolated from Hypericum scabrum,29 was characterized as the C-18 epimer of 3a (Figure 3). The consistent 13C NMR spectroscopic data of 3a and 7 in Table 1 further supported their identical carbon skeletons. The major difference of the two compounds involved the 1H NMR chemical shifts of H-18, Me-20, and Me-21 (Table 2), which may be caused by the shielding effect of the benzoyl group. Accordingly, the reported structures of garcinielliptones L and M (4 and 5) should also be revised to 4a and 5a, respectively, given their coisolation with 3. Their C-1−C-10 chemical shifts (Table 4) matched those of furoadhyperforin isomer 2b (8) (Figure 3),31 a known PPAP with the same core carbon skeleton as was established by X-ray diffraction data (CCDC 1473752, Figure 4). The consistency also supported the correctness of the revised structures 4a and 5a. The type C PPAP 7-epi-nemorosone (6)6 was isolated as keto−enol tautomeric mixtures. Its NMR spectroscopic data were not directly recorded, but the data of its O-methyl derivative (9) were reported. If the positions of the bridgehead substituents switched in 6, it should possess the same structure as plukenetione D or E (6a),28 another PPAP possessing keto−enol tautomeric forms. As shown in Table 5, the chemical shifts for C-5−C-10 of O-methyl-7-epi-nemorosone (9) were consistent with those of O-acetylplukenetione D (10) and sampsonione M (11), a C-7 endo PPAP with a benzoyl substituent (Figure 5),30 indicating that 6 should also be a type A structure, to support the structural query by Cuesta-Rubio.7
4
5
1
73.8
73.7
74.6
2
171.8
171.7
171.7
3
119.9
120.4
120.3
4
190.7
190.5
190.8
5
63.9
64.2
63.6
6
40.2
40.2
39.5
7
43.1
43.2
44.1
8
44.9
45.2
47.1
9
206.0
205.9
205.7
10
208.6
208.4
208.5
11
40.7
40.7
47.6
12, 16
20.8
21.0
17.0
13, 15
20.5
20.9
14
111
8
27.9 11.8
17
26.8
26.7
26.7
18
93.0
94.0
93.5
19
71.3
71.1
71.0
20
26.1
26.7
25.1
21
25.0
25.2
27.0
22
29.2
29.2
29.1
23
119.5
119.5
119.5
24
134.1
134.1
134.2
25
25.9
25.9
26.0
26
18.0
18.0
18.1
27
27.5
27.6
26.4
28
122.3
122.3
122.2
29
133.3
133.4
133.5
30
25.8
25.9
25.9
31
17.8
17.9
17.9
32
15.7
15.9
12.8
33
24.1
23.9
39.2
34
24.8
35
124.3
36
132.3
37
25.6
38
17.8 DOI: 10.1021/acs.jnatprod.6b00754 J. Nat. Prod. 2017, 80, 108−113
Journal of Natural Products
■
Table 5. Selected 13C NMR Data for Compounds 9−11 in CDCl3 9
10
11
1 2 3 4 5 6 7 8 9 10
73.0 170.1 122.0 193.3 63.4 41.9 48.6 49.5 209.2 197.8
71.8 158.8 130.9 197.5 64.3 42.1 48.3 50.0 208.5 193.2
68.0 173.2 117.9 191.2 63.0 39.8 48.5 48.5 207.3 193.1
EXPERIMENTAL SECTION
General Experimental Procedures. The experimental procedures were the same as those reported with minor modification (General Experimental Procedures, Supporting Information).26d Plant Material. The information on plant material is the same as reported earlier.26d Extraction and Isolation. The aerial parts of H. cohaerens (10.0 kg) were powdered and percolated with MeOH (2 × 16 L) at room temperature and filtered. The filtrate was concentrated in vacuo. The crude extract was subjected to silica gel column chromatography eluted with a petroleum ether−acetone gradient (1:0, 8:1, 4:1, 2:1, and 0:1) to afford five fractions, A−E. Fraction B (86.4 g) was separated over an MCI gel column (MeOH−H2O from 8:2 to 10:0) to afford five fractions (Fr. B1−B4). Fr. B2 (22.0 g) was separated over an MCI gel column (MeOH−H2O from 85:15 to 100:0) to give four fractions (Fr. B2a−B2d). Fr. B2a (5.0 g) was separated on a silica gel column, eluted with petroleum ether−acetone (9:1), to afford 8 (46 mg). Furoadhyperforin isomer 2b (8): colorless block crystals (MeOH); mp 173−175 °C; [α]23D +25 (c 0.2, MeOH); UV (MeOH) λmax (log ε) 206 (3.88), 281 (3.87) nm; IR (KBr) νmax 3443, 2965, 2926, 2854, 1732, 1641, 1617, 1454, 1407, 1247, 1083, 964, 801, 597 cm−1; 1 H NMR (acetone-d6, 600 MHz) δ 5.04 (t, J = 7.5 Hz, H-35), 4.99 (m, H-23), 4.96 (m, H-28), 4.76 (dd, J = 10.5, 9.2 Hz, H-18), 3.01 (dd, J = 15.0, 9.2 Hz, H-17a), 2.91 (dd, J = 15.0, 10.5 Hz, H-17b), 2.38 (2H, brd, J = 7.5 Hz, H-22), 2.18 (m, H-11), 2.15 (m, H-34a), 2.12 (m, H-27a), 2.00 (m, H-34b), 1.87 (m, H-33a), 1.76 (m, H-13a), 1.72 (overlap, H-27b), 1.70 (brd, J = 12.9 Hz, H-6a), 1.66 (3H, s, H-26), 1.66 (3H, s, H-30), 1.66 (overlap, H-7), 1.64 (3H, s, H-37), 1.62 (3H, s, H-25), 1.59 (3H, s, H-38), 1.55 (3H, s, H-31), 1.49 (m, H-33b), 1.41 (brt, J = 12.9 Hz, H-6b), 1.29 (m, H-13b), 1.26 (3H, s, H-20), 1.22 (3H, s, H-21), 1.10 (3H, d, J = 6.8 Hz, H-12), 1.09 (3H, s, H-32), 0.89 (3H, t, J = 7.2 Hz, H-14); 13C NMR (acetone-d6, 150 MHz) δ 209.8 (C, C-10), 207.1 (C, C-9), 192.9 (C, C-4), 147.7 (C, C-2), 134.9 (C, C-24), 134.4 (C, C-29), 132.2 (C, C-36), 125.8 (CH, C-35), 123.7 (CH, C-28), 121.4 (C, C-3), 121.0 (CH, C-23), 95.2 (CH, C-18), 76.3 (C, C-1), 71.7 (C, C-19), 64.7 (C, C-5), 48.8 (CH, C-11), 48.4 (C, C-8), 45.9 (CH, C-7), 40.9 (CH2, C-6), 40.0 (CH2, C-33), 30.3 (CH2, C-22), 28.9 (CH2, C-27), 28.2 (CH2, C-13), 27.2 (CH2, C-17), 26.7 (CH2, C-34), 26.2 (CH3, C-21), 26.2 (CH3, C-25), 26.0 (CH3, C-30), 25.9 (CH3, C-37), 25.6 (CH3, C-20), 18.2 (CH3, C-26), 18.0 (CH3, C-38), 17.9 (CH3, C-31), 17.4 (CH3, C-12), 12.7 (CH3, C-32), 12.0 (CH3, C-14); positive ESIMS m/z 589 [M + Na]+; HRTOFMS m/z 567.4034 (calcd for C36H55O5, 567.4049). Crystallographic data of 8: C36H54O5, M = 566.79, orthorhombic, a = 10.5654(7) Å, b = 12.0671(8) Å, c = 25.9946(15) Å, α = 90.00°, β = 90.00°, γ = 90.00°, V = 3314.1(4) Å3, T = 100(2) K, space group P212121, Z = 4, μ(Cu Kα) = 0.578 mm−1, 12 415 reflections measured, 5140 independent reflections (Rint = 0.0453). The final R1 values were 0.0952 [I > 2σ(I)]. The final wR(F2) values were 0.2141 [I > 2σ(I)]. The final R1 values were 0.1026 (all data). The final wR(F2) values were 0.2192 (all data). The goodness of fit on F2 was 1.161. Flack parameter = 0.2(6). The Hooft parameter is 0.10(11) for 1922 Bijvoet pairs.
Figure 4. ORTEP drawing of 8.
no.
Article
The inconsistent chemical shifts of C-1−C-4 in 9 and 10 may be ascribed to their different C-2 substituents. Thus, we would suggest that the structure of 7-epi-nemorosone should be revised to plukenetione D (6a). From a biosynthesis perspective, the most likely route to the type C PPAPs would require that the first prenylation of the acylphloroglucinol occurred at C-1 (C-3 or C-5 for types A and B PPAPs) to generate an unusual MPAP (Scheme 1).1 However, these unknown MPAP intermediates with isoprenyl and acyl groups located at the same carbon atom have not yet been found in plants, while those MPAP intermediates for type A or B structures are widely distributed,34 which indirectly provides evidence against the natural occurrence of type C PPAPs. In conclusion, the structures of all the reported type C PPAPs (1−6) have been revised to corresponding type A structures (1a−6a), and, therefore, only types A and B PPAPs are likely present in plants of the family Clusiaceae.
Figure 5. Structures of revised O-methyl-7-epi-nemorosone (9), O-acetylplukenetione D (10), and sampsonione M (11). 112
DOI: 10.1021/acs.jnatprod.6b00754 J. Nat. Prod. 2017, 80, 108−113
Journal of Natural Products
■
Article
(19) Mitsopoulou, K. P.; Vidali, V. P.; Maranti, A.; Couladouros, E. A. Eur. J. Org. Chem. 2015, 2015, 287−290. (20) Simpkins, N. S. Chem. Commun. 2013, 49, 1042−1051. (21) Nuhant, P.; David, M.; Pouplin, T.; Delpech, B.; Marazano, C. Org. Lett. 2007, 9, 287−289. (22) Raikar, S. B.; Nuhant, P.; Delpech, B.; Marazano, C. Eur. J. Org. Chem. 2008, 2008, 1358−1369. (23) Zhang, Q.; Mitasev, B.; Qi, J.; Porco, J. A., Jr. J. Am. Chem. Soc. 2010, 132, 14212−14215. (24) Lindermayr, K.; Plietker, B. Angew. Chem., Int. Ed. 2013, 52, 12183−12186. (25) Grenning, A. J.; Boyce, J. H.; Porco, J. A., Jr. J. Am. Chem. Soc. 2014, 136, 11799−11804. (26) (a) Xu, G.; Feng, C.; Zhou, Y.; Han, Q. B.; Qiao, C. F.; Huang, S. X.; Chang, D. C.; Zhao, Q. S.; Luo, K. Q.; Xu, H. X. J. Agric. Food Chem. 2008, 56, 11144−11150. (b) Xu, G.; Kan, W. L. T.; Zhou, Y.; Song, J. Z.; Han, Q. B.; Qiao, C. F.; Cho, C. H.; Rudd, J. A.; Lin, G.; Xu, H. X. J. Nat. Prod. 2010, 73, 104−108. (c) Yang, X. W.; Deng, X.; Liu, X.; Wu, C. Y.; Li, X. N.; Wu, B.; Luo, H. R.; Li, Y.; Xu, H. X.; Zhao, Q. S.; Xu, G. Chem. Commun. 2012, 48, 5998−6000. (d) Liu, X.; Yang, X. W.; Chen, C. Q.; Wu, C. Y.; Zhang, J. J.; Ma, J. Z.; Wang, H.; Yang, L. X.; Xu, G. J. Nat. Prod. 2013, 76, 1612−1618. (e) Yang, X. W.; Ding, Y.; Zhang, J. J.; Liu, X.; Yang, L. X.; Li, X. N.; Ferreira, D.; Walker, L. A.; Xu, G. Org. Lett. 2014, 16, 2434−2437. (f) Zhang, J. J.; Yang, J.; Liao, Y.; Yang, X. W.; Ma, J. Z.; Xiao, Q. L.; Yang, L. X.; Xu, G. Org. Lett. 2014, 16, 4912−4915. (g) Liao, Y.; Liu, X.; Yang, J.; Lao, Y. Z.; Yang, X. W.; Li, X. N.; Zhang, J. J.; Ding, Z. J.; Xu, H. X.; Xu, G. Org. Lett. 2015, 17, 1172−1175. (h) Zhang, J. J.; Yang, X. W.; Liu, X.; Ma, J. Z.; Liao, Y.; Xu, G. J. Nat. Prod. 2015, 78, 3075−3079. (27) Hernandez, I. M.; Fernandez, M. C.; Cuesta-Rubio, O.; Piccinelli, A. L.; Rastrelli, L. J. Nat. Prod. 2005, 68, 931−934. (28) Henry, G. E.; Jacobs, H.; Carrington, C. M. S.; McLean, S.; Reynolds, W. F. Tetrahedron 1999, 55, 1581−1596. (29) Gao, W.; Hu, J. W.; Hou, W. Z.; Xu, F.; Zhao, J.; Xu, F.; Sun, H.; Xing, J. G.; Peng, Y.; Wang, X. L.; Ji, T. F.; Li, L.; Gu, Z. Y. Tetrahedron Lett. 2016, 57, 2244−2248. (30) Hu, L. H.; Sim, K.-Y. Tetrahedron 2000, 56, 1379−1386. (31) Yang, J. B.; Liu, R. D.; Ren, J.; Wei, Q.; Wang, A. G.; Su, Y. L. J. Asian Nat. Prod. Res. 2016, 18, 436−442. (32) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; et al. Gaussian 09, Revision C.01; Gaussian, Inc.: Wallingford, CT, 2010. (33) Lodewyk, M. W.; Siebert, M. R.; Tantillo, D. J. Chem. Rev. 2012, 112, 1839−1862. (34) Singh, I. P.; Bharate, S. B. Nat. Prod. Rep. 2006, 23, 558−591.
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jnatprod.6b00754. Computational details of 3 and 3a; MS and NMR spectra of 8 (PDF) Crystallographic file for 8 (CIF)
■
AUTHOR INFORMATION
Corresponding Author
*Tel/Fax (G. Xu): (86) 871-65217971. E-mail: xugang008@ mail.kib.ac.cn. ORCID
Gang Xu: 0000-0001-7561-104X Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS The work was financially supported by the Natural Sciences Foundation of Yunnan Province (No. 2015FA032, 2016FB017), Foundation of State Key Laboratory of Phytochemistry and Plant Resources in West China (P2015-ZZ07), the Foundation from Youth Innovation Promotion Association CAS to X.W.Y. and G.X., and the West Light Foundation of the Chinese Academy of Sciences to X.W.Y.
■
REFERENCES
(1) Ciochina, R.; Grossman, R. B. Chem. Rev. 2006, 106, 3963−3986. (2) (a) Adam, P.; Arigoni, D.; Bacher, A.; Eisenreich, W. J. Med. Chem. 2002, 45, 4786−4793. (b) Boubakir, Z.; Beuerle, T.; Liu, B.; Beerhues, L. Phytochemistry 2005, 66, 51−57. (3) Yang, X. W.; Li, M. M.; Liu, X.; Ferreira, D.; Ding, Y.; Zhang, J. J.; Liao, Y.; Qin, H. B.; Xu, G. J. Nat. Prod. 2015, 78, 885−895. (4) De Oliveira, C. M. A.; Porto, A. M.; Bittrich, V.; Vencato, I.; Marsaioli, A. J. Tetrahedron Lett. 1996, 37, 6427−6430. (5) Weng, J. R.; Tsao, L. T.; Wang, J. P.; Wu, R. R.; Lin, C. N. J. Nat. Prod. 2004, 67, 1796−1799. (6) De Oliveira, C. M. A.; Porto, A. L. M.; Bittrich, V.; Marsaioli, A. J. Phytochemistry 1999, 50, 1073−1079. (7) Cuesta-Rubio, O.; Velez-Castro, H.; Frontana-Uribe, B. A.; Cardenas, J. Phytochemistry 2001, 57, 279−283. (8) Ahmad, N. M.; Rodeschini, V.; Simpkins, N. S.; Ward, S. E.; Blake, A. J. J. Org. Chem. 2007, 72, 4803−4815. (9) Takagi, R.; Inoue, Y.; Ohkata, K. J. Org. Chem. 2008, 73, 9320− 9325. (10) Couladouros, E. A.; Dakanali, M.; Demadis, K. D.; Vidali, V. P. Org. Lett. 2009, 11, 4430−4433. (11) Castro, M. L.; do Nascimento, A. M.; Ikegaki, M.; Costa-Neto, C. M.; Alencar, S. M.; Rosalen, P. L. Bioorg. Med. Chem. 2009, 17, 5332−5335. (12) Garnsey, M. R.; Lim, D.; Yost, J. M.; Coltart, D. M. Org. Lett. 2010, 12, 5234−5237. (13) Zhang, L. J.; Chiou, C. T.; Cheng, J. J.; Huang, H. C.; Yang Kuo, L. M.; Liao, C. C.; Bastow, K. F.; Lee, K. H.; Kuo, Y. H. J. Nat. Prod. 2010, 73, 557−562. (14) Biber, N.; Mows, K.; Plietker, B. Nat. Chem. 2011, 3, 938−942. (15) Richard, J.-A.; Pouwer, R. H.; Chen, D. Y.-K. Angew. Chem., Int. Ed. 2012, 51, 4536−4561. (16) Bellavance, G.; Barriault, L. Angew. Chem., Int. Ed. 2014, 53, 6701−6704. (17) Horeischi, F.; Biber, N.; Plietker, B. J. Am. Chem. Soc. 2014, 136, 4026−4030. (18) Wu, S. B.; Long, C.; Kennelly, E. J. Nat. Prod. Rep. 2014, 31, 1158−1174. 113
DOI: 10.1021/acs.jnatprod.6b00754 J. Nat. Prod. 2017, 80, 108−113
