Total Synthesis of Norsampsones A and B, Garcinielliptones N and O, and Hyperscabrin A

Article abstract of DOI:10.1021/acs.jnatprod.8b00763

The asymmetric total synthesis of five decarbonyl polycyclic polyprenylated acylphloroglucinols norsampsnes A (3) and B (4), garcinielliptones O (5) and N (6), and hyperscabrin A (7) is described. The synthesis to construct the core substituted cyclohexanone ring of these natural products was achieved by a key Dieckmann condensation. The chirality of the molecules was introduced by the stereoselective alkylation with Evans' oxazolidinones. The synthesis could be run on grams scale, and the Dieckmann condensation was investigated through the DFT calculations to help improve the yield of garcinielliptone O (5). Determination of the absolute configuration of garcinielliptones O (5) and N (6) was also achieved.

Full text of DOI:10.1021/acs.jnatprod.8b00763

Article
pubs.acs.org/jnp
Cite This: J. Nat. Prod. XXXX, XXX, XXX−XXX
Total Synthesis of Norsampsones A and B, Garcinielliptones N and
O, and Hyperscabrin A
Changwu Zheng,† Xueying Wang,† Wenwei Fu, Yue Lu, Hongsheng Tan,* and Hongxi Xu*
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China
S
* Supporting Information
ABSTRACT: The asymmetric total synthesis of five decarbonyl polycyclic polyprenylated acylphloroglucinols norsampsnes A
(3) and B (4), garcinielliptones O (5) and N (6), and hyperscabrin A (7) is described. The synthesis to construct the core
substituted cyclohexanone ring of these natural products was achieved by a key Dieckmann condensation. The chirality of the
molecules was introduced by the stereoselective alkylation with Evans’ oxazolidinones. The synthesis could be run on grams
scale, and the Dieckmann condensation was investigated through the DFT calculations to help improve the yield of
garcinielliptone O (5). Determination of the absolute configuration of garcinielliptones O (5) and N (6) was also achieved.
toward the norsampsones and their analogues has been
reported.14 On the other hand, for many of these natural
products, their absolute configuration is still not determined or
has been achieved by the analysis of circular dichroism spectra.
It is very desirable to develop asymmetric synthesis procedures
to confirm compounds with their absolute configurations.
lants of the genera Hypericum and Garcinia of the
PClusiaceae family have long been used in traditional
medicine for the treatment of various diseases, including
bacterial and viral infections.1 The biological activity of these
plants is generally attributed to the presence of complex
polycyclic polyprenylated acylphloroglucinols (PPAPs), which
have recently become popular synthetic targets in pharma-
ceutical chemistry.2 The first total syntheses of this kind of
natural product, garsubellin A, was conducted by Shibasaki3
and Danishefsky4 in 2005. A number of other synthetic efforts
toward the PPAPs have been made especially from the groups
of Shair,5 Barriault,6 Maimone,7 Plietker,8 and Porco.9
Acompanying the isolation of bioactive complex PPAPs,
decarbonyl PPAPs such as norsampsones A (3) and B (4),10
garcinielliptones N (5) and O (6),11 and hyperscabrin A
(7)12 sometimes also were found to occur (Scheme 1). The
decarbonyl PPAPs are secondary metabolites of complex
PPAPs and proposed to be generated by the loss of the C-2/C-
3 carbonyl group in a biogenetic pathway through one or two
retro-Claisen condensation reactions followed by decarbox-
ylation.10,13 For example, norsampsones A (3) and B (4) have
been postulated as degradation products from the bioactive
nemorosone (1), while hyperscabrin A (7) and garciniellip-
tones N (6) and O (5) originate from the bioactive hyperforin
(2) or its analogues. On the other hand, decarbonyl PPAPs or
related compounds also may be used as building blocks for the
synthesis of PPAPs and their derivatives (Scheme 1).8a
Although great interest is evident in the synthesis of PPAPs,
only one achiral synthetic study of the decarbonyl PPAPs
RESULTS AND DISCUSSION
■
Retrosynthetic Analysis. Dieckmann condensation and
variants thereof are powerful reactions to produce cyclic β-keto
esters.15 The decarbonyl PPAPs that feature at least a
dicarbonyl moiety are shown in Scheme 1, which revealed
that a Dieckmann condensation with ketone or ester as the
nucleophile could be applied. Based on this strategy, a
disconnection was performed on either side of the cyclic
ketone to afford two possible linear substrates for the synthesis
(Scheme 2). Path A provides a conventional diester precursor
for the synthesis of garcinielliptone O (5). However, a model
reaction indicated that a competitive aldol reaction is a
challenge for Dieckmann cyclization.16 In path B, the resulting
linear precursor is easy to make, but a ketone has to be used as
the nucleophile. As a general asymmetric retrosynthesis
procedure for compounds 3−7 illustrated in Scheme 2, the
decarbonyl PPAPs may be disconnected to the crucial linear
intermediates 8 via Dieckmann cyclization. Preparation of 8 is
then carried out through an alkylation between 9 and 10. The
Received: September 6, 2018
© XXXX American Chemical Society and
American Society of Pharmacognosy
A
DOI: 10.1021/acs.jnatprod.8b00763
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12a and (R)-4-benzyl-2-oxazolidinone to give the enantio-
enriched compound 13 in 70% yield. Protection of the ketone
carbonyl group with ethylene glycol catalyzed by p-
toluenesulfonic acid (PTSA) followed by alkylation afforded
11a diastereoselectively in very high yield. Then, with a
sequence of reduction and iodination, the chiral 10a could be
prepared on a gram scale. Coupling of 10a with 9a was
performed using NaH as the base and with quenching by dilute
HCl to afford the linear precursor 8a in a 60% yield in nearly a
1:1 ratio (Scheme 3). The vital Dieckmann cyclization was
then tested with (S,S)-8a in the presence of a variety of bases.
The reaction with commonly used MeONa did not proceed.
With NaH or lithium bis(trimethylsilyl)amide (LHMDS) as
the base, the yield was around 40% and the diastereoselectivity
was about 3:1. Improved results were obtained in the presence
of t-BuOK that gave two diastereomers (6:1 dr) smoothly in a
73% yield. The isomers could be separated by column
chromatography and determined to be norsampsones A (3)
and B (4) by comparing their 1H NMR and 13C NMR spectra
with reported data.10 The other precursor, (R,S)-8a, was also
processed under the optimized conditions to give two
diastereomers (10:1 dr), which, however, could not be
separated by column chromatography (Scheme 4).
Scheme 1. Examples of Bioactive Complex PPAPs,
Decarbonyl PPAPs, and Their Mutual Transformation
Total Synthesis of Garcinielliptones N (6) and O (5)
and Hyperscabrin A (7). Having completed the total
synthesis of norsampsones A (3) and B (4), the synthesis to
the second type of decarbonyl PPAPs illustrated by
garcinielliptone O (5) was evaluated, which consists of three
chiral centers with an ester at the C-6 quaternary carbon
center. With a modified synthetic pathway to 8a employed,17
the key precursor 8b was obtained in six steps in a total 13%
yield (Scheme 5). The Dieckmann condensation was first
carried out with t-BuOK as the base, in which two separable
diastereoisomers were detected, with the product 21 isolated
as the major one along with another isomer, 22, in a ratio of
1.3:1 (Scheme 6 and Table 1, entry 1). Determination of their
structures by NMR analysis revealed compounds 21 and 22 to
be epimers of each other, and that was also verified by
tautomerization reactions in the presence of t-BuOK. However,
none of their NMR spectroscopic parameters were identical to
those of garcinielliptone O (5).
Scheme 2. Strategies for the Asymmetric Synthesis of
Decarbonyl PPAPs
In order to improve the yield of product 5, a preliminary
mechanistic study was performed. In the presence of t-BuOK
in tetrahydrofuran (THF) at room temperature, compounds
21 and 22 are presumably formed from nonselective
protonation from either face of the ketoester enolate product
via TS B, as TS C is highly unfavorable. Density functional
theory (DFT) quantum mechanics calculations suggested that
the potassium ketoester enolate leading to compounds 21 and
22 is significantly more stable by 2 kcal/mol than the
corresponding one that generated compound 5. The Die-
ckmann condensation under these conditions is reversible, as
the in situ-generated MeOK is likely to attack the ketone
carbonyl group to open the cyclohexanone core structure, with
product ratios under thermodynamic control. It was reasoned
that the difference in activation energy for the formation of the
tetrahedral intermediates A and B should be small. When
cyclization is conducted at a temperature higher than the
boiling point of the methanol byproduct, the reaction should
be rendered irreversible. Based on the above calculations, the
reaction was then performed in toluene at reflux with NaH as
the base. Although 20% yields of garcinielliptone N (6) and
hyperscabrin A (7) resulted due to decarboxylation, the yield
enantio-enriched compound 10 would be easily synthesized
from compound 12 via a four-step reaction with the use of a
chiral auxiliary.
Total Synthesis of Norsampsones A (3) and B (4). The
total synthesis of norsampsones A (3) and B (4) was first
accomplished. Both of these two molecules feature three chiral
centers and one as a quaternary carbon center. The ketone
carbonyl group at the C-2 position made a Dieckmann
cyclization quite challenging, as a competitive aldol reaction
may occur during cyclization. The synthesis was started with
B
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Scheme 3. Synthesis of the Key Linear Precursor 8a
configuration of naturally occurring garcinielliptones N (6)
and O (5) was not determined previously, comparison of the
specific rotations of the synthetic samples with the reported
data11 revealed the absolute configuration of garcinielliptone N
Scheme 4. Synthesis of Norsampsones A (3) and B (4) and
Analogues via Dieckmann Condensation
([α]27 = −37.6 (c 0.40, CHCl3)] [lit. [α] = −42 (c 0.38,
D
CHCl3)) and garcinielliptone O ([α]27 = −258 (c 0.35,
D
CHCl3)] [lit. [α] = −277 (c 0.16, CHCl3)) to be 2R,4S,6R and
2R,4S,6S, respectively. Furthermore, the absolute configura-
tions of norsampsones A (3) and B (4) and hyperscabrin A (7)
were also confirmed by total synthesis in addition to the
previous circular dichroism analysis performed.
In view of the biogenetic proposal for the generation of
dicarbonyl PPAPs, which are hypothesized as being degraded
from complex PPAPs,10,13 it is reasonable to speculate that all
of the diastereoisomers currently prepared via the Dieckmann
cyclization should be naturally occurring products, although
compounds 16, 17, 21, and 22 have not been reported in the
literature so far. The cytotoxicities of compounds norsamp-
sones A (3) and B (4), garcinielliptones N (6) and O (5),
hyperscabrin A (7), 21, and 22 were evaluated against several
cancer cell lines (A549, SNU-1, 786-O, and KMS-11);
however, all were deemed inactive (IC50 > 10 μM).
of garcinielliptone O (5) was improved to 17% (Table 1, entry
2). Lowering the temperature to 70 °C in order to reduce the
decarboxylation led to an incomplete reaction (Table 1, entry
3). Replacement of NaH with LHMDS further increased the
yield of garcinielliptone O (5) to 21% without decarboxylation
products being observed (Table 1, entry 4). The product ratio
of 1:2.5 for compound 5 vs 21 and 22 is also consistent with
the small difference (<0.2 kcal/mol) for the calculated
transition state energy of the two major competing pathways.
The mixture of compounds 21 and 22 was then treated with
NaH to give garcinielliptone N (6) and hyperscabrin A (7) in
43% and 29% yields, respectively (Scheme 7). Under a high
temperature with LiCl/DMSO, the compounds decomposed.
The NMR and MS data of garcinielliptones N (6) and O (5)
and hyperscabrin A (7) were in good agreement with data
reported.11,12
EXPERIMENTAL SECTION
■
General Experiment Procedures. All glassware was dried with a
hot air gun, and all reactions were carried out under an atmosphere of
dry N2 unless otherwise stated. All reagents and dry solvents were
used as received from the supplier. Melting points were performed
using a Gallenkamp melting point apparatus and are uncorrected.
Optical rotations were recorded as dilute solutions in the indicated
solvent in a 25 mm glass cell using a JASCO P-1010 polarimeter at λ
= 589 nm. IR spectra were carried out on either a neat oil or a solid
using a PerkinElmer Spectrum 983G instrument. Wavelengths (ν) are
1
reported in cm−1. H and 13C NMR were performed on Bruker AV-
400 or Agilent 400 NMR spectrometers in CDCl3 with 0.03%
(CH3)4Si. Chemical shifts (δ) are quoted in ppm; coupling constants
(J) in Hz. All spectra are referenced to the CDCl3 peaks at 7.26 ppm
or (CH3)4Si peaks at 0.00 ppm for proton and 77.0 ppm for carbon
unless otherwise stated. The following abbreviations apply: (br)
broad, (s) singlet, (d) doublet, (t) triplet, (q) quartet, and (m)
Determination of the Absolute Configuration and
Inhibitory Effect on Cancer Cells. As the absolute
C
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Scheme 5. Synthesis of the Key Linear Precursor 8b
Scheme 6. Synthesis of Garcinielliptones O (5) and Analogues
multiplet. Mass spectrometry was performed on a SYNAPT G2-Si
HDMS (Waters Corp., Manchester, UK). Flash column chromatog-
raphy was performed using silica gel (300−400 mesh).
Table 1. Challenges in the Synthesis of Garcinielliptone O
(5)
a
entry
1
conditions
yield of 5 yield of 21 yield of 22
Procedures for the Synthesis of 8a. To a solution of 3,3-
dimethyl-5-oxo-5-phenylpentanoic acid 12a18 (3 g, 13.6 mmol) in
THF (56 mL) was added triethylamine (3.6 mL, 27 mmol) and
pivaloyl chloride (PivCl) (2 mL, 16.4 mmol) at 0 °C. After stirring for
1 h at 0 °C, LiCl (0.7 g, 6.4 mmol) and (R)-4-benzyl-2-oxazolidinone
(2.9 g, 16.4 mmol) were added, and the resulting mixture was warmed
to rt. After reaction for 20 h at rt, the mixture was concentrated in
vacuo, and the residue was dissolved in EtOAc, washed with 1 M HCl,
saturated NaHCO3, and brine, and dried over Na2SO4. The solvent
was removed under reduced pressure. The crude product was purified
by silica gel with 10% EtOAc/hexanes to yield the title compound, 13
t-BuOK, THF, rt
<5%
17%
8%
43%
24%
31%
37%
32%
18%
17%
18%
b
2
3
NaH, toluene, reflux
NaH, toluene, 70 °C
LHMDS, THF, reflux
c
4
21%
a
The reaction was performed at 0.3 mmol scale, and usually <5% of
b
additional isomers could be detected during the reaction. About 20%
yields of garcinielliptone N (6) and hyperscabrin A (7) were isolated.
c
36% yield of starting material recovered.
D
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Scheme 7. Synthesis of Garcinielliptone N (6) and Hyperscabrin A (7)
(3.5 g, 70%), as a white powder: [α]27 −33.3 (c 0.65, CHCl3); FT-
until a white solid precipitated. Then MgSO4 powder was added to
dry the mixture for 15 min, and the mixture was filtered through
Celite. The filtrate was concentrated to run the column with 10%
EtOAc/hexane on silica gel to afford the product 15 as an oil (413
D
1
IR νmax 2960, 1783, 1684, 1202, 1137 cm−1; H NMR (400 MHz,
CDCl3) δ 7.96 (2H, d, J = 7.4 Hz), 7.52 (1H, t, J = 7.3 Hz), 7.44 (2H,
t, J = 7.6 Hz), 7.36−7.16 (5H, m), 4.72−4.58 (1H, m), 4.21−4.10
(2H, m), 3.29−3.18 (5H, m), 2.73 (1H, dd, J = 12.9, 9.3 Hz), 1.24
(3H, s), 1.22 (3H, s); 13C NMR (101 MHz, CDCl3) δ 200.0, 171.9,
153.4, 138.2, 135.3, 132.7, 129.3, 128.8, 128.4, 128.0, 127.2, 765.9,
55.1, 46.9, 43.9, 37.9, 33.3, 28.7, 28.6; HRESIMS m/z 380.1876 [M +
H]+ (calcd for C23H26NO4, 380.1861).
mg, 65% yield): [α]25 −28.8 (c 0.45, CHCl3); FT-IR νmax 3460,
D
2964, 1225 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.45 (2H, d, J = 8.4
Hz), 7.37−7.23 (3H, m), 5.22−5.18 (1H, m), 4.06−3.94 (2H, m),
3.77−3.64 (3H, m), 3.58 (1H, dd, J = 11.2, 5.1 Hz), 2.21−2.02 (3H,
m), 2.00−1.83 (2H, m), 1.71 (3H, s), 1.71−1.64 (1H, m), 1.64 (3H,
s), 0.94 (3H, s), 0.93 (3H, s); 13C NMR (101 MHz, CDCl3) δ 143.8,
132.3, 128.1, 127.7, 125.7, 124.7, 111.2, 64.1, 63.6, 63.4, 49.7, 48.9,
36.0, 30.9, 27.2, 26.8, 26.4, 25.9, 17.8; HRESIMS m/z 319.2272 [M +
H]+ (calcd for C20H31O3, 319.2273).
To a stirred solution of (R)-13 (3.5 g, 9.6 mmol) and ethylene
glycol (2.2 mL, 38.4 mmol) in benzene (20 mL) was added p-
toluenesulfonic acid monohydrate (83 mg, 0.48 mmol), and the
mixture was heated to reflux for 36 h using Dean−Stark conditions.
The solvent was removed in vacuo, and purification conducted by
flash column chromatography with 10% EtOAc/hexanes to yield
A solution of 15 (1.1 g, 3.5 mmol) in toluene (20 mL) was stirred
vigorously. Then PPh3 (5.3 mmol, 1.4 g), imidazole (0.72 g, 10.6
mmol), and I2 (1.3 g, 4.9 mmol) were added into the solution
sequentially at rt. The mixture was stirred vigorously for 5 min at rt,
and 1.5 mL of CH3CN was added dropwise to convert the sticky
brown solid on the bottom to a white precipitate. The reaction was
monitored by TLC and quenched by aqueous Na2S2O3. Water and
EtOAc were added, and the mixture was extracted with hexane. The
extracts were dried over Na2SO4 and concentrated to a small volume,
from which PPh3O precipitated. Hexanes were added, and the
mixture was filtered to remove the PPh3O. The filtrate was
concentrated and purified by column chromatography with 1%
EtOAc/hexane on silica gel (treated with 5% Et3N/hexanes) to give
10a as an oil (1.3 g, 85% yield): [α]27D −45.3 (c 0.55, CHCl3); FT-IR
compound 14 as a colorless oil (2.8 g, 68% yield): [α]27 −31.8 (c
D
1
0.3, CHCl3); FT-IR νmax 2955, 1779, 1704, 1198 cm−1; H NMR
(400 MHz, CDCl3) δ 7.44 (2H, d, J = 7.0 Hz), 7.38−7.20 (8H, m),
4.73−4.59 (1H, m), 4.15−4.09 (2H, m), 4.02−3.91 (2H, m), 3.71−
3.60 (2H, m), 3.38 (1H, dd, J = 13.3, 3.1 Hz), 3.12 (1H, d, J = 17.6
Hz), 2.93 (1H, d, J = 17.6 Hz), 2.72 (1H, dd, J = 13.2, 10.1 Hz), 2.25
(1H, d, J = 15.2 Hz), 2.15 (1H, d, J = 15.2 Hz), 1.13 (6H, s); 13C
NMR (101 MHz, CDCl3) δ 171.9, 153.4, 143.7, 135.6, 129.4, 128.8,
127.9, 127.6, 127.1, 125.6, 110.9, 65.7, 63.6, 63.3, 55.1, 47.6, 44.1,
37.9, 33.1, 30.1, 30.1; HRESIMS m/z 424.2137 [M + H]+ (calcd for
C25H30NO5, 424.2124).
To a solution of 14 (2.0 g, 4.7 mmol) in THF (25 mL) was added
sodium bis(trimethylsilyl)amide (NaHMDS) (2.0 M in THF, 3.6 mL,
7.1 mmol) dropwise over 5 min at −78 °C. After the mixture was
stirred at −78 °C for 1 h, prenyl bromide (1.1 mL, 9.4 mmol) was
added dropwise over 5 min at −78 °C, and the mixture was stirred at
−78 °C for 7 h. A saturated NH4Cl aqueous solution was added to
the reaction mixture, and the product was extracted with EtOAc. The
combined extracts were dried over Na2SO4. The organic phase was
concentrated under reduced pressure, and the crude product was
purified by silica gel column chromatography (eluent hexane/EtOAc,
10:1) to give the desired product 11a (2.2 g, 97% yield) as a colorless
1
νmax 2963, 2888, 1390, 1225 cm−1; H NMR (400 MHz, CDCl3) δ
7.44 (2H, d, J = 6.9 Hz), 7.40−7.15 (3H, m), 5.09 (1H, t, J = 7.0 Hz),
4.00 (2H, t, J = 4.3 Hz), 3.76−3.63 (2H, m), 3.50 (1H, dd, J = 9.8, 3.1
Hz), 3.12 (1H, dd, J = 9.8, 7.2 Hz), 2.33−2.15 (1H, m), 2.12−2.03
(1H, m), 2.01 (1H, d, J = 15.3 Hz), 1.94 (1H, d, J = 15.3 Hz), 1.86−
1.78 (1H, m), 1.69 (3H, s), 1.66 (3H, s), 0.96 (3H, s), 0.95 (3H, s);
13C NMR (101 MHz, CDCl3) δ 143.9, 131.8, 128.1, 127.7, 125.7,
123.8, 110.8, 63.7, 63.5, 49.0, 48.4, 37.8, 29.1, 26.6, 26.0, 25.9, 18.2,
10.8; HRESIMS m/z 429.1298 [M + H]+ (calcd for C20H30IO2,
429.1291).
oil: [α]28 −37.9 (c 1.40, CHCl3); FT-IR νmax 2963, 1781, 1695,
At 0 °C, to a solution of 9a (883 mg, 3.5 mmol) in DMF (10 mL)
was added NaH (140 mg, 60% in mineral oil, 3.5 mmol) slowly, and
the mixture was warmed to rt and stirred for 30 min. Next, the
mixture was cooled to 0 °C again and 10a (750 mg, 1.75 mmol) was
added dropwise. The mixture was stirred at rt for 48 h, quenched by
5% dilute HCl solution (5 mL), and stirred for an additional 2 h. The
mixture was then extracted by hexanes, with the organic layer dried
over Na2SO4 and the solvent removed under a vacuum. The residue
was purification by flash chromatography with 5% EtOAc/hexane on
silica gel to give (R,S)-8a (248 mg, 28% yield) and (S,S)-8a (284 mg,
32% yield) as oils.
D
1381, 1225 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.45 (2H, d, J = 6.9
Hz), 7.40−7.15 (8H, m), 5.20−5.15 (1H, m), 4.76−4.60 (1H, m),
4.47 (1H, dd, J = 11.3, 3.5 Hz), 4.16−3.98 (4H, m), 3.73−3.59 (2H,
m), 3.19 (1H, dd, J = 13.3, 3.1 Hz), 2.63−2.47 (2H, m), 2.33 (1H, d,
J = 12.9 Hz), 2.08 (1H, d, J = 15.4 Hz), 2.01 (1H, d, J = 15.4 Hz),
1.67 (3H, s), 1.63 (3H, s), 1.11 (3H, s), 1.04 (3H, s); 13C NMR (101
MHz, CDCl3) δ 176.3, 153.2, 144.1, 135.7, 133.1, 129.3, 128.8, 128.0,
127.6, 127.1, 125.6, 122.0, 110.7, 65.1, 63.5, 63.5, 55.6, 48.9, 47.8,
37.6, 36.9, 27.6, 26.7, 25.8, 25.7, 17.7; HRESIMS m/z 492.2749 [M +
H]+ (calcd for C30H38NO5, 492.2750).
LiAlH4 (LAH) powder (190 mg, 5 mmol) was dispersed in dry
THF (5 mL) portionwise at 0 °C carefully. At this temperature, a
solution of 11a (1.0 g, 2 mmol) in THF (5 mL) was added dropwise
into the mixture very slowly. After addition, the mixture was warmed
to rt and stirred for 0.5 h. The reaction was diluted with ether and
quenched by the addition of 0.19 mL of H2O, 0.19 mL of 15%
aqueous NaOH, and 0.57 mL of H2O at 0 °C very slowly and
carefully. The mixture was then warmed to rt and stirred for 30 min
(S,S)-8a: [α]27 −78.3 (c 1.00, CHCl3); FT-IR νmax 2966, 1743,
D
1
1712, 1693, 1448, 1209 cm−1; H NMR (400 MHz, CDCl3) δ 7.87
(2H, d, J = 7.3 Hz), 7.51 (1H, t, J = 7.3 Hz), 7.42 (2H, t, J = 7.6 Hz),
5.05−5.00 (2H, m), 4.79 (1H, t, J = 6.5 Hz), 3.65 (3H, s), 3.02 (1H,
d, J = 15.9 Hz), 2.72 (1H, d, J = 15.9 Hz), 2.67 (2H, d, J = 6.5 Hz),
2.46−2.32 (2H, q, J = 6.9 Hz), 2.22 (2H, q, J = 7.2 Hz), 2.12−1.94
(2H, m), 1.89 (1H, dd, J = 14.6, 10.4 Hz), 1.83−1.69 (2H, m), 1.65
(3H, s), 1.62 (3H, s), 1.60 (3H, s), 1.59 (3H, s), 1.50 (3H, s), 1.46
E
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(3H, s), 1.01 (3H, s), 0.96 (3H, s); 13C NMR (101 MHz, CDCl3) δ
207.1, 199.8, 173.6, 138.5, 135.3, 132.5, 129.8, 128.4, 127.9, 125.3,
122.85, 117.59, 62.18, 52.02, 46.67, 41.08, 39.36, 37.62, 32.31, 30.14,
29.13, 25.87, 25.85, 25.67, 25.6, 25.0, 22.6, 18.2, 17.9, 17.6;
HRESIMS m/z 509.3630 [M + H]+ (calcd for C33H49O4, 509.3631).
7.17 (5H, m), 4.74−4.60 (1H, m), 4.22−4.02 (2H, m), 3.29 (1H, dd,
J = 13.4, 3.2 Hz), 3.20 (1H, d, J = 16.8 Hz), 3.14 (1H, d, J = 16.8 Hz),
2.76 (1H, d, J = 13.0 Hz), 2.73 (1H, d, J = 13.0 Hz), 2.58 (1H, p, J =
6.9 Hz), 1.15 (3H, s), 1.14 (3H, s), 1.08 (3H, s), 1.06 (3H, s); 13C
NMR (101 MHz, CDCl3) δ 214.5, 172.0, 153.4, 135.4, 129.4, 128.9,
127.2, 65.8, 55.1, 49.5, 43.6, 41.9, 37.9, 32.9, 28.5, 28.3, 18.08, 18.05;
HRESIMS m/z 344.1856 [M − H]+ (calcd for C20H26NO4,
344.1862).
To a stirred solution of (R)-1-(4-benzyl-2-oxooxazolidin-3-yl)-
3,3,6-trimethylheptane-1,5-dione (18) (13.7 g, 43 mmol) in ethylene
glycol (9.6 mL, 170 mmol) were added trimethoxymethane (7.1 mL,
64.5 mmol) and tetrabutylammonium tribromide (TBABr3) (1.03 g,
2.15 mmol), and the mixture was stirred at room temperature for 2
days. The reaction was quenched with water and extracted with
EtOAc. The combined organic layers were dried (Na2SO4) and
filtered, and the solvent was evaporated to afford a crude oil, which
was purified by flash chromatography on silica gel with 10% EtOAc/
hexanes to give 19 (8.3 g, 50% yield) as a colorless oil: [α]27D −29.4
(c 1.35, CHCl3); FT-IR νmax 2960, 1779, 1705, 1360, 1212 cm−1; 1H
NMR (400 MHz, CDCl3) δ 7.36−7.21 (5H, m), 4.75−4.61 (1H, m),
4.18−4.07 (2H, m), 4.02−3.82 (4H, m), 3.34 (1H, dd, J = 13.3, 3.1
Hz), 3.12 (1H, d, J = 17.3 Hz), 2.93 (1H, d, J = 17.3 Hz), 2.71 (1H,
dd, J = 13.3, 9.9 Hz), 1.97 (1H, d, J = 15.2 Hz), 1.89−1.78 (2H, m),
1.17 (6H, s), 0.91 (6H, d, J = 8.3 Hz); 13C NMR (101 MHz, CDCl3)
δ 172.0, 153.5, 135.6, 129.4, 128.8, 127.1, 114.8, 65.8, 63.7, 63.6, 55.1,
44.3, 38.5, 37.9, 34.9, 32.5, 30.1, 30.1, 17.4, 17.3; HRESIMS m/z
390.2280 [M + H]+ (calcd for C22H32NO5, 390.2280).
(R,S)-8a: [α]27 +46.5 (c 1.50, CHCl3); FT-IR νmax 2966, 1742,
D
1
1712, 1694, 1448, 1209 cm−1; H NMR (400 MHz, CDCl3) δ 7.88
(2H, d, J = 7.2 Hz), 7.57−7.47 (1H, m), 7.47−7.37 (2H, m), 5.05−
5.00 (2H, m), 4.85 (1H, t, J = 6.2 Hz), 3.68 (3H, s), 3.01 (1H, d, J =
15.8 Hz), 2.74 (1H, d, J = 15.8 Hz), 2.68−2.59 (2H, m), 2.49−2.28
(2H, m), 2.26−2.04 (4H, m), 1.80−1.69 (2H, m), 1.65 (3H, s), 1.64
(3H, s), 1.62−1.59 (1H, m), 1.59 (6H, s), 1.50 (3H, s), 1.45 (3H, s),
1.01 (3H, s), 0.95 (3H, s); 13C NMR (101 MHz, CDCl3) δ 207.4,
199.9, 173.3, 138.6, 135.2, 132.5, 132.5, 130.0, 128.4, 127.9, 125.8,
122.8, 117.8, 63.5, 52.1, 46.6, 42.1, 39.6, 37.8, 33.2, 30.5, 30.4, 25.9,
25.7, 25.5, 25.5, 24.7, 22.5, 18.1, 17.9, 17.5; HRESIMS m/z 509.3622
[M + H]+ (calcd for C33H49O4, 509.3631).
Procedures for the Synthesis of Norsampsone A (3) and
Norsampsone B (4). To a solution of (S,S)-8a (50 mg, 0.1 mmol) in
THF (10 mL) at 0 °C was added t-BuOK (33 mg, 0.3 mmol) in one
portion. The mixture turned yellow immediately. After stirring at 0 °C
for 5 min, the reaction was quenched by saturated NH4Cl solution
and extracted by EtOAc three times, and the organic layer was dried
over Na2SO4. The solvent was removed under reduced pressure, with
the crude product purified using silica gel with 5% EtOAc/hexanes to
yield the natural products norsampsones A (28 mg, 62%) and B (5
mg, 11%) as colorless oils. A similar procedure was used for the
cyclization of (R,S)-8a, and a mixture of the two products 16 and 17
with total 65% yield (1:10 dr) was obtained (the two compounds
could not be separated).
Compound 11b. A similar procedure to that used for 14 afforded
11b (0.56 g, 95% yield) as a colorless oil: [α]27 −69.4 (c 1.15,
D
1
CHCl3); FT-IR νmax 3028, 2962, 1781, 1732, 1693, 1208 cm−1; H
Norsampsone A (3): [α]27 +31.7 (c 0.50, CHCl3); FT-IR νmax
NMR (400 MHz, CDCl3) δ 7.38−7.20 (5H, m), 5.24−5.12 (1H, m),
4.72−4.59 (1H, m), 4.34 (1H, dd, J = 11.4, 3.6 Hz), 4.13−4.01 (4H,
m), 3.95−3.84 (2H, m), 3.20 (1H, dd, J = 13.2, 3.1 Hz), 2.61−2.48
(2H, m), 2.28 (1H, d, J = 13.9 Hz), 1.94−1.80 (1H, m), 1.75 (2H, s),
1.66 (3H, s), 1.62 (3H, s), 1.13 (3H, s), 1.10 (3H, s), 0.92 (3H, d, J =
6.1 Hz), 0.89 (3H, d, J = 6.1 Hz); 13C NMR (101 MHz, CDCl3) δ
176.4, 153.2, 135.8, 133.1, 129.4, 128.8, 127.1, 122.0, 114.3, 65.1,
63.8, 63.6, 55.6, 49.1, 38.6, 37.6, 36.1, 35.0, 27.6, 26.4, 25.8, 17.7,
17.4, 17.3; HRESIMS m/z 458.2903 [M + H]+ (calcd for C27H40NO5,
458.2906).
Compound 20. A similar procedure to that used for 15 afforded 20
as an oil (358 mg, 63% yield): [α]27D −18.4 (c 0.70, CHCl3); FT-IR
νmax 3428, 2969, 2882, 1469, 1024 cm−1; 1H NMR (400 MHz,
CDCl3) δ 5.21 (1H, t, J = 7.2 Hz), 4.06−3.86 (4H, m), 3.76−3.64
(1H, m), 3.64−3.51 (1H, m), 2.27−2.08 (2H, m), 1.94−1.79 (3H,
m), 1.69 (3H, s), 1.65−1.61 (2H, m), 1.63 (3H, s), 1.02 (3H, s), 0.98
(3H, s), 0.91 (3H, s), 0.90 (3H, s); 13C NMR (101 MHz, CDCl3) δ
132.3, 124.8, 115.1, 64.1, 63.8, 63.7, 49.7, 39.7, 35.5, 35.2, 27.3, 26.8,
26.4, 25.9, 17.8, 17.44, 17.39; HRESIMS m/z 307.2253 [M + Na]+
(calcd for C17H32O3Na, 307.2249).
D
1
2968, 2925, 1734, 1717, 1699 cm−1; H NMR (400 MHz, CDCl3) δ
7.74 (2H, d, J = 7.2 Hz), 7.51 (1H, t, J = 7.2 Hz), 7.40 (2H, t, J = 7.2
Hz), 5.05 (1H, 5, J = 7.2 Hz), 5.03 (1H, t, J = 7.2 Hz), 4.82 (1H, t, J =
6.8 Hz), 4.49 (1H, s), 2.84−2.71 (2H, m), 2.55−2.41 (2H, m), 2.32−
2.20 (3H, m), 1.95 (1H, dd, J = 14.4, 12.7 Hz), 1.88−1.76 (3H, m),
1.71 (3H, s), 1.70 (3H, s), 1.63 (6H, s), 1.59 (3H, s), 1.56 (3H, s),
1.23 (3H, s), 1.10 (3H, s); 13C NMR (101 MHz, CDCl3) δ 208.6,
197.4, 139.2, 135.4, 133.6, 133.1, 132.7, 128.8, 127.9, 123.3, 122.8,
118.7, 66.3, 64.7, 44.9, 44.0, 40.4, 34.1, 32.7, 27.6, 27.4, 26.1, 25.9,
23.0, 18.5, 18.1, 17.8, 16.9; HRESIMS m/z 477.3365 [M + H]+ (calcd
for C32H45O3, 477.3369).
Norsampsone B (4): [α]27 −33.8 (c 0.50, CHCl3); FT-IR νmax
D
1
3967, 2925, 1698, 1448 cm−1; H NMR (400 MHz, CDCl3) δ 8.01
(2H, d, J = 7.4 Hz), 7.52 (1H, t, J = 7.3 Hz), 7.43 (2H, t, J = 7.3 Hz),
5.11 (1H, t, J = 6.7 Hz), 5.01 (1H, t, J = 7.2 Hz), 4.73 (1H, t, J = 6.8
Hz), 4.48 (1H, s), 2.59 (1H, dd, J = 15.0, 7.6 Hz), 2.53−2.39 (3H,
m), 2.35−2.12 (5H, m), 1.91−1.74 (2H, m), 1.70 (3H, s), 1.63 (3H,
s), 1.60 (3H, s), 1.58 (6H, s), 1.50 (3H, s), 1.14 (3H, s), 1.01 (3H, s);
13C NMR (101 MHz, CDCl3) δ 209.9, 207.1, 196.0, 138.6, 135.6,
133.3, 133.2, 132.9, 128.9, 128.7, 123.4, 123.1, 118.8, 67.4, 66.8, 41.5,
41.2, 39.4, 32.3, 32.2, 27.5, 26.1, 25.9, 25.9, 25.9, 24.5, 22.9, 18.2,
18.2, 17.8; HRESIMS m/z 477.3366 [M + H]+ (calcd for C32H45O3,
477.3369).
Compound 10b. A similar procedure to that used for 10a afforded
10b as an oil (1.1 g, 81% yield): [α]27 −9.8 (c 1.0, CHCl3); FT-IR
D
1
νmax 2961, 2886, 1470, 1099 cm−1; H NMR (400 MHz, CDCl3) δ
5.10 (1H, t, J = 7.4 Hz), 4.06−3.84 (4H, m), 3.49 (1H, dd, J = 9.8, 3.2
Hz), 3.13 (1H, dd, J = 9.8, 7.0 Hz), 2.33−2.21 (1H, m), 2.06 (1H, dt,
J = 15.2, 7.7 Hz), 1.85 (1H, p, J = 6.5 Hz), 1.79−1.73 (1H, m), 1.69−
1.67 (7H, m), 1.59 (1H, d, J = 15.4 Hz), 1.03 (3H, s), 1.01 (3H, s),
0.91 (3H, d, J = 6.9 Hz), 0.90 (3H, d, J = 6.8 Hz); 13C NMR (101
MHz, CDCl3) δ 131.8, 123.9, 114.6, 63.8, 49.1, 39.1, 37.1, 35.3, 29.1,
26.6, 26.0, 25.9, 18.2, 17.4, 17.3, 11.2; HRESIMS m/z 417.1271 [M +
Na]+ (calcd for C17H31IO2Na, 417.1266).
epi-Norasmpsone B (17) (with the minor product epi-
norasmpsone A as mixture): FT-IR νmax 2925, 1716, 1699, 1448
1
cm−1; H NMR (400 MHz, CDCl3) δ 7.98 (2H, d), 7.58−7.50 (1H,
m), 7.49−7.41 (2H, m), 5.20 (1H, d, J = 8.0 Hz), 4.99 (2H, dd, J =
13.9, 6.8 Hz), 4.42 (1H, s), 2.55−2.38 (3H, m), 2.39−2.27 (3H, m),
2.28−2.17 (2H, m), 1.79−1.70 (4H, m), 1.67 (3H, s), 1.66 (4H, s),
1.63 (3H, s), 1.62 (3H, s), 1.59 (4H, s), 1.13 (3H, s), 1.04 (3H, s);
13C NMR (101 MHz, CDCl3) δ 210.6, 205.4, 197.5, 139.0, 134.9,
133.4, 133.1, 132.8, 128.6, 128.0, 122.7, 122.5, 118.4, 67.8, 66.7, 46.1,
43.9, 37.8, 35.8, 33.0, 27.4, 26.8, 25.9, 25.8, 25.7, 22.2, 18.0, 17.9,
17.7, 16.5; HRESIMS m/z 477.3365 [M + H]+ (calcd for C32H45O3,
477.3369).
Compound 8b. A similar procedure to that used for 8a afforded 8b
(205 mg, 58% yield) as an oil: [α]27 −96.8 (c 1.0, CHCl3); FT-IR
D
νmax 2965, 2929, 2875, 1732, 1699 cm−1; 1H NMR (400 MHz,
CDCl3) δ 5.03 (1H, t, J = 6.5 Hz), 4.90 (1H, t, J = 6.6 Hz), 3.65 (3H,
s), 3.62 (3H, s), 2.60 (2H, d, J = 6.8 Hz), 2.52−2.37 (2H, m), 2.26
(1H, d, J = 16.1 Hz), 2.12−1.95 (2H, m), 1.79−1.73 (2H, m), 1.63
(3H, s), 1.60 (3H, s), 1.56 (4H, s), 1.52 (3H, s), 1.00 (3H, d, J = 3.9
Hz), 0.99 (3H, d, J = 3.6 Hz), 0.92 (3H, s), 0.88 (3H, s); 13C NMR
(101 MHz, CDCl3) δ 214.4, 172.4, 172.3, 135.3, 129.6, 125.4, 117.8,
Procedures for the Synthesis of 8b. Compound 18. A similar
procedure to that used for 13 afforded 18 (1.8 g, 90%) as a colorless
oil: [α]27 −31.4 (c 0.45, CHCl3); FT-IR νmax 2968, 2873, 1778,
D
1711, 1693, 1359, 1102 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.40−
F
DOI: 10.1021/acs.jnatprod.8b00763
J. Nat. Prod. XXXX, XXX, XXX−XXX

Journal of Natural Products
Article
57.4, 52.2, 52.1, 48.9, 42.1, 41.9, 37.4, 33.4, 31.2, 29.5, 25.9, 25.6,
25.0, 24.4, 18.2, 18.0, 17.9; HRESIMS m/z 423.3109 [M + H]+ (calcd
for C25H43O5, 423.3110).
Hz), 2.06−2.00 (2H, m), 1.85 (1H, dt, J = 14.8, 8.3 Hz), 1.65 (3H, s),
1.60 (3H, s), 1.57−1.53 (1H, m), 1.51 (6H, s), 0.99 (1H, m), 0.98
(3H, d, J = 6.8 Hz), 0.96 (3H, d, J = 6.5 Hz), 0.93 (3H, s), 0.74 (3H,
s); 13C NMR (101 MHz, CDCl3) δ 210.4, 208.0, 132.9, 132.4, 123.6,
121.8, 47.5, 43.9, 42.9, 40.0, 34.4, 28.0, 27.5, 26.0, 25.8, 25.77, 21.9,
17.9, 17.8, 17.3; HRESIMS m/z 333.2799 [M + H]+ (calcd for
C22H37O2, 333.2794).
Cytotoxicity Testing. Cytotoxic activities against the human-
derived cell lines A 549 (lung carcinoma), SNU-1 (gastric carcinoma),
786-O (renal cell adenocarcinoma), and KMS-11 (multiple myeloma)
were determined as previously reported.19 Staurosporine was included
as a positive control.
Procedures for the Synthesis of Garcinielliptone O (5),
Garcinielliptone N (6), and Hyperscabrin A (7). To a solution of
8b (130 mg, 0.3 mmol) in THF (18 mL) at rt was added LHMDS
(0.6 mL, 0.6 mmol, 1.0 mol/L in THF) dropwise. The mixture was
then heated to reflux for 1 h. The reaction was cooled and quenched
with saturated NH4Cl solution and extracted by EtOAc three times,
and the organic layer was dried over Na2SO4. The solvent was
removed under reduced pressure. The crude product was purified by
passage over silica gel with 5% EtOAc/hexanes to yield
garcinielliptone O (5) (24 mg, 21% yield) and compounds 21 (43
mg, 37% yield) and 22 (21 mg, 18% yield) as colorless oils.
ASSOCIATED CONTENT
* Supporting Information
■
Garcinielliptone O (5): [α]27 −258 (c 0.35, CHCl3); FT-IR νmax
D
S
2968, 2928, 2874, 1730, 1688, 1448 cm−1; 1H NMR (400 MHz,
CDCl3) δ 5.13 (1H, t, J = 7.3 Hz), 5.04 (1H, t, J = 7.5 Hz), 3.75 (3H,
s), 3.71 (1H, s), 2.53−2.43 (3H, m), 2.28 (1H, dd, J = 14.6, 7.6 Hz),
2.18 (1H, dd, J = 14.2, 6.2 Hz), 1.73 (3H, s), 1.67 (1H, m), 1.67 (3H,
s), 1.59 (3H, s), 1.57 (1H, m), 1.56 (3H, s), 1.28 (1H, dd, J = 14.2,
12.4 Hz), 1.06 (3H, d, J = 6.7 Hz), 1.02 (3H, s), 1.00 (3H, d, J = 6.7
Hz), 0.99 (3H, s); 13C NMR (101 MHz, CDCl3) δ 210.2, 203.9,
172.2, 135.3, 132.9, 122.8, 118.1, 69.4, 61.4, 52.4, 52.4, 45.7, 43.4,
42.5, 36.8, 33.2, 27.4, 26.5, 25.9, 25.8, 18.1, 17.9, 17.8, 17.1, 15.6;
HRESIMS m/z 391.2850 [M + H]+ (calcd for C24H39O4, 391.2848).
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.jnat-
prod.8b00763.
Data comparison of the synthetic and natural products,
1
computational details, and H and 13C NMR spectra of
all new compounds (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: ths97029@163.com (H. S. Tan).
*E-mail: xuhongxi88@gmail.com (H. X. Xu).
■
Compound 21: [α]27 +39.8 (c 0.8, CHCl3); FT-IR νmax 2964,
D
1
2926, 2873, 1747, 1731, 1688 cm−1; H NMR (400 MHz, CDCl3) δ
5.14−4.99 (2H, m), 3.74 (3H, s), 3.68 (1H, s), 2.78−2.51 (2H, m),
2.46−2.30 (1H, m), 2.29−2.18 (1H, m), 2.15−2.04 (1H, m), 1.95
(1H, dd, J = 14.4, 3.8 Hz), 1.80−1.61 (11H, m), 1.60 (3H, s), 1.14
(3H, s), 1.06 (3H, s), 1.03 (3H, d, J = 6.7 Hz), 1.00 (3H, d, J = 7.0
Hz); 13C NMR (101 MHz, CDCl3) δ 210.5, 207.0, 172.2, 135.4,
133.2, 122.7, 118.9, 67.3, 62.0, 52.4, 44.5, 42.9, 42.8, 34.6, 32.6, 27.2,
26.6, 25.9, 25.8, 18.2, 18.1, 17.9, 17.0, 15.9; HRESIMS m/z 391.2844
[M + H]+ (calcd for C24H39O4, 391.2848).
ORCID
Hongxi Xu: 0000-0001-6238-4511
Author Contributions
†C. W. Zheng and X. Y. Wang contributed equally.
Notes
Compound 22. [α]27 −47.8 (c 0.50, CHCl3); FT-IR νmax 2964,
D
The authors declare no competing financial interest.
1
2926, 1729, 1688, 1461 cm−1; H NMR (400 MHz, CDCl3) δ 5.14
(1H, t, J = 7.0 Hz), 5.02 (1H, t, J = 7.2 Hz), 3.86 (1H, s), 3.73 (3H,
s), 2.79−2.60 (1H, m), 2.50 (1H, dd, J = 14.3, 8.2 Hz), 2.39−2.23
(2H, m), 2.22−2.09 (1H, m), 2.04−1.91 (2H, m), 1.72 (4H, s), 1.67
(3H, s), 1.62 (3H, s), 1.61 (3H, s), 1.08 (3H, s), 1.06 (3H, d, J = 7.1
Hz), 1.04 (3H, d, J = 6.7 Hz), 0.98 (3H, s); 13C NMR (101 MHz,
CDCl3) δ 210.0, 205.1, 173.3, 135.7, 132.8, 123.0, 118.8, 69.4, 60.8,
52.4, 42.1, 41.2, 40.7, 33.1, 32.8, 26.9, 25.9, 25.9, 25.1, 24.2, 18.4,
18.1, 17.9, 17.1; HRESIMS m/z 391.2845 [M + H]+ (calcd for
C24H39O4, 391.2848).
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (81602990), A Professor of Special Appointment
(Eastern Scholar) at Shanghai Institutions of Higher Learning,
and the Shanghai Sailing Program (17YF1419500), for
financial support. We thank Dr. J. Wai and J. Wang at WuXi
Apptec (Shanghai) for computational assistance.
To a mixture of 21 and 22 (50 mg, 0.13 mmol) in THF (2.0 mL)
at rt was added NaH (26 mg, 0.64 mmol, 60% dispersion in mineral
oil) in one portion. The mixture was then heated to reflux for 6 h. The
reaction was cooled, quenched with saturated NH4Cl solution, and
extracted by EtOAc three times, with the organic layer dried over
Na2SO4. The solvent was removed under reduced pressure. The crude
product was purified by silica gel with 5% EtOAc/hexanes to yield
garcinielliptone N (6) (18 mg, 43% yield) and hyperscabrin A (7) (12
mg, 29% yield) as a colorless oil.
REFERENCES
■
(1) (a) O’Hara, M.; Kiefer, D.; Farrell, K.; Kemper, K. Arch. Fam.
Med. 1998, 7, 523−536. (b) Liu, C.; Ho, P. C. L.; Wong, F. C.; Sethi,
G.; Wang, L. Z.; Goh, B. C. Cancer Lett. 2015, 362, 8−14. (c) Brito, L.
D.; Berenger, A. L. R.; Figueiredo, M. R. Food Chem. Toxicol. 2017,
109, 847−862.
(2) (a) Ciochina, R.; Grossman, R. B. Chem. Rev. 2006, 106, 3963−
3986. (b) Richard, J. A.; Pouwer, R. H.; Chen, D. Y. K. Angew. Chem.,
Int. Ed. 2012, 51, 4536−4561. (c) Richard, J. A. Eur. J. Org. Chem.
2014, 2014, 273−299. (d) Yang, X. W.; Grossman, R. B.; Xu, G.
Chem. Rev. 2018, 118, 3508−3558.
Garcinielliptone N (6): [α]27 −37.6 (c 0.40, CHCl3); FT-IR νmax
D
1
2965, 2926, 1728, 1700, 1456 cm−1; H NMR (400 MHz, CDCl3) δ
5.10 (1H, t, J = 8.0 Hz), 5.05 (1H, t, J = 8.0 Hz), 3.60 (1H, s), 2.44−
2.27 (3H, m), 2.18 (1H, dd, J = 13.8, 5.8 Hz), 2.09 (1H, dd, J = 6.4,
3.6 Hz), 2.00−1.89 (1H, m), 1.70 (3H, s), 1.67 (1H, m), 1.66 (3H,
s), 1.57 (6H, s), 1.54 (1H, m), 1.16 (1H, d, J = 6.4 Hz), 1.03 (3H, s),
1.03 (3H, d, J = 6.4 Hz), 1.00 (3H, s), 0.99 (3H, d, J = 6.4 Hz); 13C
NMR (101 MHz, CDCl3) δ 210.8, 208.7, 133.1, 132.8, 123.2, 121.4,
70.6, 51.0, 48.2, 43.4, 42.9, 34.8, 27.5, 27.4, 26.6, 25.8, 25.7, 18.0,
17.8, 17.2, 15.8; HRESIMS m/z 333.2792 [M + H]+ (calcd for
C22H37O2, 333.2794).
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