Total Synthesis of Dapholdhamine B and Dapholdhamine B Lactone

Article abstract of DOI:10.1021/jacs.9b05641

The intriguing structural complexity and bioactivities of the Daphniphyllum alkaloids have long attracted much attention. Herein, we report the first and enantioselective total synthesis of Daphniphyllum alkaloid dapholdhamine B and its lactone derivative. The chemical structure of dapholdhamine B contains a unique aza-adamantane core skeleton and eight contiguous stereocenters, including three contiguous fully substituted stereocenters, which present a formidable synthetic challenge. This concise approach used to achieve the first synthesis of an aza-adamantane natural product features a vinylogous Mannich reaction, an optimized α-bromo-α,β-unsaturated ketone synthesis, a substrate-dependent intramolecular aza-Michael addition, a key annulation via amide activation, an S_N2′-type lactonization, and a facile Horner-Wadsworth-Emmons reaction that converts the hemiacetal moiety to the corresponding homologated carboxylic acid.

Full text of DOI:10.1021/jacs.9b05641

Article
Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX−XXX
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Total Synthesis of Dapholdhamine B and Dapholdhamine B Lactone
†
†
†
Lian-Dong Guo, Jieping Hou, Wentong Tu, Yan Zhang, Yue Zhang, Louxi Chen, and Jing Xu*
Department of Chemistry and Shenzhen Grubbs Institute, Southern University of Science and Technology, Shenzhen, China
*
S Supporting Information
ABSTRACT: The intriguing structural complexity and
bioactivities of the Daphniphyllum alkaloids have long
attracted much attention. Herein, we report the first and
enantioselective total synthesis of Daphniphyllum alkaloid
dapholdhamine B and its lactone derivative. The chemical
structure of dapholdhamine B contains a unique aza-
adamantane core skeleton and eight contiguous stereocenters,
including three contiguous fully substituted stereocenters,
which present a formidable synthetic challenge. This concise
approach used to achieve the first synthesis of an aza-
adamantane natural product features a vinylogous Mannich reaction, an optimized α-bromo-α,β-unsaturated ketone synthesis, a
substrate-dependent intramolecular aza-Michael addition, a key annulation via amide activation, an S 2′-type lactonization, and
N
a facile Horner−Wadsworth−Emmons reaction that converts the hemiacetal moiety to the corresponding homologated
carboxylic acid.
15
INTRODUCTION
A-type), and Sarpong (daphlongamine H and isodaphlong-
■
The genus Daphniphyllum comprises evergreen trees and
shrubs native to the Asia-Pacific region, which have long been
amine H; calyciphylline B-type) (Figure 1).
Dapholdhamine B (1, Figures 1 and 2) belongs to the
1a
used in traditional Chinese medicine. Various Daphniphyllum
alkaloids have exhibited diverse bioactivities, such as
antitubulin polymerization, anticarcinogenic, anti-HIV, vaso-
relaxant, and cytotoxic activities. More than 330 Daphni-
phyllum alkaloids have been isolated from the genus
Daphniphyllum to date, comprising a structurally fascinating
unexplored daphnezomine A-type subfamily and was isolated
1
,2
1
and diverse natural product family. From a chemical structure
perspective, these alkaloids can be categorized into over a
dozen subfamilies on the basis of their distinct structural
1
backbones. Highly challenging and congested polycyclic ring
systems, along with promising bioactivities, make these
1
b−d,3
alkaloids intriguing synthetic targets.
Since Heathcock’s
4a,b
pioneering syntheses of methyl homodaphniphyllate and
codaphniphylline (daphniphylline-type), methyl homoseco-
daphniphyllate and secodaphniphylline (secodaphniphyl-
line-type), bukittinggine (bukittinggine-type), and daphni-
4
c
4
d
4e
4f
4
g
lactone A (daphnilactone A-type), many impressive total
syntheses of various Daphniphyllum alkaloids have been
5
reported by the groups of Carreira (daphmanidin E;
6
daphmanidin A-type), Smith (calyciphylline N; daphmanidin
7
7a,b
7c
A-type), Li (daphenylline,
daphnilongeranin B, daphni-
7
b
7c
paxianine A, daphniyunnine E, dehydrodaphnilongeranin
B, hybridaphniphylline B, himalenine D, and longer-
acinphyllin A; calyciphylline A-type), Hanessian (isoda-
phlongamine H; a putative member of calyciphylline B-type
alkaloids), Fukuyama (daphenylline; calyciphylline A-type),
Zhai (daphenylline and daphnilongeranin B; calyciphylline
A-type), Dixon (himalensine A; calyciphylline A-type), Qiu
daphenylline; calyciphylline A-type), ourselves (himalensine
A; calyciphylline A-type), Gao (himalensine A; calyciphylline
7
c
7c
7b
7
d
8
9
Figure 1. Common skeletons of previously synthesized Daphniphyl-
lum alkaloids, along with daphnezomine A-type alkaloids.
1
0
1
1
12
13
(
Received: May 26, 2019
1
4
©
XXXX American Chemical Society
A
DOI: 10.1021/jacs.9b05641
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Journal of the American Chemical Society
Article
22
tion. The C −N bond can be formed by an intramolecular
1
aza-Michael addition (IMAM) of sulfonylamide 4. Finally, the
aminomethylene group in 4 can be introduced using a
vinylogous Mannich reaction of readily available chiral
diketone 5.
Our synthesis began with an L-prolinamide-catalyzed
23
asymmetric Robinson annulation of known compound 6 to
24
afford diketone 5 (Scheme 2; 85%, 94% ee). Selective methyl
Scheme 2. Synthesis of IMAM Precursor 13
Figure 2. Adamantane-type natural products.
16
and structurally assigned in 2009 by Hao et al. The chemical
structure of dapholdhamine B contains a rare aza-adamantane
core skeleton and eight contiguous stereocenters, including
three contiguous fully substituted stereocenters, which present
a daunting synthetic challenge. To our knowledge, dapholdh-
amine B and its congeners daphnezomines A and B (Figure
1
7
1
), acosmine-type diaza-adamantanes (such as panacos-
18 19a
mine), and the indole alkaloids nareline and scholarisine
1
9b
H
(Figure 2) are among the only known aza-adamantane
natural products. Representative oxa- and oxa, aza-adamantane
20
natural products, such as tetrodotoxin and terengganensine
2
1
A, have been synthesized previously. Herein, we report the
first and asymmetric total synthesis of 1, which is also the first
synthesis of an aza-adamantane natural product.
enol ether formation followed by a vinylogous Mannich
reaction produced tertiary amine 8, which was then
RESULTS AND DISCUSSION
■
25
As shown in Scheme 1, our retrosynthetic analysis of 1
indicated that the key C-9 tertiary hydroxyl group could be
introduced via an intramolecular oxa-Michael (IMOM)
reaction. The equally crucial C −N bond could be formed
deallylated and tosylated to give sulfonylamide 9. Notably,
diastereomeric enrichment was observed during the purifica-
tion process. Subjecting this sulfonylamide to conjugate
11
26
addition under Luche’s conditions formed the critical
through an S 2-type reaction, and formation of the cyclo-
N
quaternary center to afford diketone 10 as a single
diastereomer. It was postulated that the C-6 epimer of 9
could not undergo the conjugate addition. Subsequently,
treating 10 with lithium bis(trimethylsilyl)amide (LHMDS)
selectively generated the corresponding lithium enolate, which
was then treated with sulfinimidoyl chloride 11 to trigger a
hexenone motif in enone 2 was envisaged to be accessible from
amide 3 using Huang’s amide-activation−annulation reac-
Scheme 1. Retrosynthetic Analysis of Dapholdhamine B
27
Mukaiyama dehydrogenation, affording desired enone 12 in
5% yield. Subsequent oxidative cleavage of the PMB group
7
afforded sulfonylamide 13.
With IMAM precursor 13 in hand, triggering the IMAM
reaction and introducing the isopropyl group into the skeleton
of compound 13 in the same step would be preferred (Table
1
). These transformations would have ideally been achieved
through an IMAM/alkylation or IMAM/aldol cascade reaction
using sulfonylamide 13 and appropriate electrophiles, such as
2
-iodopropane or acetaldehyde, under basic conditions.
However, these attempts, based on racemic model substrate
±)-13, were all unsuccessful. In particular, extensive
(
investigation of the IMAM/aldol cascade reaction using
various bases and additives led only to the formation of
IMAM product 15. No trace of desired IMAM/aldol product
1
4 was detected by NMR or LC−MS. Subsequent traditional
aldol or Mukaiyama aldol reactions using 15 led only to a
B
DOI: 10.1021/jacs.9b05641
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Table 1. Study of the IMAM Reaction
Table 2. Study of Vinyl Bromide Synthesis
c
a
b
c
1
4
15
entry
conditions
17 (%)
a
entry
conditions
(%)
(%)
1
2
3
4
5
6
7
8
TBAB, BF ·Et O, DCM, r.t., 0.5 h
decomp.
NR
decomp.
trace
NR
20
b
3
2
1
2
3
4
5
6
7
8
NaH (1.5 equiv), 0 °C to r.t.
ND
ND
ND
ND
ND
80
85
96
92
80
85
LiBr, TFA, THF, r.t., 0.5 h
LiBr, TFA, THF, 60 °C, 2 h
LiBr, DMF, 150 °C, 12 h
[AcMIm]Br, 65 °C, 2 h
NaH (1.5 equiv), ZnCl (3 equiv), 0 °C to r.t.
2
DBU (2 equiv), r.t.
e
DBU (2 equiv), ZnCl (3 equiv), r.t.
2
d
LDA (1.1 equiv), −78 °C to r.t.
LiBr, CH CN, reflux, 12 h
e
3
LDA (1.1 equiv), ZnCl (2 equiv), −78 °C to r.t. ND
2
LiBr, CH CN, 120 °C (sealed tube), 12 h
LiBr, CH CN, MW, 100 °C, 0.5 h
LiBr, CH CN, MW, 120 °C, 10 min
LiBr, CH CN, MW, 120 °C, 12 min
O (2/1), MW, 120 °C, 1 h
LiBr, HOAc, CH CN, MW, 120 °C, 12 min
LiBr, DMF, MW, 120 °C, 12 min
HBr·Py, CH CN, MW, 120 °C, 12 min
30
41
52
46
d
3
KHMDS (1.1 equiv), −78 °C to r.t.
ND
ND
75
85
e
3
KHMDS (1.1 equiv), ZnCl (2 equiv),
2
9
1
3
−
78 °C to r.t.
d
0
a
b
c
d
3
0
.2 mmol; THF, 0.1 M. Not detected. Isolated yield. Base, −78
C, 1 h, then acetaldehyde added dropwise. Base, −78 °C, 1 h, then
e
11
LiBr, CH
3
CN/H
2
NR
<10
NR
trace
°
f
12
13
14
3
ZnCl , 30 min, then acetaldehyde added dropwise.
2
e
3
retro-IMAM reaction product in about 20% yield, with a large
amount of 15 recovered. Substrate 15 was postulated to
strongly favor the retro-aldol reaction in the corresponding
reaction equilibrium. The unsuccessful alkylation might be
attributed to steric hindrance by our substrate and the bulky
electrophile, 2-iodopropane.
a
b
0
.2 mmol. Bromine source, 10 equiv; Lewis acid or protonic acid, 2
equiv; solvent, 0.1 M. Isolated yield. 2.0 mmol. Most of the starting
material was recovered. Most of the starting material was
decomposed.
c d e
f
Scheme 3. Synthesis of IMAM Precursors 4 and 20
Owing to the unsuccessful IMAM/alkylation and IMAM/
aldol attempts, we decided to first introduce the isopropyl
group into the core skeleton, envisaging that a subsequent
IMAM reaction should also work well. However, the desired α-
halogenation of α,β-unsaturated ketone 12 proved to be
extremely difficult, with all traditional methods resulting in
2
8
failure, possibly due to severe steric hindrance at the C-1
position. Fortunately, an optimized α-bromination method was
29
developed on the basis of a reported example using epoxide
3
0
1
6, which was produced from enone 12 via an epoxidation
reaction (Table 2). Various bromine sources, including
3
1
32
TBAB, LiBr, [AcMIm]Br, and HBr·Py, were screened
with substrate 16. LiBr was found to be the only effective
bromine source, while the other bromine sources gave very
poor results (no reaction, decomposition, or only trace
amounts of 17). Although LiBr/TFA conditions (Table 2,
entries 2 and 3) gave poor results, neutral conditions using
anhydrous acetonitrile were found to give the best results in
this bromination step (Table 2, entry 7). Furthermore,
microwave conditions improved the reaction yield from 30
to 52% (Table 2, entry 9, 0.2 mmol scale) or 46% (Table 2,
entry 10, 2 mmol scale), producing a sufficient amount of vinyl
bromide 17 for further investigation.
different outcomes from the IMAM trials. Treating substrate
20 under different acidic or basic conditions did not produce
even trace amounts of IMAM product 21 (Table 3).
Furthermore, when MeOH or EtOH was used as solvent, a
vinylogous retro-Dieckmann reaction of substrate 20 occurred,
followed by an IMAM reaction to give product 22 or 23,
respectively. Substrate 20 was assumed to strongly favor the
retro-IMAM reaction in the corresponding reaction equili-
brium.
Subsequently, a Suzuki coupling reaction between vinyl
bromide 17 and boronate 18 furnished diene 19 in 90% yield
33
using XPhos Pd G2 as catalyst. Other ligands, such as PPh3
or AsPh , gave lower or irreproducible yields (Scheme 3). After
The presence of an isopropenyl group was also postulated to
provide better stabilization of the resulting enolate anion.
Pleasingly, the desired IMAM reaction was successfully
triggered when sulfonylamide 4 was treated with potassium
bis(trimethylsilyl)amide (KHMDS) and TBSCl (Scheme 4).
To further improve the overall synthetic efficiency, the silyl
enol ether from the aforementioned IMAM reaction mixture
3
oxidative removal of the PMB group, sulfonylamide 4 was
produced in 76% yield from 19. Alternatively, partial
hydrogenation of diene 19 was attempted, followed by
oxidative cleavage of the PMB group, to afford sulfonylamide
2
0 (in racemic form, synthesized from racemic 19).
Interestingly, the seemingly trivial structural difference
between IMAM precursors 4 and 20 resulted in completely
was treated with excess KHMDS and PhNTf to give enol
2
C
DOI: 10.1021/jacs.9b05641
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Article
Table 3. Study of the IMAM Reaction of 20
a
entry
conditions
yield of 21
1
2
3
4
5
6
7
8
9
1
PTSA (2 equiv), DCM, r.t., 12 h
PTSA (2 equiv), PhMe, 80 °C, 12 h
DBU (2 equiv), PhMe, reflux, 3 h
NR
decomp.
NR
NR
NR
ND
ND
NR
NR
NR
DBU (2 equiv), CH CN, reflux, 3 h
3
DBU (2 equiv), ZnCl (3 equiv), CH CN, MW, 120 °C, 1 h
2
3
b
DBU (2 equiv), EtOH, 75 °C, 12 h
NaOMe (5 equiv), MeOH, 60 °C, 1.5 h
c
LDA (2 equiv), ZnCl (2 equiv), THF, −78 °C to r.t., 3 h
2
NaH (2 equiv), DCM, r.t., 12 h
KHMDS (1.1 equiv), THF, −78 °C to r.t.
0
a
b
c
0
.1 mmol; solvent, 0.05 M. Ethyl ester 22 isolated in 60% yield as a single isomer. Methyl ester 23 isolated in 75% yield as a single isomer.
Scheme 4. Key Annulation via Amide Activation Reaction
and Unsuccessful IMOM Attempts
we hoped that an efficient and high-yielding annulation would
proceed to construct the additional cyclohexenone ring motif.
To this end, the carbonyl group in 25 was reduced and
eliminated to give compound 26. A Suzuki coupling reaction
between enol triflate 26 and the borane obtained from treating
amide 27 with 9-BBN produced key amide intermediate 3.
Subjecting compound 3 to Huang’s amide-activation−
22
annulation reaction under Tf O/2-fluoropyridine conditions,
2
with subsequent acid hydrolysis of the corresponding imine
intermediate, afforded desired tetracycle 28 bearing the
cyclohexanone moiety in 82% yield.
On the basis of our original synthetic design, it was
envisaged that the key C-9 hydroxyl group could be introduced
into the skeleton via an IMOM reaction (Scheme 4). To this
end, compound 28 was partially hydrogenated to give enone
3
(
0 in 65% yield, along with a small amount of allylic alcohol 29
21%). Furthermore, primary alcohol 30 was oxidized to its
carboxylic acid derivative 32. However, neither primary alcohol
0 nor carboxylic acid 32 underwent the planned IMOM
3
reaction under various basic or acidic conditions (NaOAc,
DBU, NaOMe, NaH, pyrrolidine, PTSA, HCl aq., or PPTS),
failing to give desired tetrahydrofuran 31 or lactone 33,
respectively.
In the amide-activation−annulation step, we were pleased to
observe the generation of tetrahydrofuran 34 in approximately
10% yield, along with desired enone 28 (82%, Scheme 5). As
enone 28 could not be further converted into 34 under the
same acidic workup conditions as those used in the annulation
step, the plausibility of the debenzylation/IMOM pathway
could be ruled out. Therefore, we propose that the formation
of the tetrahydrofuran moiety occurs through the formation of
cationic intermediate 35, followed by oxygen trapping and
debenzylation.
Inspired by the aforementioned critical observation, we
proposed that compound 29 or its carboxylic acid derivative
triflate 24. Homogeneous hydrogenation of 24 using
(Scheme 6) would undergo an S
conditions via a similar cationic intermediate. Pleasingly, this
pivotal S
N
2′-type reaction under acidic
34
Crabtree’s catalyst, followed by treatment with TBAF/
AcOH in the same pot, produced desired ketone 25 in 62%
yield. The C-2 stereochemistry was clearly assigned later by
single crystal X-ray diffraction of compound 29. At this stage,
2′-type reaction finally paved the way for the total
N
synthesis of dapholdhamine B. One-pot global hydrogenation/
hydrogenolysis of the C −C double bond, C-11 ketone, and
3
4
D
DOI: 10.1021/jacs.9b05641
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Journal of the American Chemical Society
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Scheme 5. Formation of Compound 34 and the Proposed
the formation of lactone 36 via the proposed pivotal S 2′-type
N
Mechanism That Inspired the Key S 2′ Reaction
reaction. Hydroboration of the C −C double bond followed
N
10
11
by oxidation produced compound 37. The lactone moiety of
3
6 was simultaneously reduced to the corresponding lactol
moiety in the hydroboration reaction. To our surprise, this
lactol motif was highly stable, with all attempts at reduction or
homologation proving unsuccessful. Consequently, we decided
to construct the remaining C −N bond first, with the aim to
1
1
change the reactivity of the lactol. Removal of the N-tosyl
group using sodium naphthalenide followed by an S 2-type
N
36
reaction successfully afforded 38, which possessed the pivotal
aza-adamantane core skeleton. The structure of 38 was
37
unambiguously confirmed by single crystal X-ray diffraction.
As compound 38 contains all of the stereogenic centers of 1, all
stereoconfigurations in 1 were confirmed. After extensive
investigation, the critical homologation of lactol 38 was
38
achieved using a Horner−Wadsworth−Emmons reaction
with sodium hydride and phosphonate 39 to give intermediate
0, which then underwent one-pot acid hydrolysis to give
4
thioester 41. Compounds 40 and 41 did not need to be
isolated, as basic hydrolysis of the thioester motif in the same
pot successfully produced dapholdhamine B (1, 80%). As an
authentic sample of natural 1 was not available, comparing the
Scheme 6. Total Synthesis of Dapholdhamine B and
Dapholdhamine B Lactone
1
13
H and C NMR data of the natural product with our
synthetic sample was difficult because the NMR chemical shifts
of our synthetic amino acid were extremely pH-sensitive (see
the Supporting Information). Consequently, a small amount of
synthetic 1 was treated with HCl to quantitatively give
dapholdhamine B lactone (42). Furthermore, basic hydrolysis
of 42 also produced 1 quantitatively. Through extensive NMR
analysis (see the Supporting Information), we clearly assigned
the chemical structure of 42, which, along with the
unambiguous structural assignment of the last intermediate
3
8, allowed the identity of synthetic 1 to be confirmed beyond
a doubt.
CONCLUSIONS
■
In summary, we have accomplished the first and asymmetric
total synthesis of Daphniphyllum alkaloid dapholdhamine B in
1 steps. This is also the first synthesis of an aza-adamantane
natural product. Our concise approach features the following:
i) a vinylogous Mannich reaction to introduce the key C-6
2
(
aminomethyl group; (ii) an optimized α-bromo-α,β-unsatu-
rated ketone synthesis, because all other known methods
failed; (iii) a substrate-dependent IMAM reaction to construct
the critical C −N bond; (iv) a key annulation strategy via an
1
amide activation reaction that formed the cyclohexanone
moiety in a highly efficient manner; (v) introduction of a
critical C-9 hydroxyl group via an S 2′-type reaction inspired
N
by the observation of a side product from the amide-
activation−annulation step; and (vi) a facile Horner−Wads-
worth−Emmons reaction that converted the hemiacetal to the
corresponding homologated carboxylic acid. Efforts toward the
synthesis of other daphnezomine A-type alkaloids, as well as
other aza-adamantane alkaloids, are currently ongoing in our
laboratory.
C-14 O-benzyl group using a high pressure of hydrogen (80
bar) efficiently converted compound 28 into tetracyclic diol
ASSOCIATED CONTENT
■
2
9. The absolute stereochemistry of 29 was unambiguously
35
*
S
Supporting Information
assigned by single crystal X-ray diffraction. A one-pot
selective oxidation (TEMPO/PIDA, then Pinnick oxidation)
of the C-14 primary alcohol followed by acid workup triggered
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/jacs.9b05641.
E
DOI: 10.1021/jacs.9b05641
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Article
Experimental procedures and spectral data for all new
compounds (PDF)
Crystallographic Information File for compound 16
(g) Yamada, R.; Fukuyama, T.; Yokoshima, S. Synthetic Studies of the
Daphniphyllum Alkaloids: A cooperative reaction of proximal
functional groups forming a tetracyclic system. Org. Lett. 2018, 20,
4
504−4606. (h) Li, Y.; Dong, Q.; Xie, Q.; Tang, P.; Zhang, M.; Qin,
(
CIF)
Crystallographic Information File for compound 29
CIF)
Crystallographic Information File for compound 38
CIF)
Y. Enantioselective synthesis of ABCF tetracyclic framework of
Daphniphyllum alkaloid calyciphylline N. Org. Lett. 2018, 20, 5053−
(
5057. (i) Qiu, Y.; Zhong, J.; Du, S.; Gao, S. Synthetic studies on
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AUTHOR INFORMATION
Corresponding Author
xuj@sustech.edu.cn
■
Xie, Q.-X.; Tang, P.; Xue, F.; Qin, Y. Asymmetric synthesis of ABC
tricyclic core in Daphniphyllum alkaloid 21-deoxy-macropodumine D.
Tetrahedron Lett. 2018, 59, 1999−2004. (l) Cox, J. B.; Wood, J. L.
Synthetic studies toward longeracemine: The intramolecular [4 + 2]
cycloaddition of 3H-pyrroles. Tetrahedron 2018, 74, 4539−4549.
*
ORCID
Jing Xu: 0000-0002-5304-7350
Author Contributions
J.H., W.T., Y.Z.: These authors contributed equally.
(m) Gao, L.; Cheng, B.; Yue, H.; Cao, S.; Wang, J.-L.; Xu, L. A
†
bioinspired approach for construction of the [7−5-6−5] all-carbon
tetracyclic core of logeracemin A. Org. Chem. Front. 2019, 6, 813−
Notes
816. (n) Deng, M.; Yao, Y.; Li, X.; Li, N.; Zhang, X.; Liang, G. Rapid
The authors declare no competing financial interest.
construction of the ABCE tetracyclic tertiary amine skeleton in
Daphenylline enabled by an amine−borane complexation strategy.
Org. Lett. 2019, 21, 3290−3294. (o) Chen, Y.; Hu, J.; Guo, L.-D.;
Tian, P.; Xu, T.; Xu, J. Synthesis of the core structure of
daphnimacropodines. Org. Lett. 2019, 21, 4309−4312. (p) Zhang,
Y.; Guo, L.-D.; Xu, J. Efficient synthesis of the AC ring system of
daphnilactone B. Youji Huaxue 2019, 39, 1079−1084. (q) Sun, H.;
Wu, G.; Xie, X. Synthetic studies towards daphniyunnine B:
Construction of AC bicyclic skeleton with two vicinal all carbon
quaternary stereocenters. Chin. Chem. Lett. 2019, DOI: 10.1016/
j.cclet.2019.06.049. (r) Jansana, S.; Diaba, F.; Bonjoch, J. Stereo-
controlled synthesis of the daphenylline pentacyclic ACDEF ring
system. Org. Lett. 2019, DOI: 10.1021/acs.orglett.9b02211.
ACKNOWLEDGMENTS
■
We appreciate financial support from NSFC (21772082),
SZDRC Discipline Construction Program, Shenzhen Nobel
Prize Scientists Laboratory Project (C17783101), and SZSTI
(
J C Y J 2 0 1 7 0 8 1 7 1 1 0 5 1 5 5 9 9
a n d
KQJSCX20170728154233200). The authors thank Prof. X.-J.
Hao and Prof. Y. Zhang (KIB) for helpful discussions in final
product purification. We also thank Dr. X. Chang (SUSTech)
for single crystal X-ray diffraction analysis.
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