Collective enantioselective total synthesis of (+)-sinensilactam A, (+)-lingzhilactone B and (-)-lingzhiol: Divergent reactivity of styrene

Article abstract of DOI:10.1039/d0cc04064a

The collective total synthesis of (+)-sinensilactam A, (+)-lingzhilactone B, (+)-lingzhilactone C and (-)-lingzhiol has been accomplished from a common epoxide intermediate 9. Chemoselective epoxy opening with either an aryl or alkene moiety of styrene le

Full text of DOI:10.1039/d0cc04064a

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DOI: 10.1039/D0CC04064A
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Collective Enantioselective Total Synthesis of (+)-Sinensilactam A,
(+)-Lingzhilactone B and (-)-Lingzhiol: Divergent Reactivity of
Styrene
Received 00th January 20xx,
Accepted 00th January 20xx
Da-Wei Zhang a,b , Hui-Lan Fan a,b,Wenzhao Zhang d, Cheng-Ji Li a,b, Sanzhong Luo c,d,*, Hong-Bo Qin
a
DOI: 10.1039/x0xx00000x
*
Collective total synthesis of (+)-sinensilactam A, (+)-lingzhilactone synthesis, though metal-catalyzed reaction of epoxide with
B, (+)-lingzhilactone C and (-)-lingzhiol has been accomplished styrene are known.13-15
from a common epoxide intermediate 9. Chemoselective epoxy
opening with either aryl or alkene moiety of styrene led to different
Sinensilactam A can be obtained from dimethyl lingzhilactone
15 by annulation with 5-hydroxy-2-pyrrolidinone.
B
carbon skeletons which can be advanced to divergent and concise Lingzhilactone B has one more carbon at C8’ than lingzhiol,
total synthesis of four meroterpenoids.
therefore, styrene is a reasonable equivalent of aryl ketone
because it can be either oxidatively cleaved into a dicarbonyl
During the past 7 years, Ganoderma meroterpenoids have compound, or oxidized into aryl ketone (Fig. 1). The
attracted increasing attentions from phytochemical retrosynthetic analysis is outlined below. Ketoaldehyde 15 can
communities. With meroterpenoids being increasingly be obtained by ozonolysis of styrene 12, which could be
identified, such type of molecules has become the third most synthesized through an epoxy ring opening reaction with the
abundant constituent of Ganoderma. Sinensilactam A, double-bond of styrene 9. Alternatively, the epoxy ring opening
lingzhilactone
B and lingzhiol, isolated from the genus by the aryl moiety would lead to lingzhiol. Styrene 9 could be
Ganoderma by Cheng1-3, are reno-protective by inhibition of obtained sequentially by alkylation of ethyl 2-oxocyclopentane
Smad3 phosphorylation in TGF-β1-induced cellular assays. In carboxylate with aryl acetyl chloride, twice Wittig reaction,
2018, Yang’s group reported the first racemic total synthesis of regioselective allylic oxidation and epoxidation of allylic alcohol.
sinensilactam A using a rhodium catalyzed [3+2] cycloaddition
HO
OH
HO
as the key step.4 However, the synthesis required 18 steps
O
O
O
OH
OH
O
OMe
O
CHO
OH
involving harsh conditions such as high pressure (14 MPa) and
long-time heating (150 °C, 48h). A concise synthetic route under
mild conditions is still highly desirable. On the other hand, we
and others have previously reported the total syntheses of
lingzhiol and lingzhilactone B.5-12 In this communication, we
report a distinctive strategy for the collective synthesis of four
meroterpernoids, (+)-sinensilactam A, (+)-lingzhilactone B, (+)-
lingzhilactone C and (-)-lingzhiol. The key step involves a non-
metal promoted selective nucleophilic opening of epoxide by
alkene moiety of styrene, which has not been explored in total
N
O
CHO
8'
O
O
HO
O
O
O
MeO
15
(+)-Sinensilactam A
(+)-Lingzhiolactone B
HO
OMe
OH
HO
H
OH
HO
O
CO2Et
MeO
MeO
O
O
O
O
9
O
12
O
(-)-Lingzhiol
OMe
OBn
OMe
O
OMe
Cl
MeO
EtO2
C
+
O
CO2Et
18
OMe
1
Figure
1.
Structures
of
several
meroterpenoids
and
retrosynthetic analysis.
We started our total synthesis with the assembly of the chiral
intermediate 9 (Scheme 1). Alkylation of 2,5-dimethoxyphenyl-
acetyl chloride 1 with ethyl 2-oxocyclopentanecarboxylate
proceeded smoothly to give diketone 2 in 94% yield. A
resolution by baker’s yeast only recovered the starting material.
Therefore, we adopted a detour of a kinetic resolution of the
known alkyne ketoester 4. The absolute configuration of the
recovered ketone was determined to be R by its transformation
a. State Key Laboratory of Phytochemistry and Plant Resources in West China,
Kunming Institute of Botany, Chinese Academy of Sciences; Yunnan Key
laboratory of Natural Medicinal Chemistry, Kunming 650201, P. R. China.
b. University of Chinese Academy of Sciences, Beijing 100049, P. R. China.
c. Center of Basic Molecular Science, Department of Chemistry, Tsinghua University,
Beijing 100084, China
d. Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
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into the known (-)-lingzhiol.1 A 2,5-dimethoxyphenylboronic with NaOH in MeOH. The hydroxyl group was VtirewanAsrtictleoOntlhinee
DOI: 10.1039/D0CC04064A
lactone due to the directing effect of the adjacent hydroxyl
acid addition to
chiral alkyne (R)-4 gave styrene 6 in 80% yield.16 Wittig reaction group (Scheme 2, 11) during reduction. Considering the relative
of ketone 6 with the ylide generated from t-BuOK and triphenyl configurations of sinensilactam A and lingzhilactone B, inversion
methyl bromide in THF afforded diene 7 in 81% yield as an of the configuration of the hydroxyl group is needed. Our
optically pure enantiomer.17 Regioselective allylic oxidation extensive examinations of the commonly used Mitsunobu
with selenium dioxide and t-butyl hydroperoxide converted 7 conditions were futile19-23
, and no inversion occurred.
into allylic alcohol 8 in 69% yield. The regioselectivity can be Eventually, when compound 12 was treated with Tf2O and
attributed to the steric hinderance of quaternary carbon and pyridine, triflate 13 was converted into cis isomer 14 in the
the cis-stereoselectivity is possibly arisen from the chelation of presence of NaNO2 and 18-crown-624. The structure of 13 was
selenium with ester group. Next, Sharpless epoxidation18 unambiguously determined by single-crystal X-ray diffraction
produced cis-epoxy secondary alcohol 9 regioselectively in 82% analysis.
yield, which is an advanced intermediate with versatile
Switch of nucleophiles
reactivity.
Ph
OMe
OH
O
HO
MeO
MeO
O
BF3•Et2O
Ref 6, 10
lingzhiol
O
MeO
MeO
MeO
baker's yeast
resolution
O
O
CO2Et
OMe O
CO2Et
OEt
O
O
O
Cl
Cs2CO3, KI
OMe
O
OMe
CO2Et
CO2Et
Aryl attack from top face
DMF
94%
OMe O
OMe O
(cis epoxide)
O
OMe
O
1
2
3
MeO
sinensilactam A
lingzhilactone B
lingzhilactone C
<
O
CO2Et
O
CO2Et
baker's yeast
MeO
+
HO
OMe
O
OMe
O
More flat pentanone causes repulsion
with ketone when aryl attacks from top face
HCO2NH4, CuO
20% aq. sucrose
CO2Et
CO2Et
CO2Et
43% (R)-4
5a
4
(R)-4
O
HO
O
HO
OMe
Ph3PCH3Br,
t-BuOK
OMe
B(OH)2
Pd(PPh3)4
OMe
OMe
MeO
OMe
DMP
O
BF3•Et2O
HCO2H
O
CO2Et
O
DCM
85%
CO2Et
DCM
CO2Et
CO2Et
THF
81%
1,4-dioxane
80%
CO2Et
MeO
MeO
MeO
MeO
MeO
MeO
10
11
7
9
(> 99% ee)
6
HO
OMe
HO
OMe
OMe
TfO
H
Tf2O, Pyr.
H
NaBH4, MeOH
then NaOH
MeO
2 steps, 61%
OMe
HO
Vo(acac)2
TBHP
O
DCM
85%
MeO
CO2Et
SeO2, TBHP
DCM
CO2Et
O
O
13
DCM
82%
O
12
MeO
O
MeO
69%
8
(> 99% ee)
9
OMe
NaNO2
18-crown-6
Scheme 1. Construction of a chiral Common Intermediate 9
H
OH
DMF
67%
MeO
O
We embarked on the first asymmetric synthesis of
sinensilactam A and lingzhilactone B because their enantiomers
have different bioactivities.3 To accomplish this, the double
bond instead of the aryl ring should preferentially engage in
nucleophilic attack (Scheme 2). Similar aryl-epoxide opening
has previously been reported, it was found that the aryl attack
occurs from the opposite face of epoxide 6, 10. In our case, the
space-demanding cis-geometry of the neighboring hydroxyl
group may reinforce this aryl preference. To overturn this
preference, we sought for a stereoelectronic approach by
oxidizing the cyclopentanol to cyclopentanone. By doing so, the
reactivity of the epoxide moiety will be enhanced due to the
electron-withdrawing effect, facilitating the less-nucleophilic
alkene-attack. In addition, the flattened cyclopentanone ring
would disfavor the aryl attack as a result of steric repulsion
between the approaching aryl methoxy group and ketone
moiety.
14
O
13 (x-ray)
Scheme 2. Construction of bicyclic styrene 12
From styrene lactone 14, the total synthesis was achieved
following Yang’s procedure (Scheme 3). Dihydroxylation and
subsequent Pb(OAc)4-mediated cleavage of the resulted diol
proceeded smoothly to afford the key intermediate 15, which
was then deprotected with BBr3 to complete the total synthesis
of (+)-lingzhilactone B. Further protection of aldehyde into
acetal gave (+)-lingzhilactone C. From ketoaldehyde 15, we tried
to utilize 5-ethoxy-2-pyrrolidinone, instead of 5-hydroxy-2-
pyrrolidinone, in order to improve the yield. As known, the in-
situ generation of N-acyliminium intermediate from 5-ethoxy-
2-pyrrolidinone proceeded much faster at lower temperature
(1h v.s. 5h, 0 °C v.s. 40 °C). Unfortunately, we encountered
serious issues during purification as its Rf value was the same as
product. Finally, total synthesis of (+)-sinensilactam A was
achieved by condensation of 15 with 5-hydroxy-2-pyrrolidinone
To our delight, after oxidation into ketone with DMP, the
desired styrene-addition adduct 11 was obtained when treated
.
with BF3 Et2O. Lactone 12 was obtained through reduction of
ketone with NaBH4, followed by lactonization upon treatment
2 | J. Name., 2012, 00, 1-3
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(66% yield) and subsequent demethylation with BBr3 (52%
yield). The synthetic samples have rotations of +50.3 (c 0.07,
MeOH) [literature value: +35.7 (c 0.11, MeOH)]3 for (+)-
sinensilactam A, +154.8 (c 0.08, acetone) for (+)-lingzhilactone
B and +114.3 (c 0.06, DMSO) for (+)-lingzhilactone C.
View Article Online
DOI: 10.1039/D0CC04064A
Scheme 4. Total synthesis of (-)-lingzhiol
OMe
MeO
O
1)OsO4, t-BuOH
HO
O
H
OH
OMe
OH
/THF/H2
O
Ref. 4
80%
The synthetic strategy is straightforward and the conditions
are mild. The synthetic sample has a rotation of -60.7 (c 0.12,
MeOH) [literature value: -94.2 (c 0.36, MeOH)].1 Our NMR data
of synthetic samples are all in agreement with those of
literature.
2) Pb(OAc)4
DCM
OH
OH
CHO
MeO
O
CHO
O
2 steps, 75%
O
O
O
14
O
15
(> 99% ee)
(+)-Lingzhilactone B
H
O
N
Ref. 4
66%
OH
EtOH
91%
CH(OEt)3
p-TsOH
HO
To demonstrate the utility of our synthetical strategy, (+)-
sinensilactam A isomer and (+)-epi-lingzhilactone B, which are
C6’ epimer of natural products, were also prepared following
similar operations (Scheme 5). From styrene 12, similar
transformation of double bond afforded 20 in 78% yield. It was
then demethylated to give (+)-epi-lingzhilactone B in good yield
(81%). When similar operations of pyrrolidionone installation
and demethylation were performed, (+)-sinensilactam A isomer
was isolated in a comparable yield. The structure of 21 was
confirmed by single-crystal X-ray diffraction analysis.
HO
O
MeO
OH
OH
O
OMe
O
Ref. 4
52%
O
OH
OEt
OEt
O
N
O
N
O
O
O
O
O
HO
HO
16
O
O
(+)-Lingzhilactone C
(+)-sinensilactam A
Scheme 3. Completion of synthesis of (+)-sinensilactam A
Next, total synthesis of lingzhiol was investigated from epoxy
styrene 9 (Scheme 4). The hydroxyl group of 9 was protected as
benzyl ether 17 in 75% yield, with a purpose to prevent the
undesired semipinacol rearrangement under Lewis acid
catalysis.25 Benzyl ether 17 underwent aryl-epoxide opening
reaction to give the expected tetracyclic styrene 18 by TMSOTf
HO
MeO
OH
OMe
OMe
1)OsO4, t-BuOH
H
BBr3
HO
O
O
/THF/H2
O
OH
6'
OH
DCM
81%
.
CHO
catalysis.6 Initial experiment with BF3 Et2O gave the desired
2) Pd(OAc)4
DCM
2 steps, 78%
CHO
MeO
O
O
O
O
O
O
(+)-epi-lingzhilactone B
product in 40% isolated yield. After further screening of Lewis
acid and temperature, the optimal 51% isolated yield was
obtained with 2.5 equiv. TMSOTf in DCM at 0°C. Under the same
12
20 (> 99% ee)
H
O
N
p-TsOH
OH
DCM
69%
A
HO
O
OH
O
.
MeO
O
conditions, BF3 Et2O afforded desired product in 45% yield. No
OMe
BBr3
alkene-attack product was observed in these cases. Routine
OsO4-catalyzed dihydroxylation and subsequent oxidative
cleavage of diol with NaIO4 afforded ketoester 19 in 74% yield.
In this way, we took a detour of benzylic oxidation, which was
usually not effective. 8 Finally, global deprotection of dimethoxy
and benzyloxy group furnished (-)-lingzhiol in 52% yield. Our
synthesis took 10 steps and the overall yield is 2.3%.
DCM
53%
O
N
N
O
O
HO
O
O
O
HO
O
(+)-sinensilactam A isomer
21
21 (x-ray)
Scheme 5. Synthesis of two isomers
Finally, we sought for an alternative asymmetric synthesis of
the key chiral intermediate using the state-of-art
H
3
O
O
O
Lewis Acid
Semipinacol
rearrangement
enantioselective photocatalytic process. Based on our
previously developed chiral primary amine catalyzed photolytic
alkylation reaction, 23 the catalytic asymmetric synthesis of the
chiral quaternary diketoester 3, which can be readily
transformed into 7, was investigated (Scheme 6). Under the
optimal conditions,26a up to 99% ee was realized with 71%
isolate yield at 100 mg scale. It can be transformed into key
diene intermediate 7 under similar Wittig reaction condition,
possibly shortening the whole synthesis by two steps.
H
H
HO
1)
2)
H
PG
PGO
HO
O
Lewis Acid
Epoxide ring-opening
by aryl group
H
O
BnO
OMe
OMe
OBn
HO
NaH
BnBr
OMe
TMSOTf
MeO
O
O
O
O
CO2Et
CO2Et
DCM
51%
DMF
75%
tBu
Et
O
OEt
OMe
O
MeO
N
Ph3PCH3Br,
t-BuOK
O
MeO
BF3.Et2O, 45%
(> 99% ee)
17
9
18
•TfOH (20 mol %)
NH2 Et
7
+
CO2Et
Ru(bpy)3Cl2·6H2O (5 mol %)
36W CFL,NaHCO3 (1.0 equiv)
CH3CN (c = 0.2 M), rt
OMe
OBn
THF
75%
O
OH
O
3
1) NMO,OsO4
t-BuOH+THF
OH
MeO
Br
MeO
71%
MeO
BBr3
HO
O
(> 99% ee)
OMe
100 mg
O
DCM
52%
2) NaIO4
THF/H2O
74%
O
O
O
O
Scheme 6. Catalytic asymmetric construction of quaternary stereocenter
(> 99% ee)
19
(-)-lingzhiol
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J. Name., 2013, 00, 1-3 | 3
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13. Y. Ikeda, H. Yorimitsu, H. Shinokubo and K. Oshima, Adv. Synth. Catal., 2004, 346,
In summary, we have developed a collective strategy for the
concise synthesis of four meroterpenoids based on the
divergent reactivity of styrene, which is significantly different
from the widely used semipinacol rearrangement strategy in
the syntheses of similar meroterpenoids. Regioselective epoxy
ring-opening reaction with the double bond of styrene
provided the key lactone styrene 12, leading to the total
synthesis of (+)-sinensilactam A for the first time in 14 steps and
1.1% overall yield. Starting with the same intermediate, (+)-
lingzhilactone B was obtained in 13 steps and 2.7% overall yield.
On the other hand, the key reaction to (-)-lingzhiol features a
one-step construction of a 5/5/6/6 ring system by simultaneous
epoxy ring-opening and lactonization promoted by TMSOTf in
10 steps with an overall yield of 2.3%. The current strategy
View Article Online
1631-1634.
DOI: 10.1039/D0CC04064A
14. G. P. Cerai and B. Morandi, Chem. Commun., 2016, 52, 9769-9772.
15. S. H. Teng, M. E. Tessensohn, R. D. Webster and J. S. Zhou, Acs Catal., 2018, 8, 7439-
7444.
16. C. H. Oh, H. H. Jung, K. S. Kim and N. Kim, Angew Chem Int Edit, 2003, 42, 805-808.
17. R. Rengarasu and M. E. Maier, Asian J. Org. Chem., 2017, 6, 108-117.
18. K. B. Sharpless and R. C. Michaelson, J. Am. Chem. Soc., 1973, 95, 6136-6137.
19. P. O'Brien, C. M. Rosser and D. Caine, Tetrahedron Lett., 2003, 44, 6613-6615.
20. F. Mazraati Tajabadi, R. H. Pouwer, M. Liu, Y. Dashti, M. R. Campitelli, M. Murtaza, G.
D. Mellick, S. A. Wood, I. D. Jenkins and R. J. Quinn, J. Med. Chem., 2018, 61, 6609-
6628.
21. J. A. Davy, J. W. Mason, B. Moreau and J. E. Wulff, J. Org. Chem., 2012, 77, 6332-
6339.
22. S.-Z. Jiang, T. Lei, K. Wei and Y.-R. Yang, Org. Lett., 2014, 16, 5612-5615.
23. P. Yates, R. S. Grewal, P. C. Hayes and J. F. Sawyer, Can. J. Chem., 1988, 66, 2805-
2815.
24. A. Nakazato, K. Sakagami, A. Yasuhara, H. Ohta, R. Yoshikawa, M. Itoh, M. Nakamura
and S. Chaki, J. Med. Chem., 2004, 47, 4570-4587.
25. Z. L. Song, C. A. Fan and Y. Q. Tu, Chem Rev, 2011, 111, 7523-7556.
provides a detour from the problematic benzylic oxidation in 26. Y. Zhu, L. Zhang and S. Luo, J. Am. Chem. Soc., 2014, 136, 14642-14645.
the total synthesis of this series of natural products. Finally, a
catalytic asymmetric synthesis of the key chiral intermediate 3
was also achieved by using the established chiral primary
aminocatalytic protocol. It should be noted that the
construction of all-carbon quaternary center is quite efficient
under rather mild conditions, and may have further application
in total synthesis.
This work was financially supported by High End Talent
Program of Yunnan Province to Dr. H-B. Q. (2015HA028), NSFC
(21372229, 21861132003 and 21672217) and State Key
Laboratory of Phytochemistry and Plant Resources in West
China (Y83802A), Kunming Institute of Botany, CAS.
Conflicts of interest
There are no conflicts to declare.
Notes and references
Corresponding Author
* E-mail: qinhongbo@mail.kib.ac.cn.
ORCID：0000-0003-2603-9520
*Email: luosz@tsinghua.edu.cn
ORCID：0000-0001-8714-4047
1. Y.-M. Yan, J. Ai, L. L. Zhou, A. C. K. Chung, R. Li, J. Nie, P. Fang, X.-L. Wang, J. Luo, Q. Hu,
F.-F. Hou and Y.-X. Cheng, Org. Lett., 2013, 15, 5488-5491.
2. Y.-M. Yan, X.-L. Wang, L.-L. Zhou, F.-J. Zhou, R. Li, Y. Tian, Z.-L. Zuo, P. Fang, A. C. K.
Chung and F.-F. Hou, J. Ethnopharmacol., 2015, 176, 385-393.
3. Q. Luo, L. Tian, L. Di, Y.-M. Yan, X.-Y. Wei, X.-F. Wang and Y.-X. Cheng, Org. Lett., 2015,
17, 1565-1568.
4. W. Shao, J. Huang, K. Guo, J. Gong and Z. Yang, Org. Lett., 2018, 20, 1857-1860.
5. R. Long, J. Huang, W. Shao, S. Liu, Y. Lan, J. Gong and Z. Yang, Nat. Commun., 2014, 5,
5707.
6. D. Chen, H.-M. Liu, M.-M. Li, Y.-M. Yan, W.-D. Xu, X.-N. Li, Y.-X. Cheng and H.-B. Qin,
Chem. Commun., 2015, 51, 14594-14596.
7. D. Chen, W. D. Xu, H. M. Liu, M. M. Li, Y. M. Yan, X. N. Li, Y. Li, Y. X. Cheng and H. B.
Qin, Chem. Commun., 2016, 52, 8561-8564.
8. K. Sharmah Gautam and V. B. Birman, Org. Lett., 2016, 18, 1499-1501.
9. L.-M. Mehl and M. E. Maier, J. Org. Chem., 2017, 82, 9844-9850.
10. R. Rengarasu and M. E. Maier, Asian J. Org. Chem., 2017, 6, 108-117.
11. X. Li, X. Liu, X. Jiao, H. Yang, Y. Yao and P. Xie, Org. Lett., 2016, 18, 1944-1946.
12. D. Chen, X.-M. Li, H.-M. Liu, M.-M. Li, Y.-X. Cheng and H.-B. Qin, Tetrahedron Lett.,
2016, 57, 2877-2879.
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