Synthetic Studies of Haliclonin A: Construction of the 3-Azabicyclo[33.1]nonane Skeleton with a Bridge that Forms the 17-Membered Ring

Article abstract of DOI:10.1055/s-0037-1609150

The core structure of haliclonin A, a 3-azabicyclo[3.3.1]nonane with a bridge that forms a 17-membered ring, was constructed. The synthesis features a ring-closing metathesis that constructs the macrocyclic ring, the stereoselective introduction of carbon units via the intramolecular cyclopropanation of a diazoester, the conjugate addition of an organocopper reagent, and the formation of 3-azabicyclo [3.3.1] nonane skeleton via an unexpected 1,5-hydride shift.

Full text of DOI:10.1055/s-0037-1609150

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
©
Georg Thieme Verlag Stuttgart · New York
2018, 29, A–D
letter
A
en
Synlett
K. Orihara et al.
Letter
Synthetic Studies of Haliclonin A: Construction of the
-Azabicyclo[3.3.1]nonane Skeleton with a Bridge that Forms
3
the 17-Membered Ring
Kensuke Oriharaa
Fumiki Kawagishia,b
Satoshi Yokoshima*a
Tohru Fukuyama*a
HO
0
0
0
0
0-
0
0
3
4-
0
3
6
0-
0
6
2
S
S
CO H
2
N
O
N
2
4 steps
a
Graduate School of Pharmaceutical Sciences, Nagoya University,
Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan
yokosima@ps.nagoya-u.ac.jp
fukuyama@ps.nagoya-u.ac.jp
Graduate School of Pharmaceutical Sciences, University of Tokyo,
H
O
N
O
MeO
OMe
AcO
N
CHO
haliclonin A
b
Ts
7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
Received: 24.11.2017
Accepted after revision: 17.12.2017
Published online: 29.01.2018
a
b
The bridge blocks
HO
the b-face.
DOI: 10.1055/s-0037-1609150; Art ID: st-2017-u0858-l
R
N
Abstract The core structure of haliclonin A, a 3-azabicyclo[3.3.1]nonane
with a bridge that forms a 17-membered ring, was constructed. The
synthesis features a ring-closing metathesis that constructs the macro-
cyclic ring, the stereoselective introduction of carbon units via the
intramolecular cyclopropanation of a diazoester, the conjugate addition
of an organocopper reagent, and the formation of 3-azabi-
cyclo[3.3.1]nonane skeleton via an unexpected 1,5-hydride shift.
O
O
N
N
R
Reactions
would occur
from the a-face.
CHO
haliclonin A (1)
Figure 1 Structure of haliclonin A and structural analysis of the
skeleton
Key words alkaloids, conjugate addition, heterocycles, hydride shift,
macrocycles, marine natural products, ring-closing metathesis
bridge blocked the β-face of the cyclohexane core, thereby
forcing reactions to occur from the α-face. Based on this
strategy, our synthesis commenced with the construction
of the 17-membered ring on the cyclohexane ring (Scheme
1). Birch reduction of 3,5-dimethoxybenzoic acid (2), fol-
lowed by alkylation with 3, afforded carboxylic acid 4.
Treatment of 4 with 2.05 equivalents of n-butyllithium gen-
erated dianion 5, which stereoselectively reacted with alkyl
A series of marine natural products having a nitrogen-
containing core structure fused with macrocyclic rings
1,2
were isolated from sponges. Haliclonin A (1, Figure 1, a),
one such marine natural product, was isolated from the
sponge Haliclona sp. by Oh, Shin, and coworkers in 2009.3
The core structure of haliclonin
A
is
a
3-azabi-
5
cylo[3.3.1]nonane fused with 17-membered and 15-mem-
bered macrocyclic rings containing a formamide, a skipped
diene, and an allyl alcohol moiety. These characteristic
structural features have attracted the attention of synthetic
chemists. Huang and coworkers reported the first total syn-
thesis of haliclonin A in 2016, in which an organocatalytic
conjugate addition of nitromethane and a palladium-
mediated carbonyl–enone coupling reaction were used to
bromide 6 to furnish 7 as the sole isomer. After methyla-
tion of the carboxylic acid moiety, the resulting ester was
reduced with lithium aluminum hydride to give alcohol 8.
Upon treatment with the Grubbs second-generation cata-
lyst, 8 underwent a smooth ring-closing metathesis to give
a mixture of the geometrical isomers,6 which was sub-
sequently hydrogenated to afford 9.
We next focused on introducing carbon units onto the
cyclohexane ring (Scheme 2). The alcohol moiety in 9 was
converted into diazoester 10 according to our two-step pro-
4
construct the 3-azabicyclo[3.3.1]nonane skeleton. Herein,
we disclose our synthetic studies of haliclonin A, in which
the 3-azabicyclo[3.3.1]nonane skeleton with a bridge that
formed the 17-membered ring was constructed.
We envisioned that the bridge, which formed the 17-
membered ring, could control the stereochemistry of the
reactions on the cyclohexane core (Figure 1, b). That is, the
7
cedure using N,N′-ditosylhydrazine. When 10 was heated
in toluene in the presence of a catalytic amount of copper
8
complex 11, cyclopropanation proceeded to give 12. After
opening the lactone ring under basic conditions, the result-
ing carboxylic acid was treated with p-toluenesulfonic acid
in dichloromethane to induce hydrolysis of the enol ether
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D

B
Synlett
K. Orihara et al.
Letter
O
CO2H
Br
O
N2
CO2H
OH
O
Br
O
3
b
Br
a
MeO
N
OMe
MeO
N
OMe
a, b
MeO
OMe
MeO
OMe
2
4
Ts
9
Ts
10
O
Br
t-Bu
CO2H
O
N
R
NTs
O
OLi
6
Cu
O
N
1
MeO
OMe
t-Bu
c,d
1
H
d, e
MeO
OMe
N
MeO
N
OMe
O
c
Li
Ts
5
7
Ts 12
O
HO
O
OH
OH
c, d
e, f
f
g
MeO
N
OMe
MeO
OMe
H
H
O
N
N
MeO
N
O
Ts
Ts
8
9
Ts
1
Ts
14
Scheme 1 Construction of the 17-membered ring. Reagents and
3
conditions: (a) Li, liq NH -THF, –78 °C; 3; (b) n-BuLi, THF, –78 °C; 6,
3
O
O
HMPA, –78 to 0 °C; (c) MeI, K CO , DMF, r.t.; (d) LiAlH , THF, 0 °C to r.t.,
2
3
4
4
8% (3 steps from 6); (e) Grubbs II, CH Cl , r.t.; (f) H , Pd/C, MeOH, r.t.
ClMg
CuI
2
2
2
H
O
N
H
O
N
h
moiety and cleavage of the cyclopropane ring, leading to
the formation of vinylogous ester 13. If the treatment of 12
with a Brønsted or Lewis acid was performed before the
opening of the lactone then a mixture of 13 and 25 was
afforded (Figure 2).
9
Ts
Ts
15
16
Scheme 2 Stereoselective introduction of the carbon units. Reagents
and conditions: (a) BrCH COBr, pyridine, THF, 0 °C, 92% (3 steps from 8);
b) TsNHNHTs, DBU, THF, 0 °C, 68%; (c) 11 (5 mol%), toluene, reflux,
2
(
6
8%; (d) aq NaOH, MeOH, r.t.; (e) p-TsOH·H O, CH Cl , r.t., 60%
2
2
2
O
O
O
O
(2 steps); (f) DIBAL, CH Cl , –78 °C; aq HCl, r.t.; (g) MsCl, Et N,
2
2
3
ClCH CH Cl, 60 °C, 58% (2 steps); (h) vinylMgCl, CuI, THF, r.t., 73%.
2
2
H
H
MeO
N
O
O
N
OMe
18, which was coupled with amine 19 to give amide 20. For-
Ts
1
Ts
mation of a dithiane using 1,3-propanedithiol liberated a
3
25
primary alcohol moiety12 that was oxidized with Dess–
Martin periodinane to furnish aldehyde 21.1
3,14
Heating 21
Figure 2
in toluene with a mixture of camphorsulfonic acid and
quinoline at 60 °C promoted the formation of hemiaminal
22. To our surprise, attempted reduction of the hemiaminal
moiety with triethylsilane in the presence of trifluoroacetic
acid afforded 24, which had a ketene dithioacetal moiety.
The intermediate 23, an acyliminium ion, could potentially
induce a 1,5-hydride shift. The same reaction also occurred
in the absence of triethylsilane to give 24, which featured
the 3-azabicyclo[3.3.1]nonane skeleton.15
In conclusion, we have achieved the construction of the
core structure of haliclonin A, a 3-azabicyclo[3.3.1]nonane
with a bridge that forms a 17-membered ring. The synthe-
sis featured a ring-closing metathesis to construct the
macrocyclic ring, the stereoselective introduction of carbon
units via intramolecular cyclopropanation of a diazoester,
the conjugate addition of an organocopper reagent, and the
formation of a 3-azabicyclo[3.3.1]nonane skeleton via an
unexpected 1,5-hydride shift. The most advanced com-
Reduction of the two carbonyl groups in 13 with di-
isobutylaluminum hydride, followed by acidic hydrolysis,
gave enone 14 with a lactol moiety. Dehydration of the lac-
tol moiety by treatment with methanesulfonyl chloride and
triethylamine produced cyclic enol ether 15. The conjugate
addition of a vinyl group to the enone moiety in 15 and
protonation of the resulting enolate after workup proceed-
ed stereoselectively from the opposite side of the bridge to
9,10
give 16 in 73% yield as the sole isomer.
The vinyl group that had been stereoselectively intro-
duced was used to construct the 3-azabicyclo[3.3.1]nonane
skeleton (Scheme 3). Reduction of the ketone moiety in 16
and subsequent protection of the resulting secondary
alcohol with an acetyl group afforded 17. Conversion of the
enol ether moiety in 17 into the corresponding acetal,
ozonolysis of the vinyl group, and oxidation of the resulting
11
aldehyde with sodium chlorite furnished carboxylic acid
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D

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Synlett
K. Orihara et al.
Letter
O
O
References and Notes
(
1) (a) Sakai, R.; Higa, T.; Jefford, C. W.; Bernardinelli, G. J. Am.
Chem. Soc. 1986, 108, 6404. (b) Sakai, R.; Kohmoto, S.; Higa, T.;
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a, b
c–e
H
H
AcO
N
O
N
(c) Cimino, G.; Mattia, C. A.; Mazzarella, L.; Puliti, R.;
Ts
Ts
1
6
17
Scognamiglio, G.; Spinella, A.; Trivellone, E. Tetrahedron 1989,
45, 3863. (d) Cimino, G.; Scognamiglio, G.; Spinella, A.;
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J. Org. Chem. 1992, 57, 2480. (f) Kobayashi, J.; Tsuda, M.;
Kawasaki, N.; Matsumoto, K.; Adachi, T. Tetrahedron Lett. 1994,
MeO
MeO
O
O
H2N
R
1
9
H
AcO
N
H
H
N
OH
f
AcO
N
R
O
O
35, 4383. (g) Kong, F.; Andersen, R. J.; Allen, T. M. J. Am. Chem.
Ts
Ts
1
8
20
Soc. 1994, 116, 6007. (h) Harrison, B.; Talapatra, S.; Lobkovsky,
E.; Clardy, J.; Crews, P. Tetrahedron Lett. 1996, 37, 9151. (i) Guo,
Y.; Trivellone, E.; Scognamiglio, G.; Cimino, G. Tetrahedron 1998,
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W. Y.; Scheuer, P. J.; Williamson, R. T.; Kelly, M. J. Org. Chem.
R =
H
S
S
S
S
OH
O
R
O
g, h
i
N
H
2000, 65, 8465. (l) El Sayed, K. A.; Kelly, M.; Kara, U. A. K.; Ang,
N
AcO
N
R
AcO
N
K. K. H.; Katsuyama, I.; Dunbar, D. C.; Khan, A. A.; Hamann, M. T.
J. Am. Chem. Soc. 2001, 123, 1804. (m) Peng, J.; Hu, J.-F.; Kazi, A.
B.; Li, Z.; Avery, M.; Peraud, O.; Hill, R. T.; Franzblau, S. G.;
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Wahyuono, S.; Hamann, M. T. J. Am. Chem. Soc. 2003, 125,
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H.; Cavalcanti, B. C.; Pessoa, C. O.; Moraes, M. O.; Macedo, M. L.;
Ferreira, A. G.; Hajdu, E.; Pinheiro, U. S.; Berlinck, R. G. S. J. Nat.
Prod. 2007, 70, 538. (o) Hwang, B. S.; Oh, J. S.; Jeong, E. J.; Sim, C.
J.; Rho, J.-R. Org. Lett. 2012, 14, 6154.
O
Ts
Ts
21
22
S
S
H
S
S
H
R
j
N
c,d
N
H
O
O
AcO
N
AcO
N
(2) For reviews, see: (a) Hu, J.-F.; Hamann, M. T.; Hill, R.; Kelly, M. In
Ts
Ts
2
3
24
The Alkaloids: Chemistry and Biology;
6
V0o.
l
Academic Press: London,
2
003, 207. (b) Delpech, B. In The Alkaloids: Chemistry and
Scheme 3 Construction of the 3-azabicyclo[3.3.1]nonane skeleton.
Reagents and conditions: (a) DIBAL, CH Cl , –78 °C; (b) Ac O, pyridine,
Biology;
7
V3o.
l
Hans-Joachim, K., Ed.; Academic Press: London, 2014,
2
2
2
223. (c) Amat, M.; Pérez, M.; Ballette, R.; Proto, S.; Bosch, J. In
CH Cl , r.t., 88% (2 steps); (c) p-TsOH·H O, MeOH, 60 °C; (d) O , MeOH,
2
2
2
3
The Alkaloids: Chemistry and Biology;
Academic Press: London, 2015, 159.
7
4Vo.
l
Hans-Joachim, K., Ed.;
–
78 °C; Me S, r.t.; (e) NaClO , NaH PO , 2-methyl-2-butene, t-BuOH-
2 2 2 4
H O, r.t.; (f) (Z)-octa-4,7-dien-1-ylamine (19), HBTU, i-Pr NEt, CH Cl ,
2
2
2
2
(
3) Jang, K. H.; Kang, G. W.; Jeon, J.-E.; Lim, C.; Lee, H.-S.; Sim, C. J.;
r.t., 62% (4 steps); (g) HSCH CH CH SH, BF ·OEt , CH Cl , r.t., 48%; (h)
2
2
2
3
2
2
2
Dess–Martin periodinane, NaHCO , CH Cl , r.t., 67%; (i) CSA, quinoline,
Oh, K.-B.; Shin, J. Org. Lett. 2009, 11, 1713.
3
2
2
toluene, 60 °C; (j) TFA, ClCH CH Cl, 50 °C, 62% (2 steps).
(4) (a) Guo, L.-D.; Huang, X.-Z.; Luo, S.-P.; Cao, W.-S.; Ruan, Y.-P.; Ye,
J.-L.; Huang, P.-Q. Angew. Chem. Int. Ed. 2016, 55, 4064. (b) Luo,
S.-P.; Guo, L.-D.; Gao, L.-H.; Li, S.; Huang, P.-Q. Chem. Eur. J.
2
2
2
013, 19, 87.
pound in this synthesis included a dithioketal moiety that
could play a pivotal role in the total synthesis of haliclonin
A.
(
5) The stereochemistry of 7 was deduced according to the litera-
tures: (a) Bennett, N. J.; Elliott, M. C.; Hewitt, N. L.; Kariuki, B.
M.; Morton, C. A.; Raw, S. A.; Tomasi, S. Org. Biomol. Chem. 2012,
10, 3859. (b) Koch, E.; Studer, A. Angew. Chem. Int. Ed. 2013, 52,
4933.
Funding Information
(6) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1,
53.
9
This work was financially supported by JSPS KAKENHI (Grant
Numbers 25221301 and 16H01141) and by the Platform Project for
Supporting Drug Discovery and Life Science Research from the Japan
(
(
(
7) Toma, T.; Shimokawa, J.; Fukuyama, T. Org. Lett. 2007, 9, 3195.
8) Corey, E. J.; Myers, A. G. Tetrahedron Lett. 1984, 25, 3559.
9) The stereochemistry of 16 was confirmed on the basis of the
Agency for Medical Research and Development (AMED).
)(
1
coupling constants in H NMR spectroscopy. For details, see
Supporting Information.
(
10) (1R,15R,22R,Z)-4-Tosyl-22-vinyl-17-oxa-4-azatricy-
Supporting Information
clo[13.6.2.015,20]tricos-18-en-21-one
To a solution of 15 (25.9 mg, 53.4 μmol) and CuI (7.5 mg, 53.4
μmol) in THF (1.5 mL) was added vinylmagnesium chloride in
THF (1.45 M, 73.6 μL, 0.107 mmol) at 0 °C. After stirring for 1 h
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609150.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
at 0 °C, aq NH was added, and the mixture was extracted with
3
EtOAc. The combined organic phases were washed with brine,
dried over anhydrous MgSO , and concentrated under reduced
4
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D

D
Synlett
K. Orihara et al.
Letter
pressure. The residue was purified by preparative TLC (30%
EtOAc/hexane) to afford 16 (20.0 mg, 39.0 μmol, 73%) as a color-
(15) (1R,15R,16S,20R,21R)-20-[(1,3-Dithian-2-ylidene)methyl]-
18-[(Z)-octa-4,7-dien-1-yl]-17-oxo-12-tosyl-12,18-diazatri-
cyclo[13.4.2.11 ]docosan-21-yl acetate
,16
less foam. IR (neat): 2930, 2856, 1700, 1645, 1540, 1456, 1339,
1
1
157, 913. H NMR (400 MHz, CDCl ): δ = 7.70 (d, J = 8.2 Hz, 2
To a solution of 21 (2.0 mg, 2.53 μmol) in toluene (0.5 mL) was
added CSA (1.2 mg, 5.17 μmol) and quinoline (0.3 μL, 24.9 μmol)
at room temperature. After stirring for 9.5 h at 80 °C, 1 N HCl
was added, and the mixture was extracted with EtOAc. The
combined organic phases were washed with brine, dried over
Na SO , and concentrated under reduced pressure. This material
3
H), 7.26 (d, J = 8.2 Hz, 2 H), 6.37 (dd, J = 6.0, 2.8 Hz, 1 H), 5.65
ddd, J = 16.6, 10.1, 9.1 Hz, 1 H), 5.16 (d, J = 16.6 Hz, 1 H), 5.13 (d,
J = 9.1 Hz, 1 H), 4.42 (dd, J = 6.0, 2.3 Hz, 1 H), 3.65 (d, J = 11.0 Hz,
H), 3.51 (d, J = 11.0 Hz, 1 H), 3.34 (t, J = 6.4 Hz, 2 H), 3.20 (ddd,
J = 16.0, 11.0, 5.5 Hz, 1 H), 3.09 (ddd, J = 16.0, 11.0, 4.6 Hz, 1 H),
(
1
2
4
2
2
.98 (m, 1 H), 2.43 (m, 1 H), 2.41 (s, 3 H), 2.27 (ddd, J = 11.5, 5.5,
.8 Hz, 1 H), 2.07 (dd, J = 13.3, 13.3 Hz, 1 H), 1.94 (m, 1 H), 1.64
was used for the next step without further purification. To a
solution of the crude material in 5% TFA/DCE (0.5 mL) was
stirred at 50 °C. After stirring for 1 h at 50 °C, the mixture was
concentrated under reduced pressure. The residue was purified
by preparative TLC (50% EtOAc/hexane) to afford 24 (1.2 mg,
1.56 μmol, 62%, 2 steps) as a colorless oil. IR (neat): 2923, 2551,
13
(m, 1 H), 1.55 (m, 2 H), 1.26–1.37 (m, 17 H). C NMR (100 MHz,
CDCl ): δ = 213.0 (C), 143.8 (CH), 142.7 (CH), 140.7 (C), 138.1
3
(C), 129.4 (CH), 127.1 (CH), 115.9 (CH ), 98.7 (CH), 72.2 (CH ),
2
2
50.6 (CH), 47.0 (CH ), 46.8 (CH), 44.3 (CH ), 40.8(CH), 36.4 (C),
2 2
–1
1
35.5 (CH ), 34.1 (CH ), 28.1 (CH ), 27.8 (CH ), 27.5 (CH ), 27.4
1737, 1541, 1276, 1159, 1000, 990 cm . H NMR (400 MHz,
2
2
2
2
2
(
CH ), 27.3 (CH ), 26.5 (CH ), 24.8 (CH ), 24.6 (CH ), 21.5 (CH ),
CDCl ): δ = 7.67 (d, J = 8.2 Hz, 2 H), 7.30 (d, J = 8.2 Hz, 2 H), 5.80
2
2
2
2
2
3
3
2
5
0.8 (CH2). HRMS (ESI+): m/z calcd for C30H43N O SNa:
36.2811; found: 536.2803.
(dddd, J = 17.4, 11.9, 6.4, 3.7 Hz, 1 H), 5.74 (d, J = 10.0 Hz, 1 H),
5.47 (ddd, J = 10.1, 6.4, 5.5 Hz, 1 H), 5.42 (ddd, J = 10.1, 6.4, 6.4
Hz, 1 H), 5.03 (dd, J = 17.4, 1.8 Hz, 1 H), 4.97 (m, 1 H), 4.97 (m, 1
H), 3.52 (ddd, J = 13.7, 10.1, 6.4 Hz, 1 H), 3.31–3.24 (m, 3 H),
3.19–3.00 (m, 3 H), 2.92–2.74 (m, 8 H), 2.50 (m, 1 H), 2.41 (s, 3
H), 2.29 (m, 1 H), 2.17–1.97 (m, 4 H), 1.97 (s, 3 H), 1.82 (m, 1 H),
1.74 (m, 1 H), 1.73 (m, 1 H), 1.68 (m, 1 H), 1.56–1.25 (m, 19 H),
1
4
(
11) (a) Lindgren, B. O.; Nilsson, T. Acta Chem. Scand. 1973, 27, 888.
b) Kraus, G. A.; Roth, B. J. Org. Chem. 1980, 45, 4825. (c) Kraus,
(
G. A.; Taschner, M. J. J. Org. Chem. 1980, 45, 1175. (d) Bal, B. S.;
Childers, W. E.; Pinnick, H. W. Tetrahedron 1981, 37, 2091.
(
12) After acidic hydrolysis of the cyclic acetal moiety in 20 with
aqueous acetic acid at 80 °C, the resulting hemiacetal was
treated with O-methylhydroxylamine hydrochloride in pyridine
with the goal of cleaving the hemiacetal. The reaction did not
occur, even at 80 °C. When the reaction was carried out at 100
13
0.96 (m, 1 H). C NMR (100 MHz, CDCl ): δ = 170.6 (C), 169.7
3
(C), 143.1 (C), 136.9 (CH), 136.1 (C), 132.5 (C), 129.8 (CH), 129.7
(CH), 128.6 (CH), 127.6 (CH), 127.1 (CH), 114.7 (CH ), 70.9 (CH),
2
54.5 (CH ), 50.3 (CH ), 48.2 (CH ), 46.5 (CH ), 43.2 (CH), 41.6
2
2
2
2
°
C, the hemiacetal moiety was opened, forming an oxime ether,
(CH), 38.3 (CH ), 37.8 (CH), 31.5 (CH ), 30.4 (CH ), 30.0 (CH ),
2
2
2
2
and lactone formation occurred between the liberated hydroxy
group and the amide moiety.
29.7 (CH ), 29.6 (C), 29.4 (CH ), 29.0 (CH ), 28.6 (CH ), 28.1
2 2 2 2
(CH ), 27.7 (CH ), 27.1 (CH ), 26.9 (CH ), 26.5 (CH ), 25.8 (CH ),
2
2
2
2
2
2
(
(
13) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155.
14) Swern or PCC oxidation caused oxidation of the thioacetal
moiety, giving the mono-S-oxide. TPAP oxidation yielded the
desired aldehyde 21 in a moderate yield, accompanied by the
production of a sizable amount of the corresponding S-oxide.
25.0 (CH ), 24.7 (CH ), 23.1 (CH ), 21.5 (CH ), 21.1 (CH ). HRMS
2 2 2 3 3
(ESI+): m/z calcd for C42H62N O S Na 793.3718; found:
2
5 3
793.3699.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–D