Total synthesis and structural revision of incargutines A and B

Article abstract of DOI:10.1055/s-0033-1339484

We achieved the first total synthesis of (±)-incargutines A and B, which were isolated from the roots of Incarvillea arguta, utilizing In(OTf) ₃-catalyzed enolization of cyclohexenone derivatives subsequent to an intramolecular Alder-Rickert reaction. At first, we synthesized the proposed structures of incargutines A and B. The spectral data of the synthetic proposed compounds did not correspond to those of the natural products. Then, we synthesized the methyl regioisomers of the proposed structures. Spectral data of these synthetic compounds were identical to those of natural incargutines A and B. Therefore, the structures of incargutines A and B were clearly established to be the methyl regioisomers. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1339484

1998▌
LETTER
letter
Total Synthesis and Structural Revision of Incargutines A and B
Total Synthesis of Incargutines A and B
Atsushi Kinbara,a Takehiro Yamagishi,a Hiroki Ouchi,a Hiroaki Miyaoka*b
a
School of Pharmaceutical Sciences, Ohu University, Misumido 31-1, Tomita-machi, Koriyama, Fukushima 963-8611, Japan
b
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Fax +81(42)6763073; E-mail: miyaokah@toyaku.ac.jp
Received: 12.06.2013; Accepted after revision: 01.07.2013
by a Lewis acid catalyzed enolization and subsequent in-
tramolecular Alder–Rickert reaction.5,6 For example, the
reaction of cyclohexenone 3 in the presence of 20 mol%
of In(OTf)3 gave 4-phenylindane derivative 6 in 55%
Abstract: We achieved the first total synthesis of (±)-incargutines
A and B, which were isolated from the roots of Incarvillea arguta,
utilizing In(OTf)3-catalyzed enolization of cyclohexenone deriva-
tives subsequent to an intramolecular Alder–Rickert reaction. At
first, we synthesized the proposed structures of incargutines A and yield (Scheme 1).6 The reaction pathway is estimated to
B. The spectral data of the synthetic proposed compounds did not
correspond to those of the natural products. Then, we synthesized
involve the In(OTf)3-catalyzed enolization of 3 to gener-
ate dienol intermediate 4 in situ, followed by an intramo-
the methyl regioisomers of the proposed structures. Spectral data of
lecular Alder–Rickert reaction via diene 5 with extrusion
these synthetic compounds were identical to those of natural incar-
of ethylene gas. By utilizing this cascade reaction, the au-
gutines A and B. Therefore, the structures of incargutines A and B
were clearly established to be the methyl regioisomers.
thors anticipated that the synthesis of (±)-incargutines A
and B could be achieved.
Key words: total synthesis, incargutine, enols, Alder–Rickert reac-
tion, indium
CO2Et
In(III)
CO2Et
OH
O
In(OTf)3
(20 mol%)
Incargutines A and B were isolated as novel biphenyl nat-
ural products from the roots of Incarvillea arguta in
2009.1 The proposed structures, except for the absolute
configuration of C-7, were elucidated to be 1 and 2 by 1D
and 2D NMR spectroscopy and mass spectrometry (Fig-
ure 1). Biphenyl natural products possessing a 4-phenyl-
indane moiety have rarely been isolated.1–3 The
biosynthesis of incargutines has attracted attention given
their unique structures.4 It was revealed that incargutines
possess moderate cytotoxicity against tumor cell lines,
where incargutine A in particular demonstrated equiva-
lent cytotoxicity against LOVO cells (IC50 0.47 μg/mL) as
observed with doxorubicin.1
toluene
100 °C
55%
CO2Et
3
CO2Et
CO2Et
4
OH
In(OTf)3
EtO2C
HO
H2C CH2
CO2Et
5
CO2Et
12
MeO
13
OMe
6
10
11
CHO
Scheme 1 In(OTf)3-catalyzed one-pot synthesis of 4-phenylindane
derivative 6
3
7
5
1
4
Our retrosynthetic plan is indicated in Scheme 2. (±)-Inc-
argutines A (1) and B (2) would be synthesized from phe-
nylindane A by conversion of the ethoxycarbonyl group at
C-4 into a formyl group, conversion of the alkoxycarbon-
yl group into a hydroxy group at C-4′, and deoxygenation
of the phenolic hydroxy group at C-5. Phenylindane A
would be obtained by utilizing the aforementioned
In(OTf)3-catalyzed one-pot synthesis of the 4-phenylin-
dane derivative from cyclohexenone B as a key step. Cy-
clohexenone B would be obtained by the arylation of
cyclohexenone C. Cyclohexenone C would be provided
by alkylation of cyclohexenone D with alkyl iodide E.
1'
3'
5'
OH
incargutine A (1)
OH
incargutine B (2)
4-phenylindane
Figure 1 Proposed structures of incargutines A, B and structure of
4-phenylindane
The authors have recently demonstrated a one-pot synthe-
sis of phenol derivatives from cyclohexenone derivatives
SYNLETT 21709013, 2415, 1998–2002
Advanced online publication: 12.08.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1339484; Art ID: ST-2013-U0544-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
Total Synthesis of Incargutines A and B
1999
R1
CO2Et
of HMPA to afford 6-alkylcyclohexenone 14 in 74%
yield. The TBS group in 14 was deprotected using TBAF
to give enone 15 in 99% yield. Enone 15 was converted
into iodide 16 in 87% yield by treatment with 4-iodo-
phenylmagnesium chloride8 in situ prepared from 1,4-di-
iodobenzene with i-PrMgCl, followed by workup with
10% HCl. Protection of the ketone in 16 with 1,2-bis(tri-
methylsilyloxy)ethane and TMSOTf9 gave acetal 17 in
75% yield. Acetal 17 was treated with i-PrMgCl to gener-
ate the alkynyl and aryl dianion intermediate, followed by
treatment with ClCO2Et to give the diester. The acetal
moiety was hydrolyzed with TsOH·H2O in acetone and
water to give cyclohexenone 18 in 54% yield (2 steps).
Cyclohexenone 18 is a substrate of the In(OTf)3-catalyzed
one-pot synthesis of the 4-phenylindane derivative. The
compounds 14–18 were diastereomeric mixtures, their
diastereomeric ratio and stereochemistry could not be de-
termined.
CO2Et
4
OH
O
5
4'
CO2R2
OH
CO2R2
A
B
incargutine A (1): R1 = CHO
incargutine B (2): R1 = CH(OMe)2
R4
R4
OR3
OR3
+
I
O
O
E
D
C
Scheme 2 Retrosynthetic analysis of incargutines A and B
Iodide 12 corresponding to E in the synthetic plan was
prepared from known alcohol 77 (Scheme 3). The primary
hydroxy group of alcohol 7 was protected in the form of a
mesitoate ester by treatment with 2,4,6-Me3C6H2COCl,
Et3N, and DMAP to give 8 in 77% yield. The benzyl ether
8 was subjected to hydrogenolysis in the presence of 10%
Pd/C. Swern oxidation of the primary alcohol, and Corey–
Fuchs dibromoolefination of the resulting aldehyde af-
forded dibromoolefin 9 in 93% yield (3 steps). Treatment
of dibromoolefin 9 with n-BuLi and then TBSCl gave al-
kyne 10 in 91% yield. Deprotection of the mesitoyl group
in 10 using LAH and tosylation of the primary alcohol by
treatment with TsCl, Et3N, and DMAP afforded tosylate
11 in 84% (2 steps). Iodide 12 was prepared by treatment
of tosylate 11 with NaI in 91% yield.
R
O
O
OEt
c
a
OEt
O
13
14: R = TBS
15: R = H
b
I
16
CO2Et
O
O
O
e, f
d
I
CO2Et
17
18
O
a
b–d
Scheme 4 Reagents and conditions: (a) LDA, then 12, HMPA, THF,
–78 °C to r.t., 74%; (b) TBAF, THF, 30 °C, 99%; (c) 1,4-diiodoben-
zene, i-PrMgCl, THF, r.t. then 10% HCl aq, 87%; (d) 1,2-bis(trimeth-
ylsilyloxy)ethane, TMSOTf, CH2Cl2, –70 °C, 75%; (e) i-PrMgCl,
then ClCO2Et, THF, 40 °C; (f) TsOH·H2O, H2O, acetone, r.t., 54%
(2 steps).
HO
Mes
O
OBn
OBn
7
8
O
O
Br
e
Mes
O
Mes
O
Br
TBS
9
10
Examination of the In(OTf)3-catalyzed one-pot synthesis
of 4-arylindane 19 from cyclohexene 18 was performed
(Scheme 5). Treatment of 18 with 20 mol% of In(OTf)3 in
xylene at 130 °C for five hours afforded 4-arylindane 19
in 56% yield.6 Investigation of the proposed structures of
incargutines A and B from 4-arylindane 19 was per-
formed. The regioselective reduction of 4-arylindane 19
with BH3·SMe2 afforded diol 20 in 84% yield. Following
protection of the primary hydroxy group in 20 with
TBSCl and Et3N (89%), the phenolic hydroxy group in 21
was converted into the triflate with Tf2O and Et3N to give
triflate 22 in 80% yield. The Pd(0)-catalyzed
hydrogenolysis10 of triflate 22 with formic acid afforded
ethyl ester 23 in 79% yield. Reduction of ester 23 with
LiBH4 gave a primary alcohol, which was oxidized with
Dess–Martin periodinane to give the aldehyde. The alde-
f, g
R
h
TBS
11: R = OTs
12: R = I
Scheme 3 Reagents and conditions: (a) 2,4,6-Me3C6H2COCl,
Et3N, DMAP, CH2Cl2, r.t., 77%; (b) H2, 10% Pd/C, MeOH, 40 °C;
(c) (COCl)2, DMSO, Et3N, CH2Cl2, –78 °C to 0 °C; (d) CBr4, Ph3P,
pyridine, CH2Cl2, r.t., 93% (3 steps); (e) n-BuLi, TBSCl, THF, –78 °C
to r.t., 91%; (f) LAH, THF, r.t.; (g) TsCl, Et3N, DMAP, CH2Cl2, r.t.,
84% (2 steps); (h) NaI, acetone, reflux, 91%.
Cyclohexenone 18 corresponding to B in the synthetic
plan was prepared from commercially available 3-eth-
oxycyclohex-2-enone (13, Scheme 4). Cyclohexenone 13
was treated with LDA and then iodide 12 in the presence
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1998–2002

2000
A. Kinbara et al.
LETTER
Table 1 Comparison of 1H NMR Data for Natural Incargutines A, B
and 1, 2 at H-11a
hyde was treated with MeMgBr to afford the secondary
alcohol, which was oxidized with Dess–Martin periodin-
ane to give the ketone. Deprotection of the TBS group
with TBAF afforded alcohol 24 in 84% yield (5 steps).
The Baeyer–Villiger reaction of methyl ketone 24 with
Position
1
Incargutine A
2
Incargutine B
0.80
H-11
1.29
0.80
1.26
11
MCPBA and Sc(OTf)3 gave the acetate, and Dess–
a 400 MHz, CDCl3, δ (ppm).
Martin oxidation of the primary alcohol to give the aldehyde
followed by hydrolysis of the acetyl group with 10% HCl
afforded the proposed structure of incargutine A (1) in
41% yield (3 steps). The proposed structure of incargutine
B (2) was synthesized by treatment of 1 with CH(OMe)3
and Amberlyst-1512 in 82% yield.
of 25 and 26 was subsequently performed according to a
scheme similar to that employed for the synthesis of com-
pounds 1 and 2.
MeO
OMe
CHO
OR1
CO2Et
OR2
OH
9
9
a
b
e
18
OH
incargutine A (25)
OH
incargutine B (26)
CO2Et
CO2Et
19
20: R1 = R2 = H
21: R1 = TBS, R2 = H
22: R1 = TBS, R2 = Tff
c
Figure 2 Revised structures of incargutines A and B
d
OH
OTBS
Cyclohexenone 13 was treated with LDA and then known
aldehyde 2713 in the presence of DMPU to afford alcohol
28 in 74% yield (Scheme 6). Alcohol 28 was converted
into the mesylate followed by treatment with DBU to af-
ford α,β-unsaturated enone 29 as a sole product in 72%
yield (2 steps). The stereochemistry of 29 was not deter-
mined. α,β-Unsaturated enone 29 was treated with
MeMgBr in the presence of CuI and DMPU to give meth-
ylated enone 30 as a mixture of two diastereomers (2.2:1)
in 91% yield. The TBS group in 30 were deprotected us-
ing TBAF to give enone 31 in 91% yield. Enone 31 was
converted into cyclohexenone 33, a substrate of the
In(OTf)3-catalyzed one-pot synthesis of a 4-phenylindane
derivative, according to our developed synthetic method.
k–m
n
f–j
1
2
CO2Et
O
24
23
Scheme 5 Reagents and conditions: (a) In(OTf)3 (20 mol%), xylene,
130 °C, 56%; (b) BH3·SMe2, THF, r.t., 84%; (c) TBSCl, Et3N,
CH2Cl2, r.t., 89%; (d) Tf2O, Et3N, CH2Cl2, r.t., 80%; (e) Pd(OAc)2,
Ph3P, HCO2H, Et3N, DMF, 60 °C, 79%; (f) LiBH4, THF, 50 °C;
(g) Dess–Martin periodinane, NaHCO3, CH2Cl2, r.t.; (h) MeMgBr,
THF, r.t.; (i) Dess–Martin periodinane, NaHCO3, CH2Cl2, r.t.;
(j) TBAF, THF, r.t., 84% (5 steps); (k) MCPBA, Sc(OTf)3, CH2Cl2,
r.t.; (l) Dess–Martin periodinane, NaHCO3, CH2Cl2, r.t.; (m) 10% In(OTf)3-catalyzed enolization and subsequent intramo-
HCl aq, THF, r.t., 41% (3 steps); (n) CH(OMe)3, Amberlyst-15,
MeCN, r.t., 82%.
lecular Alder–Rickert reaction was carried out by treat-
ment of enone 33 with 20 mol% of In(OTf)3 in xylene at
130 °C to afford 4-arylindane 34 in 52% yield. Incidental-
The spectral data of synthetic compounds 1 and 2 were not ly, the compounds 30–33 were used as diastereomeric
identical with those of natural incargutines A and B, re- mixtures in Scheme 6, their diastereomeric ratio besides
1
spectively. In the H NMR spectra, the chemical shift at compound 30 and stereochemistry was not determined.
H-11 of the synthetic compounds was observed markedly Synthesis of compounds 2514 and 2615 from 4-arylindane
downfield compared with that of the natural products (Ta- 34 was subsequently performed according to the devel-
ble 1). Thus, discrepancies in the spectroscopic data of oped synthetic method of compounds 1 and 2. Spectral
synthetic and natural incargutines A and B led to the con- data of synthetic compounds 25 and 26 were identical to
clusion that the proposed structures of the natural com- those of natural incargutines A and B, respectively. There-
pounds were incorrect.
fore, the structures of incargutines A and B have clearly
been determined to be those presented as 25 and 26, re-
spectively.
The actual structures of incargutines A and B may be con-
cluded to be 25 and 26, respectively, on the basis of a
comparison of the 1H NMR data (Figure 2). The synthesis
Synlett 2013, 24, 1998–2002
© Georg Thieme Verlag Stuttgart · New York

LETTER
Total Synthesis of Incargutines A and B
2001
References and Notes
TBS
TBS
OEt
(1) Fu, J.-J.; Jin, H.-Z.; Shen, Y.-H.; Qin, J.-J.; Wang, Y.;
a
b, c
+
13
Huang, Y.; Zeng, Q.; Yan, S.-K.; Zhang, W. D. Helv. Chim.
Acta 2009, 92, 491.
CHO
(2) Okpekon, T.; Millot, M.; Champy, P.; Gleye, C.; Yolou, S.;
Bories, C.; Loiseau, P.; Laurens, A.; Hocquemiller, R. Nat.
Prod. Res. 2009, 23, 909.
(3) Dai, J.; Krohn, K.; Flörke, U.; Draeger, S.; Schulz, B.; Kiss-
Szikszai, A.; Antus, S.; Kurtán, T.; van Ree, T. Eur. J. Org.
Chem. 2006, 3498.
(4) Hill, R. A.; Sutherland, A. Nat. Prod. Rep. 2009, 26, 725.
(5) Kinbara, A.; Yamagishi, T.; Hanzawa, N.; Kawashima, E.;
Miyaoka, H. J. Org. Chem. 2012, 77, 8999.
(6) Kinbara, A.; Yamagishi, T.; Fujishige, T.; Miyaoka, H.
Chem. Pharm. Bull. 2013, 61, 768.
OH
O
28
27
O
R
O
TBS
OEt
OEt
f
d
O
29
30: R = TBS
31: R = H
e
32
I
CO2Et
CO2Et
(7) Donohoe, T. J.; O’Riordan, T. J. C.; Peifer, M.; Jones, C. R.;
Miles, T. J. Org. Lett. 2012, 14, 5460.
O
OH
(8) Matt, B.; Moussa, L.; Chamoreau, L.-M.; Afonso, C.;
Proust, A.; Amouri, H.; Izzet, G. Organometallics 2012, 31,
35.
j
g–i
k
(9) Tsunoda, T.; Suzuki, M.; Noyori, R. Tetrahedron Lett. 1980,
21, 1357.
(10) Cacchi, S.; Ciattini, P. G.; Morea, E.; Ortar, G. Tetrahedron
Lett. 1986, 27, 5541.
(11) Kotsuki, H.; Arimura, K.; Araki, T.; Shinohara, T. Synlett
1999, 462.
(12) Patwardhan, S. A.; Dev, S. Synthesis 1974, 348.
(13) Bertolini, T. M.; Nguyen, Q. H.; Harvey, D. F. J. Org. Chem.
2002, 67, 8657.
(14) Experimental Procedure and Analytical Data of
(±)-Incargutine A (25)
CO2Et
CO2Et
OH
33
34
OR1
OTBS
OR2
n
o–s
t–v
25
w
To a solution of alcohol 39 (85.5 mg, 0.305 mmol) in CH2Cl2
(5.0 mL) were added MCPBA (65%, 306 mg, 2.75 mmol)
and Sc(OTf)3 (75.1 mg, 0.153 mmol) at 0 °C under Ar
atmosphere, and the mixture was stirred at r.t. for 96 h. The
reaction mixture was extracted with CH2Cl2, and the organic
layer was washed with sat. aq NaHCO3 solution (3×) and
10% Na2S2O3 aq solution. The organic layer was dried over
MgSO4, filtered, and concentrated under reduced pressure.
The residue was purified by a silica gel column
26
CO2Et
35: R1 = R2 = H
36: R1 = TBS, R2 = H
37: R1 = TBS, R2 = Tf
CO2Et
O
38
39
l
m
Scheme 6 Reagents and conditions: (a) LDA, then 27, DMPU, THF,
–78 °C, 74%; (b) MsCl, Et3N, CH2Cl2, 0 °C; (c) DBU, toluene, 60 °C,
72% (2 steps); (d) MeMgBr, CuI, DMPU, THF, 0 °C, 91%; (e) TBAF,
THF, 30 °C, 91%; (f) 1,4-diiodobenzene, i-PrMgCl, 1,4-dioxane,
80 °C then 10% HCl aq, 77%; (g) 1,2-bis(trimethylsilyloxy)ethane,
TMSOTf, CH2Cl2, –70 °C; (h) i-PrMgCl, then ClCO2Et, THF, 40 °C;
(i) TsOH·H2O, H2O, acetone, r.t., 42% (3 steps); (j) In(OTf)3 (20 mol%),
xylene, 130 °C, 52%; (k) BH3·SMe2, THF, r.t., 96%; (l) TBSCl, Et3N,
CH2Cl2, r.t., 97%; (m) Tf2O, pyridine, CH2Cl2, r.t., 95%;
(n) Pd(OAc)2, Ph3P, HCO2H, Et3N, DMF, 60 °C, 83%; (o) LiBH4,
THF, 50 °C; (p) Dess–Martin periodinane, NaHCO3, CH2Cl2, r.t.;
(q) MeMgBr, THF, r.t.; (r) Dess–Martin periodinane, NaHCO3,
CH2Cl2, r.t.; (s) TBAF, THF, r.t., 73% (5 steps); (t) MCPBA,
Sc(OTf)3, CH2Cl2, r.t.; (u) Dess–Martin periodinane, NaHCO3, CH2Cl2, r.t.;
(v) 10% HCl aq, THF, r.t., 40% (3 steps); (w) CH(OMe)3,
Amberlyst-15, MeCN, r.t., 93%.
chromatography (hexane–EtOAc, 4:1) to give a mixture of
the product and unidentified contaminants, which was used
for the next reaction without further purification. To a
suspension of the above mixture and NaHCO3 (156 mg, 1.86
mmol) in CH2Cl2 (5.0 mL) was added Dess–Martin
periodinane (157 mg, 0.371 mmol) at 0 °C, and the mixture
was stirred at r.t. for 1 h. The reaction was quenched by
addition of a mixture of sat. aq Na2S2O3 solution and sat. aq
NaHCO3 solution (1:1), and the mixture was extracted with
EtOAc. The organic layer was washed with H2O and brine,
dried over MgSO4, filtered, and concentrated under reduced
pressure. The crude product was used for the next reaction
without further purification. To a solution of the above crude
product in THF (3.0 mL) was added 10% HCl aq solution
(3.0 mL) at 0 °C, and the mixture was stirred at r.t. for 12 h.
The reaction mixture was extracted with EtOAc. The organic
layer was washed with sat. aq NaHCO3 solution, H2O and
brine, and then dried over MgSO4, filtered, and concentrated
under reduced pressure. The residue was purified by a
preparative TLC (hexane–EtOAc, 8:1) to give (±)-incar-
gutine A (25, 30.8 mg, 40% yield, 3 steps) as a white solid;
mp 166–167 °C. IR (neat): 3259, 1663, 1610, 1585, 1515,
1438 cm–1. 1H NMR (400 MHz, CDCl3): δ = 10.18 (1 H, s),
7.69 (1 H, d, J = 7.8 Hz), 7.31 (2 H, d, J = 8.5 Hz), 7.24 (1
H, m), 6.91 (2 H, d, J = 8.5 Hz), 4.91 (1 H, m), 3.59 (1 H, m),
3.26–3.40 (2 H, m), 2.36 (1 H, m), 1.79 (1 H, m), 0.82 (3 H,
d, J = 6.9 Hz). 13C NMR (100 MHz, CDCl3): δ = 192.7,
In conclusion, the authors achieved the first total synthesis
of (±)-incargutines A and B using our developed
In(OTf)3-catalyzed one-pot synthesis of a 4-phenylindane
derivative. Our findings reveal that the actual structures of
incargutines A and B are 25 and 26, respectively, which
represent the methyl regioisomers of 1 and 2, respectively.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1998–2002

2002
A. Kinbara et al.
LETTER
155.3, 148.4, 146.5, 144.3, 133.0, 130.9, 129.9, 129.7,
129.7, 128.4, 115.4, 115.4, 37.7, 33.3, 29.9, 19.7. MS–FAB:
m/z = 253 [M + H]+. HRMS–FAB: m/z [M + H]+ calcd for
C17H17O2: 253.1229; found: 253.1218.
and concentrated under reduced pressure. The residue was
purified by a preparative TLC (hexane–EtOAc, 5:1) to give
(±)-incargutine B (26, 11.5 mg, 93% yield) as a colorless oil.
IR (neat): 3375, 1612, 1592, 1519, 1214, 1108 cm–1. 1H
NMR (400 MHz, CDCl3): δ = 7.36 (1 H, d, J = 7.8 Hz), 7.27
(2 H, m), 7.08 (1 H, d, J = 7.8 Hz), 6.86 (2 H, d, J = 8.4 Hz),
5.41 (1 H, s), 4.81 (1 H, m), 3.55 (1 H, m), 3.37 (6 H, s),
2.92–3.04 (2 H, m), 2.30 (1 H, m), 1.71 (1 H, m), 0.80 (3 H,
d, J = 6.9 Hz). 13C NMR (100 MHz, CDCl3): δ = 154.6,
146.9, 142.0, 138.7, 134.1, 132.2, 129.8, 129.8, 127.6,
124.6, 115.1, 115.1, 102.7, 53.2, 53.2, 38.2, 33.3, 29.3, 19.9.
MS–FAB: m/z = 267, 298 [M]+. HRMS–FAB: m/z [M]+
calcd for C19H22O3: 298.1569; found: 298.1579.
(15) Experimental Procedure and Analytical Data of
(±)-Incargutine B (26)
To a solution of (±)-incargutine A (25, 10.5 mg, 0.0416
mmol) and CH(OMe)3 (0.050 mL, 0.440 mmol) in MeCN
(2.0 mL) was added Amberlyst-15 (7.3 mg) at 0 °C, and the
mixture was stirred at r.t. for 1 h. The reaction was quenched
by addition of a sat. aq NaHCO3 solution. The mixture was
filtered and then extracted with EtOAc. The organic layer
was washed with H2O and brine, dried over MgSO4, filtered,
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