Total synthesis of (+)-aculeatin D and (+)-6-epi-aculeatin D

Article abstract of DOI:10.1055/s-0029-1218546

The stereoselective total synthesis of spiroketal natural product (+)-aculeatin D and unnatural (+)-6-epi-aculeatin D has been accomplished. Sharpless kinetic resolution of secondary allylic alcohol and phenyliodine(III) bis(trifluoroacetate) (PIFA)-mediated oxidative spirocyclization were used as key steps in this synthesis. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218546

LETTER
51
Total Synthesis of (+)-Aculeatin D and (+)-6-epi-Aculeatin D
(
+)-Aculea
.
tinD and
(+
S
)-6-epi-Aculea
.
tinD Yadav,* K. V. Raghavendra Rao, K. Ravindar, B. V. Subba Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160512; E-mail: yadavpub@iict.res.in
Received 7 September 2009
R1
Abstract: The stereoselective total synthesis of spiroketal natural
Me
( )11
O
O
O
product (+)-aculeatin D and unnatural (+)-6-epi-aculeatin D has
been accomplished. Sharpless kinetic resolution of secondary allyl-
ic alcohol and phenyliodine(III) bis(trifluoroacetate) (PIFA)-medi-
ated oxidative spirocyclization were used as key steps in this
synthesis.
R2
A (R1 = H, R2 = OH) (1)
D (R1 = OH, R2 = H) (4)
R1
Key words: (+)-aculeatin D, (+)-6-epi-aculeatin D, Sharpless ki-
netic resolution, spirocylization
Me
( )11
O
R2
O
Spiroketal natural products such as aculeatin A–D (1–4,
Figure 1) were recently isolated from Amomum aculea-
tum by Heilmann et al.1 The Amomum aculatum (Zingi-
beraceae) is a herbaceous plant that is distributed
throughout Malaysia, Indonesia and Papua New Guinea.
It is traditionally used as a folk medicine to treat fever and
malaria.2 The aculeatins A–D represent a novel class of
natural compounds that comprise an unusual 1,7-dioxa-
dispiro[5.1.5.2]pentadecane spirocyclic system. These
compounds have been found to exhibit antiprotozoal ac-
tivity against some Plasmodium and Trypanosoma spe-
cies. In addition, they also show antibacterial activity
against the KB cell lines. The observed biological activity
of the aculeatins may be attributed to the presence of the
Michael acceptor moiety.3 Due to their fascinating biolog-
O
B (R1 = H, R2 = OH) (2)
epi-D (R1 = OH, R2 = H) (5)
Me
( )6
HO
( )
Me
11
OH
O
O
O
O
C (3)
O
Figure 1 Aculeatins A–D and 6-epi-aculeatin D
ical activities and novel structural features, these com- the anti-1,3-diol moiety for the synthesis of (+)-aculeatin
pounds have attracted the attention of several synthetic D and its 6-epimer.
chemists.4
In a continuation of our interest in the synthesis of biolog-
The presence of the hidden 1,3-dihydroxy units was the ically active natural products,we herein report an efficient
major concern in designing different synthetic routes to and concise synthetic route for the total synthesis of the
aculeatins. The majority of approaches utilize stepwise spiroketal natural product (+)-aculeatin D (4), which we
approaches to construct the 1,3-diol motif with the desired chose because of its well-documented cytotoxicity
relative configuration, either by 1,3-induced asymmetric (IC50 = 0.35 mg/mL), and the unnatural (+)-6-epi-aculeat-
reduction or by intramolecular Michael addition and/or in D (5), utilizing Sharpless kinetic resolution and PIFA-
Chiron approach. In most of the approaches, phenylio- mediated oxidative spirocyclization as key steps.
dine(III) bis(trifluoroacetate) (PIFA)-mediated oxidative
The retrosynthetic analysis of (+)-aculeatin D (4) and its
6-epimer (+)-epi-aculeatin D (5) is depicted in Scheme 1.
Accordingly, the spiroketal system could be generated via
phenolic oxidation of an appropriate ketone 6, which, in
turn, could be prepared from protected anti-1,3-diol 7.
The key intermediate 7 could be synthesized from epoxy-
alcohol 8 by regioselective reductive ring-opening. The
starting epoxyalcohol 8 could be prepared from allylic al-
spirocyclization has been employed as a key step to con-
struct the dispiroskeleton.4 In recent years, Sharpless ki-
netic resolution has become one of the most valuable and
versatile protocols for the synthesis of enantiomerically
pure chiral secondary epoxy alcohols5 because they readi-
ly undergo regioselective ring-opening reactions with var-
ious nucleophiles.6 As a result, this reaction has found
extensive use in the synthesis of various natural products.7
cohol 9 using Sharpless kinetic resolution.
Here we successfully employed this strategy to construct
The synthesis of (+)-aculeatin D began with the commer-
cially available 1-tetradecanol (10), which was oxidized
under Swern conditions and subsequently converted into
a,b- unsaturated ester 11 using Wittig olefination in 86%
SYNLETT 2010, No. 1, pp 0051–0054
Advanced online publication: 09.12.2009
DOI: 10.1055/s-0029-1218546; Art ID: D24709ST
x
x.
x
x.
2
0
1
0
© Georg Thieme Verlag Stuttgart · New York

52
J. S. Yadav et al.
LETTER
OH
TBSO
OTBS
O
TBSO
OTBS
O
O
O
Me
12
Me
Me
11
11
(+)-aculeatin D (4)
(+)-6-epi-aculeatin D (5)
7
6
OH
OH
OH
O
Me
Me
OH
Me
11
11
11
10
9
8
Scheme 1 Retrosynthetic analysis of (+)-aculeatin D and (+)-6-epi-aculeatin D
yield (two steps).8 The chemoselective reduction of 11 us- diastereomers.12 Debenzylation and alkyne reduction of
ing DIBAL-H in CH2Cl2 gave the allylic alcohol 12 in alcohol 15 was achieved in a single step using Pd/C under
95% yield.9 The allylic alcohol 12 was then oxidized to a hydrogen atmosphere, to provide the diol 16 in 92%
the corresponding aldehyde in 90% yield using IBX in yield.13 Secondary alcohol 16 was then converted into the
DMSO and subsequently subjected to zinc-mediated ally- corresponding ketone 6 under Swern oxidation conditions
lation to furnish the secondary allylic alcohol 9 in 75% (Scheme 2).14
yield.10 Racemic allylic alcohol 9 was subjected to Sharp-
Cleavage of the TBS-ethers from compound 6 with TBAF
less kinetic resolution using (–)-DIPT and Ti(Oi-Pr)4 to
achieve the chiral epoxy alcohol 8 and allylic alcohol 8a
(Scheme 2).
in THF gave the corresponding diol, which was used with-
out further purification for the oxidative spirocyclization
using PIFA in acetone–water (10:1, v/v solution) to fur-
The resulting epoxyalcohol 8 was subjected to regioselec- nish the (+)-aculeatin D (4) and its thermodynamically
tive reductive ring-opening with Red-Al® to provide the more stable 6-epimer (+)-6-epi-aculeatin D (5; which is
anti-1,3-diol fragment 13.11 The diol 13 was then protect- stabilized by a favorable anomeric effect),15 in good yield
ed as its di-TBS ether using TBSOTf and 2,6-lutidine to (Scheme 3). The physical and spectral data of these com-
give 7 in 95% yield. The terminal olefin 7 was then sub- pounds were in agreement with those reported in the liter-
jected to OsO4-catalyzed dihydroxylation and NaIO4-me- ature.4,16
diated cleavage to give the aldehyde 14, which was further
treated with n-BuLi and p-benzyloxyphenylacetylene in
THF to afford the secondary alcohol 15 as a mixture of
In conclusion, we have accomplished an efficient and
short total synthesis of naturally occurring biologically
active spiroketal natural product (+)-aculeatin D and its
a, b
c
d, e
CO2Et
Me
OH
Me
g
OH
Me
11
11
11
12
11
10
OH
O
OH
HO
OH
Me
Me
f
11
Me
Me
11
8
+
11
9
OH
13
11
8a
TBSO
OTBS
TBSO
OTBS
k
h
i, j
CHO
Me
Me
11
11
14
7
TBSO
OTBS
TBSO
OTBS
m
l
6
Me
Me
11
11
HO
16
HO
15
OBn
OH
Scheme 2 Reagents and conditions: (a) (COCl)2, DMSO, Et3N, CH2Cl2, –78 to –40 °C, 85%; (b) PPh3=CHCO2Et, benzene, reflux; (c)
DIBAL-H, CH2Cl2, 0 °C→r.t., 2 h, 95%; (d) IBX, DMSO, CH2Cl2, r.t., 5 h, 90%; (e) Zn, allyl bromide, sat. NH4Cl, 2 h, 75%; (f) (–)-DIPT,
Ti(Oi-Pr)4, TBHP, CH2Cl2, –20 °C, 48 h, 43% (isolated yield of epoxyalcohol 8); (g) Red-Al, THF, 0 °C, 1 h, 82%; (h) TBSOTf, 2,6-lutidine,
CH2Cl2, 5 h, 95%; (i) OsO4, NMO, acetone–H2O (4:1), 90%; (j) NaIO4, THF–H2O (3:1), 88%; (k) p-benzyloxyphenylacetylene, n-BuLi, THF,
–78 °C, 1 h, 92%; (l) H2 (1 atm), 10% Pd-C, EtOAc, r.t., 5 h, 92%; (m) (COCl)2, DMSO, Et3N, CH2Cl2, –78 to –40 °C, 86%.
Synlett 2010, No. 1, 51–54 © Thieme Stuttgart · New York

LETTER
(+)-Aculeatin D and (+)-6-epi-Aculeatin D
53
OH
O
TBSO
OTBS
OH
12Me
O
O
O
O
12Me
a
Me
+
11
O
(+)-aculeatin D
(4)
O
OH
6
(+)-6-epi-aculeatin D
(5)
Scheme 3 Reagents and conditions: (a) TBAF, THF, 0 °C, 30 min, and PhI(O2CCF3)2, acetone–H2O (10:1), r.t., 4 h, 60% (each isomer in
30% yield).
(9) Galatsis, P. Encyclopedia of Reagents for Organic
Synthesis; John Wiley & Sons: New York, 2001.
(10) Chao, J. L. Tetrahedron 1996, 52, 5643.
(11) Tanner, D.; Groth, T. Tetrahedron 1997, 53, 16139.
(12) Smith, A. B. III.; Lee, D. J. Am. Chem. Soc. 2007, 129,
10957.
6-epimer. Highlights of this synthetic venture includes the
Sharpless kinetic resolution of the secondary allylic alco-
hol, which was successfully employed for the construc-
tion of the anti-1,3-diol system, and PIFA-mediated
spiroketalization. The present strategy employs a minimal
use of protecting groups and the introduction of the aro-
matic system towards the end of the synthesis provides
sufficient flexibility for the construction of various ana-
logues.
(13) Bolshakov, S.; Leighton, J. Org. Lett. 2005, 7, 3809.
(14) Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651.
(15) (a) Deslongchamps, P. Stereoelectronic Effects in Organic
Chemistry; Pergamon Press: Oxford, 1984. (b) Graczyk,
P. P.; Mikolajczyk, M. Top. Stereochem. 1994, 21, 159.
(16) (1R)-1-[(2R,3R)-3-Tridecyloxiran-2-yl]-3-buten-1-ol (8):
colorless oil; [a]D25 +5.8 (c 1.0, CHCl3); IR (neat): 3384,
2919, 2850, 1639, 1464, 1283, 1066, 883 cm–1; 1H NMR
(300 MHz, CDCl3): d = 5.90–5.74 (m, 1 H), 5.18–5.08 (m,
2 H), 3.56–3.47 (m, 1 H), 2.88–2.83 (t, J = 2.2 Hz, 1 H),
2.72–2.68, (q, J = 2.2 Hz, 1 H), 2.38–2.31 (m, 2 H), 1.88 (br
Acknowledgment
K.V.R.R and K.R. thank the CSIR, New Delhi, for the award of fel-
lowships.
s, 1 H), 1.30–1.24 (m, 24 H), 0.88 (t, J = 6.6 Hz, 3 H); 13
C
References and Notes
NMR (75 MHz, CDCl3): d = 133.6, 118.1, 68.1, 60.4, 55.4,
38.1, 31.9, 31.5, 29.7, 29.6 (× 2), 29.5 (× 2), 29.4, 29.3 (× 2),
25.9, 22.6, 14.1; ESI-MS: m/z = 319 [M + Na]+; HRMS:
m/z [M + Na]+ calcd for C19H36O2Na: 319.2613; found:
319.2599.
(1) (a) Heilmann, J.; Mayr, S.; Brun, R.; Rali, T.; Sticher, O.
Helv. Chim. Acta 2000, 83, 2939. (b) Heilmann, J.; Brun,
R.; Mayr, S.; Rali, T.; Sticher, O. Phytochemistry 2001, 57,
1281.
(4R,6R)-1-Nonadecene-4,6-diol (13): white solid; mp 83–
85 °C, [a]D25 –10.7 (c 1.0, CHCl3); IR (neat): 3507, 3354,
2918, 2849, 1643, 1467, 1356, 1069 cm–1; 1H NMR (400
MHz, CDCl3): d = 5.86–5.74 (m, 1 H), 5.18–5.08 (m, 2 H),
3.99–3.84 (m, 2 H), 2.28–2.21 (m, 2 H), 1.59–1.56 (m, 2 H),
1.33–1.23 (m, 24 H), 0.88 (t, J = 6.5 Hz, 3 H); 13C NMR (75
MHz, CDCl3): d = 134.6, 118.1, 69.2, 68.1, 42.0, 41.8, 37.4,
31.9, 29.7–29.5 (× 7), 29.3, 25.7, 22.6, 14.1; ESI-MS: m/z =
321 [M + Na]+; HRMS: m/z [M + Na]+ calcd for
(2) Holdsworth, K. D.; Mahana, P. Int. J. Crude Drug Res. 1983,
21.
(3) For the importance of Michael acceptor moieties for
cytotoxicity, see, for example: Buck, S. B.; Hardouin, C.;
Ichikawa, S.; Soenen, D. R.; Gauss, C.-M.; Hwang, I.;
Swingle, M. R.; Bonness, K. M.; Honkanen, R. E.; Boger,
D. L. J. Am. Chem. Soc. 2003, 125, 15694.
(4) (a) Wong, Y. S. J. Chem. Soc., Chem. Commun. 2002, 686.
(b) Falomir, E.; Alvarez-Bercedo, P.; Carda, M.; Marco,
J. A. Tetrahedron Lett. 2005, 46, 8407. (c) Baldwin, J. E.;
Adlington, R. M.; Sham, V. W. W.; Marquez, R.; Bulger,
P. G. Tetrahedron 2005, 61, 2353. (d) Alvarez-Bercedo, P.;
Falomir, E.; Carda, M.; Marco, J. A. Tetrahedron 2006, 62,
9641. (e) Peuchmaur, M.; Wong, Y. S. J. Org. Chem. 2007,
72, 5374. (f) Chandrasekhar, S.; Rambabu, C.;
Shyamsunder, T. Tetrahedron Lett. 2007, 48, 683.
(g) Ramana, C. V.; Srinivas, B. J. Org. Chem. 2008, 73,
3915. (h) Zhen, Z. B.; Gao, J.; Wu, Y. J. Org. Chem. 2008,
73, 7310.
C19H38O2Na: 321.2769; found: 321.2773.
tert-Butyl({(1R,3R)-3-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-1-
tridecyl-5-hexenyl}oxy)-dimethylsilane (7):
colorless oil; [a]D25 –15.0 (c 1.0, CHCl3); IR (neat): 2927,
2856, 1636, 1464, 1253, 1075, 833 cm–1; 1H NMR (300
MHz, CDCl3): d = 5.85–5.70 (m, 1 H), 5.07–4.98 (m, 2 H),
3.85–3.69 (m, 2 H), 2.24–2.17 (m, 2 H), 1.57–1.48 (m, 2 H),
1.33–1.22 (m, 24 H), 0.92–0.81 (m, 21 H), 0.09–0.06 (m,
12 H); 13C NMR (75 MHz, CDCl3): d = 135.0, 116.7, 70.1,
69.8, 45.0, 42.5, 37.8, 31.9, 30.9, 29.7 (× 6), 29.6, 29.3, 25.9
(× 6), 25.6, 25.0, 22.6, 14.1, –3.9, –4.0, –4.1, –4.3; ESI-MS:
m/z = 527 [M + H]+; HRMS: m/z [M + H]+ calcd for
C31H67O2Si2: 527.4679; found: 527.4668.
(5) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.;
Ikeda, M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103,
6237.
(5R,7R)-1-[4-(Benzyloxy)phenyl]-5,7-di[1-(tert-butyl)-
1,1-dimethylsilyl]oxy-1-icosyn-3-ol (15): colorless oil;
[a]D25 +11.2 (c 1.0, CHCl3); IR (neat): 3450, 2926, 2854,
1608, 1507, 1462, 1249 cm–1; 1H NMR (300 MHz, CDCl3):
d = 7.45–7.32 (m, 7 H), 6.90 (d, J = 8.8 Hz, 2 H), 5.06 (s,
2 H), 4.84 (d, J = 3.2 Hz, 1 H), 4.16 (br s, 1 H), 3.74–3.65
(m, 1 H), 2.11–1.86 (m, 3 H), 1.78–1.70 (m, 2 H), 1.33–1.21
(m, 24 H), 0.94–0.83 (m, 21 H), 0.07 (s, 6 H), 0.06 (s, 6 H);
13C NMR (75 MHz, CDCl3): d = 158.8, 136.6, 135.2, 133.0,
(6) Sharpless, K. B.; Behrens, C. H.; Katsuki, T.; Lee, A. W. M.;
Martin, V. S.; Takatani, M.; Viti, S. M.; Walker, F. J.;
Woodard, S. S. Pure. Appl. Chem. 1983, 55, 589.
(7) Karsuki, T. In Comprehensive Asymmetric Catalysis, Vol. 2;
Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer:
Berlin, 1999, 621–648.
(8) Corey, E. J.; Clark, D. A.; Goto, G.; Marfat, A.; Mioskowski,
C.; Samuelsson, B.; Hammarstroem, S. J. Am. Chem. Soc.
1980, 102, 1436.
Synlett 2010, No. 1, 51–54 © Thieme Stuttgart · New York

54
J. S. Yadav et al.
LETTER
128.6 (× 2), 128.0, 127.4 (× 2), 124.9, 114.7 (× 2), 88.5,
85.0, 69.9, 69.3, 61.5, 46.1, 45.2, 37.3, 32.1, 31.9, 29.7 (× 8),
29.6, 29.3, 26.4, 25.9, 25.8, 24.9, 23.4, 22.6, 18.0, 17.9, 14.1,
–3.8, –4.1 (× 2), –4.4; ESI-MS: m/z = 737 [M + H]+; HRMS:
m/z [M + Na]+ calcd for C45H76O4NaSi2: 759.5054; found:
759.5068.
(5R,7R)-5,7-Di[1-(tert-butyl)-1,1-dimethylsilyl]oxy-1-(4-
hydroxyphenyl)icosan-3-ol (16): colorless oil; [a]D25 +8.2
(c 1.0, CHCl3); IR (neat): 3440, 2926, 2855, 1621, 1463,
1254, 1077 cm–1; 1H NMR (300 MHz, CDCl3): d = 7.05 (d,
J = 8.4 Hz, 2 H), 6.74 (d, J = 8.3 Hz, 2 H), 5.40 (br s, 1 H),
3.94–3.60 (m, 3 H), 2.76–2.54 (m, 2 H), 1.80–1.51 (m, 6 H),
1.41–1.21 (m, 24 H), 0.93–0.84 (m, 21 H), 0.11 (s, 6 H),
0.04 (s, 6 H); 13C NMR (75 MHz, CDCl3): d = 153.7, 134.1,
129.4, 115.1, 71.7, 70.2, 70.0, 48.9, 46.4, 44.1, 39.5, 37.3,
31.9, 30.7, 29.6 (× 8), 29.3, 25.9 (× 5), 25.8, 24.9, 22.6, 18.0,
17.8, 14.1, –3.8, –4.2 (× 2), –4.4; ESI-MS: m/z = 651 [M +
H]+; HRMS: m/z [M + Na]+ calcd for C38H74O4NaSi2:
673.5023; found: 673.4998.
(5S,7R)-5,7-Di[1-(tert-butyl)-1,1-dimethylsilyl]oxy-1-(4-
hydroxyphenyl)icosan-3-one (6): colorless oil; [a]D25 +8.0
(c 1.0, CHCl3); IR (neat): 3449, 2925, 2853, 1724 (keto),
1637, 1442, 1260, 1082 cm–1; 1H NMR (300 MHz, CDCl3):
d = 7.03 (d, J = 8.3 Hz, 2 H), 6.73 (d, J = 8.4 Hz, 2 H), 5.12
(br s, 1 H), 4.24–4.15 (m, 1 H), 3.69–3.62 (m, 1 H), 2.85–
2.41 (m, 6 H), 1.69–1.66 (m, 2 H), 1.33–1.21 (m, 24 H),
0.90–0.86 (s, 12 H), 0.84 (s, 9 H), 0.07 (s, 12 H); 13C NMR
(75 MHz, CDCl3): d = 208.6, 135.1, 129.4, 125.0, 115.2
(× 2), 70.0, 67.4, 51.1, 46.3, 45.7, 37.6, 32.1, 31.9, 29.6
(× 6), 29.3, 28.5, 26.3, 25.9 (× 7), 25.0, 23.4, 22.6, 14.1, –
4.1, –4.2, –4.3, –4.4; ESI-MS: m/z = 649 [M + H]+; HRMS:
m/z [M + H]+ calcd for C38H73O4Si2: 649.5047; found:
649.5041.
Aculeatin D: colorless oil; [a]D25 +40.0 (c 1.0, CHCl3); IR
(neat): 3426, 2923, 2853, 1660 (keto), 1628, 1459, 1061,
1013 cm–1; 1H NMR (300 MHz, CDCl3): d = 6.90 (dd,
J = 10.5, 3.2 Hz, 1 H), 6.77 (dd, J = 10.5, 3.2 Hz, 1 H), 6.07
(dd, J = 10.0, 1.5 Hz, 1 H), 6.03 (dd, J = 10.0, 1.5 Hz, 1 H),
4.05–3.96 (m, 1 H), 3.77–3.62 (m, 1 H), 2.20 (m, 1 H), 1.97
(m, 1 H), 1.73 (m, 1 H), 1.45–1.35 (m, 2 H), 1.31–1.06 (m,
28 H), 0.81 (t, J = 6.9 Hz, 3 H); 13C NMR (75 MHz, CDCl3):
d = 185.6, 151.5, 149.2, 127.0, 126.8, 108.9, 82.8, 69.0, 68.1,
43.9, 42.8, 35.8, 34.5, 32.1, 31.9, 30.3, 29.8–29.5 (× 4), 29.3,
28.9, 28.8, 28.5, 25.7, 21.7; ESI-MS: m/z = 419 [M + H]+,
441 [M + Na]+; HRMS: m/z [M + Na]+ calcd for
C26H42O4Na: 441.2980; found: 441.2970.
6-epi-Aculeatin D: colorless oil; [a]D25 +5.0 (c 1.0, CHCl3);
IR (neat): 3426, 2923, 2853, 1660 (keto) cm–1; 1H NMR (300
MHz, CDCl3): d = 6.77 (dd, J = 10.5, 3.2 Hz, 1 H), 6.72 (dd,
J = 10.5, 3.2 Hz, 1 H), 6.06 (dd, J = 10.0, 1.9 Hz, 1 H), 6.03
(dd, J = 10.0, 1.9 Hz, 1 H), 4.04–3.90 (m, 1 H), 3.75–3.67
(m, 1 H), 2.37–2.15 (m, 3 H), 2.01–1.93 (m, 3 H), 1.86–1.56
(m, 3 H), 1.35–1.15 (m, 24 H), 0.83 (t, J = 7.3 Hz, 3 H); 13
NMR (75 MHz, CDCl3): d = 185.3, 151.4, 149.8, 128.7,
C
128.6, 109.6, 79.5, 68.1, 63.9, 41.4, 40.5, 38.7, 35.8, 34.6,
31.9, 30.3, 29.6 (× 4), 29.5, 29.3, 28.9, 23.7, 22.9, 14.0; ESI-
MS: m/z = 419 [M + H]+.
Synlett 2010, No. 1, 51–54 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.