Stereoselective total synthesis of (+)-boronolide, (+)-anamarine, 8-epi-spicegerolide

Article abstract of DOI:10.1016/j.tetlet.2013.12.061

A stereoselective total synthesis of the naturally occurring cytotoxic lactones (+)-boronolide, (+)-anamarine, and 8-epi-spicigerolide is described. d-Xylose has been used as a chiral source to construct the four contiguous oxygenated stereogenic centers

Full text of DOI:10.1016/j.tetlet.2013.12.061

Tetrahedron Letters 55 (2014) 1398–1401
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Stereoselective total synthesis of (+)-boronolide, (+)-anamarine,
8-epi-spicegerolide
⇑
B. V. Subba Reddy , V. Veerabhadra Reddy, K. Praneeth
Natural Product Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A stereoselective total synthesis of the naturally occurring cytotoxic lactones (+)-boronolide, (+)-anama-
Received 24 October 2013
Revised 14 December 2013
Accepted 17 December 2013
Available online 21 December 2013
rine, and 8-epi-spicigerolide is described. D-Xylose has been used as a chiral source to construct the four
contiguous oxygenated stereogenic centers of target molecules. The diastereoselective allylation was per-
formed using Brown’s protocol and the lactone moiety was prepared by ring closing metathesis.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
a
,b-Unsaturated lactones
Natural products
-Xylose
D
Brown’s allylation
Ring-closing metathesis
a
,b-Unsaturated lactone moiety is frequently found in several
In most cases, the Sharpless asymmetric dihydroxylation,6a–d
asymmetric aldol reaction,6e,f or the chiron approach6g–o has been
employed to construct the four contiguous oxygenated stereogenic
natural products which display a broad spectrum of biological
activities such as anticancer, antibacterial, and/or antifungal
behavior.1a,b The inherent biological activity of these pyranone
containing natural products is presumably due to the presence of
a Michael acceptor in their skeleton which enables them to bind
with a target enzyme.1c Examples of such molecules include (+)-
boronolide (1), (+)-anamrine (2), and spicigerolide (3) (Fig. 1). Of
these, (+)-boronolide (1) was isolated from the bark and branches
of Tetradenia fruiticosa2 and also from the leaves of Tetradenia
barbera,3 whereas the anamarine and spicegerolide were isolated
from the flowers and leaves of an unclassified Peruvian hyptis
species.4
The relative stereochemistry of these compounds was estab-
lished by X-ray studies5,4a and their absolute stereochemistry
was confirmed by chemical degradation.3,4b Numerous synthetic
approaches have been reported for the synthesis of these natural
products.6
centers, while the six-membered
a,b-unsaturated-d-lactone
ring was constructed through ring-closing olefin metathesis
(RCM).6b–f,h,j,o–r Despite the numerous approaches reported, the
development of a simple and modular approach involving readily
accessible chiral precursors with well defined stereochemistry
would provide an easy access to these natural products.
Following our interest in the total synthesis of biologically ac-
tive natural products,7 we herein report a simple and convenient
approach for the total synthesis of (+)-boronolide, (+)-anamarine
and 8-epi-spicigerolide. As per our strategy, the construction of
four contiguous oxygenated stereocenters of lactones (1), (2), and
(3) was achieved from
D-xylose as the configuration of hydroxyl
groups of the side chain coincides with
D-xylose. The key reactions
involved in this approach are the diastereoselective allylation and
ring closing metathesis. As shown in retrosynthetic analysis, the
total synthesis of (1), (2), and (3) could be accomplished from
the corresponding lactones (4), (5), and (6) which in turn could
be prepared by the ring-closing metathesis of acrylyl esters derived
from compounds (7), (8), and (9) respectively. The key intermedi-
ates (7), (8), and (9) could easily be prepared by diastereoselective
allylation of aldehydes, which are derived from a common inter-
O
OAc OAc
OAc
OAc OAc
O
OAc OAc
O
O
OAc OAc
O
O
OAc OAc
8-epi-spicigerolide (3)
(+)-boronolide (1)
(+)-anamarine (2)
mediate 10 which in turn could be prepared from
D-xylose
Figure 1. Pyranone containing natural products.
(Scheme 1).
According to our approach, the synthesis of (1), (2), and (3) be-
gan from -xylose which was converted into -xylofuranoside 10
in three steps.8 Thus treatment of
-xylose with allyl alcohol in
D
D
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: basireddy@iict.res.in (B.V. Subba Reddy).
D
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.12.061

B. V. Subba Reddy et al. / Tetrahedron Letters 55 (2014) 1398–1401
1399
O
temperature afforded the
a
,b-unsaturated lactone 4 in 85% yield.
OAc OAc
OAc OAc
Removal of the benzyl groups using 1 M solution of TiCl4 in DCM
at 0 °C for 4 h gave the trihydroxy lactone which was then peracet-
ylated with acetic anhydride in the presence of pyridine to furnish
the target (+)-boronolide (1) in 53% yield. The spectral data of the
synthetic boronolide (1) was identical with the data reported for
the natural product (Scheme 2).1,18
O
OAc OAc
O
O
OAc OAc
O
OAc
OAc OAc
O
O
O
2
1
3
O
OBn OBn
OBn OBn
After successful synthesis of (+)-boronolide (1), we next at-
tempted the synthesis of 2 and 3 from the intermediate 10. Thus
treatment of hemi-acetal 10 with MeLi (1.6 M in ether) in anhy-
drous ether at ꢀ20 °C afforded the diol as a separable diastereo-
meric mixture (9:1) favoring 21 as a major product in 82% yield
via a chelation controlled mode. Protection of the hydroxy groups
of 21 using benzyl bromide in the presence of NaH furnished the
benzyl ether 22 in 90% yield. Removal of the isopropylidene group
of 22 using p-TSA in methanol gave the diol 23 in 80% yield. Protec-
tion of the primary alcohol of 23 using TBSCl gave the TBDMS ether
24 in 90% yield. The secondary OH of 24 was then protected as its
benzyl ether 25 in 85% yield using benzyl bromide in the presence
of NaH in DMF. Desilylation of 25 using TBAF in THF gave the alco-
hol 26 in 78% yield which was then oxidized under Swern condi-
tions to give the key intermediate 27 to the synthesis of 2 and 3
(Scheme 3).
O
OBn OBn
OBn
OBn OBn
O
OBn OBn
O
5
4
6
OBn OBn
C4H9
OBn OBn
OH
OBn
OBn
OH OBn
OBn OBn
OH
O
OBn OBn
8
7
9
O
OH
OBn
O
10
Wittig olefination of 27 with triethyl phosphonoacetate16 gave
D-Xylose
the (E)-a,b-unsaturated ester 28a as a sole product in 93% yield.
Scheme 1. Retrosynthetic analysis of (+)-boronolide (1), (+)-anamarine (2) and
8-epi-spicigerolide (3).
Reduction of the ester 28a using DIBAL-H in dry DCM at ꢀ78 °C
afforded the corresponding aldehyde which was subsequently
subjected to enantioselective allylation using allylBIpc2, which
was prepared in situ from allylmagnesium bromide and (+)-DIPCl
the presence of pyridinium-p-toluenesulfonate gave the O-allyl-D-
xylofuranoside. Protection of C-3 and C-5 hydroxyl groups as iso-
propylidene acetal followed by protection of C-2 hydroxy group
as a benzyl ether afforded the fully protected O-allylglycoside 11.
Removal of the allyl group from 11 gave the hemi-acetal 10 in
40% yield using Gigg and Warren conditions 10. Thus obtained
hemiacetal 10 was used as a common intermediate for subsequent
steps.
During the synthesis of (+)-boronolide (1), the hemi-acetal 10
was treated with propyltriphenylphosphonium bromide10 (pre-
pared from n-propyl bromide and triphenylphosphine) in the pres-
ence of NaHMDS in dry THF at ꢀ20 °C to afford the olefin 12 as a
9:1 mixture of Z- and E-isomers. Reduction of the olefinic mixture
12 in the presence of 10% Pd/C gave the saturated compound 13.
Protection of the hydroxyl group of 13 with benzyl bromide in
the presence of NaH in DMF afforded the benzyl ether 14 in 85%
yield. Removal of the isopropylidene group with p-TsOH in MeOH
at 0 °C gave diol 15 in which the primary hydroxyl group was pro-
tected as its TBDMS ether and the secondary alcohol was protected
as its benzyl ether to give 16 in 85% yield. Deprotection of the silyl
ether 16 with TBAF in THF at 0 °C gave the primary alcohol 18 in
78% yield. Swern oxidation of the alcohol 1811 gave the aldehyde
O
O
OH
OBn
OAllyl
OBn
b
a
c
O
O
D-Xylose
O
O
11
10
OBn OBn
OR OBn
C4H9
OH OBn
f, g
d, e
C4H9
OR1 OR2
O
O
O
O
1
2
12
15
16
=
, R , R
H
13, R = H
14, R = Bn
1
2
=
=
H
, R TBS, R
OBn OBn
OBn OBn
OBn OBn
C4H9
j
h, i
k
C4H9
C4H9
OR1 OR2
O
OBn
19
OH OBn
7
17, R1 = TBS, R2 = Bn
18, R1 = H, R2 = Bn
OBn OBn
C4H9
OBn OBn
m
l
C4H9
O
OBn
OBn
O
19 in quantitative yields without any epimerization at
a-stereo-
genic center. Since the allylation of 19 with achiral reagents12 af-
fords the poor results, we turned our attention to chiral allylating
agents.
O
20
O
4
OAc OAc
n
Asymmetric allylation of the aldehyde 19 under Keck’s condi-
tions13 gave the homoallylic alcohol 7 with low diastereoselectivi-
ty (8:2). Therefore, Brown’s protocol14 was adopted for asymmetric
allylation. Accordingly, Brown’s allylating reagent (allylBIpc2) was
prepared from allylmagnesium bromide and (+)-DIPCl (dii-
sopinocampheylboron chloride), which was then treated with 19
in anhydrous ether at ꢀ80 °C to furnish the desired homoallylic
alcohol 7 in 82% yield with high diastereoselectivity (9:1). Esterifi-
cation of 7 with acrylyl chloride afforded the acrylyl ester 20,
which was easily separated from its diastereomer by simple silica
gel column chromatography. Ring-closing metathesis (RCM) of the
acrylate 20 with Grubbs first generation catalyst15 in DCM at room
O
OAc
1
O
Scheme 2. Synthesis of (+)-boronolide (1). Reagents and conditions: (a) Ref. 9; (b)
(i) t-BuOK, DMSO (ii) Hg(OAc)2, THF/H2O; (c) n-PrPPh3Br, NaHMDS, THF, ꢀ20 °C to
rt, 5 h, 75%; (d) (i) H2, Pd/C, NaHCO3, MeOH, rt, 2 h, 86%; (e) NaH, BnBr, DMF, 0 °C,
6 h, 85%; (f) p-TSA, MeOH, 0 °C, 3 h, 80%; (g) TBSCl, imidazole, DCM, 0 °C to rt, 1 h,
90%; (h) NaH, BnBr, DMF, 0 °C to rt, 3 h, 85%; (i) TBAF, THF, 0 °C to rt, 2 h, 78%; (j)
Dess–Martin periodinane, CH2Cl2, 0 °C to rt, 2 h, 80%; (k) AllylBIpc2 [prepared from
allylmagnesium bromide and (+)-DIPCl], Et2O, ꢀ80 °C (82%, 9:1 diastereomeric
mixture); (l) Acrylyl chloride, Et3N, DMAP, DCM, 0 °C to rt, 3h, 85%; (m) Grubb’s first
generation catalyst, DCM, rt, 6h, 85%; (n) i) TiCl4 (1M in DCM), DCM, 0 °C to rt, 4h; ii)
Ac2O, Pyridine, DMAP, 0 °C to rt (overall 2 steps 53%).

1400
B. V. Subba Reddy et al. / Tetrahedron Letters 55 (2014) 1398–1401
OH OBn
OBn OBn
DIBAL-H (1 M in toluene) in dry DCM at ꢀ78 °C afforded the
d, e
b, c
a
aldehyde which was then subjected to allylation with allylBIpc2,
prepared from allylmagnesium bromide and (+)-DIPCl (dii-
sopinocampheylboron chloride), in anhydrous ether at ꢀ80 °C to
furnish the homoallylic alcohol 9 (92% de) in 82% overall yield over
two steps. Esterification of the alcohol 9 with acryloyl chloride
gave the acryloyl ester 29b, which was subsequently subjected to
RCM reaction using Grubb’s first generation catalyst to afford the
perbenzylated lactone 6 in 85% yield. Finally the debenzylation of
6 with TiCl4 followed by peracetylation with Ac2O afforded the
8-epi-spicegerolide 3 in 62% overall yield over two steps.18
10
O
O
OH
OH OH OBn
21
23
OBn OBn
OBn OBn
f, g
O
OBn OBn
27
OTBSOBn OBn
25
Scheme 3. Synthesis of common intermediate 27. Reagents and conditions: (a)
MeLi (1.6 M), Et2O, ꢀ20 °C, 4 h, 82%; (b) NaH, BnBr, DMF, 0 °C, 6 h, 90%; (c) p-TSA,
MeOH, 0 °C, 3 h, 80%; (d) TBSCl, imidazole, DCM, 0 °C to rt, 1 h, 90%; (e) NaH, BnBr,
DMF, 0 °C to rt, 3 h, 85%; (f) TBAF, THF, 0 °C to rt, 2 h, 78%; (g) DMSO, (COCl)2, DCM,
ꢀ78 °C, Et3N, 3 h, 80%.
In summary, we have developed a modular approach for the
enantioselective synthesis of (+)-boronolide (1) and (+)-anamarine (2)
and 8-epi-spicigerolide (3) starting from
D-xylose. The notable
features of this synthetic strategy are highly diasteroselective
Brown’s allylation and ring closing metathesis to construct
(diisopinocampheylboron chloride), in anhydrous ether at ꢀ80 °C
to furnish the desired homoallylic alcohol 8 (92% de) in 82% overall
yield over two steps. Esterification of 8 with acrylyl chloride
afforded the acryloyl ester 29a which was then subjected to RCM
reaction using Grubbs first generation catalyst to afford the perb-
enzylated lactone 5 in 85% yield. Eventually, the debenzylation of
5 with TiCl4 followed by peracetylation with Ac2O furnished the
anamarine (2) in 62% overall yield over two steps (Scheme 4).18
Similarly, Still-Gennari olefination17 of 27 with bis(2,2,2-trifluo-
romethyl)(methoxycarbonylmethyl) phosphonate gave the cis-
olefinic ester 28b in 84% yield. Reduction of the ester 28b with
a
,b-unsaturated lactone functionality.
Acknowledgements
V.B.R. and K.P. thanks CSIR, New Delhi, India for financial sup-
port in the form of fellowships. B.V.S. thanks CSIR, New Delhi for
financial support as a part of XII five year plan program under title
ORIGIN (CSC-0108).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2013.12.
061.
OBn OBn
OBn OBn
b
a(i)
EtO2C
OBn OBn
28a
O
OBn OBn
References and notes
27
1. (a) Hoffmann, H. M. R.; Rabe, J. Angew. Chem. Int. Ed. Engl. 1985, 24, 94;
(b) Marco, J. A.; Carda, M.; Murga, J.; Falomir, E. Tetrahedron 2007, 63, 2929;
(c) Aptula, A. O.; Roberts, D. W. Chem. Res. Toxicol. 2006, 19, 1097.
OBn OBn
OBn OBn
c
O
OBn OBn
2. Franca, N. C.; Polonsky, J. C. R. Hebd. Seances Acad. Sci., Ser. C 1971, 273, 439.
3. Davies-Coleman, M. T.; Rivett, D. E. A. Phytochemistry 1987, 26, 3047.
4. (a) Alemany, A.; Marquez, C.; Pascual, C.; Valverde, S.; Ripoll, M. M.; Fayos, J.;
Perales, A. Tetrahedron Lett. 1979, 20, 3583; (b) Pereda-Miranda, R.; Fragoso-
OH
OBn OBn
O
29a
8
´
Serrano, M.; Cerda-Garcıa-Rojas, C. M. Tetrahedron 2001, 57, 47.
OBn OBn
OAc OAc
5. Kjaer, A.; Norrestam, R.; Polonsky, J. Acta. Chem. Scand., Ser. B 1985, 39, 745.
6. (a) Honda, T.; Horiuchi, S.; Mizutani, H.; Kanai, K. J. Org. Chem. 1996, 61, 4944;
(b) Kumar, P.; Naidu, S. V. J. Org. Chem. 2006, 71, 3935; (c) Gao, D.; O’ Doherty,
G. A. Org. Lett. 2005, 7, 1069; (d) Prasad, K. R.; Penchalaiah, K. J. Org. Chem. 2011,
76, 6889; (e) Trost, B. M.; Yeh, V. S. C. Org. Lett. 2002, 4, 3513; (f) Diaz-Oltra, S.;
Murga, J.; Falomir, E.; Carda, M.; Marco, J. A. Tetrahedron 2004, 60, 2979; (g)
Nagano, H.; Yasui, H. Chem. Lett. 1992, 1045; (h) Ghosh, A. K.; Bilcer, G.
Tetrahedron Lett. 2000, 41, 1003; (i) Chandrasekhar, M.; Raina, S.; Singh, V. K.
Tetrahedron Lett. 2000, 41, 4969; (j) Carda, M.; Rodriguez, S.; Segovia, B.; Marco,
J. A. J. Org. Chem. 2002, 67, 6560; (k) Chandrasekhar, M.; Chandra, K. L.; Singh, V.
K. J. Org. Chem. 2003, 68, 4039; (l) Hu, S. G.; Hu, T. S.; Wu, Y. L. Org. Biomol.
Chem. 2004, 2, 2305; (m) Ramesh, P.; Meshram, H. M. Tetrahedron Lett. 2012,
53, 4008; (n) Lichtenthaler, F. W.; Lorenz, K.; Ma, W. Y. Tetrahedron Lett. 1987,
28, 47; (o) Falomir, E.; Murga, J.; Carda, M.; Marco, J. A. Tetrahedron Lett. 2003,
44, 539; (p) Raghavan, S.; Krishnaiah, V. Tetrahedron Lett. 2006, 47, 7611; (q)
Sabitha, G.; Reddy, C. N.; Gopal, P.; Yadav, J. S. Tetrahedron Lett. 2010, 51, 5736;
(r) Kumar, K. S.; Reddy, C. S. Org. Biomol. Chem. 2012, 10, 2647.
7. Kishore, Ch.; Reddy, A. S.; Yadav, J. S.; Reddy, B. V. S. Tetrahedron Lett. 2012, 53,
4551.
8. Ireland, R. E.; Norbeck, D. W. J. Am. Chem. Soc. 1985, 107, 3279.
9. Gigg, R.; Warren, C. D. J. Chem. Soc. C 1968, 1903.
10. Motoyoshi, H.; Ishigami, K.; Kitahara, T. Tetrahedron 2001, 57, 3899.
11. For reviews on the Swern oxidation, see: (a) Tidwell, T. T. Synthesis 1990, 857;
(b) Tidwell, T. T. Org. React. 1990, 39, 297.
12. (a) Keck, G. E.; Boden, E. P. Tetrahedron Lett. 1984, 25, 265; (b) Nagaoka, H.;
Rutsch, W.; Schmid, G.; Iio, H.; Johnson, M. R.; Kishi, Y. J. Am. Chem. Soc. 1980,
102, 7962; (c) Paquette, L. A.; Mitzel, T. M. J. Am. Chem. Soc. 1996, 118, 1931.
13. (a) Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467; (b)
Keck, G. E.; Geraci, L. S. Tetrahedron Lett. 1993, 34, 7827.
e
d
O
OBn OBn
O
OAc OAc
O
O
O
2
5
OBn OBn
OBn
OBn
OH
MeO2C
b
a(ii)
27
OBn OBn
OBn OBn
28b
9
O
O
c
OBn OBn
O
OBn OBn
d
OBn OBn
OBn OBn
6
29b
O
e
O
OAc OAc
OAc OAc
3
Scheme 4. Synthesis of anamarine (2) and 8-epi-spicegerolide (3). Reagents and
conditions: (a) (i) PPh3CHCO2Et, benzene, rt, 2 h, 93%; (ii) NaH/THF, 0 °C, (CF3CH2-
O)2P(O)CH2COOCH3, 30 min, then, ꢀ78 °C, THF, 30–45 min, 84%; (b) (i) DIBAL-H,
CH2Cl2, ꢀ78 °C to rt, 0.5 h, 80%; (ii) AllylBIpc2 [prepared from allylmagnesium
bromide and (+)-DIP-Cl], Et2O, ꢀ80 °C (82%, 92:8 diastereomeric mixture); (c)
Acrylyl chloride, Et3N, DMAP, DCM, 0 °C to rt, 3 h, 85%; (d) Grubbs first generation
catalyst, DCM, rt, 6 h, 85%; (e) (i) TiCl4 (1 M in dichloromethane), DCM, 0 °C to rt,
6 h; (ii) Ac2O, Et3N, DMAP, DCM, 0 °C to rt (overall 2 steps 62%).
14. (a) Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401; (b) Brown, H. C.;
Bhat, K. S.; Randad, R. S. J. Org. Chem. 1989, 54, 1570.
15. For reviews, see: (a) Grubbs, R. H. Tetrahedron 2004, 60, 7117; (b) Trnka, T. M.;
Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18; (c) Fürstner, A. Angew. Chem., Int. Ed.
2000, 39, 3012.

B. V. Subba Reddy et al. / Tetrahedron Letters 55 (2014) 1398–1401
1401
16. (a) Horner, L.; Hoffman, H.; Wippel, H. G.; Klahre, G. Chem. Ber. 1959, 92, 2499;
(b) Wadsworth, W. S., Jr.; Emmons, W. D. J. Am. Chem. Soc. 1961, 83, 1733; (c)
Wadsworth, W. S., Jr. Org. React. 1977, 25, 73.
1028 cm; 1H NMR (300 MHz, CDCl3): d 6.88 (ddd, J = 1.5, 2.2, 6.7 Hz, 1H), 6.05
(ddd, J = 2.2, 3.7, 9.8 Hz, 1H), 5.83 (m, 2H), 5.39–5.29 (m, Hz, 2H), 5.18 (m, 1H),
5.03–4.88 (m, 2H), 2.45 (m, 2H), 2.07 (s, 3H), 2.06 (s, 3H), 2.03 (s, 3H), 1.17 (d,
J = 6.7 Hz); 13C NMR (75 MHz, CDCl3): d 170.0, 169.86, 169.83, 169.76, 163.5,
144.5, 133.0, 125.5, 121.5, 75.8, 71.9, 71.6, 70.4, 67.3, 29.1, 21.0, 20.91, 20.86,
17. Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405.
18. Spectral data for selected compounds:
Boronolide (1): ½a D25
ꢁ
+14 (c 0.5, CHCl3); IR (neat):
t
max 2927, 1744, 1219 cm; 1
H
20.6, 15.8; HRMS (ESI) calcd for
C20H26O10Na [M+Na] 449.1424, found:
NMR (500 MHz, CDCl3): d 6.89 (ddd, J = 9.8, 6.2, 2.4 Hz, 1H), 6.06 (ddd, J = 9.8,
2.7, 0.7 Hz, 1H), 5.34–5.39 (m, 2H), 5.04 (dt, J = 6.2, 5.7 Hz, 1H), 4.55 (ddd,
J = 12.0, 5.7, 4.0 Hz, 1H), 2.48 (dddd, J = 18.2, 12.0, 2.6, 2.6 Hz, 1H), 2.28 (dddd,
J = 18.3, 10.1, 6.1, 0.9 Hz, 1H), 2.09 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 1.52 (q,
J = 7.1 Hz, 2H), 1.17–1.30 (m, 4 H), 0.83 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3): d 170.3, 169.8, 169.5, 162.3, 144.1, 121.3, 75.1, 71.5, 70.6, 70.4, 30.1,
26.9, 25.2, 22.3, 20.8, 20.6, 20.5, 13.7; HRMS (ESI) calcd for C18H26O8Na, [M+Na]
393.1629, found: 393.1626.
449.1422.
8-epi-Spicegerolide (3): ½a D25
ꢁ
+34 (c 0.9, CHCl3); IR (neat): tmax 2925, 1735, 1457,
1372 cm; 1H NMR (500 MHz, CDCl3): d 6.89 (dt, J = 9.6, 6.4, 2.2 Hz, 1H), 6.1–
6.03 (m, 1H), 5.89–5.82 (m, 1H), 5.42 (dd, J = 6.7, 2.8 Hz, 1H), 5.30–5.26 (m,
1H), 5.23–5.19 (m, 1H), 5.05–4.90 (m, 2H), 2.51–2.39 (m, 2H), 2.13 (s, 6H), 2.07
(s, 3H), 2.03 (s, 3H), 1.23 (d, J = 6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 170.2,
170.1, 169.9, 169.9, 163.5, 144.8, 132.7, 128.6, 121.4, 73.7, 70.9, 69.2, 66.9,
66.2, 21.0, 20.9, 20.8, 20.7, 14.4; HRMS (ESI) calcd for C20H26O10Na, [M+Na]
449.1418, found: 449.1415.
Anamarine (2): ½a D25
+15 (c 0.5, CHCl3); IR (neat): tmax 2935, 1745, 1223,
ꢁ