Stereoselective total synthesis of synparvolide B and epi-synparvolide A

Article abstract of DOI:10.1016/j.tetlet.2009.03.006

Stereoselective total synthesis of synparvolide B and epi-synparvolide A has been achieved following a convergent approach. Noyori asymmetric Transfer Hydrogenation of ketone and Wadsworth-Emmons olefination reaction are the key steps involved.

Full text of DOI:10.1016/j.tetlet.2009.03.006

Tetrahedron Letters 50 (2009) 2420–2424
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Tetrahedron Letters
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Stereoselective total synthesis of synparvolide B and epi-synparvolide A
*
P. Srihari , E. Vijaya Bhasker, A. Bal Reddy, J. S. Yadav
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Stereoselective total synthesis of synparvolide B and epi-synparvolide A has been achieved following a
convergent approach. Noyori asymmetric Transfer Hydrogenation of ketone and Wadsworth–Emmons
olefination reaction are the key steps involved.
Received 4 February 2009
Revised 27 February 2009
Accepted 4 March 2009
Available online 9 March 2009
Ó 2009 Published by Elsevier Ltd.
a
,b-Unsaturated d-lactone-motif containing molecules continue
15.10 The primary alcohol was selectively mono protected as tosyl-
ate11 16 and treated with NaBH4 to result in a terminal methyl
compound 17.12 The primary hydroxyl group was converted to io-
dide 11 upon treatment with I2, triphenyl phosphine, and imidaz-
ole (Scheme 2). The synthesis of the other fragment 12 is shown in
Scheme 3 which departs from the prior work at the readily avail-
able alkyne 13.9 Thus alkyne 13 was lithiated with n-BuLi and then
treated with ethylchloroformate to get substituted propargylic es-
ter 14. The ester 14 was treated with N-methyl methoxy aminohy-
drochloride salt to get Weinreb amide 1213 in 90% yield.
With the two intermediates 11 and 12 in hand, the rest was to
couple them and proceed further for the target synthesis. The alkyl
lithium derived from iodide 11 was coupled with Weinreb amide
12 to get the ketone 10.14 Stereoselective reduction of the ketone
with (S,S)-Noyori catalyst15 afforded required 1,3-anti-isomer 18
in 86% yield (Scheme 4).
to attract medicinal chemists due to their wide occurrence in large
number of plants displaying potent biological activities.1 Very of-
ten these molecules are isolated in low quantities and thus be-
comes the limit for further evaluation towards biological activity.
A few examples include Fostriecin 1,2 tarchoanthuslactone 2,3 ana-
marine 3,4 spicigerolide 4,5 and synrotolide 56. (Fig. 1). In 1996, Da-
vies-Coleman and Rivett have isolated three new poly hydroxy
d-pyrones namely synparvolide A 6, synparvolide B 7 and syn-
parvolide-C 8 from the leaves of Syncolostemon parviflorus, a
medicinal plant which is used as an emetic to treat loss of appetite.
The structures of synparvolide A–C were established based on
spectral, chiroptical and chemical evidences.7 A thorough search
for the literature showed no synthetic reports for these com-
pounds. And also as these compounds are not available abun-
dantly, total synthesis was the only attractive solution for their
ready accessibility towards biological screening. This feature also
allows synthesizing and identifying the analogs with better thera-
peutic properties.
As the yield for the coupling reaction was not satisfactory to our
expectations, alternatively, the compound 18 was also synthesized
starting from alcohol 17 following the Scheme 5.
Our own interest in the synthesis of the naturally occurring bio-
logically active lactone containing molecules has inspired us to
take up the total synthesis of these less abundant a,b-unsaturated
The alcohol 17 was oxidized to aldehyde 21 and treated with
(methoxymethyl)triphenylphosphonium chloride in presence of n-
BuLi to get enol ether 22. The enol ether was hydrolyzed16 to get
the homologated aldehyde 23, and was further treated with lithiated
alkyne (prepared in situ by treatment of alkyne 13 with n-BuLi to get
the mixture of easily separable diastereomers 18 and 18a (7.5:2.5)
containing the desired isomer 18 as the major product. The forma-
tion of the major 1,3-anti diastereomer can be explained based on
the prechelation of the lithium bromide with alkoxy aldehyde favor-
ing the nucleophilic attack from less hindered side.17
The generated free secondary alcohol 18 was protected as ben-
zyl ether 19 and the triple bond was reduced partially to cis double
bond 20 under Lindlar’s conditions. Thus the geometry of all the
carbons with required asymmetric centers was set and the remain-
ing was to complete the total synthesis by converting 1,3-diol to
lactone ring. Selective PMB deprotection followed by Swern oxida-
tion of the compound 20 yielded aldehyde 24. The aldehyde was
d-lactone containing molecules. Towards this direction, we have
recently reported the total synthesis of dodoneine8 and synrotolide
diacetate.9 In the present communication, we describe the first
stereoselective total synthesis of synparvolide B.
Our approach relies on a convergent strategy wherein the two
fragments 11 and 12 are coupled and then proceeds further for
the total synthesis. The alkyl halide 11 is readily synthesized start-
ing from L(+)-DET in five steps and Weinreb amide 12 can be ob-
tained from 13 which is synthesized starting from homo
propargyl alcohol 14 (Scheme 1).
Initially, the synthesis began with masking of L(+)-DET as cyclo-
hexylydine acetal with cyclohexanone and pTSA followed by
reduction of the ester functionalities with LiAlH4 to yield diol
subjected to modified Wadsworth–Emmons reaction to yield
a,b-
* Corresponding author. Tel.: +91 4027191490; fax: +91 4027160512.
E-mail addresses: srihari@iict.res.in, sriharipabbaraja@yahoo.com (P. Srihari).
unsaturated ester 9 exclusively.18 One-pot ketal deprotection,
0040-4039/$ - see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2009.03.006

P. Srihari et al. / Tetrahedron Letters 50 (2009) 2420–2424
2421
O
O
O
HO
OPO3H2
HO
O
HO
HO
OH
O
O
Fostriecin 1
Tarchonanthuslactone 2
OAc
OAc OAc
OAc
OAc
OH
O
O
OAc OAc
O
OAc OAc
Anamarine 3
O
O
OH
OAc
O
Spicigerolide 4
OAc
Synrotolide 5
OAc
OAc
O
OH
O
H
H
H
H
O
OH
O
O
OAc
OH
OAc
OH
Synparvolide C 8
O
O
O
Synparvolide A 6
Synparvolide B 7
Figure 1.
OTBS
OAc
5'
1'
4'
2'
OPMB
5
6
4
OTBS
MeO
O
6'
OBn
O
3'
OAc OH
O
2
O
O
O
3
O
O
10
9
7
OTBS
I
OTBS
OMe
N
O
O
OPMB
+
OPMB
O
13
12
11
OH
L(+)-DET
14
Scheme 1. Retrosynthesis.
OH
OH
TsO
OH
HO
I
O
O
O
O
O
c
O
d
O
a
O
b
L(+)-DET
16
17
11
15
Scheme 2. Reagents and conditions: (a) (i) cyclohexanone, TsOH, benzene, reflux, 6 h; (ii) LiAlH4, THF, reflux, 3 h, 78% for two steps; (b) n-BuLi, TsCl, THF–DMSO, ꢀ15 to 0 °C
to rt, 2 h, 86%; (c) NaBH4, DMSO, 80 °C, 2 h, 88%; (d) I2, TPP, imidazole, benzene, 0 °C to rt, 30 min 84%.
OTBDMS
OTBDMS
OTBDMS
PMBO
b
O
a
PMBO
PMBO
Me
CO2Et
N
13
14
12
MeO
i
Scheme 3. Reagents and conditions: (a) (i) n-BuLi, ClCO2Et, THF, ꢀ78 °C to 0 °C, 1 h, 86%; (b) (Me(OMe)NH2)Cl, PrMgCl, THF, ꢀ20 °C, 1 h, 90%.

2422
P. Srihari et al. / Tetrahedron Letters 50 (2009) 2420–2424
OTBS
OTBS
OPMB
OPMB
b
I
O
a
O
O
O
OH
O
O
O
10
18
11
Scheme 4. Reagents and conditions: (a) t-BuLi, Et2O, 12, ꢀ78 °C, 30 min 33%; (b) (S,S)-Noyori catalyst (20 mol %), i-PrOH, 86%.
OMe
OH
CHO
O
O
O
O
O
O
O
c
a
b
O
O
23
17
22
21
OTBS
OTBS
OPMB
+
OPMB
d
O
O
O
OH
O
OH
18a
18
(7.5:2.5)
OTBS
OPMB
OPMB
OTBS
O
e
OBn
O
f
O
OBn
O
19
20
Scheme 5. Reagents and conditions: (a) DMSO, (COCl)2, TEA, DCM, ꢀ78 °C, 3 h, 87%; (b) ClPPh3CH2OCH3, n-BuLi, THF, ꢀ20 to 0 °C to rt, 2 h, 84%; (c) Hg(OAc)2, NaBH4, THF,
0 °C, 30 min 72%; (d) 13, n-BuLi, LiBr, 4 A mol. sieves. THF, ꢀ78 °C to ꢀ50 °C, 1.5 h, 90%; (e) NaH, BnBr, THF, 0 °C to rt, 3 h, 92%; (f) Pd/BaSO4, quinoline, H2 atm. toluene, rt,
20 min 93%.
CHO
a
b
OTBS
O
OBn
24
OTBS
MeO
O
O
20
OBn
O
O
9
OH
OAc
c
e
d
O
OH
25
OBn
OAc OBn
26
O
O
O
OAc
O
OAc OH
O
7
Scheme 6. Reagents and conditions: (a) (i) DDQ, DCM:H2O (8:1), 2 h, 80%; (ii) PCC, NaOAc, DCM, 0 °C to rt, 2 h, 90%; (b) MeO2CCH2P(O)(OCH2CF3)2, NaH, THF, 0 °C to ꢀ78 °C,
1 h, 83%; (c) AcOH:1 N HCl:THF (1:1:1), 65 °C, 4 h, 65%; (d) Ac2O, pyridine, DCM, 0 °C to rt, 2 h, 84%; (e) TiCl4, DCM, 0 °C to rt, 2 h, 78%.

P. Srihari et al. / Tetrahedron Letters 50 (2009) 2420–2424
2423
OAc
OAc
O
mCPBA
DCM, 0 oC to rt.
OAc OBn
26
O
OAc
OBn
27
O
O
O
OAc
OAc
O
mCPBA
DCM, 0 oC to rt.
3 h, 80%
O
OAc OH
O
OAc OH
6a
7
O
O
epi-synparvolide A
Scheme 7. Synthesis of epi-synparvolide A.
5. Pereda-Miranda, R.; Fragoso-Serrano, M.; Cerda-Garcia-Roas, C. M. Tetrahedron
2001, 57, 47–53.
6. Davies-Coleman, M. T.; English, R. B.; Rivett, D. E. A. Phytochemistry 1987, 26,
1497–1499.
7. Davies-Coleman, M. T.; Rivett, D. E. A. Phytochemistry 1996, 41, 1085–1092.
8. Srihari, P.; Rajendar, G.; Srinivasa Rao, R.; Yadav, J. S. Tetrahedron Lett. 2008, 49,
5590–5592.
9. Srihari, P.; Prem Kumar, B.; Subbarayudu, K.; Yadav, J. S. Tetrahedron Lett. 2007,
48, 6977–6981.
10. Chattopadhyay, A.; Dhotare, B. Tetrahedron: Asymmetry 1998, 2715–2723.
11. Kotsuki, H.; Kadota, I.; Ochi, M. J. Org. Chem. 1990, 55, 4417–4422.
12. Hiyama, T.; kobayashi, K.; Nishide, K. Bull. Chem. Jpn. 1987, 60, 2127–2137.
13. Kramp, G. J.; Kim, M.; Gais, H.-J.; Vermeeren, C. J. Am. Chem. Soc. 2005, 127,
17910–17920.
14. Prusov, E.; Röhm, H.; Maier, M. E. Organometallics 2006, 8, 1025–1028. In our
case tert.butyl ketone was formed as the major by product (ꢁ50% yield).
15. (a) Matsumara, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1997,
119, 8738–8739; A similar procedure was followed as given in: (b) Jung, W.-H.;
harrison, C.; Shin, Y.; Fournier, J.-H.; Balachandran, R.; Raccor, B. S.; Sikorski, R.
P.; Vogt, A.; Curran, D. P.; Day, B. W. J. Med. Chem. 2007, 50, 2951–2966.
16. Bettelli, E.; Cherubini, P.; D0Andrea, P.; Passacantilli, P.; Piancatelli, G.
Tetrahedron 1998, 54, 6011–6981.
17. (a) Marshall, J. A.; Lu, Z.-H.; Johns, B. A. J. Org. Chem. 1998, 63, 817–823. The
major product was compared with the compound obtained earlier by Noyori
reduction and was also characterized by NOE correlations.; For reaction model
see: (b) Guillarme, S.; Ple, K.; Banchet, A.; Liard, A.; Haudrechy, A. Chem. Rev.
2006, 106, 2355–2403; For other asymmetric alkynylation reaction of
aldehydes see: (c) Braga, A. L.; Appelt, H. R.; Silveira, C. C.; Wessjohann, L. A.;
Schneider, P. H. Tetrahedron 2002, 58, 10413–10416; (d) Anand, N. K.; Carreira,
E. M. J. Am. Chem. Soc. 2001, 123, 9687–9688.
TBS deprotection, and lactonization of compound 9 were achieved
by treating with a mixture of AcOH:1 N HCl:THF (1:1:1) solution to
yield 2519 in 65% yield. With the required skeleton in hand the rest
was to manipulate the protective groups. Thus the precursor for
the target synthesis was achieved by diacetylation of the two sec-
ondary alcohols in 25 to give the diacetate 26. TiCl4 mediated deb-
enzylation20 without affecting acetate moieties or double bond
gave the desired target compound 7 in 78% yield (Scheme 6). The
product 7 obtained was characterized and its rotation was found
to be similar with a small variation to that of the natural product
[
a]
D
ꢀ12.2 (c 1.2, CHCl3) {lit.7
[a
]
D
ꢀ11 (c 1.0, CHCl3). Also the 1H
NMR and 13C NMR were comparable with the data of the natural
product.21 Thus the structure of the natural product synparvolide
B has been confirmed with 6R, 30S, 50S and 60S, 1Z configuration
and is in agreement as established by Rivette et al.
Attempts to synthesize the synparvolide A by epoxidation of
compound 26 with mCPBA were unsuccessful which may be attrib-
uted to steric hindrance by benzyl moiety and lactone ring. How-
ever, when epoxidation was attempted on compound 7, we
ended up with the other isomer which is attributed to the chela-
tion of mCPBA with hydroxyl group. Thus, we have also accom-
plished the synthesis of epi-synparvolide A 6a (Scheme 7).
In conclusion, we have accomplished the first total synthesis of
synparvolide B and re-confirmed its structure. Also an analog of
synparvolide A, epi-synparvolide A has been synthesized. Stereo-
controlled reduction using Noyori catalyst, coupling of alkyl iodide
with Weinreb amide, Wadsworth–Emmons olefination, and one-
pot ketal and TBS deprotection followed by lactonization are the
key steps involved in this synthesis. Investigations for the biologi-
cal activity of the presently synthesized compounds and synthesis
of other analogs are currently underway.
18. Srihari, P.; Bhasker, E. V.; Harshavardhan, S. J.; Yadav, J. S. Synthesis 2006, 23,
4041–4045.
19. Friesen, R. W.; Bissada, S. Tetrahedron Lett. 1994, 35, 5615–5618.
20. Enders, D.; Dhulut, S.; Steinbusch, D.; Herrbach, A. Chem. Eur. J. 2007, 13, 3942–
3949.
21. Analytical data for selected intermediates and synparvolide B: Spectral data for
compound 10: Colorless oil; ½a D25
ꢂ
+0.5 (c 1.2, CHCl3). 1H NMR (300 MHz, CDCl3);
IR (neat) mmax: 2955(s), 2932(s), 2234(w), 1648(s), 1613(m), 1513(s), 1465(m),
1250(s), 1099(s), 1036(m), 839(s), 779(s), 580(w) cmꢀ1 1H NMR (300 MHz,
;
CDCl3): d 7.24 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 4.73 (t, J = 6.6 Hz, 1H),
4.46 (m, 2H), 4.04 (dt, J = 12.6, 4.7 Hz, 1H), 3.80 (s, 3H), 3.84–3.73 (m, 1H),
3.64–3.50 (m, 1H), 2.28–2.64 (m, 2H), 2.05–1.96 (m, 2H), 1.68–1.51 (m, 9H),
1.42–1.32 (m, 2H), 1.28 (d, J = 6.0 Hz, 3H), 0.90 (s, 9H), 0.15 (s, 3H), 0.11 (3H);
13C NMR (75 MHz, CDCl3): d 184.0, 159.1, 130.2, 129.2, 113.7, 109.1, 94.1, 83.0,
77.2, 76.2, 72.7, 65.2, 59.6, 55.2, 48.4, 38.0, 36.8, 36.5, 25.6, 25.0, 23.8, 23.7,
18.0, 17.5, ꢀ4.6, ꢀ5.1; mass (ESI-MS) m/z: 548 (M++NH4); HRMS(ESI) calcd for
C30H46O6NaSi (M+Na)+, 530.3063; found 530.3056. Compound 18: Colorless oil;
Acknowledgment
A.B.R. thanks CSIR, New Delhi for financial assistance.
½
a 2D5
ꢂ
ꢀ10.7 (c 1.2, CHCl3); IR (neat)
m
max: 3450 (br m), 2933 (s), 2857 (m), 1613
(w), 1513 (s), 1363 (w), 1249 (s), 1099 (s), 838 (s), 779 (m)cmꢀ1
;
1H NMR
References and notes
(300 MHz, CDCl3): d 7.19 (d, J = 9.0 Hz, 2H), 6.81 (d, J = 9.0 Hz, 2H), 4.62–4.54
(m, 2H), 4.38 (dd, J = 14.3, 11.3 Hz, 2H), 3.93–3.45 (m, 2H), 3.78 (s, 3H), 3.77–
3.68 (m, 1H), 3.58–3.45 (m, 2H), 2.99 (d,–OH, J = 6.0 Hz, 2H), 1.91 (q, J = 6.0 Hz,
2H), 1.84–1.77 (m, 2H), 1.66–1.34 (m, 10H), 1.24 (d, J = 6.0 Hz, 3H), 0.88 (s, 9H),
0.12 (s, 3H), 0.09 (s, 3H); 13C NMR (75 MHz, CDCl3): d 159.0, 130.4, 129.1,
113.6, 109.1, 86.4, 84.1, 78.9, 76.3, 72.6, 65.9, 60.5, 59.8, 55.1, 39.8, 38.7, 36.7,
36.6, 25.7, 25.0, 23.9, 23.8, 18.1, 17.1, ꢀ4.5, ꢀ5.1; mass (ESI-MS) m/z: 550
(M++NH4); HRMS (ESI) calcd for C30H52NO6Si (M+NH4)+, 532.3220; found
1. (a) Davies-Coleman, M. T.; Rivett, D. E. A. Fortschritte der Chemie organischer
Naturstoffe 1989, 55, 1; (b) Buck, S. B.; Hardouin, C.; Ichikwaya, 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, 15694–15695; (c) Bialy, L.; Waldman, H. Chem.
Eur. J. 2004, 10, 2759–2780; (d) Negishi, E.; Kotora, M. Tetrahedron 1997, 53,
6707–6738; (e) Davies-Coleman, M. T.; Rivett, D. E. A. Prog. Chem. Org. Nat. Prod.
1989, 55, 1–35; (f) Dickinson, J. M. Nat. Prod. Rep. 1993, 10, 71–97; (g) Collett, L.
A.; Davies-Coleman, M. T.; Rivett, D. E. A. Prog. Chem. Org. Nat. Prod. 1998, 75,
181–209.
2. Hohanson, G. C.; French, J. C. J. Org. Chem. 1985, 50, 462–466.
3. Bohlmann, F.; Suwita, A. Phytochemistry 1979, 18, 677–679.
4. Alemany, A.; Marquez, C.; Pascual, C.; Valverde, S.; Martinez-Ripoll, M.; Fayos,
J.; Perales, A. Tetrahedron Lett. 1979, 20, 3583–3586.
532.3211. Compound 18a: Colorless oil; ½a D25
ꢂ
ꢀ2.5 (c 1.2, CHCl3); 1H NMR
(300 MHz, CDCl3): d 7.23 (d, J = 8.6 Hz, 2H), 6.85 (d, J = 8.6 Hz, 2H), 4.66–4.56
(m, 2H), 4.40 (dd, J = 14.7, 11.3 Hz, 2H), 3.78 (s, 3H), 3.83–3.73 (m, 1H), 3.69–
3.48 (m, 3H), 3.05 (br s, OH, 1H), 1.94 (q, J = 6.2 Hz, 2H), 1.90–1.82 (m, 2H),
1.66–1.50 (m, 8H), 1.43–1.32 (m, 2H), 1.26 (d, J = 6.0 Hz, 3H), 0.89 (s, 9H), 0.13
(s, 3H), 0.10 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
159.0, 130.3, 129.1,
113.6,109.0, 86.3, 84.3, 80.1, 76.3, 72.5, 65.7, 61.0, 59.7, 55.0, 40.1, 38.6, 36.7,

2424
P. Srihari et al. / Tetrahedron Letters 50 (2009) 2420–2424
36.5, 25.7, 25.0, 23.8, 23.7, 18.1, 17.2, ꢀ4.4, ꢀ5.1. Synparvolide B 7: Colorless
found 326.1362. Epi synparvolide A 6a: Colorless viscous oil; ½a D25
ꢂ
ꢀ4 (c 0.2,
viscous oil; ½a 2D5
ꢂ
ꢀ12.2 (c 1.2, CHCl3); lit. ½a D25
ꢂ
ꢀ11 (c 1.0, CHCl3); IR (neat) mmax
,b unsaturated-d-lactone),
1H NMR (400, MHz,
:
CHCl3); IR (neat) mmax: 3447 (br m, OH), 2925 (w), 1732 (s), 1710 (sh, a,b
3442 (br m, OH), 2926 (m), 1733 (s), 1710 (sh,
a
unsaturated-d-lactone), 1377 (m), 1236 (s), 1035 (s), 856 (w), 768 (m) cmꢀ1
;
1377 (m), 1236 (s), 1034 (s), 950 (w), 759 (m) cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 6.88 (ddd, J = 9.8 Hz, 5.4 Hz, 3.0 Hz, 1H), 6.05
(ddd, J = 9.8, 2.2, 1.1 Hz, 1H), 5.17–5.01 (m, 2H), 4.81–4.72 (m, 1H), 3.84–3.76
(m, 1H), 3.27 (dd, J = 6.4, 4.3 Hz, 1H), 3.08–3.04 (m, 1H), 2.94 (br s, OH, 1H),
2.57–2.40 (m, 2H), 2.14 (s, 3H), 2.08 (s, 3H), 1.94–1.70 (m, 2H), 1.24 (d,
J = 6.4 Hz, 3H); 13C NMR (75 MHz, CDCl3): 171.8, 170.2, 162.7, 143.8, 121.6,
75.8, 71.9, 70.8, 64.8, 59.0, 58.1, 36.0, 26.3, 21.1, 20.8, 16.3; mass (ESI-MS), m/z:
343 (M++H); HRMS (ESI) calcd for C16H26NO8 (M+NH4)+, 342.1314; found
342.1319.
CDCl3): d 6.86 (ddd, J = 9.9, 5.1, 3.0 Hz, 1H), 6.01 (ddd, J = 9.9, 1.8, 1.5 Hz, 1H),
5.61 (dd, J = 11.0, 6.7 Hz, 1H), 5.55 (dd, J = 11.0, 6.9 Hz, 1H), 5.36 (ddd, J = 9.0,
6.6, 2.6 Hz, 1H), 5.11–5.05 (m, 1H), 4.98 (dq, J = 6.5, 4.8 Hz, 1H), 4.40–4.34 (m,
1H), 2.91 (br, OH, 1H), 2.43–2.37 (m, 2H), 2.09 (s, 3H), 2.04 (s, 3H), 1.80–1.60
(m, 2H), 1.20 (s, 3H); 13C NMR (75 MHz, CDCl3): d 171.6, 170.2, 163.7, 144.9,
135.8, 127.6, 121.4, 73.9, 72.0, 70.8, 64.6, 38.4, 29.8, 21.0, 20.9, 16.2; mass (ESI-
MS) m/z: 349 (M++Na); HRMS (ESI) calcd for C16H22NaO7 (M+Na)+, 326.1365;