First stereoselective synthesis of synargentolide A and revision of absolute stereochemistry

Article abstract of DOI:10.1016/j.tetlet.2009.08.109

The first stereoselective total synthesis of synargentolide A isolated from Syncolostemon argenteus has been achieved from commercially available (R)-benzyl glycidyl ether using Sharpless asymmetric epoxidation and cross-metathesis reactions as the key st

Full text of DOI:10.1016/j.tetlet.2009.08.109

Tetrahedron Letters 50 (2009) 6298–6302
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
First stereoselective synthesis of synargentolide A and revision
of absolute stereochemistry
*
Gowravaram Sabitha , Peddabuddi Gopal, C. Nagendra Reddy, J. S. Yadav
Organic Division I, 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:
The first stereoselective total synthesis of synargentolide A isolated from Syncolostemon argenteus has
been achieved from commercially available (R)-benzyl glycidyl ether using Sharpless asymmetric epox-
idation and cross-metathesis reactions as the key steps. Comparing the spectral data of the synthesized
and naturally occurring synargentolide A, the C40 and C60- stereogenic centers of the natural synargento-
lide A were assigned a corrected anti relationship.
Received 11 August 2009
Revised 26 August 2009
Accepted 30 August 2009
Available online 2 September 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
d-Lactones
Cross-metathesis
Sharpless epoxidation
Lithium acetylide
Revision
Naturally isolated 6-substituted-
a
,b-unsaturated-d-lactones
became the interesting synthetic goals. The structure of synargen-
tolide A was proposed to be 1 by Davies-Coleman and Rivett7 on
the basis of spectroscopic findings, Mosher ester analysis, and
acetonide formations. Alberto Marco et al.12 synthesized the pub-
lished structure of synargentolide A 1 and found that the spectro-
scopic data of the synthetic product did not match with those
reported for the natural product and therefore stated that the
proposed structure for the synargentolide A 1 differs from the
actual one.
gained great attention of researcher due to their cytotoxic and
anti-tumor properties.1 In addition they inhibit HIV protease,2
induce apoptosis,3,4 and have proven to be anti-leukemic,5 along
with having many other relevant pharmacological properties.6
Synargentolide A (1),7 spicegerolide (2),8 hyptolide (3),9 synroto-
lide (4),10 and anamarine (5)11 isolated from Syncolostemon and
Hyptis species are examples of
a,b-unsaturated d-lactones
(Fig. 1). Due to their pharmacological properties, these molecules
OAc
1'
3'
5
4'
6'
OAc OAc
OAc OAc
4
5'
6
2'
OAc OAc
O
O
O
3
O
O
1
2
OAc
OAc OAc
published structure of
synargentolide A 1
O
2
3
OAc
OAc OAc
1'
OAc OAc
3'
5
4'
5'
6'
4
3
6
2'
O
O
OAc OAc
O
OAc OAc
O
OAc OAc
1
2
revised structure of
synargentolide A 6
O
O
5
4
Figure 1. Polyoxygenated lactones.
* Corresponding author. Tel./fax: +91 40 27191629.
E-mail address: gowravaramsr@yahoo.com (G. Sabitha).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.08.109

G. Sabitha et al. / Tetrahedron Letters 50 (2009) 6298–6302
6299
OAc
O
OAc OAc
O
O
O
+
O
O
OAc
OAc
OAc
OBn
O
O
1
9a
7
8a
+
OAc
O
OAc OAc
O
O
O
+
OAc
OAc
OAc
OBn
6
7
9b
8b
OMOM
OH
OMOM
OH
O
OBn
10
11
12
Scheme 1. Retrosynthetic analysis for the published and revised structures of synargentolide A.
OR
OMOM
R
O
c, d
e
a, b
OBn
OBn
12
13 R = H
14 R = MOM
11 R = CH2OH
15 R = CHO
OMOM
OMOM
OMOM
g, h
f
R
OH
CO2Et
O
16
17
18 R = OH
19 R = I
OMOM
OH
OMOM
MOMO
OH
O
j
k
i
OR
OBn
20
10
21
20a R = H
20b R = Bn
O
O
O
O
l, m
+
OBn
OBn
9b
9a
Scheme 2. Reagents and conditions: (a) „ –Li, DMSO, 0 °C to rt, 1 h, 92%; (b) DIEA, MOM–Cl, 2 h, 0 °C to rt, 95%; (c) Li/liq NH3, ꢀ33 °C, anhydrous THF, 0.5 h, 90%; (d) IBX,
-(+) DIPT, Ti(OiPr)4,
DMSO, anhydrous CH2Cl2, 0 °C to rt, 24 h, 95%; (e) PPh3@CHCO2Et, Ph–H, rt, 2 h, 85%; (f) DIBAL-H, anhydrous CH2Cl2, ꢀ20 °C, 1 h, 75%; (g)
L
cumenehydroperoxide, anhydrous CH2Cl2, ꢀ24 °C, 4 h, 98%; (h) TPP, I2, imidazole, Et2O/CH3CN, (3:1) 0 °C to rt, 20 min 92%; (i) Zn dust, EtOH, reflux, 2 h, 92%; (j) (a) m-CPBA,
NaHCO3, anhydrous CH2Cl2, ꢀ10 °C, 10 h, 92%, dr (1:1); (b) BnBr, NaH, anhydrous THF, 0 °C to rt, 3 h, 95%; (k) LiAlH4, anhydrous THF, 0 °C to rt, 0.5 h, 95%; (l) 2 N HCl, rt, 5 h,
93%; (m) 2,2-DMP, PPTS, anhydrous CH2Cl2, 0 °C to rt, 1 h, 95%.
O
O
OAc
OAc OAc
OAc
OAc
O
O
c,
a
b
7
1
OAc
OBn
22a
9a
8a
O
O
OAc
OAc OAc
OAc
OAc
O
O
a
c,
7
b
6
OAc
22b
OBn
8b
9b
Scheme 3. Reagents and conditions: (a) (i) Li/liq NH3, anhydrous THF, ꢀ33 °C, 0.5 h, 91%; (ii) MeOH, 2 N HCl, rt, 1 h, 93%; (iii) Ac2O, TEA, DMAP, anhydrous CH2Cl2, 0 °C to rt,
0.5 h, 94%; (b) Pd/CaCO3, quinoline, HPLC–EtOAc, rt, 2 h, 92%; (c) Gr-II, refluxing anhydrous CH2Cl2, 2 h, 65%.

6300
G. Sabitha et al. / Tetrahedron Letters 50 (2009) 6298–6302
A
OAc
OAc OAc
O
published structure of
synargentolide A 1
O
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
B
OAc
OAc OAc
O
revised structure of
synargentolide A 6
O
7.0
6.5
6.0
5.5
5.0
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
C
Figure 2. Comparison of the 1H NMR spectra of the synthetic lactones 1 (A) and 6 (B) with that of natural synargentolide A (C).

G. Sabitha et al. / Tetrahedron Letters 50 (2009) 6298–6302
6301
As a part of our current interest in naturally occurring, pharma-
2H-pyran-2-one. Sharpless asymmetric epoxidation (SAE) and
cross-metathesis (CM) are the key reactions involved.
cologically active d-lactones,13 we became interested in the syn-
thesis of synargentolide
A and to determine the absolute
configuration of the natural product.
Acknowledgments
The retrosynthesis is outlined in Scheme 1. The target molecule
1 (published structure)7 and 6 (revised structure) could be pre-
pared independently by cross-metathesis reaction of 8a and 8b
with vinyl lactone 7. The substrates 8a and 8b in turn could be ob-
tained from the commercially available (R)-benzyl glycidyl ether
12 by sequential reactions.
P.G. thanks CSIR and C.N.R. thanks UGC, New Delhi for the
award of fellowships. We thank Dr. Michael T. Davies-Coleman,
Department of Chemistry, Rhodes University, Grahamstown
6140, South Africa for sending the 1H and 13C NMR spectra of the
natural product synargentolide A.
The synthesis began with the commercially available (R)-benzyl
glycidyl ether 12 (Scheme 2). Accordingly the ring opening of epox-
ide 12 with lithium acetylide ethylene diamine complex provided
chiral homopropargyl alcohol 13 in 92% yield. The secondary hy-
droxyl group in compound 13 was protected as its MOM ether
14 using MOMCl and Hunig’s base and the subsequent removal
of benzyl group furnished alcohol 11. Oxidation of 11 using IBX
in DMSO/DCM gave the corresponding aldehyde 15, which was
References and notes
1. Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Int. Ed. 1985, 24, 94–110.
2. (a) Romines, K. R.; Chrusciel, R. A. Curr. Med. Chem. 1995, 2, 825–838; (b)
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N.; Tait, B. D. Adv. Med. Chem. 2000, 5, 159–195; (d) Hagen, S. E.; Domagala, J.
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Urumov, A.; Zeikus, G.; Zeikus, E.; Lunney, E. A.; Pavlovsky, A.; Gracheck, S. J.;
Saunders, J. M.; VanderRoest, S.; Brodfuehrer, J. J. Med. Chem. 2001, 44, 2319–
2332; (e) Agrawal, V. K.; Singh, J.; Mishra, K. C.; Khadikar, P. V.; Jaliwala, Y. A.
ARKIVOC 2006, 162–177.
3. (a) Inayat-Hussain, S. H.; Annuar, B. O.; Din, L. B.; Taniguchi, N. Toxicol. Lett.
2002, 131, 153–159; (b) Inayat-Hussain, S. H.; Annuar, B. O.; Din, L. B.; Ali, A.
M.; Ross, D. Toxicol. In Vitro 2003, 17, 433–439; (c) Chan, K. M.; Rajab, N. F.;
Ishak, M. H. A.; Ali, A. M.; Yusoff, K.; Din, L. B.; Inayat-Hussain, S. H. Chem. Biol.
Interact. 2006, 159, 129–140.
4. For further literature related to this important biological property, see, for
example: (a) Blatt, N. B.; Glick, G. D. Bioorg. Med. Chem. 2001, 9, 1371–1384; (b)
Huang, Z. W. Chem. Biol. 2002, 9, 1059–1072.
5. Kikuchi, H.; Sasaki, K.; Sekiya, J.; Maeda, Y.; Amagai, A.; Kubohara, Y.; Ohsima,
Y. Bioorg. Med. Chem. 2004, 12, 3203–3214.
6. See, for example: (a) Stampwala, S. S.; Bunge, R. H.; Hurley, T. R.; Willmer, N. E.;
Brankiewicz, A. J.; Steinman, C. E.; Smitka, T. A.; French, J. C. J. Antibiot. 1983, 36,
1601–1605; (b) Nagashima, H.; Nakamura, K.; Goto, T. Biochem. Biophys. Res.
Commun. 2001, 287, 829–832; (c) Raoelison, G. E.; Terreaux, C.; Queiroz, E. F.;
Zsila, F.; Simonyi, M.; Antus, S.; Randriantsoa, A.; Hostettmann, K. Helv. Chim.
Acta 2001, 84, 3470–3476; (d) Lewy, D. S.; Gauss, C.-M.; Soenen, D. R.; Boger, D.
L. Curr. Med. Chem. 2002, 9, 2005–2032; (e) Larsen, A. K.; Escargueil, A. E.;
Skladanowski, A. Pharmacol. Ther. 2003, 99, 167–181; (f) Richetti, A.; Cavallaro,
A.; Ainis, T.; Fimiani, V. Immunopharmacol. Immunotoxicol. 2003, 25, 441–449;
(g) Koizumi, F.; Ishiguro, H.; Ando, K.; Kondo, H.; Yoshida, M.; Matsuda, Y.;
Nakanishi, S. J. Antibiot. 2003, 56, 603–609.
subjected to a Wittig reaction with the stable ylide to afford
a,b-
unsaturated ester 16. After reduction of 16 to allylic alcohol 17
(75%) using DIBAL-H, Sharpless asymmetric epoxidation delivered
epoxy alcohol 18 in 98% yield as a single diastereomer, which was
elaborated to allylic alcohol 10 by an iodination/reductive ring-
opening sequence.
Epoxidation of the terminal double bond in 10 using m-CPBA
provided an inseparable mixture of epoxy alcohol 20a in a ratio
of 1:1 (92% combined yield). After protection of the secondary hy-
droxyl group as benzyl ether, the resulting compound 20b was
treated with LAH to give an alcohol again as an inseparable mix-
ture (21). The MOM group was deprotected and a 1,3-diol function
in compound 21 was protected as acetonide by 2,2-dimethoxypro-
pane in the presence of PPTS and the resulting acetonides 9a and
9b were easily separable by flash chromatography. In order to con-
firm the relative configuration of 1,3-acetonides 9a and 9b, 13C
NMR chemical shifts were studied. The two methyl groups in the
acetonide part in 9a resonated at 19.0 and 29.6 ppm indicating that
the two hydroxyl groups are in a 1,3-syn orientation and further
substantiated by the appearance of the quaternary carbon in the
down-field region (98.8 ppm).14 In contrast, for the acetonide
derivative 9b signals were found at 24.8 and 23.8 ppm and quater-
nary carbon at 100.7 ppm, which were characteristic for the
methyl groups in the acetonide part of 1,3-anti diol.14
7. Collett, L. A.; Davies-Coleman, M. T.; Rivett, D. E. A. Phytochemistry 1998, 48,
651–656.
8. Pereda-Miranda, R.; Fragoso-Serrano, M.; Cerda-García-Rojas, C. M. Tetrahedron
2001, 57, 47–53.
9. Achmad, S. A.; Høyer, T.; Kjꢀr, A.; Makmur, L.; Norrestam, R. Acta Chem. Scand.
1987, 41B, 599–609.
10. Coleman, M. T. D.; English, R. B.; Rivett, D. E. A. Phytochemistry 1987, 26, 1497–
1499.
11. Alemany, A.; Márquez, C.; Pascual, C.; Valverde, S.; Martínez-Ripoll, M.; Fayos,
J.; Perales, A. Tetrahedron Lett. 1979, 20, 3583–3586.
To determine the correct absolute configuration of natural
synargentolide A, both isomers of synargentolide A 1 and 6 were
synthesized by the following steps from 9a and 9b as shown in
Scheme 3.
Removal of benzyl and acetonide groups, followed by acetyla-
tion of the three hydroxy groups was performed to provide 22a
in 95% yield (Scheme 3). The terminal triple bond was reduced par-
tially to double bond under Lindlar’s conditions to afford 8a. Final-
ly, the cross-metathesis reaction between 8a and vinyl lactone 713j
was smoothly performed using Grubbs’ second generation catalyst
to give the published structure of synargentolide A 1 (Fig. 2). This
did not turn out to be identical with the natural product but
matched with the synthesized product.12
12. García-Fortanet, J.; Murga, J.; Carda, M.; Marco, J. A. ARKIVOC 2005, 175–188.
13. (a) Sabitha, G.; Sudhakar, K.; Reddy, N. M.; Rajkumar, M.; Yadav, J. S.
Tetrahedron Lett. 2005, 46, 6567–6570; (b) Sabitha, G.; Narjis, F.; Swapna,
R.; Yadav, J. S. Synthesis 2006, 17, 2879–2884; (c) Sabitha, G.; Reddy, E. V.;
Yadagiri, K.; Yadav, J. S. Synthesis 2006, 19, 3270–3274; (d) Sabitha, G.;
Sudhakar, K.; Yadav, J. S. Tetrahedron Lett. 2006, 47, 8599–8602; (e) Sabitha,
G.; Bhaskar, V.; Yadav, J. S. Tetrahedron Lett. 2006, 47, 8179–8181; (f) Sabitha,
G.; Swapna, R.; Reddy, E. V.; Yadav, J. S. Synthesis 2006, 24, 4242–4246; (g)
Sabitha, G.; Sudhakar, K.; Yadav, J. S. Synthesis 2007, 705; (h) Sabitha, G.;
Bhaskar, V.; Yadav, J. S. Synth. Commun. 2008, 38, 1–12; (i) Sabitha, G.; Bhaskar,
V.; Reddy, S. S.; Yadav, J. S. Tetrahedron 2008, 64, 10207–10213; (j) Sabitha, G.;
Narjis, F.; Gopal, P.; Reddy, N. C.; Yadav, S. J. Tetrahedron: Asymmetry 2009, 20,
184–191; (k) Total synthesis of (+)-(6R,20S)-cryptocaryalactone and
diastereoisomer of (+)-strictifolione using RCM and CM: Sabitha, G.; Bhaskar,
V.; Reddy, S. S and Yadav, J. S. Helv. Chim. Acta, in press.; (l) Sabitha, G.; Gopal,
P.; Yadav, S. J. Tetrahedron: Asymmetry 2009, 20, 1493–1499; (m) Total
synthesis of (+)-dodoneine and its 6-epimer: Sabitha, G.; Bhaskar, V.; Reddy,
S. S and Yadav, J. S. Synthesis, in press.; (n) A concise and efficient synthesis of
(5R,7S)-kurzilactone and its (5S,7R)-enantiomer using Mukaiyama aldol
reaction: Sabitha, G.; Gopal, P.; Reddy, C, N.; Yadav, J, S. Synthesis, in press.
14. (a) Rhychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett. 1990, 31, 945; (b) Evans,
D. A.; Rieger, D. L.; Gage, J. R. Tetrahedron Lett. 1990, 31, 7099.
In a similar fashion, synthesis of 6 was commenced from 9b
(Scheme 3) independently repeating the steps as in the case of 1
and the target molecule 6 was obtained in good yield. The spectral
properties (Fig. 2) and optical rotation of the synthetic compound 6
were found to be identical with those published for the natural
synargentolide A 1 {½a D25
ꢁ
+36.5 (c 1, CHCl3), lit.7
CHCl3)}. Therefore, the structure of natural product stands revised
to be of 6.
½
a 2D5
+40 (c 1.1,
ꢁ
15. Analytical data of all the new compounds are given below:
Compound 1: ½a 2D5
ꢁ
+12.5 (c 1, CHCl3); IR (KBr) 1738, 1374, 1221, 1024 cmꢀ1 1H
;
NMR (400 MHz, CDCl3): d 6.84 (ddd, J = 8.8, 4.0, 2.4 Hz, 1H), 6.02 (dt, J = 10.4,
2.4 Hz, 1H), 5.75–5.63 (m, 2H), 5.15 (m, 1H), 5.08 (dt, J = 7.2, 4.0 Hz, 1H, CH),
4.96 (m, 1H, CH), 4.86 (m, 1H, CH), 2.39 (m, 2H, CH2), 2.28 (m, 2H, CH2), 2.12 (s,
3H, CH3), 2.04 (s, 3H, CH3), 2.0 (s, 3H, CH3), 1.18 (d, J = 6,4 Hz, 3H, CH3); 13C
NMR (75 MHz, CDCl3): d 170.2, 170.1, 170.0, 163.8, 144.5, 130.9, 128.3, 121.5,
In conclusion, we have performed a stereoselective synthesis of
the natural synargentolide A and shown it to be 6.15 Synargentolide
A is therefore 6R[4R,5R,6R-triacetyloxy-1E-heptenyl]-5,6-dihydro-

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G. Sabitha et al. / Tetrahedron Letters 50 (2009) 6298–6302
77.2, 73.7, 69.6, 69.3, 34.0, 29.5, 21.0, 20.8, 20.7, 16.0; HRMS calcd for
C18H24O8Na: 391.1368; found: 391.1355.
16.5 Hz, 0.5H), 2.41 (dd, J = 2.9, 16.5 Hz, 0.5H), 1.92 (m, acetylinic CH), 1.35 (s,
3H, CH3), 1.30 (s, 3H, CH3), 1.19 (d, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3): d 138.0, 128.3, 127.9, 127.7, 100.7, 82.1, 81.0, 74.1, 69.7 (ꢂ2C), 69.1,
24.8, 23.8, 20.0, 19.4; HRMS calcd for C17H22O3Na: 297.1466; found: 297.1457.
Compound 8a: ½a 2D5
ꢁ
+1.5 (c 1, CHCl3); IR (KBr) 1742, 1370, 1216 cmꢀ1 1H NMR
;
(300 MHz, CDCl3): d 5.66 (m, 1H), 5.30–4.93 (m, 5H), 2.35–2.14 (m, 2H), 2.06 (s,
3H, CH3), 2.01 (s, 3H, CH3), 1.99 (s, 3H, CH3), 1.15 (d, J = 6.0 Hz, 3H, CH3); 13C
NMR (75 MHz, CDCl3): d 170.1, 170.0, 169.9, 132.0, 118.8, 74.2, 70.2, 68.7, 35.3,
121.0, 20.8, 20.6, 16.3.
Compound 10: ½a 2D5
ꢁ
ꢀ10.0 (c 1, CHCl3); IR (KBr) 3446, 3295, 2897, 1040 cmꢀ1
;
1H NMR (400 MHz, CDCl3): d 5.85 (m, 1H), 5.40 (m, 1H), 5.23 (m, 1H), 4.76 (d,
J = 6.5 Hz, 1H), 4.70 (d, J = 7.3 Hz, 1H), 4.22 (m, 1H, CH), 3.57 (m, 1H, CH),
3.41(s, 3H, CH3), 2.62–2.35 (m, 2H, CH2), 1.94 (m, 1H); 13C NMR (75 MHz,
CDCl3): d 136.7, 117.2, 96.7, 80.3, 79.3, 73.4, 70.2, 55.8, 21.2; HRMS calcd for
C9H14O3Na: 193.0840; found: 193.0848.
Compound 8b: ½a 2D5
ꢁ
+22.5 (c 1, CHCl3); IR (KBr) 1744, 1372, 1222 cmꢀ1 1H NMR
;
(400 MHz, CDCl3): d 5.69 (m, 1H), 5.16 (dt, J = 7.0, 3.1 Hz, 1H, CH), 5.11–5.03
(m, 3H), 4.94 (m, 1H, CH), 2.24 (m, 2H, CH2), 2.13 (s, 3H, CH3), 2.02 (s, 3H, CH3),
2.0 (s, 3H, CH3), 1.18 (d, J = 6.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3): d 169.9.
169.8, 169.7, 132.2, 118.4, 73.7, 69.7, 67.2, 35.4, 20.8, 20.6, 20.5, 15.9; HRMS
calcd for C13H20O6Na: 295.1157; found: 295.1149.
Compound 11: ½a 2D5
ꢀ71.6 (c 1, CHCl3); IR (KBr) 3437, 3293, 2932, 1640, 1363,
ꢁ
1105 cmꢀ1 1H NMR (300 MHz, CDCl3): d 4.72 (m, 2H, CH2), 3.77–3.68 (m, 2H,
;
CH2), 3.59 (m, 1H, CH), 3.41 (s, 3H, CH3), 2.43 (m, 2H, CH2), 1.93 (m, 1H); 13C
NMR (75 MHz, CDCl3): d 96.5, 78.1, 70.2, 64.3, 55.6, 36.2, 21.6; HRMS calcd for
C7H12O3Na: 167.0684; found: 167.0684.
Compound 9a: ½a 2D5
ꢀ42.0 (c 1, CHCl3); IR (KBr) 2985, 1455, 1378, 1229,
ꢁ
1091 cmꢀ1 1H NMR (400 MHz, CDCl3): d 7.42–7.21 (m, 5H, ArH), 4.72 (ABq,
;
J = 11.3 Hz, 2H, CH2-OAr), 3.97 (m, 2H), 3.29 (m, 1H, CH), 2.68 (dd, J = 2.6,
16.4 Hz, 0.5H), 2.65 (dd, J = 2.4, 10.0 Hz, 0.5H), 1.98 (m, acetylinic CH), 1.43 (s,
3H, CH3), 1.40 (s, 3H, CH3), 1.18 (d, J = 6.4 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3): d 138.2, 128.2, 128.1, 127.6, 98.8, 80.6, 75.0, 72.8, 71.6, 70.6, 68.5, 29.6,
29.3, 19.0, 17.7; HRMS calcd for C17H22O3Na: 297.1466; found: 297.1465.
Compound 6: ½a 2D5
ꢁ
+36.5 (c 1, CHCl3); IR (KBr) 1738, 1374, 1221, 1024 cmꢀ1 1H
;
NMR (400 MHz, CDCl3): d 6.84 (ddd, J = 8.8, 4.0, 2.4 Hz, 1H), 6.02 (dt, J = 10.4,
2.4 Hz, 1H), 5.75–5.63 (m, 2H), 5.15 (m, 1H), 5.08 (dt, J = 7.2, 4.0 Hz, 1H, CH),
4.96 (m, 1H, CH), 4.86 (m, 1H, CH), 2.39 (m, 2H, CH2), 2.28 (m, 2H, CH2), 2.12 (s,
3H, CH3), 2.04 (s, 3H, CH3), 2.0 (s, 3H, CH3), 1.18 (d, J = 6,4 Hz, 3H, CH3); 13C
NMR (75 MHz, CDCl3): d 170.2, 170.1, 170.0, 163.8, 144.5, 130.9, 128.3, 121.5,
77.2, 73.7, 69.6, 69.3, 34.0, 29.5, 21.0, 20.8, 20.7, 16.0; HRMS calcd for
C18H24O8Na: 391.1368; found: 391.1355.
Compound 9b: ½a 2D5
ꢀ19.5 (c 1, CHCl3); IR (KBr) 2990, 1455, 1377, 1202,
ꢁ
1083 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.34–7.23 (m, 5H, ArH), 4.61 (ABq,
;
J = 11.7 Hz, 2H, CH2-OAr), 4.0, (m, 1H, CH), 3.74 (m, 1H, CH), 3.40 (m, 1H, CH),
2.62 (dd, J = 2.9, 16.5 Hz, 0.5H), 2.60 (dd, J = 2.9, 16.5 Hz, 0.5H), 2.42 (dd, J = 2.9,