Concise stereoselective total synthesis of leiocarpin C

Article abstract of DOI:10.1002/hlca.201200656

A simple and highly concise strategy has been developed for the stereoselective total synthesis of leiocarpin C starting from commercially available mandelic ester. The strategy utilizes the OsO₄-catalyzed cis-hydroxylation and selective reduction with K-Selectride as key steps. Copyright

Full text of DOI:10.1002/hlca.201200656

Helvetica Chimica Acta – Vol. 96 (2013)
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Concise Stereoselective Total Synthesis of Leiocarpin C
by Dasireddi Chandra Rao, Vanam Shekhar, Dorigondla Kumar Reddy, Baggu Chinnababu, and
Yenamandra Venkateswarlu*† 1
)
Division of Natural Products Chemistry, Natural Products Laboratory, Indian Institute of Chemical
Technology, Hyderabad – 500007, India
(phone: þ 91-40-27191881; fax: þ 91-40-27160512; e-mail: suresh@iict.res.in)
A simple and highly concise strategy has been developed for the stereoselective total synthesis of
leiocarpin C starting from commercially available mandelic ester. The strategy utilizes the OsO4-
catalyzed cis-hydroxylation and selective reduction with K-Selectride as key steps.
Introduction. – The styryl lactones have become a hot topic of phytochemistry and
oncopharmacology after taxol. The genus Goniothalamus (Annonaceae) comprises a
broad spectrum of styryl lactones, and its species were widely used as traditional
medicines in China as antalgic and pesticide agents [1]. The extract of the seeds of
Goniothalamus amuyon has been employed for the treatment of edema and
rheumatism [2]. Other general applications include their use as painkillers and
mosquito repellents. Taking into account their medicinal properties [3], these plants
are considered a potential source of antitumor, antifungal, and antibiotic agents [4].
Leiocarpin C (1) is a natural styryl lactone, which was isolated from the stem bark of the
tropical plant Goniothalamus leiocarpus [5]; it possesses significant cytotoxic activity
against several human tumor cell lines [6]. The synthesis of styryl lactones is of
considerable interest due to the prevalence of these structures in natural products as
biologically active compounds. Our continued interest in the total synthesis of lactones
[7] prompted us to undertake the synthesis of leiocarpin C (1). Three cumbersome
syntheses were reported in the literature for the synthesis of 1 [8]. Herein, we report a
simple synthesis of 1 using cis-dihydroxylation with OsO4 [7a][9] and selective 1,3-anti-
reduction with K-Selectride [10], starting from commercially available methyl (R)-
mandelate (¼ methyl (R)-2-hydroxy-2-phenylylacetate; 2).
Results and Discussion. – The retrosynthetic analysis for leiocarpin C (1) is depicted
in Scheme 1. As shown in Scheme 2, the secondary OH group of 2 was protected with
the (tert-butyl)(dimethyl)silyl (TBS) group using TBSCl and 1H-imidazole in
anhydrous CH2Cl2 to afford silyloxy derivative 3, which was reduced with DIBAL-H
at ꢀ 788 to give the corresponding aldehyde 90% yield. The aldehyde was subjected to
C2 homologation with ethyl (triphenylphosphoranylidene)acetate in anhydrous toluene
to furnish the Wittig product, i.e., a,b-unsaturated ester 4 with (E)-configuration in
1
)
Deceased July 17, 2013; correspondence should be addressed to Dr. K. Suresh Babu (phone: þ 91-
40-27181881; e-mail: suresh@iict.res.in)
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme 1. Retrosynthetic Analysis
Scheme 2
a) (tBu)Me2SiCl (TBSCl), 1H-Imidazole, dry CH2Cl2, 3 h, r.t.; 95%. b) 1. DIBAL-H
(¼ Diisobutylaluminium hydride), dry CH2Cl2, ꢀ 788, 30 min; 2. Ph3PCHCO2Et, dry toluene, 6 h, r.t.;
93.5% (over two steps). c) OsO4, N-methylmorpholine N-oxide (NMO), acetone/H2O 5 :1, r.t., 8 h;
90%. d) Pyridinium p-toluenesulfonate (PPTS), acetone, 2,2-dimethoxypropane, 12 h; 93%. e) 1.
DIBAL-H, dry CH2Cl2, ꢀ 788, 30 min; 90%; 2. PPh3CH3I, tBuOK THF, 08 to r.t., 15 min; 90%. f) BH3 ·
DMS, THF, 08 to r.t., 4 h, then 20% NaOH, 30% H2O2, 3 h; 89%. g) 1. 2-Iodoxybenzoic acid (IBX),
DMSO, r.t., 3 h; 90%; 2. N2CHCO2Et, SnCl2, dry CH2Cl2, 2 h; 89%. h) 1. K-Selectride, THF, ꢀ 788, 2 h;
2. LiEt3BH, ꢀ 788, 1 h; 90%. i) TsOH, MeOH, r.t., 3 h; 75%.
92% yield. Compound 4 was reacted with a catalytic amount of OsO4 in the presence of
excess N-methylmorpholine N-oxide in acetone/H2O 5 :1 to afford a,b-dihydroxy ester
5. The reaction afforded high anti-selectivity (anti/syn 90 :10) [7a][9] with respect to
the existing stereogenic center, and the anti-isomer 5 was separated chromatograph-
ically in 90% yield. The dihydroxy ester 5 was masked as acetonide using 2,2-
dimethoxypropane in the presence of a catalytic amount of TsOH to give compound 6
in 93% yield, which was reduced with DIBAL-H, at ꢀ 788 to furnish the corresponding
aldehyde in good yield. The latter was further subjected to a C1 Wittig reaction to give
the olefin 7, which was selectively hydroborated to yield the primary alcohol 8 using

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BH3 · DMS in THF. Oxidation of 8 resulted in the corresponding aldehyde in 90%
yield, which was converted into b-keto ester 9 (89% yield) by the reaction with ethyl
diazoacetate in the presence of a catalytic amount of SnCl2. The stereoselective
reduction of the ketone formation in compound 9 by using K-Selectride gave compound
10 with anti-configuration [10]. Finally, reaction of 10 with TsOH in MeOH at room
temperature afforded leiocarpin C (1) by concomitant deprotecting of the acetonide,
and the TBS groups, followed by cyclization in one pot. The physical and spectroscopic
data of compound 1 were found to be identical with those reported for the natural
product leiocarpin C ([a]2D5 ¼ ꢀ62.5 (c ¼ 0.5, CHCl3)) [5][8].
Conclusions. – In conclusion, we have accomplished the total synthesis of leiocarpin
C (1) starting from methyl (R)-mandelate (2) employing the OsO4-catalyzed cis-
hydroxylation and selective reduction with K-Selectride as key steps. This synthetic
sequence provides an easy preparation of 1 in nine steps with 28% overall yield,
compared with earlier reported overall yields of 4.6 and 24.5%, respectively [8].
The authors are grateful to MoES and CSIR, New Delhi, India, for the financial support, and to the
Director, Indian Institute of Chemical Technology (IICT), for his constant encouragement.
Experimental Part
General. Solvents were dried over standard drying agents and freshly distilled prior to use. The
reagents were purchased from Aldrich and Across, and were used without further purification unless
otherwise stated. All moisture-sensitive reactions were carried out under N2. Org. solns. were dried
(Na2SO4) and concentrated in vacuo below 408. Column chromatography (CC): silica gel (Acmeꢂs 60 –
120 mesh and 100 – 200 mesh). Optical rotations: Horiba high sensitive polarimeter SEPA-300 at 258. IR
1
Spectra: Perkin-Elmer IR-683 spectrophotometer with NaCl optics; ˜n in cmꢀ1. H- and 13C-NMR (300
and 75 MHz, resp.) spectra: Bruker Avance 300 instrument; d [ppm] rel. to Me4Si as internal standard in
CDCl3; J in Hz. MS: Agilent Technologies 1100 Series (Agilent Chemstation Software); m/z.
Methyl (R)-2-{[(tert-butyl)(dimethyl)silyl]oxy}-2-phenylacetate (3). To a cooled (08) soln. of methyl
(R)-mandelate (2; 2.5 g, 15.06 mmol) and 1H-imidazole (2.56 g, 37.65 mmol) in dry CH2Cl2 (30 ml) was
added (tert-butyl)dimethylsilyl chloride (TBSCl; 4.06 g, 27.10 mmol) portionwise, and the mixture was
stirred for 4 h. After the completion of reaction, the mixture was diluted with H2O (20 ml) and extracted
into CH2Cl2 (3 ꢁ 30 ml). The combined org. layer was washed with brine (10 ml), dried (Na2SO4), and
concentrated in vacuo to furnish the crude residue, which was purified by CC (AcOEt/hexane 0.5: 9.5) to
give 3 (4.02 g, 95%). Pale yellow liquid. [a]D25 ¼ ꢀ44.4 (c ¼ 0.25, CHCl3). IR (neat): 2954, 2932, 1759,
1256, 1129. 1H-NMR: 7.47 (d, J ¼ 7.0, 2 H); 7.36 – 7.26 (m, 3 H); 5.24 (s, 1 H); 3.68 (s, 3 H); 0.92 (s, 9 H);
0.11 (s, 3 H); 0.03 (s, 3 H). 13C-NMR: 172.2; 138.8; 128.1; 127.8; 126.1; 74.1; 51.7; 25.4; 18.0; ꢀ 5.3; ꢀ 5.4.
EI-MS: 281 ([M þ H]þ).
Ethyl (2E,4S)-4-{[(tert-Butyl)(dimethyl)silyl]oxy}-4-phenylbut-2-enoate (4). To a cooled (ꢀ 788)
soln. of 3 (2 g, 7.11 mmol) in dry CH2Cl2 (22 ml) was added dropwise DIBAL-H (1m in hexane, 7.1 ml,
7.1 mmol). After completion of the reaction, sat. Na K tartarate soln. (5 ml) was added, the mixture was
extracted with CH2Cl2 (3 ꢁ 30 ml) and concentrated under reduced pressure. Thus obtained aldehyde
(1.69 g, 6.7 mmol) was dissolved in dry toluene (50 ml), ethyl (triphenylphosphoranylidene) acetate
(2.81 g, 8.07 mmol) was added, and the mixture was refluxed for 6 h, cooled to r.t. subsequently, filtered
through Celite, and concentrated in vacuo. The residue was purified by FC (AcOEt/hexane 1:9) to give
first the (Z)-isomer 4a as an oil (0.18 g, 8%), followed by the (E)-isomer 4 as liquid (1.98 g, 92%). [a]D25
¼
ꢀ69 (c ¼ 1, CHCl3). IR (neat): 2954, 2932, 1730, 1660, 1440. 1H-NMR: 7.31 – 7.19 (m, 5 H); 6.89 (dd, J ¼
15.4, 5.1, 1 H); 6.02 (dd, J ¼ 15.4, 1.5, 1 H); 5.26 (dd, J ¼ 4.4, 1.5, 1 H); 4.18 – 4.09 (m, 2 H); 1.27 (t, J ¼ 7.3,

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Helvetica Chimica Acta – Vol. 96 (2013)
3 H); 0.90 (s, 9 H); 0.05 (s, 3 H); ꢀ 0.08 (s, 3 H). 13C-NMR: 166.7; 150.2; 141.6; 128.5; 127.6; 126.2; 118.8;
74.1; 60.4; 25.8; 18.3; 14.2; ꢀ 4.9; ꢀ 5.2. LC/MS: 343 ([M þ Na]þ).
Ethyl (2S,3S,4R)-4-{[(tert-Butyl)(dimethyl)silyl]oxy}-2,3-dihydroxy-4-phenylbutanoate (5). To a
soln. of 4 (1.8 g, 5.6 mmol) in acetone/H2O 5 :1 (15 ml) was added N-methylmorpholine N-oxide
hydrate (NMO; 1.31 g, 11.21 mmol), followed by OsO4 soln. (2.5 wt.-%. in tBuOH, 0.57 ml, 0.056 mmol,
0.01 equiv.), and the mixture was stirred for 14 h. After completion of the reaction, the mixture was
concentrated in vacuo, and the crude residue was purified by FC (AcOEt/hexane, 4 :6) to give 5 (1.79 g,
1
90%). Liquid. [a]D25 ¼ ꢀ32.9 (c ¼ 2.5, CHCl3). IR (neat): 3488, 2995, 2942, 2860, 1735. H-NMR: 7.28 –
7.42 (m, 5 H); 4.68 (d, J ¼ 8.3, 1 H); 4.52 (dd, J ¼ 5.6, 0.94, 1 H); 4.22 – 4.31 (m, 2 H); 3.83 (td, J ¼ 8.3,
1.1, 1 H); 3.05 (d, J ¼ 5.4, 1 H); 1.62 (d, J ¼ 7.6, 1 H); 1.32 (t, J ¼ 7.1, 3 H); 0.9 (s, 9 H); 0.1 (s, 3 H); ꢀ 0.2
(s, 3 H). 13C-NMR: 173.5; 141.5; 128.3; 127.9; 127.1; 77.3; 76.4; 75.1; 70.0; 61.8; 25.7; 18.0; 14.1; ꢀ 4.7;
ꢀ 5.3. HR-ESI-MS: 377.1754 ([M þ Na]þ, C18H30NaO5Siþ; calc. 377.1755).
Ethyl (4S,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-1,3-dioxolane-
4-carboxylate (6). To a cooled (08) soln. of 5 (1.2 g, 3.38 mmol) in anh. CH2Cl2 (10 ml) was added 2,2-
dimethoxypropane (0.53 ml, 4.39 mmol) and pyridinium p-toluenesulfonate (PPTS; 0.084 g, 0.33 mmol),
and mixture was stirred at r.t. for 3 h. After completion of the reaction, solid NaHCO3 (500 mg) was
added to neutralize the PPTS, and the mixture was filtered. The filtrate was concentrated to give a crude
product which was purified by CC (AcOEt/hexane 0.5 :9.5) to afford 6 (1.23 g, 93%). Colorless liquid.
1
[a]2D5 ¼ ꢀ28.2 (c ¼ 1.02, CHCl3). IR (neat): 2932, 2857, 1752, 1068, 839. H-NMR: 7.30 – 7.17 (m, 5 H);
4.83 (d, J ¼ 3.9, 1 H); 4.51 (d, J ¼ 5.9, 1 H); 4.37 (t, J ¼ 4.9, 1 H); 3.82 – 3.98 (m, 2 H); 1.40 (s, 3 H); 1.34 (s,
3 H); 1.03 (t, J ¼ 6.9, 3 H); 0.85 (s, 9 H); 0.03 (s, 3 H); ꢀ 0.18 (s, 3 H). 13C-NMR: 171.4; 140.4; 127.9;
127.6; 126.5; 111.5; 83.8; 75.2; 74.1; 61.0; 29.6; 25.7; 18.1; 14.1; ꢀ 4.9; ꢀ 4.7. LC/MS: 417 ([M þ Na]þ).
(tert-Butyl)[(R)-[(4S,5R)-5-ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl](phenyl)methoxy]dimethylsi-
lane (7). To a cooled (ꢀ 788) soln. of 6 (1.2 g, 3.038 mmol) in dry CH2Cl2 (15 ml) was added dropwise
DIBAL-H (1m in hexane, 3.01 ml, 3.038 mmol), and the mixure was stirred for 20 min at ꢀ 788. After
completion of the reaction, H2O (2 ml) was added, and the mixture was filtered over a pad of Celite and
concentrated in vacuo to give the aldehyde. Thus obtained crude aldehyde (0.9 g) was dissolved in dry
t
THF (10 ml) and reacted with PPh3CH3I salt (1.55 g, 3.84 mmol) in the presence of BuOK (0.384 g,
0.384 mmol). After completion of the reaction, the mixture was diluted with H2O, extracted with AcOEt
(3 ꢁ 10 ml), dried (NaSO4), and the combined extract was concentrated in vacuo to give a crude product
which was purified by CC (AcOEt/hexane 1:9) to yield 7 (0.80 g, 90%). Colorless liquid. [a]2D5 ¼ ꢀ24.3
(c ¼ 0.5, CHCl3). IR (neat): 2930, 2889, 2870, 1365, 1072. 1H-NMR: 7.34 – 7.27 (m, 5 H); 5.84 – 5.89 (m,
1 H); 5.20 – 5.15 (m, 2 H); 4.81 (d, J ¼ 6.0, 1 H); 4.50 (d, J ¼ 6.5, 1 H); 4.35 – 4.44 (m, 1 H); 1.41 (s, 3 H);
1.33(s, 3 H) 0.89 (s, 9 H); 0.06 (s, 3 H); ꢀ 0.12 (s, 3 H). 13C-NMR: 141.3; 132; 128.3; 128.1; 127.7; 119.7;
109.7; 87.2; 78.4; 75.3; 29.8; 26.4; 25.4; 18.1; ꢀ 4.2; ꢀ 4.4. LC/MS: 371 ([M þ Na]þ).
2-{(4R,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-
yl}ethanol (8). To a cooled (ꢀ 788) soln. of 7 (0.7 g, 2.04 mmol) in dry THF (10 ml) was added dropwise
BH3 · DMS (2m in THF, 1.125 ml, 2.25 mmol, 1.1 equiv.). After stirring for 20 min at ꢀ 788, the reaction
was quenched with 30% H2O2 (0.347 ml, 3.07 mmol) and 2m NaOH (1.53 ml, 3.07 mmol), and the
mixture was filtered over a pad of Celite, and concentrated under reduced pressure. The residue was
purified by FC (AcOEt/hexane 2 :8) to afford 8 (0.763 g, 89%). [a]2D5 ¼ ꢀ28.3 (c ¼ 1.0, CHCl3). IR
1
(neat): 3388, 2930, 2858, 1253, 1067, 837. H-NMR: 7.34 – 7.27 (m, 5 H); 4.81 (d, J ¼ 6.0, 1 H); 4.25 –
4.21(m, 1 H); 3.94(t, J ¼ 7.0, 1 H); 3.51 – 3.46 (m, 1 H); 3.26 – 3.20 (m, 1 H); 1.91 (br. s, 1 H).
13C-NMR: 170.3; 141.2; 128.0; 127.8; 127.2; 110.5; 82.5; 75.8; 73.5; 51.8; 29.6; 26.6; 25.7; 18.1; ꢀ 4.5; ꢀ 5.1.
ESI-MS: 389 ([M þ Na]þ).
Ethyl 4-{(4R,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-1,3-dioxo-
lan-4-yl}-3-oxobutanoate (9). To a cooled (08) soln. of 2-iodoxybenzoic acid (IBX; 0.687g, 2.45 mmol) in
dry DMSO (10 ml) was added 8 (0.6 g 1.63 mmol) in dry CH2Cl2 (5 ml), and the mixture was stirred for
3 h. After completion of the reaction, the mixture was poured on to chilled ice and extracted with AcOEt.
The crude extract was concentrated in vacuo, the crude was purified by CC to give pure aldehyde (0.635 g
90% yield), which was used in the next step. To a soln. of the aldehyde (0.5 g, 1.36 mmol) and ethyl
diazoacetate (0.17 g, 1.5 mmol) in dry CH2Cl2 (10 ml) was added portionswise SnCl2 (0.025 g,
0.1369 mmol) within 10 min, and the mixture was stirred for 30 min. After completion of the reaction,

Helvetica Chimica Acta – Vol. 96 (2013)
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the mixture was diluted with H2O and extracted with CH2Cl2 (3 ꢁ 10 ml). The combined org. layer was
dried (Na2SO4), and concentrated in vacuo to give a crude residue which was purified by CC (AcOEt/
hexane 2.5 :7.5) to afford 9 (0.549, 89%). [a]D25 ¼ ꢀ27.5 (c ¼ 0.5, CHCl3). IR (neat): 2931, 2857, 1745,
1
1722, 1254, 1067, 839. H-NMR (300 MHz, CDCl3): 7.36 – 7.25 (m, 5 H); 4.82 (d, J ¼ 5.0, 1 H); 4.52 (td,
J ¼ 2.0, 9.9, 1 H); 4.16 (q, J ¼ 6.9, 2 H); 3.76 (dd, J ¼ 7.9, 5.9, 1 H); 3.41(s, 2 H); 2.54 (dd, J ¼ 15.8, 8.9,
2 H); 2.30 (d, J ¼ 15.8, 1 H); 1.40 (s, 3 H); 1.33 (s, 3 H); 1.26 (t, J ¼ 6.9, 3 H); 0.88 (s, 9 H); 0.07 (s, 3 H); ꢀ
0.14 (s, 3 H). 13C-NMR (75 MHz, CDCl3): 200.3; 166.9; 141.2; 128.2; 127.7; 126.4; 109.2; 84.4; 74.9; 73.2;
61.2; 50.0; 47.5; 29.7; 27.0; 25.8; 18.2; 14.1; ꢀ 4.79. ESI-MS: 475 ([M þ Na]þ).
Ethyl (3R)-4-{(4R,5S)-5-[(R)-{[(tert-Butyl)(dimethyl)silyl]oxy}(phenyl)methyl]-2,2-dimethyl-1,3-
dioxolan-4-yl}-3-hydroxybutanoate (10). To a cooled (ꢀ 788) soln. of 9 (0.41 g, 0.90 mmol) in dry THF
(10 ml) was added a 1m soln. of K-Selectride (1.07 ml, 1.07 mmol), and the mixture was stirred for 2 h.
Then, LiEt3BH (1.076 ml, 1.077 mmol) was added, and the mixture was stirred for 1 h at ꢀ 788. After
completion of the reaction (TLC), H2O was added, and contents were extracted with Et2O and dried
(Na2SO4), and the solvent was removed in vacuo. The crude product was purified by CC (AcOEt/hexane
3 :7) to yield pure anti-isomer 10 (0.369 g, 90%). Colorless liquid. [a]2D5 ¼ ꢀ30.1 (c ¼ 1.0, CHCl3). IR
(neat): 3444, 2930, 2857, 1729, 1254, 1068, 838. 1H-NMR: 7.34 – 7.24 (m, 5 H); 4.81 (d, J ¼ 5.1, 1 H); 4.51 –
4.48 (m, 1 H); 4.14 (q, J ¼ 6.8, 2 H); 3.83 (dd, J ¼ 5.1, 0.96, 1 H); 3.70 – 3.67 (m, 2 H); 2.53 – 2.49 (m, 1 H);
2.29 – 2.25 (m, 1 H); 1.59 – 1.55 (m, 2 H); 1.41 (s, 3 H); 1.33 (s, 3 H); 1.25 (t, J ¼ 6.8 , 3 H); 0.89 (s, 9 H);
0.06 (s, 3 H); ꢀ 0.014 (s, 3 H). 13C-NMR: 172.5; 140.3; 128.3; 127.9; 127.0; 110.0; 84.5; 74.0; 73.0; 63.0;
61.3; 42.7; 34.9; 29.6; 27.1; 25.8; 18.1; 14.1; ꢀ 4.8. ESI-MS: 461 ([M þ Na]þ).
Leiocarpin C (¼(4R,6R)-6-[(1R,2R)-1,2-Dihydroxy-2-phenylethyl]-4-hydroxytetrahydro-2H-pyran-
2-one; 1). To a stirred soln. of 10 (0.12 g, 0.26 mmol) in dry CH2Cl2 (5 ml) was added a cat. amount of
TsOH under N2, and the mixture was stirred at r.t. for 3 h. After completion of the reaction, solid
NaHCO3 (0.005 g) was added. The mixture was filtered, and the solvent was removed in vacuo. The crude
residue was purified by CC (AcOEt/hexane 4 :6) to afford 1 (0.049 g, 75%). Colorless needles. [a]D25
¼
1
ꢀ62.5 (c ¼ 0.5, CHCl3). IR: 3423, 2920, 2850, 1720, 1656, 1460, 1219 and 606. H-NMR: 7.51 – 7.27 (m,
5 H); 4.92 (d, J ¼ 7.8, 1 H); 4.72 (dd, J ¼ 4.4, 9.8, 1 H ); 4.29 (quint., J ¼ 6.8, 1 H); 3.71 (d, J ¼ 8.8, 1 H);
2.87 (dd, J ¼ 5.4, 17.2, 1 H); 2.56 (dd, J ¼ 7.3, 17.2, 1 H); 2.21 – 2.14 (m, 1 H); 2.11 – 2.0 (m, 1 H).
13C-NMR: 172.0; 141.2; 128.6; 127.7; 127.3; 78.1; 68.8; 67.1; 66.7; 41.2; 40.3. ESI-MS: 275 ([M þ Na]þ).
HR-MS: 275.0907 ([M þ Na]þ, C13H16NaO5þ ; calc. 275.0895).
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Received December 21, 2012