1 Introduction

Lignans are a large class of natural products that were isolated from many plants [1, 2] (Fig. 1). They display diverse biological activities, especially antiviral and antitumor properties. For example, hinokinin (1) [3–5] has been found to exhibit antileukemic, antiviral, antifungal, and pesticidal activities [6–26]. Mammalian lignin enterolactone (2), which is formed by the action of intestinal bacteria from plant lignan precursors present in the diet, inhibit breast cancer and colon cancer, and may also inhibit cardiovascular disease [27, 28]. Furthermore, podophyllotoxin (3), steganacin (4) and tetrahydrofuran lignan burseran (5) show strong cytotoxic activity against various cancer cell lines by preventing the normal function of the mitotic spindle [29–36]. In addition, the furofuran lignan methyl piperitol (6) possesses platelet activating factor (PAF) antagonist activity [37]. Due to their interesting biological activities, several members of this family of natural products and their analogs have therefore been the target of extensive synthetic research [38–47].

Fig. 1
figure 1

Representive lignans with pharmacological activities

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We recently developed a one-pot, three-step cascade reaction from enantiomerically pure (R)-N-tert-butanesulfinyl imidates 7 and α,β-unsaturated diesters 8 [48] to generate butyrolactonimidates 11 (Scheme 1). This reaction proceeded through highly stereoselective Michael addition (7–9), followed by anion-oxidative hydroxylation (9–10) and oxygen anion cyclization (10–11). The synthesized butyrolactonimidates 11 are versatile intermediates for preparing substituted butyrolactones and furans. We also used this approach to achieve the concise total synthesis of natural product (–)-nephrosteranic acid [48]. In this paper, we report the total synthesis of lignan lactone (–)-hinokinin 1 as shown in Schemes 2 and 3.

Scheme 1
scheme 1

Synthesis of butyrolactonimidates 11 via the three-step cascade reaction

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Scheme 2
scheme 2

Synthesis of butyrolactonimidate 16. Reagents and conditions: a HCl (gas), MeOH, 0 °C, 24 h; MeOH, r.t., 48 h; then (R)-tert-butanesulfinamide 13, p-TsOH (0.05 equiv), neat, 60 °C, 24 h, 76 % in 2 steps; b LiHMDS (5.0 equiv), THF, −78 °C, 0.5 h, then Cu(OTf)2 (5.0 equiv), −78 to 60 °C, 24 h, 20 %. c LiHMDS (2.2 equiv), THF, −78 °C, 12 h, 80 %; d LiHMDS (3.3 equiv), THF, −78 °C, 0.5 h, then Cu(OTf)2 (5.0 equiv), −78 to 60 °C, 24 h, 83 %. LiHMDS Lithium hexamethyldisilazide, THF tetrahydrofuran

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Scheme 3
scheme 3

Synthesis of (–)-hinokinin (1). Reagents and conditions: a TFA (10.0 equiv), CH2Cl2, 0 °C to r.t., 80 %; b LiCl (5.0 equiv), DMSO, 100 °C, 8 h, 90 %; c NaBH4 (2.5 equiv), MeOH, 0 °C, 10 h, 78 %; d InBr3 (0.05 equiv), Et3SiH (5 equiv), CHCl3, sealed tube, 60 °C, 2 h, 60 % for 21, 20 % for 22; e PCC (5.0 equiv), PhMe, 80 °C, 5 h, 53 %. LiHMDS Lithium hexamethyldisilazide, THF tetrahydrofuran, TFA trifluoroacetic acid, DMSO dimethyl sulfoxide, PCC pyridinium chlorochromate

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2 Results and Discussion

We began our synthesis with the preparation of enantiopure (R)-N-tert-butanesulfinyl imidate 14 (Scheme 2): treatment of the known nitrile 12 [49, 50] with gaseous HCl in methanol yielded a good amount of trimethylorthoester intermediate [51], subsequent condensation of (R)-tert-butanesulfinamide 13 and the corresponding trimethylorthoester with a catalytic amount of p-TsOH without solvent afforded chiral (R)-N-tert-butanesulfinyl imidate 14 in 76 % overall yield [52–54]. With the N-sulfinyl imidate 14 in hand, we focused our attention on the construction of the pivotal butyrolactonimidate, as shown in Scheme 2. Firstly, we performed the one pot protocol between 14 and the known α,β-unsaturated diester 15 [55, 56] under optimal condition [48] {LiHMDS (5.0 equiv), −78 °C; Cu(OTf)2 (5.0 equiv), −78 to 60 °C} to afford the desired butyrolactonimidate 16 in low yield (20 %), due to the isomerization of double bond in 15 under excess LiHMDS. To our delight, the stepwise procedure provided a satisfactory result. Indeed, a LiHMDS-mediated highly stereoselective Michael addition of 14–15 produced adduct 17 in 80 % yield as the dominant stereoisomer (dr 55:2:1:0 by LC–MS). Next, the resulting Michael adduct underwent the Cu(OTf)2-mediated anion-oxidative hydroxylation and oxygen anion cyclization to deliver 16 in 83 % yield.

With the pivotal butyrolactonimidate 16 in hand, the synthesis of natural product (–)-hinokinin 1 was investigated (Scheme 3). The chiral tert-butylsulfinyl moiety in 16 was readily removed by TFA in CH2Cl2 to afford butyrolactone 18 in 80 % yield. Krapcho demethoxycarbonylation of 18 with LiCl in DMSO afforded 19 in 90 % yield as a 5:1 mixture of epimers [57–59], as determined by 1H NMR spectroscopy. The mixture of epimers could not be separated by chromatography, however this would prove to be inconsequential since this carbon would become sp2 hybridized in subsequent steps. Reduction of the ester group in mixture 19 with NaBH4 in MeOH gave alcohol 20 in 78 % yield. Subsequent reduction of the lactone group in 20 using InBr3 and Et3SiH in CHCl3 generated the desired furan 21 in 60 % yield as a mixture of epimers [60, 61]. Interestingly, besides furan 21, further aromatic oxidative coupling proceeded under this condition to deliver compound 22 in 20 % yield, which possessed the tetracyclic scaffold of dibenzocyclooctadiene lignans such as steganacin 4 (Fig. 1). The generation of 22 presumably resulted from the introduction of oxygen under this reductive condition, and the amount of 22 was considerably increased (TLC monitoring) when oxygen was intentionally bubbled into the reaction tube. Finally, heating of 21 with excess PCC in toluene completed the total synthesis of lignan lactone (–)-hinokinin 1 in acceptable yield [62, 63], which displayed identical spectral properties to the reported data [3–5, 18, 21, 24, 26].

3 Conclusion

In summary, we accomplished the total synthesis of the lignan lactone (–)-hinokinin 1 in 8 steps. The synthesis is based on a three-step cascade reaction involving highly stereoselective Michael addition, anion-oxidative hydroxylation, and oxygen anion cyclization to construct the pivotal butyrolactonimidate 16. The strategy we developed may find use in the synthesis of other pharmacologically active lignans.

4 Experiment Section

All commercially available reagents were used without further purification. All solvents were dried and distilled before use; THF was distilled from sodium. Chromatography was conducted by using 200–300 mesh silica gel. Petroleum ether refers to the 60–90 °C boiling fraction. All new compounds gave satisfactory spectroscopic analyses (IR, 1H NMR, 13C NMR, HRMS). IR spectra were recorded on a FT IR spectrometer. NMR spectra were recorded on 600/400 MHz NMR spectrometers. HRMS spectra were obtained by the ESI-TOF method. Experimental conditions and spectral data were published previously for compounds 12 [49, 50] and 15 [55, 56].

4.1 Methyl (R,Z)-3-(benzo[d][1,3]dioxol-5-yl)-N-(tert-butylsulfinyl)propanimidate (14)

  1. (1)

    A mixture of the chosen nitrile 12 (28.60 mmol, 1.0 equiv) and methanol (37.00 mmol, 1.3 equiv) was charged in a 50 mL flask, and cooled in an ice bath. Gaseous HCl was slowly bubbled into the methanolic solution of the nitrile for 20 min. The resulting mixture was kept at 0 °C for 24 h. Then, the excess of methanol and HCl was removed by washing with Et2O, white solid imidate hydrochloride was separated. The product was dried under vacuum at rt, and used as such for the subsequent methanolysis step.

  2. (2)

    At rt, a mixture of methanol (10 mL) and the solid imidate hydrochloride was set to react under stirring for 48 h. A clear solution was obtained. White solid (ammonium chloride) was formed during the reaction. Then, the mixture was filtered to cleavage NH4Cl and washed with Et2O. The solvent was removed in vacuo to get the colorless oil trimethyl-intermediate (6.5 g, 90 %).

  3. (3)

    Under N2, to neat trimethyl-intermediate (9.84 mmol, 2 equiv) was added (R)-tert-butanesulfinamide 13 (4.92 mmol, 1 equiv) and p-TsOH (0.25 mmol, 0.05 equiv). The reaction mixture was kept at 60 °C for 24 h. The resulting residue was purified by column chromatography (silica gel) to give 14 (1.3 g, 84 %) as a colorless oil. \( \left[ \alpha \right]_{D}^{23} \) −97.0 (c 0.22, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 6.64–6.72 (m, 3H), 5.09 (s, 2H), 3.51 (s, 3H), 2.86–2.93 (m, 4H), 1.18 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 175.6, 147.6, 146.0, 133.8, 121.2, 108.8, 108.2, 100.8, 55.8, 54.1, 34.8, 32.1, 21.8; HRMS [M + Na]+ calcd for C15H21NNaO4S 334.1083, found 334.1084; IR (KBr) 2948, 1608, 1491, 1443, 1245, 1076, 1040, 926, 810, 750, 591.

4.2 Dimethyl 2-((2R,3R,Z)-1-(benzo[d][1,3]dioxol-5-yl)-3-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(((R)-tert-butylsulfinyl)imino)-4-methoxybutan-2-yl)malonate (17)

Under N2, to a solution of 14 (1.90 mmol, 0.95 equiv) in dry THF (100 mL) was added LiHMDS (1 M in THF, 4.20 mmol, 2.2 equiv) at −78 °C. After the resulting solution was maintained at −78 °C for 30 min, a solution of 15 (2.00 mmol, 1.0 equiv) in THF (1 mL) was slowly added for 10 h. The resulting solution was maintained at −78 °C for another 12 h. The dr values for the first Michael addition anaylsed by LC–Ms. After the reaction was completed, the solution was quenched at −78 °C by pouring into aqueous NH4Cl (50 mL). The aqueous layer was partitioned with EtOAc (3 × 50 mL). The organic layer was separated, dried (Na2SO4), filtered, and the solvent was removed in vacuo. Flash chromatography (silica gel) of the crude reaction mixture afforded pure coupled product 17 (900 mg, 80 %). Conditions for LC–MS analysis of Michael addition product: Waters ACOUITY UPLC BEH C18, BEH C18 (2.1 × 100 mm, 1.7 micron particle size), mobile phase H2O/CH3CN (80:20); Flow = 0.2 mL/min; Detected by UV at 210 nm; Retention time for stereoisomers: 7.78 min (major), 8.25 min, 8.97 min; Dr 55:1:2:0. 17: \( \left[ \alpha \right]_{D}^{23} \) −44.2 (c 0.21, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 6.62–6.76 (m, 4H), 6.47–6.49 (m, 2H), 5.91 (s, 2H), 5.86 (s, 2H), 3.81–3.84 (m, 1H), 3.73 (s, 3H), 3.68(s, 3H), 3.67 (s, 3H), 3.59 (d, J = 4.0 Hz, 1H), 2.79–3.01 (m, 1H), 2.66–2.69 (m, 4H), 0.96 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 175.2, 169.4, 168.6, 147.5, 146.2, 145.8, 134.0, 132.2, 122.2, 122.0, 109.5, 109.3, 108.2, 108.0, 100.8, 55.6, 53.8, 53.5, 52.5, 52.4, 47.8, 42.6, 36.7, 35.4, 21.6; HRMS [M + Na]+ calcd for C29H35NNaO10S 612.1874, found 612.1876; IR (KBr) 2960, 1736, 1606, 1491, 1442, 1248, 1039, 806, 702, 591.

4.3 (3R,4R,Z)-dimethyl 3,4-bis(benzo[d][1,3]dioxol-5-ylmethyl)-5-(((R)-tert-butylsulfinyl)imino)dihydrofuran-2,2(3H)-dicarboxylate (16)

Under N2, to a solution of 17 (1.82 mmol, 1 equiv) in dry THF (200 mL) was added LiHMDS (1 M in THF, 6.00 mmol, 3.3 equiv) at −78 °C. After the resulting solution was maintained at −78 °C for 30 min, the Cu(OTf)2 (9.10 mmol, 5.0 equiv) was added at once (exposed to air for seconds). Then the reaction mixture was warmed to ambient temperature slowly and kept at 60 °C and charged with nitrogen balloon for 24 h. After the reaction was completed, the solution was kept in room temperature and quenched by pouring it into aqueous NH4Cl (100 mL). The aqueous layer was partitioned with EtOAc (3 × 100 mL). The organic layer was separated and washed with with HCl (1 N, 50 mL), water (50 mL) and aqueous NaHCO3 (50 mL), dried (Na2SO4), filtered, and the solvent was removed in vacuo. Flash chromatography (silica gel) of the crude reaction mixture afforded pure coupled product 16 (860 mg, 83 %). \( \left[ \alpha \right]_{D}^{23} \) −77.0 (c 0.15, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 6.41–6.62 (m, 6H), 5.88–5.94 (m, 4H), 3.89 (s, 3H), 3.84 (s, 3H), 2.61–2.91 (m, 5H), 2.13–2.17 (m, 1H), 1.10 (s, 9H); 13C NMR (150 MHz, CDCl3) δ 171.1, 166.1, 147.4, 146.1, 130.7, 122.4, 122.1, 109.6, 109.1, 108.2, 107.8, 101.1, 100.8, 60.4, 53.9, 53.4, 53.3, 45.8, 30.9, 22.2, 21.03, 14.2; HRMS [M + Na]+ calcd for C28H31NNaO10S 596.1561, found 596.1569; IR (KBr) 2962, 2926, 1749, 1665, 1504, 1492, 1445, 1364, 1260, 1088, 1039, 803.

4.4 (3R,4R)-dimethyl 3,4-bis(benzo[d][1,3]dioxol-5-ylmethyl)-5-oxodihydrofuran-2,2(3H)-dicarboxylate (18)

To a solution of 16 (0.80 mmol, 1.0 equiv) in DCM (30 mL) cooled in an ice-water bath was added TFA (8.00 mmol, 10.0 equiv), and the mixture was stirred at room temperature for 24 h. The reaction was quenched by the addition of sat. NaHCO3. The mixture was extracted with EtOAc (30 mL × 3), dried over Na2SO4 and then concentrated. The resulting residue was purified by column chromatography (silica gel) to give 18 (240 mg, 80 %) as a white solide. \( \left[ \alpha \right]_{D}^{23} \) +8.0 (c 0.12, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 6.72 (d, J = 8.4 Hz, 1H), 6.59–6.67 (m, 3H), 6.20–6.22 (m, 2H), 5.97(d, J = 4.8 Hz, 2H), 5.91 (d, J = 4.6 Hz, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 3.03–3.10 (m, 2H), 2.73-2.85 (m, 2H), 2.44–2.48 (m, 1H), 2.23 (m, 1H); 13C NMR (150 MHz, CDCl3) δ 175.6, 166.8, 166.7, 148.0, 147.5, 146.6, 146.3, 130.9, 130.0, 122.6, 122.1, 109.8, 109.4, 108.3, 108.0, 101.1, 100.9, 85.7, 53.6, 53.4, 46.5, 45.0, 36.6, 34.5; HRMS [M + Na]+ calcd for C24H22NaO10 493.1105, found 493.1107; IR (KBr) 2956, 2924, 1796, 1748, 1492, 1445, 1250, 1175, 1081, 1039, 930, 862, 810, 737, 651.

4.5 (3R,4R)-methyl 3,4-bis(benzo[d][1,3]dioxol-5-ylmethyl)-5-oxotetrahydrofuran-2-carboxylate (19)

To a solution of 18 (0.45 mmol, 1.0 equiv) in DMSO (9 mL) was added LiCl (2.25 mmol, 5.0 equiv), and the mixture was stirred at 100 °C for 8 h. The reaction was quenched by the addition of water (10 mL). The mixture was extracted with EtOAc (10 mL × 3), dried over Na2SO4 and then concentrated. The resulting residue was purified by column chromatography (silica gel) to give yellow oil 19 (167 mg, 90 %) as a mixture (dr 5:1). 1H NMR (400 MHz, CDCl3) δ 6.66 (d, J = 7.8 Hz, 2.4H), 6.34–6.52 (m, 4.8H), 5.92 (d, J = 6.5 Hz, 4.8H), 4.75 (d, J = 7.9 Hz, 0.2H) (minor), 4.53 (d, J = 4.6 Hz, 1H) (major), 3.78 (s, 0.6H), 3.74 (d, J = 1.8 Hz, 3H), 2.92–2.97 (m, 1.2H), 2.63–2.78 (m, 2.4H), 2.58 (m, 3.6H). 13C NMR (100 MHz, CDCl3) δ 177.2, 176.7, 170.0, 169.1, 147.8, 146.5, 131.0, 130.8, 130.4, 130.0, 122.3, 122.1, 121.7, 109.6, 109.4, 109.3, 108.9, 108.3, 108.2, 101.1, 78.5, 77.4, 52.7, 52.4, 45.7, 44.9, 44.5, 43.1, 38.4, 35.7, 34.9, 34.4. HRMS [M + Na]+ calcd for C22H20NaO8 435.1050, found 435.1040.

4.6 (3R,4R)-3,4-bis(benzo[d][1,3]dioxol-5-ylmethyl)-5-(hydroxymethyl)dihydrofuran-2(3H)-one (20)

To a solution of 19 (0.47 mmol, 1.0 eq) in MeOH (17 mL) cooled in an ice-water bath was added NaBH4 (2.50 mmol, 2.5 eq), and the mixture was stirred in an ice-water bath for 10 h. The reaction was quenched by the addition of sat. NH4Cl (5 mL). The mixture was extracted with EtOAc (10 mL × 5), dried over Na2SO4 and then concentrated. The resulting residue was purified by column chromatography (silica gel) to give 20 (140 mg, 78 %) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 6.70 (m, 2.4H), 6.55–6.66 (m, 2.4H), 6.46 (d, J = 8.2 Hz, 2.4H), 5.84–5.98 (s, 4.8H), 4.25–4.30 (m, 0.2H), 4.17–4.23 (m, 1H), 3.52 (d, J = 12.6 Hz, 1.2H), 3.13 (dd, J = 12.9, 4.8 Hz, 1.2H), 2.64–2.84 (m, 2.4H), 2.36–2.50 (m, 4.8H); 13C NMR (100 MHz, CDCl3) δ 177.4, 147.8, 146.4, 132.1, 131.3, 122.3, 121.7, 121.4, 109.5, 108.7, 108.4, 108.3, 108.3, 108.1, 101.0, 83.7, 80.4, 63.1, 61.9, 47.5, 46.6, 42.0, 41.6, 38.7, 35.3, 34.8, 34.1. HRMS [M + Na]+ calcd for C21H20NaO7 407.1101, found 407.1100.

4.7 ((3R,4R)-3,4-bis(benzo[d][1,3]dioxol-5-ylmethyl)tetrahydrofuran-2-yl)methanol (21) and ((3aR,13aR)-6,7,10,11-bis(benzo[d][1,3]dioxol)-1,3,3a,4,13,13a-hexahydrodibenzo[4,5:6,7]cycloocta[1,2-c]furan-1-yl)methanol (22)

To a freshly distilled CHCl3 solution (10 mL) was added successively 20 (0.65 mmol, 1.0 equiv), a catalytic amount of InBr3 (0.03 mmol, 0.05 equiv), and Et3SiH (3.25 mmol, 5.0 eq). The solution was maintained at 60 °C for 2 h. During the stirring of the reaction mixture at 60 °C (bath temperature), the solution turned from colorless to yellow, then to white. The reaction was monitored by TLC until the consumption of the starting lactone. After the reaction, H2O (3 mL) was added, and the resulting orange suspension was stirred continuously until the disappearance of the color. The aqueous layer was partitioned with EtOAc (3 × 10 mL). The organic layer was separated, dried (Na2SO4), filtered, and the solvent was removed in vacuo. Flash chromatography (silica gel) of the crude reaction mixture afforded product 21 (143 mg, 60 %) and 22 (48 mg, 20 %) as a colorless oil. 21: 1H NMR (400 MHz, CDCl3) δ 6.68 (m, 2.4H), 6.54 (m, 4.8H), 5.91 (s, 4.8H), 3.90–4.10 (m, 0.2H), 3.82 (td, J = 8.0, 7.0, 2.0 Hz, 1H), 3.64–3.71 (m, 1.2H), 3.54–3.59 (m, 1.2H), 3.43 (dd, J = 11.8, 2.7 Hz, 1.2H), 3.23–3.37 (m, 1.2H), 2.41–2.65 (m, 4.8H), 2.13–2.25 (m, 1.2H), 1.86–1.92 (m, 1.2H); 13C NMR (100 MHz, CDCl3) δ 147.7, 147.6, 146.0, 145.8, 133.9, 133.4, 121.6, 121.4, 109.0, 108.9, 108.2, 108.1, 100.9, 85.6, 72.4, 64.0, 47.4, 47.1, 39.0. HRMS [M + Na]+ calcd for C21H22NaO6 393.1314, found 393.1317. 22: 1H NMR (400 MHz, CDCl3) δ 6.96 (s, 1.2H), 6.85 (s, 1.2H), 6.62 (s, 1.2H), 6.48 (s, 1.2H), 5.70–6.03 (m, 4.8H), 4.15 (d, J = 7.9 Hz, 1.2H), 3.89 (dd, J = 10.4, 2.3 Hz, 1.2H), 3.53–3.78 (m, 2.4H), 3.19-3.41 (m, 1.2H), 2.55-2.98 (m, 4.8H), 2.45–2.50 (m, 1.2H), 2.08–2.16 (m, 1.2H); 13C NMR (100 MHz, CDCl3) δ 146.8, 146.3, 146.3, 145.7, 139.2, 135.3, 130.8, 127.5, 108.6, 108.0, 105.6, 105.4, 100.9, 100.7, 77.2, 73.9, 65.2, 47.8, 39.9, 38.3, 30.8, 28.2. HRMS [M + Na]+ calcd for C21H20NaO6 391.1152, found 391.1143.

4.8 (3R,4R)-3,4-bis(benzo[d][1,3]dioxol-5-ylmethyl)dihydrofuran-2(3H)-one (1)

To a solution of 21 (0.08 mmol, 1.0 eq) dry toluene (3 mL) was added PCC (0.40 mmol, 5.0 eq) and 4Å MS (30 mg), the mixture was stirred at 80 °C for 5 h. After the reaction, the mixture was filtered through a pad of Celite, and washed with EtOAc for 5 times and then concentrated. The resulting residue was purified by column chromatography (silica gel) to give (–)-hinokinin 1 (15 mg, 53 %) as a white solide. \( \left[ \alpha \right]_{D}^{23} \) −31 (c 0.21, CHCl3), {lit. [5] \( \left[ \alpha \right]_{D}^{21} \) −34 (c 2.85, CHCl3); lit. [21] \( \left[ \alpha \right]_{D}^{26} \) −30 (c 0.99, CHCl3)}; 1H NMR (400 MHz, CDCl3) δ 6.44–6.73 (m, 6H), 5.92 (s, 4H), 4.11 (dd, J = 9.0, 6.7 Hz, 1H), 3.85 (dd, J = 9.2, 6.8 Hz, 1H), 2.97 (dd, J = 14.1, 5.0 Hz, 1H), 2.83 (dd, J = 14.1, 7.3 Hz, 1H), 2.48–2.65 (m, 2H), 2.45 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 178.4, 147.8, 146.4, 146.3, 131.5, 131.2, 122.2, 121.5, 109.4, 108.8, 108.3, 108.2, 100.9, 71.1, 46.4, 41.2, 38.3, 34.8. The NMR data match those reported in the literature [3–5, 18, 21, 24, 26]. HRMS [M + Na]+ calcd for C20H18NaO6 377.1001, found 377.1004; IR (KBr), 2958, 2924, 2855, 1761, 1503, 1489, 1443, 1257, 1189, 1098, 1036, 925, 864, 807, 771, 734, 676, 515.