HETEROCYCLES

Paper | Special issue | Vol. 77, No. 2, 2009, pp. 1297-1305
Received, 15th September, 2008, Accepted, 15th October, 2008, Published online, 16th October, 2008.
DOI: 10.3987/COM-08-S(F)115

■ Stereoselective β-D-Psicofuranosylation and Synthesis of β-D-Psicofuranosylceramide

Jun'ichi Uenishi* and Atsushi Ueda

Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan

Abstract

Psicofuranosylations of alcohols and phenol 3a-e with benzyl D-psicosyl phthalate 2 occurred on the β-face to give β-D-psicoside 4a-e in excellent yields. The reaction of ceramide 5 with 2 and deprotections of acetonide and three benzoates of the resulting glycoside afforded β-D-psicosylceramide 1.

INTRODUCTION
Cerebrosides are glycoshingolipids and important components of a wide variety of issues and organs in biological system.1 They serve as structural part of cellular membranes and metabolic precursors for sphigosines and ceramides, which play important physiological and pathophysiological roles.2 Cerebrosides consist of a hexose unit and a ceramide unit linked with a glycosidic bond. Ceramide is a C-18 carbon chain aminoalcohol with N-alkanoyl moiety. Although cerebroside composes a hexose commonly galactose or glucose,3 and rarely mannose or oligosaccharide,4 only a few hexofuranosylceramides has been studied.5 D-Psicofuranose is a diastereomer of D-fructofuranose at C-3 carbon center. We are interested in hexofuranosylceramide having a D-psicosyl unit. In this paper, we describe i) β-D-psicosylation of primary and secondary alcohols and phenol and ii) synthesis of β-D-psicofuranosylceramide 1 of which structure is shown in Figure 1.

RESULTS AND DISCUSSION
D-Psicose is an expensive rare sugar.6 The chemistry of psicose has not been investigated well. D-Psicose has been provided by fermentation being converted from D-fructose by D-tagatose-3-epimerase.7 Recently, we have prepared it chemically from D-ribose in the synthetic process of (+)-sucrose.8 The synthesis of (+)-sucrose involved the psicosylation of α-D-glucose with benzyl D-psicosyl phthalate 2. This glycosylation was promoted by TMSOTf generating cyclic oxonium intermediate, as shown in Scheme 1. Glycosidation of D-glucose (R = α-D-glucosyl in 3) with 2 occurred from β-side of the furanose ring. The stereoselectivity can be explained that one of the methyl group of the acetonide covers the α-side of the cyclic oxonium ion, and glycosyl acceptor 3 is unable to attack from the α-face of the ring.9

The result encouraged us to examine glycosidations of other substrates. The reaction of 2-propanol with a 94:6 ratio of β:α diastereomeric mixtures 2 was conducted in CH2Cl2 at –40 °C in the presence of TMSOTf.10 Isopropyl β-D-psicoside 4a was obtained in 79% yield. The nmr spectrum of the crude product indicated no existence of the α−isomer. Other common Lewis acid promoters such as BF3 etherate or SnCl4 were less reactive and gave poor results. The structure was determined by NOE experiments, and the result is shown in Figure 2. Three NOE relations were observed clearly between one CH3 protons of the isopropyl group and one of C-6 protons, one of C-1 protons and the inside CH3 protons of the acetonide, and C-5 proton and the inside CH3 protons of the acetonide. The relations are clearly supported that psicoside 4a possesses β-glycosidic linkage.

The result of other glycosidation reactions with alcohols and phenol are listed in Table 1. The reaction with D-threitol 2,3-acetonide 3b gave the corresponding psicoside 4b in 91% yield. The reaction of primary alcohol proceeded faster then that of secondary alcohol. The reaction with p-methoxyphenol gave 4c in 83% yield. N-Boc protected serine methyl ester 3d and β-cholestanol 3e reacted with 2 to afford 4d and 4e in 94 and 55% yields, respectively. All the psicosylation reactions gave β-glycoside products exclusively.

Since psicosylation reactions took place quite selectively to give β−D-psicofuranosides with excellent yields, we have examined psicofuranosylation of ceramide. The reaction of O-benzoyl-N- stearoylceramide 511 with 2 occurred well under the same conditions described for 4 to give β-D-psicofuranosylceramide 6 in 75% yield as a single stereoisomer. The compound 6 was converted to 1 in two steps. Mild deprotection of acetonide with p-TsOH in a mixture of MeOH and CH2Cl2 for 3 days gave diol 7 in 72% yield based on the recovery of the starting material. Methanolysis of three benzoates accomplished full deprotections of 7 to give the desired β-D-psicofuranosylceramide 1 in 90% yield.

In conclusion, glycosidation of 3 with 2 took place on the β-side and gave β-D-psicoside 4 in good yield. Psicosylceramide 1 was first synthesized by this method.

EXPERIMENTAL
General. Melting points were taken on a Yanako micromelting apparatus and were uncorrected. 1H NMR and 13C NMR spectra were recorded on JEOL JMN-AL-300 (300 MHz and 75 MHz) or Varian Inova Unity XL-400 (400 MHz and 100 MHz) spectrometers in C6D6, CD3OD, or CDCl3 with tetramethylsilane or CDCl3 as an internal standard. IR spectra were recorded on JASCO FT/IR-410 instrument. Specific rotation was measured on a JASCO DIP-360 instrument. Low and high resolution mass spectra (LRMS and HRMS) were obtained on a JEOL JMS 303HF spectrometer. Column chromatography was carried out using Merck silica gel 60 (230-400 mesh).

General procedure for the glycosylation reaction.
A mixture of 2 (1 mmol) and 3 or 5 (1.2–1.5 mmol) was taken in a 50 mL flask and pre-dried azeotropically by evaporation with dry toluene. The residual oily material was further dried under reduced pressure over the presence of P4O10. Dry CH2Cl2 (20 mL) was added to the flask and in the case of 3a was added at this stage. The mixture was cooled to –40 °C and TMSOTf (1.5 mmol) was added. The reaction was continued during the time indicated at Table 1. To the reaction mixture, aqueous sat. NaHCO3 (10 mL) and CH2Cl2 (20 mL) were added. Organic layer was washed with water and brine and dried over MgSO4. Solvent was removed and residue was purified by flash chromatography on silica gel.
A mixtureof EtOAc in hexane was used as an eluent for the chromatography; 10% for 4a, 15% for 4b, 4c, 4d and 6, and 5% for 4e. Chemical yields are indicated in Table and physical and spectroscopic data are following.

2-Propyl 1,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-psicofuranoside (4a): Viscous liquid. Rf = 0.73 (30% EtOAc in hexane). [α]25D –25.6 (c 1.00, CHCl3). 1H NMR (300 MHz, C6D6) δ: 8.27–8.24 (2H, m), 8.20–8.17 (2H, m), 7.13–6.99 (6H, m), 4.96 (1H, d, J1a,1b = 12.1 Hz, H-1a), 4.77 (1H, d, J1a,1b = 12.1 Hz, H-1b), 4.73 (1H, d, J3,4 = 6.0 Hz, H-3), 4.59 (1H, ddd, J5,6b = 7.3, J5,6a = 6.6, J4,5 = 1.6 Hz, H-5), 4.51 (1H, dd, J3.4 = 6.0, J4,5 = 1.6 Hz, H-4), 4.35 (1H, dd, J6a,6b = 11.2, J5,6a = 6.6 Hz, H-6a), 4.31 (1H, dd, J6a,6b = 11.2, J5,6b = 7.3 Hz, H-6b), 4.05 (1H, qq, J = 6.0, 6.0 Hz, OCH(CH3)2), 1.38 (3H, s, (CH3)2C), 1.12 (3H, d, J = 6.0 Hz, OCH(CH3)2), 1.05 (3H, s, (CH3)2C), 1.05 (3H, d, J = 6.0 Hz, OCH(CH3)2). 13C NMR (75 MHz, CDCl3) δ: 166.2, 165.9, 133.2, 133.0, 130.0, 129.7, 128.4, 113.2, 109.6, 86.3, 84.1, 82.4, 65.7, 65.6, 61.2, 26.6, 25.1, 24.3, 24.1. IR (film) cm-1: 2977, 1725, 1602, 1453, 1381, 1272, 1111, 989, 871, 710, 681. MS (FAB) m/z: 493 (M+Na)+. HR-MS (FAB) m/z: Calcd for C26H30O8Na: 493.1838. Found: 493.1842.

(4-O-Benzyl-2,3-O-isopropylidene-L-threityl)-1,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-psicofuranoside (4b): Syrup. Rf = 0.51 (30% EtOAc in hexane). [α]22D –12.9 (c 1.00, CHCl3). 1H NMR (300 MHz, CDCl3) δ: 8.09–8.05 (4H, m), 7.61–7.53 (2H, m), 7.47–7.40 (4H, m), 7.28–7.23 (5H, m), 4.81 (1H, dd, J3,4 = 5.9, J4,5 = 1.3 Hz, H-4), 4.74 (1H, d, J1a,1b = 12.1 Hz, H-1a), 4.66 (1H, d, J3,4 = 5.9 Hz, H-3), 4.58–4.46 (5H, m, H-1a, 5, 6a, CH2Ph), 4.38 (1H, dd, J6a,6b = 10.4, J5,6b = 6.7 Hz, H-6b), 3.97–3.87 (2H, m), 3.78 (1H, dd, J = 9.5, 6.2 Hz), 3.71 (1H, dd, J = 9.5, 3.7 Hz), 3.54 (1H, dd, J = 10.1, 4.8 Hz), 3.50 (1H, dd, J = 10.1, 4.2 Hz), 1.53 (3H, s), 1.36 (3H, s), 1.34 (3H, s), 1.32 (3H, s). 13C NMR (75 MHz, CDCl3) δ: 165.8, 165.7, 137.7, 133.1, 133.0, 129.7, 129.7, 129.6, 128.3, 128.3, 128.2, 127.6, 127.5, 113.2, 109.8, 109.1, 85.3, 84.5, 82.2, 77.5, 77.0, 73.3, 70.3, 65.0, 63.1, 59.4, 26.8, 26.7, 26.5, 25.1. IR (film) cm-1: 2986, 1729, 1602, 1453, 1373, 1273, 1087, 871, 710. MS (FAB) m/z: 685 (M+Na)+. HR-MS (FAB) m/z: Calcd for C37H42O11Na: 685.2625. Found: 685.2619.

4-Methoxyphenyl 1,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-psicofuranoside (4c): Colorless crystals, mp 150–151 °C (EtOAc:hexane = 1:7). Rf = 0.47 (30% EtOAc in hexane). [α]24D +57.2 (c 1.02, CHCl3). 1H NMR (300 MHz, CDCl3) δ: 8.10–8.03 (4H, m), 7.61–7.55 (2H, m), 7.49–7.43 (4H, m), 7.18–7.12 (2H, m), 6.68–6.62 (2H, m), 5.02 (1H, d, J3,4 = 5.9 Hz, H-3), 4.97 (1H, dd, J3,4 = 5.9, J4,5 = 1.5 Hz, H-4), 4.72 (1H, ddd, J5,6b = 7.5, J5,6a = 6.2, J4,5 = 1.5 Hz, H-5), 4.60 (1H, dd, J6a,6b = 11.4, J5,6a = 6.2 Hz, H-6a), 4.56 (2H, s, H-1), 4.54 (1H, dd, J6a,6b = 11.4, J5,6b = 7.5 Hz, H-6b), 3.68 (3H, s), 1.54 (3H, s), 1.38 (3H, s). 13C NMR (75 MHz, CDCl3) δ: 166.0, 165.4, 155.6, 146.9, 133.1, 132.9, 129.8, 129.6, 129.6, 129.5, 128.3, 128.3, 121.7, 114.2, 113.4, 111.2, 86.0, 85.2, 81.9, 65.0, 60.4, 55.3, 26.5, 25.2. IR (KBr) cm-1: 2990, 1721, 1601, 1507, 1454, 1375, 1270, 1073, 1038, 844, 709. MS (FAB) m/z: 557 (M+Na)+. HR-MS (FAB) m/z: Calcd for C30H30O9Na: 557.1787. Found: 557.1780. Anal. Calcd for C30H30O9: C, 67.41; H, 5.66. Found: C, 67.53; H, 5.64.

O-(1,6-Di-O-benzoyl-3,4-O-isopropylidene-β-D-psicofuranosyl)-N-(tert-butoxycarbonyl)-L-serine methyl ester (4d): Syrup. Rf = 0.16 (20% EtOAc in hexane). [α]23D +3.2 (c 0.99, CHCl3). 1H NMR (300 MHz, CDCl3) δ: 8.09–8.06 (4H, m), 7.62–7.56 (2H, m), 7.50–7.44 (4H, m), 5.36 (1H, d, J = 9.0 Hz, NH), 4.75 (1H, dd, J3,4 = 5.9, J4,5 = 1.4 Hz, H-4), 4.71 (1H, d, J3,4 = 5.9 Hz, H-3), 4.64 (1H, d, J1a,1b = 12.3 Hz, H-1a), 4.55 (1H, ddd, J5,6b = 7.6, J5,6a = 7.3, J4,5 = 1.4 Hz, H-5), 4.49 (1H, d, J1a,1b = 12.3 Hz, H-1b), 4.46 (1H, ddd, J = 9.0, 3.2, 2.7 Hz, N-CH), 4.37 (1H, dd, J6a,6b = 11.2, J5,6a = 7.3 Hz, H-6a), 4.21 (1H, dd, J6a,6b = 11.2, J5,6b = 7.6 Hz, H-6b), 4.05 (1H, dd, J = 9.6, 2.7 Hz, one of CH2CHN), 3.85 (1H, dd, J = 9.6, 3.2 Hz, one of CH2CHN), 3.77 (3H, s, COOCH3), 1.50 (3H, s), 1.32 (3H, s), 1.26 (9H, s, t-Bu). 13C NMR (75 MHz, CDCl3) δ: 170.8, 165.8, 165.5, 155.3, 133.2, 133.1, 129.7, 129.6, 129.4, 128.4, 113.3, 109.5, 85.3, 84.5, 82.2, 79.7, 64.6, 62.3, 59.2, 53.2, 52.6, 28.0, 26.4, 24.9. IR (KBr) cm-1: 3396, 2983, 1703, 1509, 1452, 1271, 1105, 974, 876, 719. MS (FAB) m/z: 652 (M+Na)+. HR-MS (FAB) m/z: Calcd for C32H39NO12Na: 652.2370. Found: 652.2361.

β-Cholestanyl 1,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-psicofuranoside (4e): Oil. Rf = 0.28 (10% EtOAc in hexane). [α]22D +8.1 (c 1.00, CHCl3). 1H NMR (300 MHz, CDCl3) δ: 8.10–8.06 (4H, m), 7.60–7.56 (2H, m), 7.48–7.43 (4H, m), 4.83 (1H, dd, J3,4 = 6.0, J4,5 = 1.3 Hz, H-4), 4.70 (1H, d, J3,4 = 6.0 Hz, H-3), 4.60 (1H, d, J1a,1b = 12.1 Hz, H-1a), 4.54 (1H, d, J1a,1b = 12.1 Hz, H-1b), 4.53 (1H, ddd, J5,6a = 6.8, J5,6b = 6.1, J4,5 = 1.3 Hz, H-5), 4.48 (1H, dd, J6a,6b = 10.2, J5,6a = 6.8 Hz, H-6a), 4.40 (1H, dd, J6a,6b = 10.2, J5,6b = 6.1 Hz, H-6b), 3.81 (1H, tt, J = 10.8, 5.0 Hz, H-3'), 1.94–0.48 (52H, m). 13C NMR (75 MHz, CDCl3) δ: 166.1, 165.9, 133.1, 132.9, 130.0, 129.7, 129.7, 128.3, 128.3, 113.1, 109.6, 86.3, 83.9, 82.4, 72.7, 65.6, 61.5, 56.3, 56.1, 54.2, 44.8, 42.5, 39.9, 39.4, 37.1, 36.6, 36.1, 35.7, 35.3, 35.1, 31.9, 30.1, 28.6, 28.1, 27.9, 26.5, 25.1, 24.1, 23.7, 22.8, 22.5, 21.0, 18.6, 12.1, 12.0. IR (KBr) cm-1: 2935, 1725, 1602, 1451, 1381, 1270, 1088, 871, 710. MS (FAB) m/z: 821 (M+Na)+. HR-MS (FAB) m/z: Calcd for C50H70O8Na: 821.4968. Found: 821.4974.

3-O-Benzoyl-1-O-(1,6-di-O-benzoyl-3,4-O-isopropylidene-β-D-psicofuranosyl)-N-stearoyl-D-erythro-sphingosine (6): Colorless crystals, mp 105–107 °C (EtOAc:hexane, 1:8). Rf = 0.55 (30% EtOAc in hexane). [α]22D –0.5 (c 1.18, CHCl3). 1H NMR (300 MHz, C6D6) δ: 8.27–8.23 (2H, m), 8.19–8.16 (2H, m), 8.05–8.00 (2H, m), 7.12–6.94 (9H, m), 6.34 (1H, d, J = 9.2 Hz, NH), 6.03 (1H, dd, J3',4' = 7.1, J2',3' = 5.9 Hz, H-3'), 5.93 (1H, dt, J4',5' = 15.2, J5',6' = 6.6 Hz, H=5'), 5.67 (1H, dd, J4',5' = 15.2, J3',4' = 7.1 Hz, H-4'), 5.04–4.96 (1H, m, H-2'), 4.89 (1H, d, J1a,1b = 12.1 Hz, H-1a), 4.79 (1H, d, J1a,1b = 12.1 Hz, H-1b), 4.71 (1H, d, J3,4 = 5.9 Hz, H-3), 4.66–4.57 (2H, m, H-6), 4.42 (1H, d, J3,4 = 5.9 Hz, H-4), 4.08 (1H, dd, J5,6a = 15.8, J5,6b = 9.9 Hz, H-5), 3.95–3.86 (2H, m, H-1'), 2.22–2.05 (2H, m), 1.86–1.73 (4H, m), 1.35–1.17 (53H, m), 1.07 (3H, s), 0.92 (6H, t, J = 6.1 Hz). 13C NMR (75 MHz, CDCl3) δ: 173.0, 166.2, 165.6, 165.4, 136.8, 133.2, 132.8, 129.9, 129.7, 129.7, 129.5, 129.5, 129.2, 128.5, 128.3, 128.2, 124.2, 113.4, 109.4, 85.2, 84.9, 81.7, 75.0, 65.3, 60.2, 59.5, 51.2, 36.5, 32.1, 31.9, 29.6, 29.6, 29.5, 29.5, 29.4, 29.3, 29.2, 29.2, 28.7, 26.5, 25.7, 25.1, 22.6, 14.1. IR (KBr) cm-1: 3369, 2920, 2851, 1717, 1655, 1516, 1452, 1269, 1097, 864, 705. MS (FAB) m/z: 1102 (M+Na)+. HR-MS (FAB) m/z: Calcd for C66H97NO11Na: 1102.6959. Found: 1102.6964). Anal. Calcd for C66H97NO11: C, 73.37; H, 9.05; N, 1.30. Found: C, 73.25; H, 8.93; N, 1.35.

3-O-Benzoyl-1-O-(1,6-di-O-benzoyl-β-D-psicofuranosyl)-N-stearoyl-D-erythro-sphingosine (7): A mixture of 6 (58.2 mg, 54 μmol) and p-TsOH·H2O (31 mg, 162 µmol) in a 1:1 mixture of MeOH and CH2Cl2 (1 mL) was stirred at rt for 3 days. Aq. NaHCO3 (2 mL) was added to the mixture and the mixture was extracted with EtOAc (10 mL). The organic extract was washed with water and brine, dried over MgSO4 and evaporated. The residual oil was purified by flash column chromatography on silica gel eluted with 30% EtOAc in hexane to give 7 (29 mg) as a solid in 72% yield based on the 29% recovery of starting material (17 mg). Colorless crystals, mp 93–94 °C (EtOAc:hexane, 1:10). Rf = 0.37 (40% EtOAc in hexane). [α]24D +19.5 (c 0.94, CHCl3). 1H-NMR (400 MHz, CDCl3) δ: 8.04–8.02 (2H, m), 7.99–7.96 (2H, m), 7.90–7.88 (2H, m), 7.61–7.51 (3H, m), 7.44–7.35 (6H, m), 6.56 (1H, d, J = 9.2 Hz), 5.82 (1H, dt, J4’,5’ = 14.9, J5’,6’ = 6.8 Hz, H-5'), 5.57 (1H, dd, J3’,4’ = 7.1, J2’,3’ = 5.5 Hz, H-3'), 5.51 (1H, dd, J4’,5’ = 14.9, J3’,4’ = 7.1 Hz, H-4'), 4.79 (1H, d, J1a,1b = 12.8 Hz, H-1a), 4.70 (1H, dd, J = 11.2, 8.4 Hz), 4.54–4.48 (1H, m, H-2'), 4.45 (1H, d, J = 2.7 Hz, OH), 4.29–4.21 (4H, m), 3.93–3.91 (1H, m), 3.85 (1H, dd, J1a’,1b’ = 9.2, J1a’,2 = 7.2 Hz, H-1’a), 3.79 (1H, dd, J1a’,1b’ = 9.2, J1b’,2 = 3.2 Hz, H-1’b), 2.85 (1H, br s), 2.10–1.96 (4H, m), 1.27–1.17 (50H, m), 1.59–1.50 (2H, m), 0.88–0.85 (6H, m). 13C NMR (75 MHz, CDCl3) δ: 173.4, 167.1, 166.7, 165.5, 136.8, 133.7, 133.2, 133.1, 133.0, 130.1, 129.9, 129.8, 129.8, 129.7, 129.6, 129.0, 128.6, 128.4, 128.4, 128.3, 124.5, 107.7, 81.8, 81.8, 75.1, 74.3, 74.1, 72.8, 71.9, 66.5, 64.7, 60.1, 59.8, 59.2, 51.5, 48.8, 36.6, 32.4, 29.7, 29.6, 29.5, 29.4, 29.3, 29.3, 28.9, 25.8. IR (KBr) cm-1: 3396, 2918, 2850, 1725, 1654, 1262, 1105, 800, 710. MS (FAB) m/z: 1062 (M+Na)+. HR-MS (FAB) m/z: Calcd for C63H93NO11Na: 1062.6646. Found: 1062.6643. Anal. Calcd for C63H93NO11: C, 72.73; H, 9.01; N, 1.35. Found: C, 72.46; H, 9.18; N, 1.60.

1-O-(β-D-Psicofuranosyl)-N-stearoyl-D-erythro-sphingosine (1): To a stirred solution of 7 (29.9 mg, 28.7 μmol) in MeOH (2 mL) was added sodium methoxide (2 mg, 37 μmol) and the mixture was stirred at rt for 12 h. Amberlite IRC-50 (50 mg) was added and the mixture was stirred for 30 min. The resin was removed by filtration and the organic phase was condensed. The residue was chromatographed on silica gel eluted with 5% MeOH in CHCl3 to give 1 (18.9 mg) in 90% yield. Colorless solid, mp 89–91 °C (EtOAc:hexane, 1:4). Rf = 0.33 (10% MeOH in CHCl3). [α]24D –20.5 (c 0.80, CHCl3). 1H-NMR (400 MHz, CD3OD-CDCl3 = 1:1) δ: 5.69 (1H, dt, J4’,5’ = 15.0, J5’,6’ = 7.3 Hz, H-5'), 5.47 (1H, dd, J4’,5’ = 15.0, J3’4’ = 7.5 Hz, H-4'), 4.32–4.27 (1H, m), 4.08–4.04 (1H, m), 4.00–3.61 (8H, m), 3.58 (1H, dd, J = 9.8, 3.6 Hz), 2.20–2.16 (2H, m), 2.05–2.00 (2H, m), 1.62–1.55 (2H, m), 1.37–1.22 (50H, m), 0.89 (6H, t, J = 6.9 Hz). 13C NMR (100 MHz, CD3OD-CDCl3 = 1:1) δ: 174.3, 133.4, 128.9, 107.9, 83.3, 74.3, 71.8, 69.8, 61.3, 59.1, 57.7, 53.1, 35.7, 31.8, 31.3, 31.3, 29.1, 29.1, 29.1, 29.0, 29.0, 29.0, 29.0, 29.0, 28.9, 28.8, 28.7, 28.7, 28.7, 25.4, 22.0, 13.1. IR (KBr) cm-1: 3319, 2917, 2849, 1646, 1533, 1465, 1027, 720. MS (FAB) m/z: 750 (M+Na)+. HR-MS (FAB) m/z: Calcd for C42H81NO8Na: 750.5860. Found: 750.5855. Anal. Calcd for C42H81NO8: C, 69.28; H, 11.21; N, 1.92. Found: C, 68.99; H, 11.27; N, 1.94.

ACKNOWLEDGEMENTS
This work was supported by the 21st COE Program from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.


This paper is dedicated to Professor Emeritus Keiichiro Fukumoto on the occasion of his 75th birthday.

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