3.2. Synthesis of the SUU' Subclass Category TAGs (S)-1 and 2
3.2.1. Synthesis of 2,3-O-Isopropylidene-1-O-(p-methoxybenzyl)-sn-glycerol, (R)-7
Sodium hydride (60% mineral oil dispersion, 490mg, 20.43 mmol) was added to a 250 mL flame-dried two-necked round bottom flask with a magnetic stirrer and rinsed three times with dry THF (10 mL portions) under nitrogen atmosphere. After that, a fresh portion of dry THF (15 mL) was added and the solution cooled to 0°C. (R)-Solketal (900mg, 6.81 mmol) was added dropwise to the solution in dry THF, the mixture was then allowed to reach room temperature and stirred for 1.5 h. After that time, the solution was again cooled to 0°C and p-methoxybenzyl chloride (1226mg, 7.83 mmol) was added. Finally, the solution was refluxed at for 22h after which the mixture had a deep orange colour. The reaction was carefully quenched with water and extracted three times with dichloromethane. The combined organic extracts were washed with water and brine, then dried over MgSO4 and concentrated in vacuo. The crude concentrate was then purified by flash column chromatography using ethyl acetate:petroleum ether (2:8) as eluent affording the product (R)-7 as a slightly yellow liquid (1303mg, 76% yield). TLC (Silica, ethyl acetate:petroleum ether, 2:8): Rf = 0.39. [α]20D = -1.24 (c. 2.16, CH2Cl2). IR (NaCl, νmax / cm-1): 2935 (s), 2865 (s), 1613 (m), 1248 (vs), 1037 (s). 1H NMR (400 MHz, CDCl3) δH: 7.26 (d, J=8.8 Hz, 2H, Ph-H), 6.88 (d, J=8.8 Hz, 2H, Ph-H), 4.49 (m, 2H, PhCH2), 4.27 (m, 1H, CH sn-2), 4.04 (dd, J=8.3, 6.4 Hz, 1H, CH2 sn-3), 3.80 (s, 3H, OCH3), 3.72 (dd, J=8.3, 6.3 Hz, 1H, CH2 sn-3), 3.52 (dd, J=9.8, 5.7 Hz, 1H, CH2 sn-1), 3.44 (dd, J=9.8, 5.6 Hz, 1H, CH2 sn-1), 1.42 (s, 3H, C(CH3)2), 1.36 (s, 3H, C(CH3)2) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 159.3, 130.0, 129.4 (2), 113.8 (2), 109.4, 74.7, 73.2, 70.8, 66.9, 55.3, 26.8, 25.4 ppm. HRMS (ESI) m/z: [M + Na]+ calcd for C14H20O4Na 275.1254; found, 275.1255.
3.2.2. Synthesis of 1-O-(p-methoxybenzyl)-sn-glycerol, (S)-8
PMB-solketal (R)-7 (1300mg, 5.15 mmol) in acetonitrile (25 mL) was added to a 50 mL round bottom flask equipped with a magnetic stirrer. Subsequently, elemental iodine (392mg, 1.54 mmol) and water (1 mL) were added to the solution, and it allowed to stir for 22h at room temperature under nitrogen atmosphere. After that time, the solution was quenched with 50 mL Na2S2O3 (20% w/w aqueous solution) and extracted three times with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude concentrate was then purified by flash column chromatography, first using ethyl acetate/petroleum ether (3:7) as eluent, and then gradually increasing the proportion of ethyl acetate until the eluent was pure ethyl acetate. That afforded the product (S)-8, which solidified upon drying under vacuum into a slightly yellow solid. It was then recrystallized in hexane which afforded colourless fine needles (1092mg, 97% yield). TLC (Silica, ethyl acetate:petroleum ether, 30:70): Rf = 0.11. Mp. 43.1-43.6°C. [α]20D = +2.48 (c. 1.73, CH2Cl2). IR (NaCl, νmax / cm-1): 3389 (br), 2935 (s), 2837 (vs), 1612 (m), 1463 (m), 1247 (s), 1033 (vs). 1H NMR (400 MHz, CDCl3) δH: 7.25 (d, J=8.7 Hz, 2H, Ph-H), 6.89 (d, J=8.7 Hz, 2H, Ph-H), 4.49 (s, 2H, PhCH2), 4.88 (m, 1H, CH sn-2), 3.81 (s, 3H, OCH3), 3.71 (dd, J=11.5, 3.8 Hz, 1H, CH2 sn-3), 3.63 (dd, J=11.5, 5.6 Hz, 1H, CH2 sn-3), 3.57 (dd, J=9.6, 3.6 Hz, 1H, CH2 sn-1), 3.52 (dd, J=9.6, 3.5 Hz, 1H, CH2 sn-1), 2.59 (br s, 1H, OH), 2.10 (br s, 1H, OH) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 159.4, 129.8, 129.5 (2), 113.9 (2), 73.4, 71.5, 70. 6, 63.9, 55.3 ppm. HRMS (ESI) m/z: [M + Na]+ calcd for C11H16O4Na 235.0941; found, 235.0943.
3.2.3. Synthesis of 3-Dodecanoyl-1-O-(p-methoxybenzyl)-sn-glycerol, (R)-9a
PMB-protected glycerol (S)-8 (130mg, 0.55 mmol) and vinyl laurate (160mg, 0.71 mmol) dissolved in dichloromethane (3 mL) were added under slow magnetic stirring to a 10 mL round bottom flask. Subsequently, an immobilized Candida antarctica lipase (CAL-B) (28mg, 10% w/w) was added, and the atmosphere replaced with nitrogen gas. The mixture was allowed to stir for 4h while being monitored by TLC. After that time, the reaction was complete, and the lipase was filtered off. The solvent was removed in vacuo, the crude concentrate washed with a 15mg/mL NaHCO3 / methanol (1:1) solution and then extracted twice with hexane. The combined organic extracts were dried over Na2SO4 and concentrated in vacuo. The crude product was then purified by flash column chromatography with 4% boric acid impregnated silica gel using ethyl acetate:hexane (2:8) as eluent affording the product (I)-9a as a colourless liquid (231mg, quantitative yield). TLC (Silica, ethyl acetate:petroleum ether, 20:80): Rf = 0.27. [α]20D = -1.28 (c. 2.50, CH2Cl2). IR (NaCl, νmax / cm-1): 3449 (br), 2925 (s), 2854 (vs), 1736 (vs), 1612 (m), 1466 (m), 1377 (m), 1248 (s), 1037 (m). 1H NMR (400 MHz, CDCl3) δH: 7.25 (d, J=9.0 Hz, 2H, Ph-H), 6.88 (d, J=8.7 Hz, 2H, Ph-H), 4.49 (s, 2H, PhCH2), 4.17 (dd, J=11.5, 4.4 Hz, 1H, CH2 sn-3), 4.12 (dd, J=11.5, 6.0 Hz, 1H, CH2 sn-3), 4.01 (m, 1H, CH sn-2), 3.81 (s, 3H, OCH3), 3.52 (dd, J=9.6, 4.3 Hz, 1H, CH2 sn-1), 3.46 (dd, J=9.6, 6.2 Hz, 1H, CH2 sn-1), 2.49 (br s, 1H, OH), 2.32 (t, J=7.6 Hz, 2H, CH2COO), 1.61 (m, 2H, CH2CH2COO), 1.29-1.24 (m, 16H, CH2), 0.88 (t, J=6.8 Hz, 3H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 174.1, 159.5, 129.9, 129.6 (2), 114.0 (2), 73.3, 70.7, 69.1, 65.5, 55.4, 34.3, 32.1, 29.7, 29.6, 29.45, 29.4 (2), 29.3, 25.1, 22.8, 14.3 ppm. HRMS (ESI) m/z: [M + Na]+ calcd for C23H38O5Na 417.2611; found, 417.2610.
3.2.4-5. Synthesis of (R)-9b and (R)-9c
3.2.6. Synthesis of 3-Dodecanoyl-1-O-(p-methoxybenzyl)-2-[(9Z)-octadec-9-enoyl)]-sn-glycerol, (R)-10a
Monoacylglycerol (R)-9a (200mg, 0.51 mmol) and oleic acid (165mg, 0.58 mmol) in dry dichloromethane (5mL) were added to a flame-dried 10 mL round bottom flask equipped with a magnetic stirrer. Then 4-dimethylaminopyridine (DMAP) (50 mg, 0.41 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) (117mg, 0.61 mmol) were added to the solution and stirred at room temperature, under nitrogen for 20h. After that time, the reaction mixture was passed through a short column packed with silica gel by using ethyl acetate. The solvent was removed in vacuo, and the crude concentrate was then purified by flash column chromatography using ethyl acetate/hexane (1:9) as eluent affording the product (R)-10a as a colourless liquid (188mg, 99% yield). TLC (Silica, ethyl acetate:petroleum ether, 20:80): Rf = 0.60. [α]20D = -6.77 (c. 1.92, CH2Cl2). IR (NaCl, νmax / cm-1): 3003 (m) ,2925 (s), 2854 (s), 1743 (s), 1613 (m), 1464 (m), 1248 (s), 1172 (s), 1038 (m). 1H NMR (400 MHz, CDCl3) δH: 7.23 (d, J=8.8 Hz, 2H, Ph-H), 6.87 (d, J=8.8 Hz, 2H, Ph-H), 5.34 (m, 2H, =CH), 5.23 (m, 1H, CH sn-2), 4.45 (ABq, ΔδAB=0.04, J=11.8, 2H, PhCH2), 4.33 (dd, J=11.9, 3.9 Hz, 1H, CH2 sn-3), 4.17 (dd, J=11.9, 6.5 Hz, 1H, CH2 sn-3), 3.80 (s, 3H, OCH3), 3.55 (dd, J=5.2, 1.3 Hz, 2H, CH2 sn-1), 2.31 (t, J=7.6 Hz, 2H, CH2COO SFA), 2.27 (t, J=7.6 Hz, 2H, CH2COO MUFA), 2.01 (m, 4H, CH2CH=), 1.65-1.56 (m, 4H, CH2CH2COO), 1.36-1.22 (m, 36H, CH2), 0.88 (t, J=6.7 Hz, 6H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 173.6, 173.2, 159.5, 130.2, 129.92, 129.87, 129.5 (2), 114.0 (2), 73.1, 70.2, 68.1, 62.8, 55.4, 34.5, 34.3, 32.1 (2), 29.92, 29.87, 29.8, 29.7, 29.6 (2), 29.49 (2), 29.47 (2), 29.44, 29.36, 29.3 (2), 29.2, 27.4, 27.3, 25.1, 25.0, 22.8, 14.3 (2) ppm. [M + Na]+ calcd for C41H70O6Na 681.5065; found, 681.5050.
3.2.7-10. Synthesis of (R)-10b, (R)-10c, (R)-10d and (R)-10e
3.2.11. Synthesis of 3-Dodecanoyl-2-[(9Z)-octadec-9-enoyl)]-sn-glycerol, (R)-11a
Diacylglycerol (R)-10a (306mg, 0.465 mmol) was added to a 25mL round bottom flask in dichloromethane (6 mL) equipped with a magnetic stirrer. Water (1 mL) was pipetted to the solution, and it was cooled down to 0°C. Subsequently 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (137mg, 0.60 mmol) was added, which turned the solution to a dark green colour. The mixture was stirred under nitrogen for an hour and then the cooling bath was removed. It was allowed to stir for additional three hours at room temperature, during which the colour slowly changed to colourless with a bright red aqueous phase. When all the dark colour had vanished, the reaction was complete as indicated by TLC monitoring. The reaction mixture was extracted three times with dichloromethane and the combined organic layers washed with NaHCO3, water and brine. Then they were dried over MgSO4 and concentrated in vacuo, and the crude concentrate then purified by flash column chromatography with 4% boric acid impregnated silica gel using ethyl acetate:hexane (1:9) as eluent affording the product (R)-11a as a colourless liquid (227mg, 91% yield). TLC (Silica, ethyl acetate:petroleum ether, 20:80): Rf = 0.41. [α]20D = +2.43 (c. 4.24, CH2Cl2). IR (NaCl, νmax / cm-1): 3480 (br), 3004 (m), 2925 (vs), 2854 (vs), 1744 (s), 1466 (m), 1352 (m), 1167 (s). 1H NMR (400 MHz, CDCl3) δH: 5.34 (m, 2H, =CH), 5.08 (p, J=4.9 Hz, 1H, CH sn-2), 4.32 (dd, J = 12.0, 4.6 Hz, 1H, CH2 sn-3), 4.23 (dd, J = 12.0, 5.7 Hz, 1H, CH2 sn-3), 3.72 (br s, 2H, CH2 sn-1), 2.34 (t, J=7.5 Hz, 2H, CH2COO SFA), 2.32 (t, J=7.6 Hz, 2H, CH2COO MUFA), 2.09 (br s, 1H, OH), 2.01 (q, J=6.6 Hz, 4H, CH2CH=), 1.62 (m, 4H, CH2CH2COO), 1.39– 1.22 (m, 36H, CH2), 0.88 (t, J=6.7, 6H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 173.9, 173.5, 130.2, 129.8, 72.3, 62.1, 61.7, 34.4, 34.2, 32.0 (2), 29.9, 29.84, 29.75 (2), 29.7, 29.6, 29.5 (2), 29.4, 29.32, 29.29, 29.25 (2), 29.2, 27.4, 27.3, 25.1, 25.0, 22.8 (2), 14.3 (2) ppm. [M + Na]+ calcd for C33H62O5Na 561.4489; found, 561.4470.
3.2.12-13. Synthesis of 2-[(9Z)-Octadec-9-enoyl)]-3-tetradecanoyl-sn-glycerol, (R)-11b and (R)-11c
3.2.14. Synthesis of 3-Hexadecanoyl-2-[(9Z,12Z)-octadeca-9,12-dienoyl)]-sn-glycerol, (R)-11e
Diacylglycerol (R)-10e (1297mg, 1.82 mmol) was added to a 50mL round bottom flask in dichloromethane (5mL) equipped with a magnetic stirrer. Then water (3mL) was pipetted to the solution. Subsequently 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (412mg, 1.82 mmol) was dissolved in dichloromethane (10mL) and slowly added dropwise to the solution over a 30min period. The mixture was stirred vigorously for additional 1.5h until the characteristic dark colour had vanished. The reaction mixture was extracted three times with dichloromethane and the combined organic layers washed with NaHCO3, water and brine. Then they were dried over Na2SO4 and concentrated in vacuo, and the crude concentrate then purified by flash column chromatography with 4% boric acid impregnated silica gel using ethyl acetate:hexane (1:9) as eluent affording the product (R)-11e as a colourless liquid (390mg, 36% yield) along with unreacted (R)-10e (562mg, 43% recovery). TLC (Silica, ethyl acetate:petroleum ether, 20:80): Rf = 0.40. [α]20D = +2.45 (c. 2.57, CH2Cl2). IR (ATR, νmax / cm-1): 3213 (br), 3009 (m), 2925 (vs), 2853 (vs), 1713 (vs), 1465 (m), 1349 (m), 1162 (s). 1H NMR (400 MHz, CDCl3) δH: 5.36 (m, 4H, =CH), 5.08 (m, 1H, CH sn-2), 4.32 (dd, J=11.9, 4.6 Hz, 1H, CH2 sn-3), 4.23 (dd, J=11.9, 5.6 Hz, 1H, CH2 sn-3), 3.73 (m, 2H, CH2 sn-1), 2.77 (t, J=6.6 Hz, 2H, =CHCH2CH=), 2.32 (t, J=7.7 Hz, 2H, CH2COO PUFA), 2.31 (t, J=7.6 Hz, 4H, CH2COO SFA), 2.05 (q, J=6.8 Hz, 4H, CH2CH=), 1.65–1.58 (m, 4H, CH2CH2COO), 1.33–1.25 (m, 38H, CH2), 0.89 (t, J=6.9, 3H, CH2CH3PUFA), 0.88 (t, J=7.0, 6H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 173.9, 173.5, 130.4, 130.1, 128.2, 128.0, 72.3, 62.1, 61.7, 34.4, 34.3, 32.1, 31.7, 29.9 (3), 29.81 (2), 29.76, 29.6, 29.51, 29.50, 29.4, 29.33, 29.27 (2), 29.2, 27.4 (2), 25.8 (2), 25.1, 25.0, 22.8, 22.7, 14.3, 14.2 ppm. [M + Na]+ calcd for C37H68O5Na 615.4964; found, 615.5067.
3.2.15. Synthesis of 3-Dodecanoyl-1-[(9Z,12Z)-octadeca-9,12-dienoyl)]-2-[(9Z)-octadec-9-enoyl)]-sn-glycerol, (S)-1
Diacylglycerol (R)-11a (72mg, 0.13 mmol) and linoleic acid (43mg, 0.15 mmol) in dry dichloromethane (3 mL) were added to a 10 mL flame-dried round bottom flask equipped with a magnetic stirrer. Then 4-dimethylaminopyridine (DMAP) (13mg, 0.11 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) (31mg, 0.16 mmol) were added to the solution and stirred at room temperature, under nitrogen for 20 h. After that time, the reaction mixture was passed through a short column packed with silica gel by using ethyl acetate. The solvent was removed in vacuo, and the crude concentrate then purified by flash column chromatography using ethyl acetate:hexane (1:19) as eluent affording the product (S)-1 as a colourless liquid (91mg, 85% yield). TLC (Silica, ethyl acetate:petroleum ether, 20:80): Rf = 0.75. [α]20D = +0.03 (c. 2.96, CH2Cl2). IR (NaCl, νmax / cm-1): 3008 (s), 2926 (vs), 2855 (s), 1747 (s), 1464 (m), 1378 (m), 1161 (s). 1H NMR (400 MHz, CDCl3) δH: 5.35 (m, 6H, =CH), 5.26 (m, 1H, CH sn-2), 4.29 (dd, J=11.9, 4.3 Hz, 2H, CH2 sn-1/sn-3), 4.14 (dd, J=11.9, 6.0 Hz, 2H, CH2 sn-1/sn-3), 2.77 (t, J=6.6 Hz, 2H, =CHCH2CH=), 2.32 (t, J=7.5 Hz, 2H, CH2COO), 2.31 (t, J=7.6 Hz, 4H, CH2COO), 2.04 (q, J=6.8 Hz, 4H, CH2CH= MUFA), 2.01 (q, J=6.6 Hz, 4H, CH2CH= PUFA), 1.65-1.57 (m, 6H, CH2CH2COO), 1.38–1.21 (m, 50H, CH2), 0.89 (t, J=6.9, 3H, CH2CH3PUFA), 0.88 (t, J=6.7, 6H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 173.43, 173.38, 173.0, 130.4, 130.17, 130.15, 129.8, 128.2, 128.0, 69.0, 62.2 (2), 34.3, 34.20, 34.17, 32.1 (2), 31.7, 29.91, 29.87, 29.8 (3), 29.7, 29.6, 29.49 (2), 29.47 (2), 29.41, 29.35, 29.32, 29.28, 29.27 (2), 29.23, 29.20, 27.4, 27.34 (2), 27.32, 25.8, 25.03, 25.01, 24.98, 22.8 (2), 22.7, 14.3 (2), 14.2 ppm. [M + Na]+ calcd for C51H92O6Na 823.6786; found, 823.6766.
3.2.16-22. Synthesis of (S)-2, (R)-12a, (R)-12b, (R)-12c, (R)-12d, (R)-12e and (R)-12f
3.3. Synthesis of the USU' Subclass Category TAGs (S)-5 and 6
3.3.1. Synthesis of Oleic Acid Acetoxime Ester, 13
Oleic acid (500mg, 1.77 mmol) was added to a 100 mL flame-dried two-necked round bottom flask equipped with a magnetic stirrer in dry dichloromethane (8mL). Acetone oxime (130mg, 1.77 mmol), DMAP (43mg, 0.35 mmol) and EDCI (407mg, 2.12 mmol) were added to the solution and it stirred at room temperature, under nitrogen for 20h. After that time, the reaction mixture was flushed through a short column packed with silica gel with ethyl acetate. The solvent was removed in vacuo, and the crude concentrate then purified by flash column chromatography using ethyl acetate:hexane (1:9) as eluent affording the product 13 as a colourless liquid (596mg, quantitative yields). TLC (Silica, ethyl acetate:petroleum ether, 30:70): Rf = 0.59. IR (NaCl, νmax / cm-1): 2925 (s), 2854 (vs), 1765 (vs), 1654 (w), 1460 (m), 1377 (m), 1271 (m), 1136(s). 1H NMR (400 MHz, CDCl3) δH: 5.34 (m, 2H, =CH), 2.40 (t, J=7.6 Hz, 2H, CH2COO), 2.05 (s, 3H, (CH3)2C=N), 2.01 (m, 4H, CH2CH=), 1.99 (s, 3H, (CH3)2C=N), 1.69 (p, J=7.5 Hz, 2H, CH2CH2COO), 1.38-1.23 (m, 20H, CH2), 0.87 (t, J=6.7 Hz, 3H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 171.4, 163.8, 130.2, 129.9, 33.2, 32.0, 29.9, 29.8, 29.7, 29.5 (2), 29.3, 29.2 (2), 27.4, 27.3, 25.1, 22.8, 22.2, 17.1, 14.3 ppm. [M + Na]+ calcd for C21H39O2NNa 360.2873; found, 360.2879.
3.3.2. Synthesis of 1-O-(p-Methoxybenzyl)-3-[(9Z)-octadec-9-enoyl)]-sn-glycerol, (R)-14
PMB-protected glycerol (S)-8 (300mg, 1.41 mmol) and oleic acid acetoxime ester 13 (573mg, 1.70 mmol) were added to a flame dried 5mL round bottom flask. Subsequently, immobilized Candida antarctica lipase B (CAL-B) (70mg, 8% w/w) was added, the flask connected to a vacuum pump system (10-2 mmHg) and the resulting mixture stirred at room temperature for 6h. After that time, the vacuum was disconnected and additional CAL-B (10mg) along with dried dichloromethane (1.5mL) were added to the flask. The mixture was allowed to stir under nitrogen atmosphere overnight. Then the reaction was complete, and the lipase was filtered off. The solvent was removed in vacuo, and the crude concentrate then purified by flash column chromatography with 4% boric acid impregnated silica gel using ethyl acetate:hexane (2:8) as eluent affording the product (R)-14 as a colourless liquid (585mg, 87% yield). TLC (Silica, ethyl acetate:petroleum ether, 30:70): Rf = 0.50. [α]20D = -0.72 (c. 1.67, CH2Cl2). IR (NaCl, νmax / cm-1): 3449 (br), 2925 (s), 2854 (vs), 1739 (vs), 1612 (m), 1463 (m), 1377 (m), 1248 (s). 1H NMR (400 MHz, CDCl3) δH: 7.25 (d, J=9.1 Hz, 2H, Ph-H), 6.88 (d, J=8.8 Hz, 2H, Ph-H), 5.34 (m, 2H, =CH), 4.49 (s, 2H, PhCH2), 4.17 (dd, J=11.5, 4.5 Hz, 1H, CH2 sn-3), 4.12 (dd, J=11.5, 6.1 Hz, 1H, CH2 sn-3), 4.01 (m, 1H, CH sn-2), 3.81 (s, 3H, OCH3), 3.52 (dd, J=9.6, 4.3 Hz, 1H, CH2 sn-1), 3.46 (dd, J=9.6, 6.1 Hz, 1H, CH2 sn-1), 2.48 (d, J=4.9 Hz, 1H, OH), 2.32 (t, J=7.6 Hz, 2H, CH2COO), 2.00 (m, 4H, CH2CH=), 1.61 (m, 2H, CH2CH2COO), 1.38-1.23 (m, 20H, CH2), 0.88 (t, J=6.7 Hz, 3H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 174.1, 159.5, 130.2, 129.89, 129.87, 129.6 (2), 114.0 (2), 73.3, 70.7, 69.1, 65.5, 55.4, 34.3, 32.0, 29.9, 29.8, 29.7, 29.5 (2), 29.31, 29.25 (2), 27.4, 27.3, 25.0, 22.8, 14.3 ppm. [M + Na]+ calcd for C29H48O5Na 499.3394; found, 499.3353.
3.3.3-8. Synthesis of (R)-15a, (R)-15b, (R)-16a, (R)-16b, (S)-5 and (S)-6
3.4. Synthesis of the SUU' Subclass Category TAGs (S)-3 and 4
3.4.1. Synthesis of 3-Dodecanoyl-sn-glycerol, (R)-17
Acylglycerol (R)-9a (200mg, 0.51 mmol) dissolved in dichloromethane (3mL) was added to a 10mL round bottom flask equipped with a magnetic stirrer. Water (1mL) was pipetted to the solution, which was cooled down to 0°C. Subsequently DDQ (115mg, 0.51 mmol) was added, which turned the solution to a dark green colour. The cooling bath was removed after 30min. The solution was stirred under nitrogen atmosphere overnight with the magnetic stirrer on a full speed. After that time the reaction mixture was extracted three times with dichloromethane and the combined organic layers washed with water, aqueous NaHCO3 and brine. Then they were dried over Na2SO4, concentrated in vacuo, and the crude concentrate then purified by flash column chromatography with 4% boric acid impregnated silica gel using a gradient solvent system from ethyl acetate:hexane (1:9) to ethyl acetate:hexane (1:1) as eluent affording the product (R)-17 as a white waxy solid (139mg, 72% yield). TLC (Silica, ethyl acetate:petroleum ether, 50:50): Rf = 0.18. Mp. 53.8-54.3°C. [α]20D = -1.62 (c. 1.11, CH2Cl2). IR (ATR, νmax / cm-1): 3300 (br), 2956 (m), 2918 (vs), 2849 (vs), 1733 (s), 1463 (m), 1175 (s). 1H NMR (400 MHz, CDCl3) δH: δ 4.21 (dd, J=11.8, 4.6 Hz, 1H, CH2 sn-3), 4.15 (dd, J=11.6, 6.1 Hz, 1H, CH2 sn-3), 3.93 (m, 1H, CH sn-2), 3.70 (ddd, J=10.4, 6.4, 4.1 Hz, 1H, CH2 sn-1), 3.60 (dd, J=11.4, 5.6 Hz, 1H, CH2 sn-1), 2.51 (d, J=5.1 Hz, 1H, CHOH), 2.35 (t, J=6.1, 2H, CH2COO), 2.07 (t, J=6.1 Hz, 1H, CH2OH),1.64 (p, J=7.6 Hz, 2H, CH2CH2COO), 1.32–1.22 (m, 16H, CH2), 0.88 (t, J=6.9, 3H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 174.5, 70.4, 65.3, 63.5, 34.3, 32.1, 29.7 (2), 29.6, 29.5, 29.4, 29.3, 25.1, 22.8, 14.3 ppm. [M + Na]+ calcd for C15H30O4Na 297.2036; found, 297.2023.
3.4.2. Synthesis of [2-(p-Methoxyphenyl)-1,3-dioxolan-4-yl]methyl dodecanoate, (R)-18
Acylglycerol (R)-9a (100mg, 0.25 mmol) was added to a 10mL round bottom flask in dichloromethane (3mL) equipped with a magnetic stirrer. Water (0.5mL) was pipetted to the solution, and it was cooled down to 0°C. Subsequently DDQ (75mg, 0.33 mmol) was added, which turned the solution to a dark green colour. The mixture was stirred under nitrogen for 30 min and then the cooling bath was removed. It was allowed to stir for additional five hours at room temperature, during which the colour slowly changed to bright red. When the dark colour had vanished, the reaction was finished, and it was extracted three times with dichloromethane. The combined organic layers were washed with aqueous NaHCO3, water and brine. Then they were dried over Na2SO4, concentrated in vacuo, and the crude concentrate then purified by flash column chromatography with 4% boric acid impregnated silica gel using ethyl acetate:petroleum ether (1:9) as eluent affording the product (R)-18 as a colourless liquid (38mg, 54% yield). TLC (Silica, ethyl acetate:petroleum ether, 50:50): Rf = 0.71. [α]20D = +5.63 (c. 1.92, CH2Cl2). IR (ATR, νmax / cm-1): 2923 (s), 2853 (s), 1737 (s), 1614 (w), 1464 (m), 1248 (vs), 1160 (s), 1032 (s). 1H NMR (400 MHz, CDCl3) δH: 7.40 (dd, J=8.7, 6.2 Hz, 2H, Ph-H), 6.90 (d, J=7.8 Hz, 2H, Ph-H), 5.89 (s, 0.45H, OCH-Ph), 5.78 (s, 0.55H, OCH-Ph), 4.48 (m, 0.45H, CH sn-2), 4.43 (m, 0.55H, CH sn-2), 4.28 (dd, J=6.8, 1.8 Hz, 0.5H, CH2 sn-1), 4.23 (m, 2H, CH2 sn-3), 4.10 (dd, J=8.5, 7.1 Hz, 0.5H, CH2 sn-1), 3.95 (dd, J=8.4, 5.1 Hz, 0.5H, CH2 sn-1), 3.81 (s, 3H, OCH3), 3.77 (dd, J=8.5, 6.8 Hz, 0.5H, CH2 sn-1), 2.35 (m, 2H, CH2COO), 1.63 (p, J=7.2 Hz, 2H, CH2CH2COO), 1.33-1.24 (m, 16H, CH2), 0.88 (t, J=6.9 Hz, 3H, CH2CH3) ppm. 13C{H} NMR (101 MHz, CDCl3) δC: 173.82, 173.79, 160.8, 160.6, 129.7, 129.2, 128.3 (2), 128.1 (2), 113.93 (2), 113.91 (2), 104.8, 100.0, 74.2, 74.0, 67.6, 67.4, 64.6, 64.2, 55. 5 (2), 34.3 (2), 32.1 (2), 29.7 (4), 29.6 (2), 29.5 (2), 29.4 (2), 29.3 (2), 25.1 (2), 22.8 (2), 14.3 (2) ppm. [M + Na]+ calcd for C23H36O5Na 415.2455; found, 415.2445.
3.4.3. Conversion of Acetal (R)-18 into (R)-17
Acetal (R)-18 (32mg, 0.08 mmol) in acetonitrile (1mL) was added to a 10 mL round bottom flask equipped with a magnetic stirrer. Subsequently, elemental iodine (6mg, 0.02 mmol) and water (20μL) were added to the solution, and it allowed to stir for 22h at room temperature under nitrogen atmosphere. After that time, the solution was quenched with Na2S2O3 (20% w/w aqueous solution) and extracted three times with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude concentrate was then purified by flash column chromatography with 4% boric acid impregnated silica gel using gradient solvent system from ethyl acetate:hexane (1:9) to ethyl acetate:hexane (1:1) as eluent. That afforded the product (R)-17 as a slightly yellow solid (20mg, 91% yield).
3.4.4-11. Synthesis of (R)-8, (S)-14, (S)-19, (S)-20a, (S)-20b, (S)-3 and (S)-4