CI-1027 Glucuronide
1657
2944, 2866, 1754, 1212 cm21; HRMS (APCI) m/e 709.3448 (C36H52O14þ
Hþ requires 709.3435; s ¼ 1.8 ppm).
For (4S, 5R, 6S)-6-[60-(500-benzyloxycarbonyl-500-methyl-hexyloxy)-
20,200-dimethyl-hexanoyloxy]-4,5-diacetoxy-5,6-dihydro-4H-pyran-2-
carboxylic acid methyl ester (10): 7.3 (m, 5H), 6.41 (dd, 1H, J ¼ 1, 2.6 Hz),
6.27 (dd, 1H, J ¼ 1.2, 4.9), 5.2 (m, lH), 5.09 (s, 2H and m, IH), 3.81 (s, 3H),
3.3 (m, 4H), 2.10 (s, 3H), 2.08 (s, 3H), 1.5 (m, 8H), 1.2 (m, 4H), 1.18
(s, 6H), 1.17 (s, 3H), 1.15 (s, 3H); EIMS m/e (% relative intensity) 557
(M2Bn, 18), 301 (100). MF ¼ C34H48O12.
Preparation of (2S, 3S, 4S, 5R, 6S)-6-[600-(50-benzyloxycarbonyl-500-
methyl-hexyloxy)-20,20-dimethyl-hexanoyloxy]-3, 4, 5-trihydroxy-tetra-
hydropyran-2-carbonxylic acid methyl ester (11). A solution of triacetate
9 (2.10 g, 2.97 mmol) in MeOH (14.5 mL) was cooled in an ice bath and
treated with EtNi-Pr2 base (0.9 mL, 1.7 equiv.). The resulting reaction
mixture was stirred for 46 h while the ice bath expired and the reaction
stirred at rt. Dowex resin (50W ꢀ 2-200; 2.2 g) was added and stirred at rt
for 30 min. The mixture was filtered through celite, washed with MeOH
(15 mL), and filtrate concentrated in vacuo to give a brown oil. Purification
via chromatography on SiO2 (108g, 10.5 ꢀ 5.5 cm) gradient elution with 33%
EtOAc/hexanes (400mL), 50% EtOAc/hexanes (400mL), then 50/45/5
EtOAc/hexanes/IPA (500mL) gave 230 mg of bis ester 12 (19%), 165 mg of
recovered triacetate 9 (8%), and 787 mg of the desired triol 11 (46%). For 11, a
1
colorless viscous oil: [a]D20 ¼ 21218 (c ¼ 1, CHCl3); H NMR 7.3 (m, 5H),
5.57 (d, lH, J ¼ 8.1 Hz), 5.10 (s, 2H), 3.99 (d, 1H, J ¼ 9.8 Hz), 3.81 (s, 3H),
3.6 (m, 1H), 3.5 (m, 1H), 3.4 (m, 1H), 3.3 (m, 4H), 3.13 (d, 1H, J ¼ 2.6, OH),
3.09 (d, IH, J ¼ 2.2 Hz, OH), 1.8 (m, 1H), 1.6 (m, 1H), 1.5 (m, 4H), 1.4
(m, 4H), 1.24 (s, 3H), 1.2 (m, 2H), 1.19 (s, 3H), 1.18 (s, 6H); IR (neat) 3456,
2943, 2866, 1753, 1727cm21; HRMS (APCI) m/e 605.2992 (C30H46O11Na
requires 605.2938; s ¼ 23.96ppm). Anal. calcd. for C30H46O11: C, 61.84;
H, 7.96. Found: C, 61.75; H, 7.87.
For 6,60-oxybis[2,2-dimethylhexanoic acid] benzyl methyl ester (12):
1H NMR 7.3 (m, 5H), 5.09 (s, 2H), 3.64 (s, 3H), 3.3 (m, 4H), 1.5 (m, 8H),
1.2 (m, 4H), 1.18 (s, 6H), 1.15 (s, 6H); EIMS m/e (% relative intensity)
407 (Mþ, 100). MF ¼ C24H38O5.
Preparation of (2S, 3S, 4S, 5R, 6S)-6-[600-(500-benzyloxycarbonyl-500-
methyl-hexyloxy)-20,20-dimethyl-hexanoyloxy]-3, 4, 5-trihydroxy-tetra-
hydropyran-2-carboxylic acid (7). A solution of methyl glucuronide 11
(1.1 g, 1.9 mmol) in IPA (5.4 mL) was treated with phosphate buffer
(53 mL, pH ¼ 7, 0.1 M) then CAL-B (599 mg, Altus #13). The resulting
cloudy mixture was stirred for 8.5 h at rt. The reaction mixture was con-
centrated in vacuo to remove the IPA then filtered through celite. The
celite was washed with H2O (5 mL) then EtOAc (50 mL). The phases
were separated and the aqueous phase extracted with EtOAc (2 ꢀ 50 mL).