A novel method for stereoselective glucuronidation

Abstract

Keto Ester 6 from 11. Basic alumina (500 mg) was added to a stirred solution of 11 (84.1 mg) in CH2C12 (15 mL). After 3 h of heating at reflux the mixture was filtered and the solvent evaporated. The residue (80.5 mg, 96.5%) was shown to be pure 6 by TLC analysis.Methyl 63-Hydroxygrindelate (7b). To a solution of 6 (163 mg, 0.47 mmol) in dry E^O (20 mL) was added an ethereal solution of Zn(BH4)2. The mixture was stirred for 4 days at room temperature and under N2. After the addition of a HOAc (2 mL)-Et20 (10 mL) solution and H20 under ice cooling, the mixture was extracted with EtgO. The combined organic extracts were washed with saturated aqueous NaHC03 and brine, dried (NagSOj), and concentrated. Chromatography of the residue (151 mg) over silica gel (10 g) with hexane and with mixtures of hexane and increasing amounts of EtOAc resulted in the recovery of starting material 6 (30.6 mg) and the isolation of 7b (49 mg) and traces of 7a (TLC). The oily hydroxy ester 7b: (a)D -136.7 (c 0.7 CHClg);

Synthesis of Methyl 1-O-(4-Hydroxymethamphetaminyl)-.ALPHA.-D-glucopyranouronate

“…By applying the reported procedure, 5) a-glucuronate 15 and b-glucuronate 16 were independently treated with tributyltin methoxide (Bu 3 SnOMe) to provide the triacetyl-a-glucuronate 17 (60%), and (17) (99%), respectively. By applying the reported procedure, 6) the reaction of 17 with K 2 CO 3 in the presence of molecular sieves (MS, 3 Å), followed by treatment with trichloroacetonitrile (CCl 3 CN), provided the desired a-imidate 18 in 75%.…”

“…The NMR data of 18 were identical with those of the reported 18. 6) Coupling Reaction between (؎)-13 and 18 A mixture of 13 (0.1214 g, 0.48 mmol), 18 (0.45 g, 0.94 mmol) and MS 3 Å (0.2 g) was dried under reduced pressure, and CH 2 Cl 2 (10 ml) was added to the above mentioned mixture. The whole mixture was stirred for 10 min at room temperature under an argon atmosphere.…”

Crystal Polymorphism of Methyl 2,3,4-tri-O-acetyl-1-O-(trichloroacetimidoyl)-α-d-glucopyranouronate

“…All solvents were either of HPLC grade or distilled prior to use. Synthesis of the target glycoside donor was as follows [6,9]: …”

“…The synthetic utility of trichloroacetimidates [5] as glycoside donors has long been realized and has resulted in increased application in both glycoside formation [5] and glucuronidation [6][7][8]. The mild conditions required and the high selectivity for β-glycoside formation make trichloroacetimidates highly attractive choices as the main intermediates for many syntheses.…”

“…Hence, specific trichloroacetimidates, such as 2,3,4,6-tetra-O-benzyl-1-Otrichloroacetimidoyl-α-D-glucopyranose [10] and methyl 2,3,4-tri-O-acetyl-1-O (trichloroacetimidoyl)-α-D-glucopyranouronate 1 [6], are stable but reactive compounds.…”