Glycosylation of Triterpene Alcohols and Acids of the Lupane and A-Secolupane Series

Abstract

A series of 3- and 28-glucosides and glucosyl esters of betulinic acid (1a), 28-hydroxy-3,4-secolupa-4(23),20(29)-dien-3-oic acid (22a), dimethyl ester of 28-hydroxy-2,3-secolup-20(29)-en-2,3-dioic acid (43a), their 20(29)-dihydro derivatives (1b, 22b, 43b) and several other triterpenes of the lupane (12a, 12b) and 3,4-secolupane series (18a, 18b, 32a) has been prepared by reaction of tetra-O-acetyl-α-D-glucopyranosyl bromide in acetonitrile in the presence of mercury(II) cyanide and subsequent deacetylation of the obtained tetra-O-acetyl-β-D-glucopyranosyl derivatives. In several cases attempted glucosylation in the presence of silver silicate afforded predominantly the corresponding 1,2-orthoacetates of α-D-glucopyranose.

Advances in the synthesis and pharmacological activity of lupane-type triterpenoid saponins

“…The C-2 neighboring participating acetyl group of the sugar 39 was obviously essential to the stereoselective formation of the natural 1,2-trans glycosidic linkage. At the end of the 1990s, Klinotová et al (1997) from the Charles University of Prague in Czech Republic reported the synthesis of a series of C-3 and C-28 lupane-type glycosides. Using standard conditions of glycosylation, i.e., bromide sugar donor 39, Hg(CN) 2 as promoter in CH 3 CN, and starting from methyl betulinate (44), 3-acetyl betulinic acid (45) or betulinic acid (3), they succeeded in synthesizing C-3 methyl betulinate glucoside (40, 39%, two steps) and C-28 betulinic acid saponin (41 ?…”

Synthesis of lupane saponins from acetylated glycosyl donors by acetonitrile directed glycosylation

“…Similar orthoesters in which the alkoxyl substituent have triterpenoid structures have been previously prepared as unstable compounds from betulin derivatives by reaction with tetra-O-acetyl-glucopyranosyl bromide or by transesterification of sugar orthoesters. [30][31][32][33][34] …”

Antineoplastic Agents. 606. The Betulastatins

“…A similar synthetic approach was followed for the synthesis of peptide 11b , as shown in Scheme . The derivative 28- O -acetylbetulin was employed to prepare oxime 8 , which, upon reduction, gave the 3α/β amine mixture 9a / 9b . Separation of these amine isomers was achieved by silica gel chromatography, and 9b was found to be the major product of the reaction.…”

“…A solution of 3-oxo-28- O -acetylbetulin (0.1 g, 0.21 mmol) and NH 2 OH·HCl (0.06 g, 4 equiv) in anhydrous pyridine (5 mL) was heated at 80 °C for 2 h. The reaction was cooled to rt, diluted with CH 2 Cl 2 (15 mL), washed with 20% HCl (3 × 15 mL) and brine (3 × 15 mL), dried over Na 2 SO 4 , and filtered, and the filtrate was concentrated under reduced pressure. The crude product was separated by chromatography on silica gel and by eluting with 5:1 hexanes–EtOAc gave a colorless foamy solid (90 mg, 87%), which was crystallized from CHCl 3 –MeOH: mp 205 °C; lit .…”

“…A solution of 3-oxo-28- O -acetylbetulin (0.1 g, 0.21 mmol) and NH 2 OH·HCl (0.06 g, 4 equiv) in anhydrous pyridine (5 mL) was heated at 80 °C for 2 h. The reaction was cooled to rt, diluted with CH 2 Cl 2 (15 mL), washed with 20% HCl (3 × 15 mL) and brine (3 × 15 mL), dried over Na 2 SO 4 , and filtered, and the filtrate was concentrated under reduced pressure. The crude product was separated by chromatography on silica gel and by eluting with 5:1 hexanes–EtOAc gave a colorless foamy solid (90 mg, 87%), which was crystallized from CHCl 3 –MeOH: mp 205 °C; lit . mp 203–204 °C; R f 0.4 (9:1 hexanes–EtOAc); 1 H NMR (CDCl 3 , 400 MHz) δ 9.17 (1H, s, OH), 4.66, 4.56 (1H each, s, H-29), 4.22, 3.83 (1H each, d, J = 11 Hz, H-28), 2.96 (1H, dt, J = 14, 4 Hz, H-2 equiv), 2.42 (1H, m, H-19), 2.20 (1H, m), 2.04 (3H, s, OCOCH 3 ), l.66, 1.11, l.03, 1.02, 0.93, 0.90 (3H each, s, CH 3 ); 13 C NMR (CDCl 3 , 100 MHz) δ 171.6, 167.0, 150.1, 109.9, 62.8, 55.5, 49.9, 48.7, 47.7, 46.3, 42.7, 40.9, 40.3, 38.8, 37.5, 37.2, 34.5, 33.8, 29.7, 29.5, 27.2, 27.0, 25.2, 22.9, 21.0, 19.1, 19.0, 17.1, 16.0, 15.8, 14.6; (+)-HRAPCIMS m / z 498.3949 [M + H] + (calcd for C 32 H 51 NO 3 , 498.3947).…”