room temperature under N2. The solvent was removed in
vacuo, and the residue was partitioned between EtOAc and
H2O. Purification of the dried organic residue by silica gel
column chromatography, using petroleum ether-EtOAc
(3:1), gave abrusogenin methyl ester 2′,3′,4′,6′-tetra-O-
acetylglucopyranoside (4, 52%)9 and abrusogenin methyl
ester 3-O-â-acetate (5, 30%). A solvent effect was observed,
since glucosylation was successful only when CH2Cl2 was
used as solvent. When THF was employed in this manner,
there was no reaction (Table 1). Treatment of 4 with saturated
K2CO3 in MeOH-H2O (10:1) gave deacetylated abrusoside
A methyl ester (6, 95%).10 The â-stereochemistry of the
Table 1. Glycosylation of Abrusogenin Methyl Ester (2)
1
substituent at the C-3 position of 6 was confirmed by H
NMR (J ) 13.5 and 4.6 Hz). The stereochemistry of the
product
saccharide
reagents
conditions
rt, 24 h
(yield, %)
3
3
7
8
9
9
9
9
9
AgOTf, TMU, THF
AgOTf, TMU, CH2Cl2 rt, 15 h
NRa
4 (52)
NR
NR
NR
NR
NR
NR
NR
anomeric proton of the glucopyranosyl group was also
4
1
assigned as â by H NMR (J ) 8.3 Hz).
Ag2CO3, toluene
PPh3, DIAD, THF5
ZnBr2, THF6
rt, 4 h
rt, 15 h
-78 °C then rt, 13 h
-78 °C then rt, 13 h
Acknowledgment. We thank the Montgomery Founda-
tion Inc., Miami, FL, and Dr. Edward J. Kennelly for the
collection of the plant material used in these studies. We
also thank Dr. Y.-G. Shin for the ESMS data and the
Research Resources Center of University of Illinois at
Chicago for assistance of 500 MHz NMR experiments. This
investigation was funded in part by a Senior University
Scholar Award to A.D.K., from the University of Illinois
Foundation.
ZnCl2, THF7
AgOTf, TMU, CH2Cl2 rt, 168 h
AgOTf, TMU, THF
rt, 72 h
rt, 72 h
AgBF4, THF8
a NR: no reaction.
ester (2). Apparently, steric hindrance resulting from the
presence of a carboxylic acid methyl ester (C-29) and a
methyl group at the C-4 position makes the required
glycosylation unexpectedly difficult. Due to this steric
hindrance, glucosylation was found to be only successful in
the present investigation with 1-chloro-2,3,4,6-tetra-O-acetyl-
glucopyranose (3) in the presence of AgOTf and TMU in
CH2Cl2. Other glycosylation methods gave no reaction,
resulting in full recovery of the starting material.
Abrusogenin (1), isolated from A. precatorius leaves, was
methylated with CH2N2 to obtain abrusogenin methyl ester
(2) in order to protect the C-4 carboxylic acid group. Without
the protecting carboxylic acid functionality, glucosylation
occurred exclusively at this carboxylic acid position. 1-Chloro-
2,3,4,6-tetra-O-acetylglucopyranose (3) was prepared by the
reaction of penta-O-acetylglucopyranose (1 g) with AlCl3
(325 mg) in 5 mL of CH2Cl2. After stirring the reaction
mixture overnight at room temperature, the solvent was
removed in vacuo and the residue was partitioned between
CH2Cl2 and H2O. The CH2Cl2 layer was evaporated in vacuo,
and the residue was chromatographed over silica gel using
petroleum ether-EtOAc (3:1) to afford 3 in 67% yield. To
a CH2Cl2 solution (2 mL) of abrusogenin methyl ester (2,
20 mg) were added 150 mg of 3 in 0.5 mL of CH2Cl2 and
TMU (60 mg). AgOTf (100 mg) was slowly added to the
reaction mixture, and the solution was stirred overnight at
OL9905598
(9) Mp 286-288 °C; [R]D +20.5° (c 0.2, CHCl3); UV (MeOH) λmax
(log ꢀ) 234 (3.1), 283 (2.9) nm; IR (film) νmax 3421, 2883, 1653, 1418,
1250, 1066, 790 cm-1; 1H NMR (500 MHz, CDCl3) δ 6.61 (1H, d, J ) 6.2
Hz, H-24), 5.15 (1H, t, J ) 9.6 Hz, H-2′), 5.02 (1H, t, J ) 9.7 Hz, H-3′),
4.94 (1H, dd, J ) 9.8 and 8.0 Hz, H-4′), 4.49 (1H, dd, J ) 11.0 and 2.8
Hz, H-22), 4.47 (1H, d, J ) 7.9 Hz, H-1′), 4.25 (1H, dd, J ) 12.0 and 5.0
Hz, H-6a′), 4.12 (1H, dd, J ) 12.0 and 2.2 Hz, H-5′), 4.06 (1H, dd, J )
12.0 and 4.5 Hz, H-3), 3.70 (3H, s, COOCH3), 2.57 (1H, br t, J ) 15.8 Hz,
H-23), 2.08, 2.05, 2.02, 1.99 (12H, s, OCOCH3), 1.91 (3H, br s, CH3-27),
1.26 (3H, s, CH3-30), 0.99 (3H, d, J ) 6.7 Hz, CH3-21), 0.95 (3H, s, CH3-
18), 0.92 (3H, s, CH3-28), 0.59, 0.38 (2H, d, J ) 4.2 Hz, H-19); 13C NMR
(125 MHz, CDCl3) δ 176.8 (C-29), 170.7, 170.3, 169.5, 169.4 (OCOCH3),
166.7 (C-26), 139.7 (C-24), 128.2 (C-25), 102.0 (C-1′), 85.3 (C-3), 80.2
(C-22), 72.7 (C-5′), 71.5 (C-3′), 71.0 (C-2′), 68.7 (C-4′), 62.1 (C-6′), 54.3
(C-4), 51.7 (COOCH3), 48.8 (C-14), 47.6 (C-8), 47.4 (C-17), 45.2 (C-13),
44.9 (C-5), 40.1 (C-20), 35.4 (C-12), 32.6 (C-15), 31.4 (C-1), 29.7 (C-19),
29.6 (C-2), 28.5 (C-23), 27.9 (C-7), 27.5 (C-11), 26.3 (C-16), 25.3 (C-10),
24.9 (C-6), 22.7 (C-9), 20.8, 20.64, 20.63, 20.61 (OCOCH3), 19.3 (C-28),
17.8 (C-18), 17.2 (C-27), 12.8 (C-21), 9.8 (C-30); ESMS (negative-ion
mode) m/z 828 [M]-, 614, 347.
(10) Mp 176-178 °C; [R]D +3.3° (c 0.3, MeOH); UV λmax (log ꢀ) 231
(3.1), 279 (2.8) nm; IR (film) νmax 3450, 2921, 2851, 2333, 1699, 1323,
1072 cm-1; 1H NMR (500 MHz, C5D5N) δ 6.65 (1H, d, J ) 4.7 Hz, H-24),
4.94 (1H, d, J ) 8.3 Hz, H-1′), 4.59 (1H, m, H-22), 4.57 (1H, dd, J ) 13.5
and 4.6 Hz, H-3), 4.52 (1H, dd, J ) 11.4 and 4.0 Hz, H-6a′), 4.43 (1H, dd,
J ) 12.2 and 5.8 Hz, H-6b′), 4.22 (2H, m, H-3′ and H-4′), 3.95 (2H, m,
H-2′ and H-5′), 3.91 (3H, s, COOCH3), 2.45 (1H, m, H-23), 1.94 (3H, br
s, CH3-27), 1.52 (3H, s, CH3-30), 1.01 (3H, d, J ) 6.6 Hz, CH3-21), 0.93
(3H, s, CH3-18), 0.82 (3H, s, CH3-28), 0.53, 0.26 (2H, d, J ) 3.8 Hz, H-19);
13C NMR (125 MHz, C5D5N) δ 177.4 (C-29), 166.2 (C-26), 140.4 (C-24),
127.8 (C-25), 106.2 (C-1′), 85.6 (C-3), 80.3 (C-22), 78.6 (C-5′), 78.4 (C-
3′), 75.2 (C-2′), 71.6 (C-4′), 62.9 (C-6′), 54.6 (C-4), 51.9 (COOCH3), 49.0
(C-14), 48.1 (C-8), 47.8 (C-17), 45.3 (C-13), 44.9 (C-5), 40.1 (C-20), 35.5
(C-12), 32.9 (C-15), 32.1 (C-1), 30.0 (C-9), 29.7 (C-2), 27.9 (C-23), 27.5
(C-7), 26.4 (C-11), 25.7 (C-16), 25.3 (C-10), 23.0 (C-6), 20.1 (C-9), 19.5
(C-28), 18.0 (C-18), 17.3 (C-27), 13.1 (C-21), 10.7 (C-30); ESMS (negative-
ion mode) m/z 659 [M-1]-, 484, 423, 233, 212.
(6) Danishefsky, S. J.; Gervay, J.; Peterson, J. M.; McDonald, F. E.;
Koseki, K.; Griffith, D. A.; Oriyama, T.; Marsden, S. P. J. Am. Chem. Soc.
1995, 117, 1940.
(7) Berkowitz, D. B.; Danishefsky, S. J.; Schulte, G. K. J. Am. Chem.
Soc. 1992, 114, 4518.
(8) Liu, K. K.-C.; Danishefsky, S. J. J. Org. Chem. 1994, 59, 1895.
224
Org. Lett., Vol. 1, No. 2, 1999