DEVELOPMENT OF SYNTHETIC APPROACHES TO MACROCYCLIC GLYCOTERPENOIDS
1331
J = 13.3 Hz), 2.56 d.d (1H, 16-H, J = 18.6, 3.9 Hz),
3.72 s (3H, OCH3), 4.13 d (1H, 2′-H, J = 9.7 Hz),
5.18–5.33 m (3H, 3′-H, 4′-H, 5′-H), 5.77 d (1H, 1′-H,
J = 8.0 Hz). Mass spectrum: m/z 657.20 [M + Na]+.
Found, %: C 61.89; H 7.90. C33H46O12. Calculated, %:
C 62.45; H 7.30. M 634.71.
The mixture was filtered, the filtrate was evaporated
under reduced pressure, and the residue was subjected
to silica gel chromatography using petroleum ether–
ethyl acetate (1:1) as eluent. Yield 0.11 g (25%),
mp 219–221°C, [α]D20 = –19.4° (c = 1, CH2Cl2).
1H NMR spectrum (500 MHz, CDCl3), δ, ppm: 1.81–
1.87 m (2H, 1′-OCH2CH2), 2.013 s (6H, CH3CO),
2.015 s (6H, CH3CO), 2.049 s (6H, CH3CO), 3.58–
3.64 m (2H, 1′-OCH2), 3.75 s (6H, OCH3), 3.86–
3.92 m (2H,1′-OCH2), 4.04 d (2H, 5′-H, J = 9.5 Hz),
4.52 d (2H, 1′-H, J = 7.6 Hz), 4.96–5.01 m (2H, 2′-H),
5.19–5.27 m (4H, 3′-H, 4′-H). Mass spectrum:
m/z 731.02 [M + Na]+. Found, %: C 49.68; H 6.11.
C29H40O20. Calculated, %: C 49.15; H 5.69. M 708.21.
3,4,5-Trihydroxy-6-(hydrazinecarbonyl)tetrahy-
dro-2H-pyran-2-yl 16-hydrazinylidene-ent-beyeran-
19-oate (15). Hydrazine hydrate, 1 mL (20 mmol), was
added to a solution of 0.3 g (0.47 mmol) of compound
14 in 30 mL of methanol. The mixture was kept for
48 h at 20°C, and the precipitate was filtered off and
washed with methanol. Yield 0.22 g (90%), mp 149–
151°C, [α]D20 = –29.2° (c = 1.1, MeOH). 1H NMR spec-
trum (400 MHz, CD3OD), δ, ppm: 0.83–1.96 m (18H,
ent-beyerane), 0.84 s (3H, C20H3), 1.01 s (3H, C17H3),
1.21 s (3H, C18H3), 2.18 d (1H, 3-Heq, J = 13.8 Hz),
2.77 d.d (1H, 16-H, J = 17.9, 2.7 Hz), 3.31–3.33 m
(1H, 2′-H), 3.41–3.44 m (2H, 3-H, 4′-H), 3.57–3.63 m
(1H, 5′-H), 3.76 d (1H, 1′-H, J = 9.7 Hz), 5.42–5.45 m
(1H, OH). Mass spectrum: m/z 545.20 [M + Na]+.
Found, %: C 60.21; H 8.82; N 10.31. C26H42N4O7.
Calculated, %: C 59.75; H 8.10; N 10.72. M 522.63.
6,6′-[Propane-1,3-diylbis(oxy)]bis(3,4,5-triacet-
oxytetrahydro-2H-pyran-2-carbohydrazide) (12).
Hydrazine hydrate, 0.5 mL (10 mmol), was added to
a solution of 0.22 g (0.31 mmol) of compound 11 in
20 mL of methylene chloride. The mixture was heated
for 2 h under reflux with stirring and kept for 10 h at
20°C, and the precipitate was filtered off and washed
with methanol. Yield 0.11 g (80%), mp 234–237°C,
[α]D20 = –11.4° (c = 0.7, DMSO). IR spectrum, ν, cm–1:
3375, 3273, 3086 (NH2), 1662, 1619, 1553 [C(O)NH].
1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm:
1.70–1.78 m (2H, 1′-OCH2CH2), 2.98 t (2H, 2′-H, J =
8.3 Hz), 3.17 t (2H, 3′-H, J = 8.8 Hz), 3.36 m (2H,
4′-H, J = 9.2 Hz), 3.48–3.56 m (4H, 1′-OCH2, 5′-H),
3.71–3.79 m (2H, 1′-OCH2), 4.16 d (2H, 1′-H, J =
7.9 Hz), 9.03 s and 9.24 s (2H, NH). Mass spectrum:
m/z 478.73 [M + Na]+. Found, %: C 38.98; H 6.34.
C15H28N4O12. Calculated, %: C 39.47; H 6.18.
M 456.40.
Bis{19-[3,4,5-triacetoxy-6-(methoxycarbonyl)-
tetrahydro-2H-pyran-2-yloxy]-19-oxo-ent-beyeran-
16-yl} decanedioate (19). Potassium carbonate, 0.55 g
(4 mmol), and TBAB, 0.4 g (1.26 mmol), were added
to a solution of 0.5 g (1.26 mmol) of bromide 9 and
0.51 g (0.63 mmol) of bis-acid 3 in 50 mL of freshly
distilled methylene chloride, 5 mL of water was then
added, and the mixture was stirred for 1 h at 20°C and
heated for 16 h under reflux. The mixture was cooled,
diluted with chloroform, washed with water, and dried
over anhydrous MgSO4, the solvent was removed
under reduced pressure, and the residue was subjected
to silica gel chromatography using petroleum ether–
ethyl acetate (2:1) as eluent. After drying under re-
duced pressure, the product was a white powder. Yield
0.5 g (56%), mp 114–115°C, [α]D20 = –39.9° (c = 1.1,
3,4,5-Triacetoxy-6-methoxycarbonyltetrahydro-
2H-pyran-2-yl 16-oxo-ent-beyeran-19-oate (14).
Potassium carbonate, 0.21 mg (1.5 mmol), and tetra-
butylammonium bromide (TBAB), 0.06 g (0.2 mmol),
were added to a solution of 0.21 g (0.52 mmol) of
bromide 9 and 0.13 g (0.4 mmol) of isosteviol (1) in
20 mL of methylene chloride, and 2 mL of water was
added under stirring. The mixture was heated for 4 h
under reflux, cooled, diluted with chloroform, washed
with water, and dried over anhydrous MgSO4. The
solvent was removed under reduced pressure, and the
residue was recrystallized from ethanol. Yield 0.21 g
(85%), mp 271–272°C, [α]D20 = –47.4° (c = 1.2,
1
CHCl3). IR spectrum: ν 1759 cm–1 (C=O). H NMR
spectrum (400 MHz, CDCl3), δ, ppm: 0.70–1.90 m
[50H, ent-beyerane, (CH2)6], 0.66 s (6H, C20H3), 0.87 s
(6H, C17H3), 1.16 s (6H, C18H3), 1.96 s (6H, CH3CO),
1.98 s (6H, CH3CO), 1.99 s (6H, CH3CO), 2.11 d (2H,
3-Heq, J = 13.1 Hz), 2.25 t [4H, 16-OC(O)CH2, J =
7.4 Hz], 3.68 s (6H, C7′H3), 4.06–4.14 m (2H, 5′-H),
4.66 d.d (2H, 16-H, J = 10.7, 4.1 Hz), 5.14–5.29 m
(6H, 2′-H, 3′-H, 4′-H), 5.73 d (2H, 1′-H, J = 8.0 Hz).
Mass spectrum: m/z 1461.8 [M + Na]+. Found, %:
C 62.11; H 7.71. C76H110O26. Calculated, %: C 63.40;
H 7.70. M 1438.72.
1
CHCl3). H NMR spectrum (500 MHz, CDCl3), δ,
ppm: 0.86–1.90 m (18H, ent-beyerane), 0.69 s (3H,
C20H3), 0.97 s (3H, C17H3), 1.21 s (3H, C18H3), 2.02 s
(6H, CH3CO), 2.03 s (3H, CH3CO), 2.16 d (1H, 3-Heq,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 9 2015