Synthesis of stachisterone B
Russ.Chem.Bull., Int.Ed., Vol. 52, No. 1, January, 2003
235
m.p. 223—224 °C, [α]D18 +58.5 (c 0.9, CHCl3) (cf. Ref. 6). The
IR and 1H NMR spectra were identical to those described previꢀ
ously.5
according to TLC on Silufol plates, elution with CHCl3—MeOH,
10 : 1) and concentrated to dryness and the solid residue was
chromatographed on a column with 20 g of SiO2 (elution with
CHCl3—MeOH, 10 : 1) to give 0.19 g (83%) of compound 6,
20ꢀHydroxyecdysone 2,3:20,22ꢀdiacetonide, or (20R,22R)ꢀ
14α,25ꢀdihydroxyꢀ2β,3β:20,22ꢀbis(isopropylidenedioxy)ꢀ5βꢀ
cholestꢀ7ꢀenꢀ6ꢀone (3). A suspension of 1 (1 g, 2.08 mmol) and
phosphomolybdic acid (4 mg) in 25 mL of acetone was stirred
for 35 min at ∼25 °C. After homogenization (40 min), the reacꢀ
tion mixture was concentrated to 5 mL, diluted with 15 mL of a
2% solution of NaHCO3, and extracted with AcOEt (3×60 mL).
The extract was concentrated to dryness and the residue was
chromatographed on a column with 50 g of SiO2 (elution with
CHCl3—MeOH, 9 : 1) to give 0.95 g (82%) of compound 3, m.p.
15
m.p. 104—106 °C, [α]D –150.3 (c 1.7, CHCl3). Found (%):
C, 64.54; H, 7.70. C32H45F3O7. Calculated (%): C, 64.20;
H, 7.58. IR (KBr), ν/cm–1: 1635, 1770, 3400. UV, λmax/nm: 293.
1H NMR (CDCl3), δ: 0.82 (s, 3 H, H(18)); 0.88 (s, 3 H, H(19));
1.03 (s, 3 H, H(21)); 1.15 and 1.27 (both s, 6 H, 20,22ꢀMe2C);
1.47 (s, 3 H, H(26)); 1.49 (s, 3 H, H(27)); 1.02—2.72 (m, 17 H,
CH, CH2); 3.57 (m, 1 H, H(22), w1/2 = 15.0); 3.71 (m, 1 H,
H(2), w1/2 = 28.0); 3.96 (m, 1 H, H(3), w1/2 = 11.0); 5.89 (m, 1
H, H(15), w1/2 = 9.0); 6.01 (m, 1 H, H(7), w1/2 = 6.0).
15
234—235 °C, [α]D +39.4 (c 1.1, CHCl3) (cf. Ref. 5). The IR
14,15ꢀAnhydroꢀ20ꢀhydroxyꢀ25ꢀOꢀtrifluoroacetylecdysone
2,3:20,22ꢀdiacetonide, or (20R,22R)ꢀ2β,3β:20,22ꢀbis(isopropylꢀ
idenedioxy)ꢀ25ꢀtrifluoroacetoxyꢀ5βꢀcholestaꢀ7,14ꢀdienꢀ6ꢀone
(7). Trifluoroacetic anhydride (0.22 g, 1.05 mmol) was added
with stirring to a solution of compound 3 (0.2 g, 0.35 mmol) and
Py (2 mL) in 3 mL of CHCl3. The reaction mixture was stirred
for 17 min at ∼25 °C (until the starting compound disappeared
according to TLC on Silufol plates, elution with CHCl3—MeOH,
15 : 1) and concentrated to dryness, and the solid residue was
chromatographed on a column with 40 g of SiO2 (elution with
CHCl3—MeOH, 15 : 1) to give 0.19 g (85%) of compound 7,
1
and H NMR spectra were identical to those described previꢀ
ously.5
20ꢀHydroxyꢀ25ꢀOꢀtrifluoroacetylecdysone 20,22ꢀacetonide,
or 2β,3β,14αꢀtrihydroxyꢀ(20R,22R)ꢀ20,22ꢀisopropylidenedioxyꢀ
25ꢀtrifluoroacetoxyꢀ5βꢀcholestꢀ7ꢀenꢀ6ꢀone (4). Trifluoroacetic
anhydride (0.16 g, 0.76 mmol) was added with stirring to a
solution of compound 2 (0.2 g, 0.38 mmol) and 2 mL of Py in
3 mL of CHCl3. The reaction mixture was stirred for 20 min at
∼25 °C and concentrated, and the residue was chromatographed
on a column with 25 g of SiO2 (elution with CHCl3—MeOH,
7 : 1) to give 0.18 g (77%) of compound 4, m.p. 125—127 °C,
15
m.p. 124—125 °C, [α]D –203.6 (c 1.4, CHCl3). Found (%):
15
[α]D +33.1 (c 2.3, CHCl3). Found (%): C, 62.18; H, 7.85.
C, 65.98; H, 7.53. C35H49F3O7. Calculated (%): C, 65.81;
H, 7.73. IR (KBr), ν/cm–1: 1635, 1770, 3400. UV, λmax/nm: 292.
1H NMR (CDCl3), δ: 0.76 (s, 3 H, H(18)); 0.95 (s, 3 H, H(19));
1.12 (s, 3 H, H(21)); 1.29 (s, 6 H, 2,3ꢀMe2C); 1.38 and 1.46
(both s, 6 H, 20,22ꢀMe2C); 1.54 (s, 3 H, H(26)); 1.56 (s, 3 H,
H(27)); 1.05—2.25 (m, 15 H, CH, CH2); 2.29 (dd, 1 H, H(5),
C32H47F3O8. Calculated (%): C, 62.34; H, 7.63. IR (KBr),
1
ν/cm–1: 1635, 1770, 3400. H NMR (CDCl3), δ: 0.76 (s, 3 H,
H(18)); 0.93 (s, 3 H, H(19)); 1.14 (s, 3 H, H(21)); 1.32
and 1.41 (both s, 6 H, 20,22ꢀMe2C); 1.57 (s, 6 H, H(26),
H(27)); 1.10—2.48 (m, 18 H, CH, CH2); 3.04 (m, 1 H, H(9),
w1/2 = 26.0); 3.61 (m, 1 H, H(22)); 3.88—4.20 (m, 2 H, H(2),
H(3)), 5.78 (m, 1 H, H(7), w1/2 = 4.0).
3
3J = 12.5 Hz, J = 4.5 Hz); 2.81 (m, 1 H, H(9), w1/2 = 24.0);
3.58 (dd, 1 H, H(22), 3J = 9.6 Hz, 3J = 2.2 Hz); 4.15—4.25 (m,
2 H, H(2), H(3)); 5.96 (m, 1 H, H(15), w1/2 = 7.0); 6.06 (d, 1 H,
20ꢀHydroxyꢀ25ꢀOꢀtrifluoroacetylecdysone 2,3:20,22ꢀdiꢀ
acetonide, or (20R,22R)ꢀ14αꢀhydroxyꢀ2β,3β,20,22ꢀbis(isoꢀ
propylidenedioxy)ꢀ25ꢀtrifluoroacetoxyꢀ5βꢀcholestꢀ7ꢀenꢀ6ꢀone
(5). Trifluoroacetic anhydride (0.15 g, 0.7 mmol) was added
with stirring to a solution of compound 3 (0.2 g, 0.35 mmol) and
Py (2 mL) in 3 mL of CHCl3. The reaction mixture was stirred
for 10 min at ∼25 °C (until the starting compound disappeared
according to TLC on Silufol plates, elution with CHCl3—MeOH,
10 : 1). The mixture was concentrated to dryness and the residue
was chromatographed on a column with 40 g of SiO2 (elution
with CHCl3—MeOH, 10 : 1) to give 0.18 g (78%) of compound
4
H(7), J = 2.2 Hz).
Stachisterone B 20,22ꢀacetonide, or 14,15ꢀanhydroꢀ20ꢀ
hydroxyecdysone 20,22ꢀacetonide, or (20R,22R)ꢀ2β,3β,25ꢀtriꢀ
hydroxyꢀ20,22ꢀisopropylidenedioxyꢀ5βꢀcholestaꢀ7,14ꢀdienꢀ6ꢀone
(8). A mixture of compound 6 (0.15 g, 0.25 mmol) in 5 mL of
80% aqueous MeOH and 0.02 g of NaHCO3 was stirred for 36 h
at ∼25 °C and extracted with AcOEt (3×10 mL). The organic
layers were combined, dried with MgSO4, and concentrated.
The solid residue was chromatographed on a column with 30 g
of SiO2 (elution with CHCl3—MeOH, 10 : 1) to give 0.11 g
15
17
5, m.p. 107—109 °C, [α]D +3.2 (c 1.2, MeOH). Found (%):
(87%) of compound 8, m.p. 124—125 °C, [α]D –8.97 (c 0.7,
C, 64.39; H, 7.58. C35H51F3O8. Calculated (%): C, 64.01;
H, 7.83. IR (KBr), ν/cm–1: 1635, 1770, 3400. UV, λmax/nm: 244.
1H NMR (CDCl3), δ: 0.76 (s, 3 H, H(18)); 0.95 (s, 3 H, H(19));
1.12 (s, 3 H, H(21)); 1.29 (s, 6 H, 2,3ꢀMe2C); 1.38 and 1.40
(both s, 6 H, 20,22ꢀMe2C); 1.54 (s, 3 H, H(26)); 1.56 (s, 3 H,
H(27)); 1.05—2.25 (m, 17 H, CH, CH2); 2.29 (dd, 1 H, H(5),
MeOH). Found (%): C, 72.09; H, 9.31. C30H46O6. Calculated
(%): C, 71.68; H, 9.22. UV, λmax/nm: 291. H NMR (CDCl3):
1
0.88 (s, 3 H, H(18)); 0.96 (s, 3 H, H(19)); 1.11 (s, 3 H, H(21));
1.20 and 1.32 (both s, 6 H, 20,22ꢀMe2C); 1.47 and 1.49 (both s,
6 H, H(26), H(27)); 1.03—2.71 (m, 16 H, CH, CH2), 3.20 (m,
1 H, H(9), w1/2 = 28.0); 3.57 (dd, 1 H, H(22), 3J = 9.8 Hz, 3J =
2.0 Hz); 3.70 (m, 1 H, H(2), w1/2 = 23); 3.96 (m, 1 H, H(3),
w1/2 = 11); 5.89 (m, 1 H, H(15), w1/2 = 8); 6.01 (m, 1 H,
H(7), w1/2 = 4).
3
3J = 12.5 Hz, J = 4.5 Hz); 2.81 (m, 1 H, H(9), w1/2 = 24.0);
3.58 (dd, 1 H, H(22), 3J = 9.6 Hz, 3J = 2.2 Hz); 4.15—4.25 (m,
2 H, H(2), H(3)); 5.79 (d, 1 H, H(7), 4J = 2.2 Hz).
14,15ꢀAnhydroꢀ20ꢀhydroxyꢀ25ꢀOꢀtrifluoroacetylecdysone
20,22ꢀacetonide, or (20R,22R)ꢀ2β,3βꢀdihydroxyꢀ20,22ꢀisoꢀ
propylidenedioxyꢀ25ꢀtrifluoroacetoxyꢀ5βꢀcholestaꢀ7,14ꢀdienꢀ6ꢀ
one (6). Trifluoroacetic anhydride (0.24 g, 1.14 mmol) was added
with stirring to a solution of compound 2 (0.2 g, 0.38 mmol) and
Py (2 mL) in 3 mL of CHCl3. The reaction mixture was stirred
for 12 min at ∼25 °C (until the starting compound disappeared
Stachisterone B 2,3:20,22ꢀdiacetonide, or 14,15ꢀanhydroꢀ
20ꢀhydroxyecdysone 2,3:20,22ꢀdiacetonide, or (20R,22R)ꢀ25ꢀ
hydroxyꢀ2β,3β:20,22ꢀbis(isopropylidenedioxy)ꢀ5βꢀcholestaꢀ
7,14ꢀdienꢀ6ꢀone (9). A similar procedure starting from 0.18 g
(0.28 mmol) of compound 7 gave 0.13 g (85%) of compound 9,
24
m.p. 192—194 °C, [α]D –128.6 (c 7.9, CHCl3). Found (%):
C, 72.81; H, 10.05. C33H50O6. Calculated (%): C, 73.03; H, 9.29.