Conversion of Taxinine to Taxinine NN-1
J ournal of Natural Products, 2002, Vol. 65, No. 12 1791
s, 2-OMOM), 3.03 (1H, br d, J ) 2.9 Hz, H-3), 2.74 (1H, ddd,
J ) 15.0, 9.5, 9.0 Hz, H-14â), 2.20 (3H, d, J ) 1.5 Hz, H-18),
2.05 (1H, dd, J ) 9.0, 1.2 Hz, H-1), 1.87 (1H, m, H-6â), 1.83
(1H, m, H-7R), 1.80 (3H, s, 13-OAc), 1.79 (1H, m, H-7â), 1.76
(1H, m, H-6R), 1.65 (3H, s, H-17), 1.47 (3H, s, 9,10-acetonide),
1.42 (3H, s, 9,10-acetonide), 1.38 (1H, br dd, J ) 15.0, 9.0 Hz,
H-14R), 1.20 (3H, s, H-16), 1.12 (3H, s, H-19); 13C NMR (CDCl3,
125 MHz) δ 170.74 (s, 13-OAc), 166.14 (s, C-1′), 145.03 (d, C-3′),
142.69 (s, C-4), 138.16 (s, C-12), 135.18 (s, C-11), 134.62 (s,
q-Ph), 134.45 (d, p-Ph), 129.04 (d, m-Ph), 127.89 (d, o-Ph),
120.00 (t, C-20), 118.90 (d, C-2′), 107.03 (s, 9,10-acetonide),
95.46 (t, 2-OMOM), 82.39 (d, C-9), 79.57 (d, C-5), 77.00 (d, C-2),
74.80 (d, C-10), 71.04 (s, C-13), 56.34 (q, 2-OMOM), 47.45 (d,
C-1), 43.00 (d, C-3), 40.01 (s, C-8), 38.27 (s, C-15), 32.27 (q,
C-16), 28.97 (t, C-14), 27.35 (t, C-6), 27.31 (q, 9,10-acetonide),
26.91 (q, 9,10-acetonide), 26.16 (t, C-7), 25.85 (q, C-17), 20.98
(q, 13-OAc), 18.57 (q, C-19), 16.40(q, C-18); HREIMS m/z
608.3356 (calcd for C36H48O8, 608.3350); anal. C 70.86%, H
7.92%, calcd for C36H48O8, C 71.02%, H 7.95%.
(4.37) nm; IR (CHCl3) vmax 2956, 1738, 1710, 1640, 1376, 1240
1
cm-1; H NMR (CDCl3, 500 MHz) δ 7.77 (1H, d, J ) 16.1 Hz,
H-3′), 7.49 (2H, m, o-Ph), 7.40 (2H, m, m-Ph), 7.40 (1H, m,
p-Ph), 6.69 (1H, d, J ) 16.1 Hz, H-2′), 6.06 (1H, d, J ) 10.7
Hz, H-10), 5.85 (1H, d, J ) 10.7 Hz, H-9), 5.83 (1H, ddd, J )
10.0, 7.0, 1.0 Hz, H-13), 5.77 (1H, br t, J ) 1.7 Hz, H-20a),
5.49 (1H, br t, J ) 1.0 Hz, H-5), 5.41 (1H, br t, J ) 1.7 Hz,
H-20b), 4.66 (1H, d, J ) 6.8 Hz, 2-OMOM), 4.60 (1H, d, J )
6.8 Hz, 2-OMOM), 4.14 (1H, dd, J ) 4.6, 1.5 Hz, H-2), 3.37
(3H, s, 2-OMOM), 3.21 (1H, br d, J ) 4.6 Hz, H-3), 2.72 (1H,
ddd, J ) 15.1, 10.0, 10.0, H-14â), 2.32 (3H, d, J ) 1.0 Hz, H-18),
2.08 (1H, br d, J ) 10.0 Hz, H-1), 2.06 (3H, s, 9-OAc), 2.02
(3H, s, 10-OAc), 1.88 (1H, m, H-6â), 1.85 (1H, m, H-7R), 1.83
(1H, m, H-6R), 1.80 (1H, m, H-7â), 1.80 (3H, s, 13-OAc), 1.69
(3H, s, H-17), 1.50 (1H, dd, J ) 15.1, 7.0 Hz, H-14R), 1.14 (3H,
s, H-16), 1.12 (3H, s, H-19); 13C NMR (CDCl3, 125 MHz) δ
170.75 (s, 13-OAc), 170.25 (s, 10-OAc), 169.83 (s, 9-OAc), 166.21
(s, C-1′), 145.20 (d, C-3′), 142.56 (s, C-4), 137.40 (s, C-12),
134.32 (s, C-11), 134.11 (s, q-Ph), 130.48 (d, p-Ph), 129.04 (d,
m-Ph), 127.99 (d, o-Ph), 120.53 (t, C-20), 118.91 (d, C-2′), 95.83
(t, 2-OMOM), 79.17 (d, C-5), 77.38 (d, C-2), 76.89 (d, C-9), 72.29
(d, C-10), 70.70 (d, C-13), 56.27 (q, 2-OMOM), 47.02 (d, C-1),
44.15 (d, C-3), 43.74 (s, C-8), 37.63 (s, C-15), 31.70 (q, C-16),
28.73 (t, C-14), 27.84 (t, C-6), 27.27 (t, C-7), 26.87 (q, C-17),
21.02 (q, 10-OAc), 20.98 (q, 9-OAc), 20.79 (q, 13-OAc), 18.29
(q, C-19), 15.61 (q, C-18); HREIMS m/z 652.3251 (calcd for
13r-Acetoxy-5r-cin n a m oyloxy-2r-(m eth oxym eth oxy)-
ta xa -4(20),11-d ien e-9r,10â-d iol (14). A mixture of 13 (1.75
g, 2.88 mmol) and an 80% aqueous solution of AcOH (AcOH
44 g, H2O 11 g) was stirred for 8 h at room temperature,
diluted with a saturated aqueous solution of NaCl (100 mL),
and extracted with EtOAc (5 × 50 mL). The combined extracts
were washed with a saturated aqueous solutions of NaHCO3
(2 × 100 mL) and NaCl (2 × 100 mL), dried over Na2SO4,
filtered, and concentrated to give a pale yellow amorphous solid
(1.70 g), which was purified by flash chromatography on silica
gel [68 g, 3.0 cm i.d. column, EtOAc-hexane (2:3)] to give pure
14 (1.42 g, 87%) and recovered 13 (0.22 g, 12%). The yield of
14 based on recovered 13 is 99%. The analytical sample of 14
was obtained as colorless amorphous crystals (CHCl3): mp 95-
C
C
37H48O10, 652.3248); anal. C 67.79%, H 7.36%, calcd for
37H48O10, C 68.08%, H 7.41%.
9r,10â,13r-Tr ia cetoxy-5r-(cin n a m oyloxy)ta xa -4(20),11-
d ien -2r-ol (Ta xin in e NN-1) (1). Compound 15 (1.01 g, 1.55
mmol) was heated with concentrated HCl (1.3 mL, 15.6 mmol)
in i-PrOH (15.5 mL) for 5 h at 45-50 °C, cooled, poured into
a
saturated aqueous solution of NaHCO3 (50 mL), and
97 °C; [R]20 +146.27° (c 0.992, CHCl3); UV (MeOH) λmax (log
extracted with CHCl3 (4 × 30 mL). The combined extracts were
worked up as usual to give a white amorphous solid (0.99 g),
which was purified by flash chromatography on silica gel [50
g, 3.0 cm i.d. column, EtOAc-hexane (3:7)] to give spectro-
scopically pure taxinine NN-1 (1) (0.657 g, 70%) accompanied
by recovered 15 (0.19 g, 18%). The yield of 1 based on recovered
starting material, 15, is 85%. An analytical sample of 1 was
obtained as colorless microcrystals (EtOAc): mp 107-109 °C;
D
ꢀ) 277 (4.65), 217 (4.64), 207 (4.58) nm; IR (CHCl3) νmax 3632,
3572, 2960, 1738, 1710, 1640, 1248 cm-1; 1H NMR (CDCl3, 500
MHz) δ 7.75 (1H, d, J ) 15.9 Hz, H-3′), 7.49 (2H, m, o-Ph),
7.40 (2H, m, m-Ph), 7.40 (1H, m, p-Ph), 6.65 (1H, d, J ) 15.9
Hz, H-2′), 5.85 (1H, ddd, J ) 10.0, 7.0, 1.5 Hz, H-13), 5.81 (1H,
br t, J ) 2.0 Hz, H-20a), 5.47 (1H, br t, J ) 2.0 Hz, H-5), 5.38
(1H, br t, J ) 2.0 Hz, H-20b), 4.80 (1H, dd, J ) 9.5, 2.7 Hz,
H-10), 4.64 (1H, d, J ) 7.1 Hz, 2-OMOM), 4.59 (1H, d, J ) 7.1
Hz, 2-OMOM), 4.12 (1H, dd, J ) 9.5, 3.5 Hz, H-9), 4.08 (1H,
br d, J ) 2.9 Hz, H-2), 3.38 (3H, s, 2-OMOM), 3.16 (1H, m,
H-3), 2.71 (1H, ddd, J ) 15.1, 10.0, 9.0 Hz, H-14â), 2.50 (1H,
d, J ) 3.5 Hz, 9-OH), 2.16 (3H, d, J ) 1.0 Hz, H-18), 2.29 (1H,
d, J ) 2.7 Hz, 10-OH), 2.00 (1H, br d, J ) 9.0 Hz, H-1), 1.90
(1H, m, H-6â), 1.81 (3H, s, 13-OAc), 1.78 (1H, m, H-7â), 1.64
(1H, m, H-7R), 1.61 (3H, s, H-17), 1.51 (1H, dd, J ) 15.1, 7.0
Hz, H-14R), 1.20 (3H, s, H-16), 1.16 (3H, s, H-19); 13C NMR
(CDCl3, 125 MHz) δ 170.91 (s, 13-OAc), 166.23 (s, C-1′), 145.01
(d, C-3′), 143.21 (s, C-4), 137.40 (s, C-12), 134.42 (s, q-Ph),
134.34 (s, C-11), 130.43 (d, p-Ph), 129.02 (d, m-Ph), 127.93 (d,
o-Ph), 120.09 (t, C-20), 119.00 (d, C-2′), 95.41 (t, 2-OMOM),
79.53 (d, C-5), 78.51 (d, C-2), 77.04 (d, C-9), 71.99 (d, C-10),
70.98 (d, C-13), 56.27 (q, 2-OMOM), 47.13 (d, C-1), 44.19 (d,
C-3), 43.57 (s, C-8), 37.97 (s, C-15), 31.96 (q, C-16), 28.87 (t,
C-14), 27.90 (t, C-6), 27.01(t, C-7), 26.00 (q, C-17), 21.05 (q,
13-OAc), 18.80 (q, C-19), 15.79 (q, C-18); HREIMS m/z
568.3042 (calcd for C33H44O8, 568.3037); anal. C 69.39%, H
7.76%, calcd for C33H44O8, C 69.69%, H 7.80%.
[R]20 +81.86° (c 0.954, CHCl3); UV (MeOH) λmax (log ꢀ) 278
D
(4.39), 217 (4.40), 206 (4.34); IR (CHCl3) νmax 3612, 2960, 1740,
1712, 1638, 1236 cm-1; 1H NMR (CDCl3, 500 MHz) δ 7.77 (1H,
d, J ) 16.1 Hz, H-3′), 7.50 (2H, m, o-Ph), 7.40 (2H, m, m-Ph),
7.40 (1H, m, p-Ph), 6.66 (1H, d, J ) 10.8 Hz, H-10), 6.65 (1H,
d, J ) 16.1 Hz, H-2′), 5.88 (1H, d, J ) 10.8 Hz, H-9), 5.84 (1H,
br dd, J ) 9.5, 7.0 Hz, H-13), 5.57 (1H, br s, H-20a), 5.51 (1H,
br s, H-20b), 5.45 (1H, br t, J ) 2.7 Hz, H-5), 4.24 (1H, ddd, J
) 6.9, 6.3, 2.4 Hz, H-2), 3.22 (1H, br d, J ) 6.3 Hz, H-3), 2.66
(1H, ddd, J ) 15.0, 10.7, 9.5 Hz, H-14â), 2.28 (3H, d, J ) 1.0
Hz, H-18), 2.08 (1H, br d, J ) 10.7 Hz, H-1), 2.06 (3H, s,
9-OAc), 2.02 (3H, s, 10-OAc), 1.91 (1H, m, H-6â), 1.82 (1H, m,
H-7R), 1.78 (1H, m, H-6R), 1.77 (3H, s, 13-OAc), 1.76 (1H, m,
H-7â), 1.70 (3H, s, H-17), 1.66 (1H, br d, J ) 6.9 Hz, 2-OH),
1.32 (1H, dd, J ) 15.0, 7.0 Hz, H-14R), 1.14 (3H, s, H-16), 0.95
(3H, s, H-19); 13C NMR (CDCl3, 125 MHz) δ 170.73 (s, 13-OAc),
170.27 (s, 10-OAc), 169.86 (s, 9-OAc), 166.32 (s, C-1′), 145.52
(d, C-3′), 143.53 (s, C-4), 136.58 (s, C-12), 134.27 (s, q-Ph),
133.56 (s, C-11), 130.56 (d, p-Ph), 129.03 (d, m-Ph), 128.03 (d,
o-Ph), 119.43 (t, C-20), 118.69 (d, C-2′), 78.54 (d, C-5), 76.70
(d, C-9), 72.38 (d, C-10), 70.52 (d, C-13), 70.32 (d, C-2), 51.23
(d, C-1), 45.63 (d, C-3), 44.42 (s, C-8), 37.33 (s, C-15), 31.73 (q,
C-16), 29.18 (t, C-6), 28.35 (t, C-14), 27.55 (t, C-7), 26.89 (q,
C-17), 21.02 (q, 10-OAc), 21.01 (q, 9-OAc), 20.83 (q, 13-OAc),
17.92 (q, C-19), 15.32 (q, C-18); HREIMS m/z 608.2983 (calcd
for C35H44O9, 608.2986); anal. C 68.74%, H 7.36%, calcd for
9r,10â,13r-Tr ia ce t oxy-5r-cin n a m oyloxy-2r-(m e t h -
oxym eth oxy)ta xa -4(20),11-d ien e (15). A mixture of 14 (1.15
g, 2.04 mmol), DMAP (0.25 g, 2.04 mmol), and acetic anhydride
(3.8 mL, 40.42 mmol) in Py (20.4 mL) was stirred for 2 h at
room temperature. The reaction was quenched by addition of
2 M HCl (30 mL). Then, the mixture was poured into a
saturated aqueous solution of NH4Cl (50 mL) and extracted
with EtOAc (4 × 50 mL). The combined extracts were worked
up as usual to give white crystals (1.458 g), which were purified
by flash chromatography on silica gel [30 g, 2.5 cm i.d. column,
EtOAc-hexane (3:7)] to give spectroscopically pure 15 (1.32
g, 99%). The analytical sample of 15 was obtained as colorless
C
35H44O9, C 69.05%, H 7.29%.
Ack n ow led gm en t. This work was supported by a grant
in Aid for Scientific Research (B) No. 10555320 from the
ministry of Education, Science, Sports, and Culture of J apan.
We express our thanks to Mr. T. Sato and Mrs. H. Ando of
the Instrumental Analysis Center for Chemistry, Tohoku
University, for the measurement of HREIMS and microanaly-
microcrystals (CHCl3): mp 86-89 °C; [R]20 +95.73° (c 0.985,
D
CHCl3); UV (MeOH) λmax (log ꢀ) 278 (4.42), 217 (4.43), 206