2440
H.-X. Jiang et al. / Tetrahedron: Asymmetry 18 (2007) 2437–2441
on a Bruker AMX-300. The chemical shifts are expressed
in ppm and coupling constants are given in Hz. Microana-
lyses were carried out on a Heraeus Rapid-CHNO instru-
4.3. (ꢀ)-Gossypol and (+)-gossypol
Acetic acid (0.9 ml) and a drop of hydrochloric acid (37%)
were added in portions to a solution of (Rg,S)-4 (92 mg,
0.1 mmol) in ether (6 ml). The mixture was heated at reflux
for 1–1.5 h, with the progress of the reaction being moni-
tored by TLC. After a while, a new white precipitate began
to appear. The solid was washed with ether, dried, and
established as L-tryptophan methyl ester hydrochloride
(33 mg, 65%) to recycle. The ether mother liquor was trea-
ted with water, until the water phase showed neutrality
(pH ꢂ 7), and dried over anhydrous Na2SO4, filtered, the
filtrate was concentrated to dryness under reduced pres-
sure, and the residue was recrystallized carefully from
Et2O/PE (30–60 °C) to give 46 mg of a light yellow pow-
ment. Chiral HPLC analysis was performed on
a
Chiralpak AD-H analytical column using i-PrOH–hex-
ane–TFA = 30:70:0.1 as an eluent (0.9 ml/min), detected
at 254 nm. The amino acid ester hydrochlorides were pur-
chased from GL Biochem (Shanghai) Ltd. Racemic gossy-
pol was extracted following our own procedure.15
4.2. L-Trp-OMe-(ꢀ)-gossypol (Rg,S)-4 and L-Trp-OMe-
(+)-gossypol (Sg,S)-4
A solution of L-tryptophan methyl ester hydrochloride
(21.45 g, 0.084 mol) and NaOH (3.35 g, 0.084 mol) in
methanol was stirred at room temperature and the racemic
gossypol (21.74 g, 0.042 mol) was added. The mixture was
then allowed to warm to 50–54 °C. The progress of the
reaction was monitored by TLC. After 1.5–2 h, the reac-
tion slurry was brought to room temperature and the yel-
low precipitate was filtered. This was then washed with
methanol, and dried under reduced pressure to offer
20.5 g of L-Trp-OMe-(ꢀ)-gossypol ((Rg,S)-4) (95% de
dered (ꢀ)-gossypol. The yield is 88.5%, 94.7% ee by HPLC
24:7
analysis [tR 6.17 (major), tS 23.8 (minor)]. ½aꢁD ¼ ꢀ344:98
15
(c 0.1, CH3OH) {lit.14j ½aꢁD ¼ ꢀ354:2 (c 0.12, CHCl3);
23
½aꢁD ¼ ꢀ377 (c 0.116, CHCl3)}. 1H NMR (300 MHz,
CDCl3): d (ppm) 11.13 (s, 2H, CHO), 7.78 (s, 2H, Ar-H),
6.43 (s, 2H, –OH), 5.87 (s, 2H, –OH), 3.89 (m, 2H,
CH(CH3)2), 2.15 (s, 6H, Ar-CH3), 1.55 (d, J = 6.9 Hz,
12H, CH(CH3)2).
determined by 1H NMR), the yield is 100%.
(+)-Gossypol was obtained by the same method from L-
Trp-OMe-(+)-gossypol (Sg,S)-4 in 86.5% yield; 95.7% ee
by HPLC analysis [tR 6.14 (minor), tS 24.2 (major)].
19:7
½aꢁD ¼ ꢀ1091 (c 0.255, CHCl3). 1H NMR (300 MHz,
CDCl3): d (ppm) 13.51 (br t, J = 9.3 Hz, –NH), 9.09 (d,
J = 12 Hz, 2H), 7.98 (br s, indole NH), 7.90 (br s, –OH),
7.56 (d, J = 7.8 Hz, 2H), 7.51 (s, 2H), 6.99 (t, J = 7.2 Hz,
2H), 6.91 (br s, 2H), 6.74–6.82 (m, 4H), 4.71 (s, –OH),
4.47 (m, 2H), 3.82 (s, 6H), 3.68–3.78 (m, 2H), 3.59 (dd,
J = 14.4, 3.6 Hz, 2H), 3.23 (dd, J = 14.4, 9.6 Hz, 2H),
2.00 (s, 6H), 1.53 (d, J = 6.9 Hz, 6H), 1.52 (d, J = 6.9 Hz,
6H). 13C NMR (75 MHz, CDCl3): d (ppm) 173.4, 170.7,
161.6, 148.4, 147.0, 136.3, 131.9, 128.9, 127.8, 126.5,
124.4, 122.0, 119.7, 118.1, 115.5, 114.2, 111.1, 108.8,
103.3, 62.2, 53.1, 30.7, 27.4, 20.3, 20.2, 19.9. Anal. Calcd
for C54H54O10N4Æ1/2CH3OH: C, 70.01; H, 6.04; N, 5.99.
Found: C, 70.02; H, 5.91; N, 5.85.
26
30
½aꢁD ¼ þ364:9 (c 0.22, CH3OH) {lit.14j ½aꢁD ¼ þ357 (c
15
1
0.10, CHCl3); ½aꢁD ¼ þ375:6 (c 0.115, CHCl3)}. H NMR
(300 MHz, CDCl3): d (ppm) 11.13 (s, 2H, CHO), 7.78 (s,
2H, Ar-H), 6.43 (s, 2H, –OH), 5.87 (s, 2H, –OH), 3.89
(m, 2H, CH(CH3)2), 2.15 (s, 6H, Ar-CH3), 1.55 (d,
J = 6.9 Hz, 12H, CH(CH3)2). And L-tryptophan methyl es-
ter hydrochloride (40 mg, 78%) was recycled.
Acknowledgement
We thank the Shanghai Municipal Committee of Science
and Technology for financial support.
The methanol mother liquor was concentrated to dryness.
The residue was extracted with dichloromethane by stirring
the suspension, leaving behind the white insoluble in-
organic salt. The combined dichloromethane extract was
concentrated under reduced pressure to obtain 21 g of
L-Trp-OMe-(+)-gossypol (Sg,S)-4, to give a yield of 99%.
This was recrystallized carefully from chloroform to give
References
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a light yellow powder (>99% de determined by 1H
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26
NMR). ½aꢁD ¼ þ288 (c 0.55, CH3OH). 1H NMR
(300 MHz, CDCl3): d (ppm) 13.50 (br t, J = 9.3 Hz,
–NH), 9.06 (d, J = 11.7 Hz, 2H), 8.08 (br s, indole NH),
7.98 (br s, –OH), 7.55 (s, 2H), 7.53 (d, J = 7.8 Hz, 2H),
7.20 (d, J = 8.1 Hz, 2H), 6.93–7.03 (m, 6H), 4.93 (br s,
–OH), 4.42 (m, 2H), 3.75 (s, 6H), 3.68–3.75 (m, 2H), 3.52
(dd, J = 14.4, 4.2 Hz, 2H), 3.27 (dd, J = 14.4, 8.7 Hz,
2H), 2.03 (s, 6H), 1.53 (t, J = 6.9 Hz, 12H). 13C NMR
(75 MHz, CDCl3): d (ppm) 173.3, 170.5, 161.7, 148.7,
147.0, 136.2, 131.7, 128.9, 127.6, 126.6, 124.2, 122.1,
119.7, 118.2, 117.9, 115.5, 114.4, 111.1, 108.8, 103.4, 62.7,
53.0, 30.3, 27.3, 20.3, 20.1. Anal. Calcd for C54H54O10N4Æ
CHCl3: C, 63.62; H, 5.34; N, 5.40. Found: C, 63.77; H,
5.36; N, 5.32.