SYNTHESIS OF NEW ANTHRACYCLINE DERIVATIVES
1967
(
for 40 min at 30 C. The resulting mixture was poured into dry ether
w/v ¼ 1 : 9, 0.68 mL, 0.43 mmol) solution, and the mixture was then stirred
ꢀ
(
(
1
200 mL), the solid residue was filtered with off and washed with ether
50 mL ꢁ 3). The solid was recrystallized from acetone/ether (v/v ¼ 1 : 1,
0 mL), filtered off, washed with ether, and dried over P O to give
2 5
ꢀ
1
4-bromo DM (1c, 0.19 g, 84%) as a red solid: m.p. 176–177 C; H NMR
1
(
2
400 MHz, DMSO-d ) d 14.00 (s, 1H, PhOH), 13.30 (s, 1H, PhOH), 7.99 (bs,
6
H, NH ), 7.91 (m, 2H, ArH), 7.89 (m, 1H, ArH), 5.55 (m, 1H, C H), 5.28
0
2
4
(
2
m, 1H, C7eqH), 4.49 (m, 1H, C1
0
H), 4.21 (q, 1H, J ¼ 6.68 Hz, C
0
H), 4.00 (s,
5
H, C H), 3.97 (s, 3H, C OCH ), 3.78 (bs, 1H, C
1
0
OH), 3.60 (m, 1H, C H),
3
0
4
4
3
4
3
.05 (d, 1H, J ¼ 18.10 Hz, C H), 2.92 (d, 1H, J ¼ 18.10 Hz, C10axH), 2.44
1
0eq
(
(
(
d, 1H, J ¼ 14.21 Hz, C H), 2.07 (dd, 1H, J ¼ 14.21, 5.43 Hz, C8axH), 1.88
0 0
2 eq 2 ax
8
eq
dd, 1H, J ¼ 12.70, 9.00 Hz, C
H), 1.85 (d, 1H, J ¼ 12.70 Hz, C
H), 1.65
1
3
d, 3H, J ¼ 6.68 Hz, C
0
CH ); C NMR (100 MHz, DMSO-d ) d 187.51,
5
3
6
1
1
5
86.11, 169.25, 161.20, 161.01, 160.12, 137.98, 135.80, 134.93, 132.21,
22.01, 120.10, 119.01, 109.90, 105.23, 98.54, 84.56, 73.47, 69.37, 68.01,
5.94, 54.11, 38.42, 37.04, 34.12, 21.20,16.72.
Daunomycin-14-pyruvate Hydrochloride (2)
1
4-Bromodaunomycin hydrochloride (1c, 0.50 g, 0.78 mmol) and pyru-
vic acid sodium salt (1.03 g, 9.33 mmol) in acetone (800 mL) were refluxed for
5 h. After completing the reaction by monitored on TLC, the solvent was
1
evaporated. To the residue dissolved in dry THF (250 mL) was added etheral
ꢀ
HCl, and the mixture was stirred at À20 C for 2h. The organic solvent was
concentrated by a rotary evaporator and purified by column chromatography
on silica gel (CH Cl /CH OH/HCO H/H O ¼ 88 : 15 : 2:1) to give dauno-
2
2
3
2
2
mycin-14-pyruvate hydrochloride (2, 0.30 g, 59%) as a red powder: m.p.
ꢀ
20
ꢀ
1
1
78–180 C;[ꢁ]D þ 224.94 (c0.004,CH OH);IR(KBr)3445,2939,1732,1615,
À1
6
3
1
584, 1406, 1289, 1215, 1116, 984 cm ; H NMR (400 MHz, DMSO-d )
d 13.99 (s, 1H, PhOH), 13.29 (s, 1H, PhOH), 8.26 (bs, 2H, NH ), 7.91 (m,
2
2
H, ArH), 7.66 (m, 1H, ArH), 5.86 (d, 1H, J ¼ 8.79 Hz, C
0
H), 5.46 (d, 1H,
4
J ¼ 3.91 Hz, C H), 5.31 (d, 1H, J ¼ 18.07 Hz, C H), 5.22 (m, 1H, C
0
H),
1
7
eq
14
5
C
.12(d, 1H, J ¼ 18.07 Hz, C H), 4.96 (s, 1H, C OH), 4.23 (q, 1H, J ¼ 6.84 Hz,
1
4
9
0
H), 3.99 (s, 3H, C OCH ), 3.58 (s, 1H, C
3
0
OH), 3.33 (m, 1H, C H), 3.05 (d,
3
0
5
4
4
1
1
3
H, J ¼ 19.53 Hz, C H), 2.80 (d, 1H, J ¼ 19.53 Hz, C10axH), 2.14 (d,
1
0eq
H, J ¼ 14.65 Hz, C H), 2.09 (s, 3H, C CH ), 2.02 (dd, 1H, J ¼ 14.65,
8eq 17 3
.91 Hz, C H), 1.88 (dd, 1H, J ¼ 12.70, 9.00 Hz, C
0
3
H), 1.67 (d, 1H,
2 eq
8
ax
1
J ¼ 12.70, C
0
H), 1.37 (d, 3H, J ¼ 6.84 Hz, C
0
CH ); C NMR (100 MHz,
5 3
2
ax
DMSO-d ) d 209.86, 187.53, 185.99, 160.96, 160.73, 160.06, 159.89, 138.38,
6
135.67, 134.93, 132.86, 122.11, 119.55, 118.45, 109.86, 105.07, 98.23, 79.08,