Snider and Gao
3,4-Bisacetoxymethyl-3a,3b,4,5-tetrahydro-1,7,8,17-tet-
rahydroxy-10,15-dimethyl-2H-dibenzo[c,mn]naphtho-
[2,3-g]xanthene-6,13,18(3H)-trione (15d). To a stirred sus-
pension of 14d (673 mg, 2.04 mmol) in AcOH (5 mL) at 25 °C
was added Pb(OAc)4 (904 mg, 2.04 mmol) in one portion. The
yellow suspension became a clear orange solution. After
stirring at 25 °C for 20 min, the reaction mixture was warmed
to 75 °C and stirred for another 20 min, and a yellow
precipitate started to form. After stirring at 75 °C for another
40 min, the yellow precipitate was filtered and washed with
AcOH to give 355 mg (53%) of flavoskyrin-type dimer 15d as
a bright yellow fine solid: mp 178-180 °C; 1H NMR 16.20 (s,
1, OH), 14.60 (s, 1, OH), 11.29 (s, 1, OH), 9.73 (s, 1, OH), 6.92
(s, 1), 6.62 (s, 1), 6.49 (s, 1), 6.18 (s, 1), 4.58 (dd, 2, J ) 11.6,
3.1), 4.18 (dd, J ) 11.6, 5.5), 4.11 (dd, J ) 11.6, 5.5), 3.00-
3.10 (m, 1), 2.89-2.96 (m, 3), 2.62-2.78 (m, 3), 2.46-2.56 (m,
1), 2.16 (s, 9), 2.02 (s, 3); IR (KBr) 3387, 1746, 1711, 1621,
1588; HRMS (FAB) calcd for C36H33O12 (MH+) 657.1972, found
657.1964; 13C NMR data are not available because 16d is not
stable in solution.
(5aR*,6S,13aR,14S,17S,18S,19S,20S)-17,20-Bisacetoxy-
methyl-1,7,9,15-tetrahydroxy-3,11-dimethyl-5H,6H-6,13a,-
5a,14-[1,2,3,4]butanetetraylcycloocta[1,2-b:5,6-b′]dinaph-
thalene-5,8,13,16(14H)-tetrone (17d). A suspension of 15d
(145 mg, 0.22 mmol) in dry pyridine (10 mL) was stirred at 80
°C for 1 h under air giving a homogeneous light brown solution.
1H NMR spectra showed the formation of a mixture a rubro-
skyrin-type dimer 16d and symmetrical dimer 17d. The
reaction mixture was stirred at 110 °C for another 1 h.
Removal of pyridine gave 17d and some pyridine residue (156
mg, 108%) as a brown solid, which was used in the next step
without further purification. Pure 17d can be obtained by
recrystallization from acetone giving orange crystals: mp 260
°C (dec); 1H NMR 14.56 (s, 2, OH), 11.71 (s, 2, OH), 7.52 (s, 2),
7.12 (s, 2), 3.99 (dd, 2, J ) 11.6, 7.3), 3.80 (dd, 2, J ) 11.6,
7.9), 3.57 (br s, 2), 2.95 (dd, 2, J ) 5.5, 1.2), 2.79-2.84 (m, 2),
2.46 (s, 6), 1.95 (s, 6); 13C NMR 193.5 (2 C), 186.6 (2 C), 181.1
(2 C), 170.6 (2 C), 162.1 (2 C), 148.6 (2 C), 131.8 (2 C), 124.6
(2 C), 121.2 (2 C), 114.4 (2 C), 105.5 (2 C), 62.4 (2 C), 58.0 (2
C), 55.9 (2 C), 48.7 (2 C), 39.6 (2 C), 22.2 (2 C), 20.6 (2 C); IR
(KBr) 1743, 1686, 1614, 1572; HRMS (FAB) calcd for C36H31O12
(MH+) 655.1856, found 655.1845.
(5aR*,6S,13aR,14S,17S,18S,19S,20S)-1,7,9,15-Tetrahy-
droxy-17,20-dihydroxymethyl-3,11-dimethyl-5H,6H-6,-
13a,5a,14-[1,2,3,4]butanetetraylcycloocta[1,2-b:5,6-b′]di-
naphthalene-5,8,13,16(14H)-tetrone (17e). To a stirred
solution of crude 17d (156 mg) in MeOH (6 mL) was added
K2CO3 (304 mg, 2.2 mmol). The reaction mixture turned brown.
The resulting mixture was stirred at 25 °C for 2 h and
quenched with 3 M aqueous HCl solution. The yellow solid
that precipitated from the reaction mixture was filtered,
washed with H2O, and dried under vacuum to give 110 mg
(88% from 15d) of diol 17e as a yellow solid: mp 231-232 °C;
1H NMR 14.63 (s, 2, OH), 11.71 (s, 2, OH), 7.48 (s, 2), 7.10 (s,
2), 3.580 (dd, 2, J ) 11.0, 6.7), 3.575 (s, 2), 3.41 (dd, 2, J )
11.0, 8.6), 3.04 (d, 2, J ) 5.5), 2.75 (ddd, 2, J ) 8.6, 6.7, 5.5),
2.45 (s, 6); 13C NMR 193.9 (2 C), 186.4 (2 C), 181.9 (2 C), 161.9
(2 C), 148.4 (2 C), 132.1 (2 C), 124.4 (2 C), 121.1 (2 C), 114.5
(2 C), 105.7 (2 C), 61.4 (2 C), 58.1 (2 C), 55.7 (2 C), 48.3 (2 C),
42.9 (2 C), 22.2 (2 C); IR (KBr) 3453, 2959, 1686, 1610, 1571;
HRMS (FAB) calcd for C32H27O10 (MH+) 571.1604, found
571.1584.
without further purification. Pure 17f can be obtained by
recrystallization from CHCl3: mp 230-231 °C; 1H NMR 14.39
(s, 2, OH), 11.65 (s, 2, OH), 9.56 (s, 2), 7.58 (s, 2), 7.13 (s, 2),
4.00 (br s, 2), 3.43 (br d, 2, J ) 5.5), 3.32 (d, 2, J ) 5.5), 2.48
(s, 6); 13C NMR 197.6 (2 C), 192.9 (2 C), 187.1 (2 C), 180.4 (2
C), 162.3 (2 C), 149.0 (2 C), 131.2 (2 C), 124.9 (2 C), 121.6 (2
C), 114.3 (2 C), 105.9 (2 C), 62.0 (2 C), 58.2 (2 C), 53.7 (2 C),
48.0 (2 C), 22.2 (2 C); IR (KBr) 3418, 1711, 1682, 1616, 1570;
HRMS (FAB) calcd for C32H23O10 (MH+) 567.1291, found
567.1316.
(5aR*,6S,13aR,14S,17S,18S,19S,20S)-17,20-Diacetyl-
1,7,9,15-tetrahydroxy-3,11-dimethyl-5H,6H-6,13a,5a,14-
[1,2,3,4]butanetetraylcycloocta[1,2-b:5,6-b′]dinaphthalene-
5,8,13,16(14H)-tetrone (17h). To a stirred solution of MeMgBr
(3.0 M in ether, 200 µL, 0.6 mmol) in dry THF (1 mL) at 0 °C
was added a solution of crude 17f (67 mg) in dry THF (2 mL)
over 5 min. The resulting mixture was stirred at 0 °C for 30
min and quenched with 2 M aqueous HCl solution. The organic
layer was separated and the aqueous layer was extracted with
CH2Cl2 (3 × 50 mL). The combined organic layers were washed
with brine and dried (Na2SO4). Removal of the solvent gave
crude 17g as a brown residue that was dissolved in CHCl3 (2
mL). Dess-Martin periodinane (40 mg, 0.095 mmol) was added
to the reaction mixture in one portion. The reaction mixture
was stirred at 25 °C for 2 h and concentrated to give brown
residue, which was purified by flash chromatography on 10%
oxalic acid impregnated silica gel (1:1 pentane/ether) to give
a mixture of bis ketone 17h and oxalic acid, which was diluted
with CH2Cl2, washed with H2O and brine, dried (Na2SO4) and
concentrated to give 10 mg (36% for 3 steps) of bis ketone 17h
as a yellow solid: 1H NMR 14.39 (s, 2, OH), 11.68 (s, 2, OH),
7.61 (s, 2), 7.12 (s, 2), 3.84 (br s, 2), 3.43 (br d, 2, J ) 5.5), 3.31
(d, 2, J ) 5.5), 2.48 (s, 6), 2.00 (s, 6).
1,7,9,15a-Tetrahydroxy-5H,6H-6,13a,5a,14-[1,2,3,4]bu-
tanetetraylcycloocta[1,2-b:5,6-b′]dinaphthalene-5,8,13,-
15,16(14H)-pentone (18). To a stirred solution of 10b (35 mg,
0.073 mmol) in CHCl3 (1 mL) was added solid NaHCO3 (31
mg, 0.363 mmol) and m-CPBA (90%, 70 mg, 0.403 mmol) at
25 °C. The reaction mixture was stirred at 25 °C for 1 h and
concentrated to give an orange solid. Flash chromatography
on 10% oxalic acid impregnated silica gel (8:1 to 4:1 hexanes/
EtOAc) gave a mixture of 18 and oxalic acid, which was diluted
with CH2Cl2, washed with H2O and brine, dried (Na2SO4) and
concentrated to give 12 mg (33%) of 18 as a yellow solid: mp
241 °C; 1H NMR 14.06 (s, 1, OH), 11.85 (s, 1, OH), 11.24 (s, 1,
OH), 7.64-7.69 (m, 4), 7.28-7.32 (m, 2), 3.951 (br s, 1), 3.947
(s, 1, OH), 3.73 (br s, 1), 3.09 (d, 1, J ) 4.9), 2.83 (d, 1, J )
4.9), 2.49 (d, J ) 12.2), 2.17-2.23 (m, 2), 1.57 (d, 1, J ) 12.2);
1H NMR (DMSO-d6) 14.15 (s, 1, OH), 11.84 (s, 1, OH), 11.12
(s, 1, OH), 7.79 (dd, 1, J ) 8.0, 8.5), 7.76 (dd, 1, J ) 8.0, 8.5),
7.59 (d, 1, J ) 8.0), 7.56 (d, 1, J ) 8.0), 7.38 (d, 1, J ) 8.5),
7.35 (d, 1, J ) 8.5), 3.74 (br s, 1), 3.52 (br s, 1), 2.86 (d, 1, J )
4.9), 2.74 (d, 1, J ) 4.9), 2.35 (d, J ) 12.2), 1.92-2.01 (m, 2),
1.64 (d, 1, J ) 12.2); 13C NMR 199.9, 194.1, 193.4, 193.1, 186.0,
183.1, 160.9, 160.7, 136.9, 136.5, 133.8, 132.7, 124.1, 123.8,
119.2, 118.6, 116.7, 115.7, 106.1, 75.2, 63.8, 59.9, 56.4, 51.3,
47.7, 44.6, 34.0, 26.0; IR (KBr) 3409, 2948, 1730, 1660, 1615,
1575, 1436; HRMS (FAB) calcd for C28H19O9 (MH+) 499.1029,
found 499.1007.
7a,15a-Dichloro-1,9-dihydroxy-5H,6H-6,13a,5a,14-
[1,2,3,4]butanetetraylcycloocta[1,2-b:5,6-b′]dinaphthalene-
5,7,8,13,15,16(14H)-hexone (21). To a stirred solution of 10b
(31 mg, 0.064 mmol) in DMF (3 mL) was added Oxone (197
mg, 0.32 mmol) and 3 mL of 3 M aqueous HCl solution. The
resulting reaction mixture was stirred at 25 °C for 30 min.
The yellow solid that precipitated from the solution was
filtered, washed with H2O and dried under vacuum to give 25
mg (71%) of 21 as a pale yellow solid: mp 207 °C (dec); 1H
NMR 11.24 (s, 2, OH), 7.67-7.74 (m, 4), 7.38 (dd, 2, J ) 7.9,
1.2), 4.12 (s, 2), 3.32 (d, 2, J ) 4.3), 2.79 (d, 2, J ) 13.4), 2.16
(dd, 2, J ) 13.4, 4.3); 13C NMR 195.4 (2 C), 189.5 (2 C), 187.7
(2 C), 163.3 (2 C), 137.3 (2 C), 131.7 (2 C), 125.8 (2 C), 120.1
(5aR*,6S,13aR,14S,17S,18S,19S,20S)-17,20-Diformyl-
1,7,9,15-tetrahydroxy-3,11-dimethyl-5H,6H-6,13a,5a,14-
[1,2,3,4]butanetetraylcycloocta[1,2-b:5,6-b′]dinaphthalene-
5,8,13,16(14H)-tetrone (17f). To a stirred solution of diol 17e
(27 mg, 0.047 mmol) was added Dess-Martin periodinane (40
mg, 0.095 mmol) in one portion. The reaction mixture was
stirred at 25 °C for 1 h and concentrated to give a yellow solid
1
(67 mg). The H NMR spectra showed a quantitative conver-
sion to bis aldehyde 17f and byproduct from the Dess-Martin
periodinane. The crude material was used in the next step
6868 J. Org. Chem., Vol. 70, No. 17, 2005