Synthesis of Furanonaphthoquinones
J ournal of Natural Products, 1999, Vol. 62, No. 7 967
and purification by preparative TLC eluting with CHCl3-
MeOH afforded pure compounds.
[M•+] (calcd for C14H8O5, 256.0372); EIMS m/z 256 [M•+], 241,
149, 115, 91, 83, 69, 57.
2-Meth yl-2-[2′-(4′,9′-d ih yd r on a p h th o[2′,3′-b]fu r a n -4′,9′-
d ion ylm eth yl)a m in o]-1,3-p r op a n ed iol (15): yellow solid
(8.6 mg, 61%), mp 193-195 °C; H NMR (DMSO) δ 0.92 (3H,
Th e F or m a tion of 25. To a solution of 24 (14 mg, 0.055
mmol) in CH2Cl2 (3 mL) was added 2-amino-2-methyl-1,3-
propanediol (115 mg, 1.1 mmol) and anhydrous MgSO4 (100
mg), and the mixture was stirred for 24 h. The solution was
then filtered and evaporated to dryness, and the residue
dissolved in MeOH (2 mL). The resulting solution was adjusted
to pH 6-7 by HOAc, sodium cyanoborohydride (17 mg, 0.28
mmol) was added, and the mixture was stirred for 30 min.
The solution was diluted with H2O and extracted with EtOAc
three times, and the combined EtOAc extracts were dried over
Na2SO4. Evaporation and purification by preparative TLC,
eluting with CHCl3-MeOH afforded pure compound 25 as a
yellow solid (9.4 mg, 50%): 1H NMR (CD3OD) δ 1.43 (3H, s),
3.57 (1H, d, J ) 10.8), 3.71 (1H, d, J ) 10.8), 4.02 (3H, s), 4.17
(1H, d, J ) 8.4), 4.55 (1H, d, J ) 8.4), 6.98 (1H, d, J ) 2.0),
7.57 (1H, d, J ) 8.8), 7.78 (1H, d, J ) 8.8), 7.99 (1H, d, J )
2.0); 13C NMR δ 23.3, 57.2, 68.7, 72.9, 77.4, 109.6, 119.7, 122.0,
123.3, 132.7, 134.9, 138.0, 151.3, 152.2, 163.3, 167.9, 173.5,
1
s), 2.08 (1H, br s), 3.27 (4H, d, J ) 5.5), 3.88 (2H, s), 4.47 (2H,
dd, J ) 5.5), 6.91 (1H, s), 7.85 (1H, m), 8.07 (2H, m); 13C
NMR (DMSO) δ 18.8, 39.4, 57.5, 64.9, 79.6, 105.1, 126.7, 126.8,
131.5, 132.6, 133.1, 134.4, 134.7, 151.6, 164.8, 172.9, 180.8;
HRFABMS m/z 316.1182 [MH+] (calcd for C17H18NO5, 316.1185);
EIMS m/z 226 [M+ - C4H9O2], 197, 169, 141, 114, 113, 76.
2-Meth yl-2-[2′-(4′,9′-d ih yd r on a p h th o[2′,3′-b]fu r a n -4′,9′-
d ion ylm et h yl)a m in o]-1-p r op a n ol (16): yellow solid (12.6
1
mg, 96%), mp 187-189 °C; H NMR (CD3OD) δ 1.13 (6H, s),
3.42 (2H, s), 3.93 (2H, s), 6.91 (1H, s), 7.81 (2H, m), 8.16 (2H,
m); 13C NMR (DMSO) δ 24.0, 39.6, 54.2, 68.6, 105.1, 126.7,
126.9, 131.4, 132.6, 133.1, 134.4, 134.7, 151.6, 164.9, 173.0,
180.9; HRFABMS m/z 300.1244 [MH+] (calcd for C17H17NO4,
300.1234).
2-H yd r oxym et h yl-2-[2′-(4′,9′-d ih yd r on a p h t h o[2′,3′-b]-
fu r an -4′,9′-dion ylm eth yl)am in o]-1,3-pr opan ediol (17): yel-
low solid (13.7 mg, 94%), mp > 320 °C; 1H NMR (DMSO) δ
3.38 (6H, d, J ) 5.0), 3.99 (2H, s), 4.38 (3H, t, J ) 5.0), 6.93
(1H, s), 7.84 (2H, m), 8.07 (2H, m); 13C NMR (DMSO) δ 60.0,
61.3, 104.7, 126.3, 126.4, 131.1, 132.2, 132.6, 134.0, 134.3,
151.2, 164.3, 172.5, 180.5; HRFABMS m/z 332.1143 [MH+]
(calcd for C17H17NO6, 332.1134).
2-E t h yl-2-[2′-(4′,9′-d ih yd r on a p h t h o[2′,3′-b]fu r a n -4′,9′-
d ion ylm eth yl)a m in o]-1,3-p r op a n ed iol (18): yellow solid
(12.9 mg, 89%), mp > 320 °C; 1H NMR (CD3OD) δ 0.93 (3H, t,
J ) 7.5), 1.50 (2H, q, J ) 7.5), 3.53 (4H, d, J ) 4.1), 3.95 (2H,
s), 6.91 (1H, s), 7.81 (2H, m), 8.17 (2H, m); 13C NMR (DMSO)
δ 7.1, 22.3, 48.6, 58.9, 62.1, 104.7, 126.3, 126.4, 131.0, 132.2,
132.7, 134.0, 134.3, 151.2, 164.2, 172.5, 180.5; HRFABMS m/z
330.1354 [MH+] (calcd for C18H19NO5, 330.1341).
180.9; HRFABMS m/z 342.0975 [M + 1+] (calcd for C18H17
-
NO6, 342.0978); CIMS m/z 342 [MH+], 309, 254, 212, 140.
P r otection of 2-Am in o-2-m eth yl-1,3-p r op a n ed iol. To a
solution of 2-amino-2-methyl-1,3-propanediol (4.0 g, 38 mmol)
in N,N-dimethylformanide (25 mL) was added benzyl chloro-
formate (5.72 mL, 38 mmol). After the mixture was stirred
for 4 h, 2,2-dimethoxypropane (10 mL) and pyridinium p-
toluenesulfonate (300 mg) were added to this solution, which
was allowed to stir for another 20 h. Then the solution was
diluted with H2O and extracted with EtOAc three times. The
combined extracts were washed with H2O and dried over
Na2SO4. Evaporation gave crude product, which was crystal-
lized from hexane-EtOAc to afford pure 27 as white crystals
(8.0 g, 75%): mp 109 °C; 1H NMR δ 1.28 (3H, s), 1.42 (3H, s),
1.43 (3H, s), 3.66 (2H, d, J ) 12.0), 3.90 (2H, d, J ) 12.0), 5.08
(2H, s), 7.31-7.37 (5H, m); 13C NMR δ 18.8, 19.2, 27.8, 49.3,
66.3, 67.1, 98.2, 128.0, 128.1, 128.5, 136.5, 155.3; EIMS m/z
279 [M•+], 264, 248, 221.
3-[2′-(4′,9′-Dih yd r on a p h t h o[2′,3′-b]fu r a n -4′,9′-d ion yl-
m eth yl)a m in o]-1,2-p r op a n ed iol (19): yellow solid (12.6 mg,
1
95%), mp 148-150 °C; H NMR (CD3OD) δ 2.65 (1H, dd, J )
8.0, 12.0), 2.80 (1H, dd, J ) 4.0, 12.0), 3.51 (2H, d, J ) 5.0),
3.75 (1H, m), 3.99 (2H, s), 6.92 (1H, m), 7.82 (2H, m), 8.15
(2H, m); 13C NMR (DMSO) δ 45.8, 52.0, 64.3, 70.6, 105.2, 126.3,
126.5, 131.0, 132.2, 132.7, 134.0, 134.3, 151.4, 163.3, 172.6,
180.5; HRFABMS m/z 302.1034 [MH+] (calcd for C16H15NO5,
302.1028).
Hyd r ogen olysis of 27. To a solution of 27 (1.92 g, 6.9
mmol) in absolute MeOH (30 mL) was added palladium on
activated carbon (10%, 200 mg). The mixture was stirred for
2 h under hydrogen, and the solution filtered, and evaporated
under vacuum to give pure 28 as a colorless liquid (0.98 g,
98%): 1H NMR (CD3COCD3) δ 0.96 (3H. s), 1.32 (3H, s), 1.34
(3H, s), 1.97 (2H, br s), 3.40 (2H, d, J ) 12.0), 3.60 (2H, d, J
) 12.0); 13C NMR (CD3COCD3) δ 20.8, 20.9, 25.6, 46.6, 70.1,
97.4; CIMS m/z 146 [MH+], 130, 88, 73, 57.
Th e F or m a tion of 29. To a solution of 24 (10 mg, 0.039
mmol) in CH2Cl2 (3 mL) was added 28 (180 mg, 1.2 mmol)
and MgSO4 (100 mg). The mixture was stirred for 20 h. The
solution was filtered, diluted with H2O, and extracted with
EtOAc. The combined extracts were washed with H2O and
dried over Na2SO4. After removal of the solvent by evaporation,
the residue was dissolved in MeOH (2 mL). The resulting
solution was adjusted to pH 6-7 by HOAc and sodium
cyanoborohydride (12 mg, 0.19 mmol) added, and the mixture
was stirred for 30 min. The solution was diluted with H2O and
extracted with EtOAc three times, and the EtOAc extracts
were combined and dried over Na2SO4. Evaporation and
purification by preparative TLC, eluting with CHCl3-MeOH,
afforded pure compound 29 as a pink solid (6.8 mg, 46%): 1H
NMR (CD3OD) δ 1.25 (3H, s), 1.58 (3H, s), 1.76 (3H, s), 4.12
(3H, s), 4.45 (1H, d, J ) 13.1), 4.69 (1H, d, J ) 13.1), 7.06
(1H, d, J ) 2.0), 7.28 (1H, d, J ) 8.8), 7.66 (1H, d, J ) 2.0),
8.25 (1H, d, J ) 8.8), 8.30 (1H, s); 13C NMR (CD3OD) δ 19.4,
21.4, 28.6, 57.1, 58.3, 67.7, 99.1, 109.1, 109.7, 112.5, 119.4,
120.9, 123.3, 125.2, 126.1, 132.5, 141.6, 149.4, 164.0, 176.6;
HREIMS m/z 367.1420 [M•+] (calcd for C21H21NO5, 367.1420);
EIMS m/z 367 [M•+], 255, 239, 210, 152, 71, 59.
8-F or m yl-4-h yd r oxy-5-m et h oxyn a p h t h o[2,3-b]fu r a n
(23). To a solution of 2219 (1.4 g, 4.5 mmol) in CH2Cl2 (50 mL)
was added R,R-dichloromethyl methyl ether (4.15 mL, 45
mmol) and aluminum chloride (0.65 g, 6.7 mmol) at 0 °C. The
mixture was stirred for 30 min. Then the solution was diluted
with H2O and extracted with EtOAc three times. The EtOAc
was collected and extracted with 5% aqueous NaOH solution
three times. The combined basic solution was acidified with
HCl and extracted with EtOAc three times. The combined
extracts were washed with H2O and dried over Na2SO4.
Evaporation and column chromatography on Si gel with CHCl3
followed by preparative TLC eluting with hexane-EtOAc gave
pure compound 23 as a yellow solid (275 mg, 25.3%): mp 158-
161 °C; 1H NMR δ 4.17 (3H, s), 6.74 (1H, d, J ) 8.0), 7.01 (1H,
d, J ) 2.4), 7.63 (1H, d, J ) 2.4), 7.75 (1H, d, J ) 8.0), 9.11
(1H, s), 9.69 (1H, s), 10.11 (1H, s); 13C NMR (CDCl3) δ 56.5,
97.8, 100.4, 104.0, 109.9, 115.7, 125.8, 130.7, 140.0, 145.4,
148.5, 157.7, 162.4, 192.0; HREIMS m/z 242.0579 [M•+] (calcd
for C14H10O4, 242.0579); EIMS m/z 242 [M•+], 214, 199, 171,
115, 87.
8-F or m yl-5-m eth oxy-4,9-d ih yd r on a p h th o[2,3-b]fu r a n -
4,9-d ion e (24). Salcomine (20 mg) was added to a solution of
23 (90 mg, 0.37 mmol) in MeCN (10 mL), and the mixture was
stirred for 40 min while oxygen was bubbled through. The
solution was then filtered and evaporated. Column chroma-
tography of the residue on Si gel with CHCl3 afforded pure
Hyd r olysis of 29. To a solution of 29 (4.5 mg, 0.012 mmol)
in a mixture of MeOH and H2O (95:5, 2 mL) was added
p-toluenesulfonic acid (10 mg). The mixture was stirred for
20 h at room temperature. The solution was then diluted with
H2O and extracted with EtOAc three times. The combined
extracts were washed with H2O and dried over Na2SO4.
1
compound 24 as a yellow solid (55 mg, 58%): mp 199 °C; H
NMR δ 4.09 (3H, s), 6.98 (1H, d, J ) 2.0), 7.40 (1H, d, J )
8.8), 7.78 (1H, d, J ) 2.0), 8.04 (1H, d, J ) 8.8), 10.64 (1H, s);
13C NMR δ 56.9, 109.0, 118.1, 120.6, 131.8, 132.1, 135.1, 135.2,
149.4, 150.6, 163.3, 174.5, 179.1, 191.6; HREIMS m/z 256.0372