H2O (0.6 mL) was added to the reaction mixture, which was then
heated under reflux overnight. The reaction mixture was cooled to
room temperature and extracted by 0.5% HCl aq. The aqueous phase
was washed with Et2O, treated with 5% NaOH aq, and extracted
with CH2Cl2. The organic phase was dried over Na2SO4 and
spongitine A was accomplished in 41% yield over 5 steps from
the known vinyl indole 5. The absolute stereochemistry of the
naturally obtained spongotine A was also determined. Further
studies about the generality of our coupling reaction and the
application to other heterocycles are also underway in our
laboratory.
evaporated in vacuo to give diamine (S)-1 (495 mg, 89%) as a
1
colorless solid: mp 124 °C; [R]22 +27.8 (c 0.20, CH3OH); H
D
NMR (300 MHz, CDCl3) δ 8.17 (d, 1H, J ) 1.5 Hz), 7.77 (d, 2H,
J ) 8.1 Hz), 7.49 (s, 1H), 7.46 (d, 1H, J ) 8.7 Hz), 7.34 (dd, 1H,
J ) 8.4, 1.5 Hz), 7.25 (d, 2H, J ) 7.8 Hz), 4.16 (dd, 1H, J ) 6.9,
4.5 Hz), 3.03 (dd, 1H, J ) 12.6, 4.5 Hz), 2.83 (dd, 1H, J ) 12.6,
6.9 Hz), 2.36 ppm (s, 3H); 13C NMR (67.8 MHz, CDCl3) δ 145.1,
136.0, 134.8, 129.9, 128.0, 126.7, 126.3, 125.3, 123.1, 121.0, 118.4,
116.8, 50.7, 48.2, 21.7 ppm; IR (KBr) 3099, 1596 cm-1; HRMS
(FAB) calcd for C17H18BrN3NaO2S [M + Na]+ 430.0201, found
430.0180.
Experimental Section
Typical Procedure of Experiment in Table 1. Diamine 3 (1.1
mmol) was added to a solution of keto aldehyde 2 (1 mmol) in
solvent (20 mL) at 0 °C under N2 atmosphere and stirred for 20
min. Oxidant (1.1 mmol) was added to the reaction mixture at
0 °C. The mixture was allowed to warm to room temperature and
stirred overnight. The reaction mixture was quenched by sat.
Na2S2O3 aq and solvent was evaporated in vacuo. Saturated
NaHCO3 aq (20 mL) was added to the residue and the mixture
was stirred for 30 min. The solid was filtered, washed with cold
H2O and cold Et2O, and dried in vacuo to give compound 4.
(-)-Spongotine A.13 Diamine (S)-1 (100 mg, 0.245 mmol) was
added to a solution of keto aldehyde 2 (38.6 mg, 0.223 mmol) in
CH3CN (4.5 mL) at 0 °C under N2 atmosphere and the mixture
was stirred for 20 min. NCS (32.7 mg, 0.245mmol) was added to
the reaction mixture at 0 °C. The mixture was allowed to warm to
room temperature and stirred overnight. The reaction mixture was
quenched by sat. Na2S2O3 aq and solvent was evaporated in vacuo.
Saturated NaHCO3 aq (10 mL) was added to the residue and the
mixture was stirred for 30 min. The solid was filtered, washed with
cold H2O and cold Et2O, and dried in vacuo to give crude compound
8 (133.0 mg). HRMS (EI) calcd for C27H21N4O3SBr [M+] 560.0517,
found 560.0512. Crude compound 8 (30.0 mg) in MeOH (1.0 mL)
and 2 N NaOH (0.7 mL) was heated under reflux for 15 min. The
reaction mixture was cooled to room temperature and solvent was
removed in vacuo. H2O and AcOEt were added to the residue and
the organic phase was extracted with AcOEt. The organic phase
was dried over Na2SO4 and evaporated in vacuo. Residue was
purified by SiO2 column chromatography (AcOEt) to give spon-
1
Compound 4a: brown solid; mp 166-168 °C; H NMR (300
MHz, DMSO-d6) δ 12.1 (br s, 1H), 8.84 (s, 1H), 8.24-8.21 (m,
1H), 7.51-7.48 (m, 1H), 7.26-7.18 (m, 2H), 6.96 (br s, 1H), 3.63
ppm (br s, 4H); 13C NMR (67.8 MHz, DMSO-d6 + TFA (ca. 1%))
δ 179.6, 163.2, 138.1, 136.2, 126.0, 123.0, 122.2, 121.2, 113.5,
112.3, 44.3 ppm; IR (KBr) 3348, 3152, 1622, 1589, 1495, 1441
cm-1; HRMS (FAB) calcd for C12H12N3O [M + H]+ 214.0980,
found 214.0981.
Compound 4b:13 brown solid; mp 121-122 °C; 1H NMR (300
MHz, DMSO-d6 + TFA (ca. 1%)) δ 12.85 (br s, 1H), 10.97 (br s,
1H), 10.84 (b s, 1H), 8.55 (d, 1H, J ) 3.6 Hz), 8.16-8.14 (m,
1H), 7.62-7.60 (m, 1H), 7.40-7.31 (m, 2H), 4.54-4.50 (m, 1H),
4.17 (t, 1H, J ) 8.7 Hz), 3.64 (dd, 1H, J ) 8.7, 2.7 Hz), 1.38 ppm
(d, 3H, J ) 6.6 Hz); 13C NMR (67.8 MHz, DMSO-d6 + TFA (ca.
1%)) δ 173.6, 161.5, 139.7, 136.9, 124.9, 124.3, 123.4, 121.0, 113.1,
113.0, 54.0, 52.2, 20.5 ppm; IR (KBr) 3069, 1705, 1583, 1516,
1435, 1238, 750 cm-1; HRMS (FAB) calcd for C13H14N3O [M +
H]+ 228.1137, found 228.1142.
gotine A (11.0 mg, 51%) as a pale yellow solid: mp 229 °C; [R]22
D
1
-14.3 (c 0.20, CH3OH); H NMR (300 MHz, DMSO-d6 + TFA
(ca. 1%)) δ 12.87 (br s, 1H), 11.51 (br s, 1H), 11.35 (br s, 1H),
11.16 (br s, 1H), 8.57 (d, 1H, J ) 3.3 Hz), 8.19-8.16 (m, 1H),
7.67 (m, 2H), 7.64-7.61 (m, 1H), 7.56 (d, 1H, J ) 8.4 Hz), 7.38
(t, 1H, J ) 7.2 Hz), 7.35 (t, 1H, J ) 6.9 Hz), 7.25 (d, 1H, J ) 8.4
Hz), 5.88 (dd, 1H, J ) 12.0, 9.3 Hz), 4.52 (t, 1H, J ) 12.0 Hz),
4.09 ppm (t, 1H, J ) 9.3 Hz); 13C NMR (67.8 MHz, DMSO-d6 +
TFA (ca. 1%)) δ 172.8, 161.4, 139.9, 137.5, 137.0, 125.7, 124.7,
124.6, 123.8, 123.6, 122.2, 121.0, 119.9, 114.6, 114.5, 113.2, 113.1,
112.4, 54.4, 51.2 ppm; IR (KBr) 2361, 2341, 1615, 1582, 1447
cm-1; HRMS (FAB) calcd for C20H16BrN4O [M + H]+ 407.0507,
found 407.0514.
Total Synthesis of (-)-Spongotine A. Diazide 7. To a solution
of diol 6 (200 mg, 0.478 mmol) in dry toluene (5.0 mL) was added
triphenylphosphine (384 mg, 1.46 mmol), diethyl azodicarboxylate
(40% solution in toluene, 0.64 mL, 1.46 mmol), and diphenylphos-
phoryl azide (0.31 mL, 1.46 mmol) at 0 °C. The mixture was
allowed to warm to room temperature and stirred overnight. Solvent
was evaporated in vacuo and the residue was purified by SiO2
column chromatography (hexane/AcOEt ) 9/1) to give diazide 7
(207 mg, 92%) as a colorless oil. [R]23 +23.5 (c 0.20, CH3OH);
D
1H NMR (300 MHz, CDCl3) δ 8.17 (d, 1H, J ) 1.8 Hz), 7.77 (d,
2H, J ) 8.1 Hz), 7.62 (s, 1H), 7.46-7.37 (m, 2H), 7.27 (d, 2H, J
) 8.1 Hz), 4.84-4.80 (m, 1H), 3.68-3.60 (m, 2H), 2.36 ppm (s,
3H); 13C NMR (75.5 MHz, CDCl3) δ 145.8, 135.9, 134.6, 130.2,
127.1, 127.0, 126.9, 125.1, 120.8, 119.3, 117.4, 117.1, 58.1, 54.5,
21.6 ppm; IR (KBr) 2251, 2170, 2104 1597, 1487 cm-1; HRMS
(FAB) calcd for C17H14BrN7NaO2S [M + Na]+ 482.0011, found
482.0014. (Caution: Diazide compounds are potentially explosive.)
Diamine (S)-1. A solution of diazide 7 (625 mg, 1.36 mmol)
and triphenylphosphine (891 mg, 3.39 mmol) in toluene (9.0 mL)
was heated under reflux for 15 min and cooled to room temperature.
Acknowledgment. This work was financially supported by
Grant-in-Aid for Scientific Research (A) and Grant-in-Aid for
Scientific Research for Exploratory Research from the Japan
Society for the Promotion of Science and by Grant-in-Aid for
Scientific Research on Priority Areas (17035047) from the
Ministry of Education, Culture, Sports, Science, and Technol-
ogy, Japan. K. M. thanks the Japan Society for the Promotion
of Science (JSPS) for a Research Fellowship for Young
Scientists.
Supporting Information Available: Experimental details and
detailed spectroscopic data of all new compounds. This material is
(13) Jung et al. mentioned broadening or doubling of the 1H NMR signals
of spongotine A was observed in neutral solution (DMSO-d6), and the NMR
spectrum was measured with TFA in DMSO-d6 in ref 7. So the NMR spectra
of compound 4b and spongotine A were measured with TFA in DMSO-d6.
JO701668S
J. Org. Chem, Vol. 72, No. 23, 2007 8949