5058
M. Valpuesta et al. / Tetrahedron 58 .2002) 5053±5059
each, J1.2Hz, OCH 2O), 4.1±3.9 ,m, 3H, H-8, H-80,
H-14), 3.96 ,s, 3H, OMe), 3.28 ,dd, 1H, J16.4, 3.8 Hz,
H-13), 3.05 ,ddd, 1H, J11.0, 6.0, 4.5 Hz, H-6), 2.9±2.8
,m, 2H, H-5, H-60), 2.65 ,dd, 1H, J16.4, 11.1 Hz, H-130),
2.60 ,m, 1H, H-50); 13C NMR ,CDCl3) d 147.8, 144.8,
143.6, 140.3 ,C-1, C-3, C-9, C-10), 134.5 ,C-2), 128.9,
128.5, 123.2 ,C-4a, C-12a, C-14a), 116.0 ,C-8a), 121.1
,C-12), 106.7 ,C-11), 103.0 ,C-4), 101.0, 100.6
,2£OCH2O), 59.3 ,OMe), 54.8 ,C-14), 52.0 ,C-8), 47.2
,C-6), 31.8 ,C-13), 30.0 ,C-5); MS ,m/z) 353 ,M1, 14),
352 ,16), 204 ,29), 148 ,100%); EI-HRMS calcd for
C20H19NO5 353.1263, found 353.1251.
petroleum ether)]; IR ,KBr) nmax 3560, 1615, 1480, 1445,
1235, 1225, 1055 cm21; 1H NMR ,CDCl3) d 6.66, 6.58 ,two
d, 1H each, J7.8 Hz, H-11, H-12), 6.32 ,s, 1H, H-4), 5.88,
5.87 ,two s, 2H each, 2£OCH2O), 5.17 ,t, 1H, J7.3 Hz,
H-14), 4.11 ,s, 3H, OMe), 3.96 ,d, 1H, J15.2Hz, H-8),
3.54 ,d, 1H, J14.4 Hz, H-13), 3.5±3.4 ,bs, OH), 3.44 ,d,
H-130), 3.0±2.9 ,m, 1H, H-5), 2.71 ,dt, 1H, J12.5, 3.6,
3.6 Hz, H6), 2.5±2.4 ,m, 2H, H-50, H-60), 2.11 ,s, 3H,
NMe); 13C NMR ,CDCl3) d 147.7, 146.6, 145.2, 141.4
,C-1, C-3, C-9, C-10), 134.8, 133.4, 133.2, 129.2 ,C-2,
C-4a, C-12a, C-14a), 124.0 ,C-12), 118.7 ,C-8a), 106.2
,C-11), 104.9 ,C-4), 100.7, 100.5 ,2£OCH2O), 71.9
,C-14), 59.6 ,OMe), 59.5 ,C-6), 52.2 ,C-8), 46.1 ,C-13),
43.0 ,NMe), 33.3 ,C-5); MS ,m/z) 385 ,M1, 10), 367 ,1),
220 ,13), 148 ,100%).
0
1H, J15.2Hz, H-8 ), 2.96 ,dd, 1H, J14.4, 7.3 Hz,
4.1.6. Stylopine *2b). In a manner similar to that described
above for compound 2a, compound 6b ,118 mg,
0.33 mmol) gave 2b ,91 mg, 85%) as white solid, mp
193±1948C [lit.16 mp 194±1958C ,EtOH)].
4.1.10. Dihydroprotopine *7b). To a solution of protopine
,1b, 75 mg, 0.21 mmol) in methanol ,7 mL), NaBH4
,30 mg, 0.8 mmol) was added and the mixture stirred for
4 h at room temperature. The solvent was removed in vacuo,
water ,1 mL) was added to the residue and the mixture was
extracted with CHCl3 ,2£15 mL). The organic phase was
dried over MgSO4, concentrated in vacuo and puri®ed by
chromatography ,CHCl3/CH3OH, 8:1) to give compound 7b
,52mg, 69%). White crystals, mp 147±148 8C [lit.17 143±
1448C ,ethanol)]; IR ,KBr) nmax 3530±3480, 1617, 1480,
1445, 1250, 1235, 1040 cm21; 1H NMR ,CDCl3) d 7.06 ,s,
1H, H-1), 6.68 and 6.61 ,two d, 1H each, J7.9 Hz, H-11,
H-12), 6.58 ,s, 1H, H-4), 5.90±5.85 ,m, 4H, 2£OCH2O),
5.26 ,d, 1H, J7.5 Hz, H-14), 3.98 ,d, 1H, J15.1 Hz,
H-8), 3.5 ,bs, OH), 3.48 ,d, 1H, J14.0 Hz, H-13), 3.42
,d, 1H, J15.1 Hz, H-80), 2.99 ,ddd, 1H, J14.0, 12.0,
4.0 Hz, H-5), 2.81 ,ddd, 1H, J12.0, 4.0, 3.0 Hz, H-6),
2.66 ,dd, 1H, J14.0, 7.5 Hz, H-130), 2.6±2.4 ,m, 2H,
H-50, H-60), 2.09 ,s, 3H, NMe); 13C NMR ,CDCl3) d
146.6, 146.4, 146.2, 145.5 ,C-2, C-3, C-9, C-10), 139.1,
133.2, 131.6 ,C-12a, C-14a, C-4a), 119.1 ,C-8a), 123.7
,C-12), 110.2, 106.3, 105.6 ,C-1, C-11, C-4), 100.8, 100.6
,2£OCH2O), 71.0 ,C-14), 59.6 ,C-6), 52.3 ,C-8), 46.8
,C-13), 42.6 ,NMe), 33.5 ,C-5); MS ,m/z) 355 ,M1, 1),
337 ,M218, 21), 188 ,24), 148 ,100%).
4.1.7. cis-N-Methyl-1-methoxystylopinium iodide *3a).
To
a solution of 1-methoxystylopine ,2a, 25 mg,
0.06 mmol) in acetone ,6 mL), methyl iodide was added.
After stirring at room temperature for 90 min, the mixture
was ®ltered. The solid was dried in vacuo and cis-N-methyl-
1-methoxystylopinium iodide ,3a) was obtained ,34 mg,
97%) as a yellow solid, mp 254±2558C. [Found C, 51.17;
H, 4.38; N, 2.90. C21H22NO5I requires C, 50.92; H, 4.48; N,
2.83%]; IR ,KBr) nmax 1615, 1495, 1465, 1270 cm21; UV
l
max ,log 1) ,MeOH) 212 ,4.58), 246 ,4.03), 278 ,4.13); 1H
NMR ,CDCl31TFA) d 6.81, 6.62,two d, 1H each,
J8.0 Hz, H-11, H-12), 6.43 ,s, 1H, H-4), 6.03, 5.99,
5.97, 5.96 ,4s, 1H each, 2£OCH2O), 4.88 ,d, 1H,
J16.0 Hz, H-8), 4.86 ,dd, 1H, J11.2, 5.3 Hz, H-14),
4.69 ,d, 1H, J16.0 Hz, H-80), 4.09 ,s, 3H, OMe), 3.8±
3.5 ,m, 2H, H-6, H-5), 3.47 ,dd, 1H, J18.5, 5.3 Hz,
H-13), 3.31 ,s, 3H, NMe), 3.30 ,m, 1H, H-60), 3.15 ,dd,
0
1H, J18.5, 6.2Hz, H-5 ), 2.85 ,dd, 1H, J18.5, 11.2Hz,
H-130); 13C NMR ,CDCl31TFA) d 150.6, 146.9, 144.5,
139.2 ,C-1, C-3, C-9, C-10), 134.6 ,C-2), 121.4, 121.0,
115.5, 106.5 ,C-4a, C-12a, C-14a, C-8a), 120.9 ,C-12),
109.7 ,C-11), 102.7 ,C-4), 102.4, 101.6 ,2£OCH2O), 62.7
,C-14), 61.2,C-8), 59.9 ,OMe), 51.3 ,C-6), 51.0 ,NMe),
33.1 ,C-13), 23.5 ,C-5); MS ,m/z) 353 ,M215, 29), 205
,15), 204 ,12), 148 ,100%).
4.1.11. trans-N-Methyl-1-methoxystylopinium iodide
*4a). To a solution of dihydrocoulteropine ,7a, 64 mg,
0.17 mmol) in chloroform ,15 mL), a few drops of TFA
were added and the mixture was stirred for 30 min. The
solvent was removed in vacuo and the water by azeotropic
distillation. The residue was dissolved in methanol and satu-
rated methanolic potassium iodide was added. The solid was
®ltered to obtain the iodide 4a ,62mg, 75%) as a yellow
solid, mp 268±2698C; IR ,KBr) nmax 1620, 1590, 1500,
1450, 1280 cm21; UV lmax ,log 1) ,MeOH) 208 ,4.48),
4.1.8. cis-N-Methylstylopinium iodide *3b). In a manner
similar to that described above, compound 2b ,25 mg,
0.06 mmol) gave a mixture of cis/trans isomers 3b/4b,
,1:2) as a white solid ,28 mg, 97%). Preparative TLC
,SiO2, CHCl3/MeOH, 10:1) yielded pure isomer 4b
,physical and spectroscopic data are given below) and a
3b/4b mixture enriched in 3b. See Table 3 for spectral
data of 3b obtained from a mixture of isomers.
1
4.1.9. Dihydrocoulteropine *7a). To a solution of coulter-
opine 1a ,150 mg, 0.39 mmol) in dry C6H6 ,15 mL), a
suspension of LiAlH4 ,15 mg, 0.39 mmol) in dry Et2O
,15 mL) was added and the mixture stirred for 1 h at room
temperature. The solvent was removed in vacuo, the
reaction crude being washed with 5% HCl ,2mL) and
extracted with chloroform ,2£20 mL). The organic layer
was dried ,MgSO4), concentrated in vacuo and crystallized
from C6H6/hexane to give compound 7a ,142mg, 94%) as a
white solid, mp 189±1908C [lit.8 193±1948C ,C6H6/
250 ,4.06), 274 ,4.15); H NMR ,CDCl31TFA) d 6.83,
6.73 ,two d, 1H each, J8.1 Hz, H-11, H-12), 6.46 ,s, 1H,
H-4), 6.01 ,d, 1H, J1.0 Hz, OCH2O), 5.99 ,s, 2H,
OCH2O), 5.95 ,d, 1H, J1.0 Hz, OCH2O), 4.96 ,dd, 1H,
J12.4, 3.8 Hz, H-14), 4.88 ,d, 1H, J15.8 Hz, H-8),
4.74 ,d, 1H, J15.8 Hz, H-80), 4.53 ,dd, 1H, J18.5,
3.8 Hz, H-13), 4.29 ,dd, 1H, J11.9, 5.2Hz, H-6), 4.00
,s, 3H, OMe), 3.81 ,ddd, 1H, J11.9, 4.5, 12.0 Hz, H-60),
3.43 ,ddd, 1H, J18.2, 12.0, 5.2 Hz, H-5), 3.11 ,s, 3H,
NMe), 3.05 ,dd, 1H, J18.2, 4.5 Hz, H-50), 2.84 ,dd, 1H,