Synthesis of Phytochrome and Related Tetrapyrroles
J . Org. Chem., Vol. 62, No. 9, 1997 2905
22.98, 17.40, 15.08. Anal. Calcd for C25H30O4N2: C, 71.07;
H, 7.16; N, 6.63. Found: C, 71.01; H, 7.19; N, 6.63.
δ 179.57, 161.10, 143.40, 129.00, 128.06, 121.06, 116.83, 92.97,
51.08, 45.57, 40.25, 23.28, 23.12 (2), 21.68, 19.11, 17.02; MS
(EIMS) m/z 302 (M+), 270, 255, 242, 227, 111, 91, 78, 63;
HRMS calcd for C17H22O3N2 302.1630, found: 302.1627.
Z-63a : colorless solid, mp 268-69 °C; Rf 0.38 (30% EtOAc/
Hyd r a zid e 55d . This material was prepared in a fashion
identical to that for hydrazide 20a described above, using 147
mg (1.50 mmol) of 4-pentynoic acid, 290 mg (1.50 mmol) of
N-aminopyrrole 18b in 20 mL of anhydrous THF, and 860 mg
(4.50 mmol, 3.0 equiv) of EDCI, which was stirred for 72 h at
rt. Purification by flash chromatography (silica gel, 15%
EtOAc/hexanes) gave 409 mg (96%) of 55d as a white micro-
crystalline solid: mp 154-5 °C (EtOAc/hexanes); Rf 0.53 (40%
EtOAc/hexanes); IR (KBr) 3261, 2936, 1699, 1531, 1445, 1267,
hexanes); [R]25 ) 40.18° (c 5.5, MeOH); IR (CH2Cl2) 3435,
D
1727, 1680, 1551, 1409, 1299, 1150, 1084 cm-1
;
1H NMR
(CDCl3) δ 1.29 (d, J ) 7.3 Hz, 3H), 1.34 (d, J ) 6.9 Hz, 3H),
1.74 (m, 4H), 2.28 (dq, J ) 7.3 Hz, 1H), 2.40 (m, 2H), 2.77 (dq,
1H), 2.79 (m, 2H), 3.82 (s, 3H), 5.27 (d, J ) 1.92 Hz, 1H), 8.14
(br s, 1H), 8.83 (br s, 1H); 13C NMR (CDCl3) δ 180.06, 161.99,
141.93, 129.67, 128.16, 120.49, 117.23, 90.22, 50.98, 43.75,
42.28, 23.27, 23.24, 23.16, 21.95, 17.68, 14.77; MS (CIMS) m/z
303 (M + 1)+; HRMS calcd for C17H22O3N2 302.1630, found
302.1627. These data are identical to those of an authentic
sample (following paper).
1
1248, 1097, 792, 686 cm-1; H NMR (CDCl3) δ 1.73 (m, 4H),
2.04 (d, 1H), 2.51 (m, 3H), 2.62 (m, 3H), 2.77 (m, 2H), 3.78 (s,
3H), 6.74 (s, 1H), 8.80 (br s, 1H); MS (EIMS) m/z 274 (M+).
Anal. Calcd for C15H18O3N2: C, 65.68; H, 6.61; N, 10.21.
Found: C, 65.78; H, 6.65; N, 10.25.
29c: colorless gum (solidifies in freezer); Rf 0.48 (30%
N-P yr r olo En a m id e 56b. This material was prepared in
a fashion identical to that for N-pyrrolo enamide 56a described
above (method B), using 70.0 mg (0.20 mmol) of hydrazide 55b
in 7.0 mL of THF and 1.21 mL (1.21 mmol) of 1.0 M TBAF in
THF. After the mixture was heated at reflux for 1 h, workup
and purification by preparative TLC (silica gel, 250 µm, 30%
EtOAc/hexanes) gave 49 mg (70%) of 56b as a colorless gum:
EtOAc/hexanes); [R]25 ) 37.01° (c 5.2, MeOH); 1H NMR
D
(CDCl3) δ 1.30 (2d, 6H, Me), 1.72 (m, 4H), 2.26 (m, 2H), 2.29
(m, 1H), 2.59 (m, 1H), 2.78 (m, 2H), 3.81 (s, 3H), 4.15 (d, J )
1.8 Hz, 1H), 4.24 (d, J ) 1.8 Hz, 1H), 8.08 (br s, 1H).
P h otolysis of N-P yr r olo En a m id e en t-56a (f en t-29c,
32b, en t-E-63a , en t-Z-63a ). Photolysis of 277 mg (0.92 mmol)
of N-pyrrolo enamide ent-56a for 16 h at -10 °C (300 nm,
piperylene), by following the general procedure described
above, afforded 127 mg (46%) of ent-63a as a 55:72 E/ Z
mixture, 26 mg (9%) of recovered ent-56a , 26 mg (9%) of
pyrrole 32b, and 36 mg (13%) of 1,5-isomer ent-29c (not shown;
cf. Scheme 5). Purification was accomplished by preparative
TLC. Except for specific rotations, these materials were
identical to the enantiomers derived from 56a above. Specific
rotations: ent-29c, [R]25D ) -36.66° (c 2.7, MeOH); ent-E-63a ,
[R]25D ) -38.08° (c 2.7, MeOH); ent-Z-63a , [R]25D ) -40.98° (c
4.88, MeOH).
P h otolysis of N-P yr r olo En a m id e 56b (f 29d , 32b,
E-63b, Z-63b). Photolysis of 41.2 mg (0.12 mmol) of N-pyrrolo
enamide 56b for 17 h at -10 °C (300 nm, piperylene), by
following the general procedure described above, afforded 15.4
mg (37%) of 63b as a 1:1 E/ Z mixture, 8 mg (20%) of recovered
56b, 4 mg (10%) of pyrrole 32b, and 8 mg (20%) of 1,5-isomer
29d (not shown; cf. Scheme 5). Purification was accomplished
by preparative TLC (silica gel).
Rf 0.53 (30% EtOAc/hexanes); [R]25 ) -11.92° (c 16, MeOH);
D
1H NMR (CDCl3) δ (two atropisomers) 1.20, 1.27. 1.40, 1.45
(4d, J ) 6.4 HZ, 6H), 1.75 (m, 4H), 2.50 (m, 2H), 2.70 (m, 1H),
2.80 (m, 2H), 3.00 (m, 1H), 3.41, 3.73, 3.76 (3s, 6H), 3.60 (m,
1H), 3.85, 3.93, 4.20, 4.25 (4dd, J ) 1 Hz, 2H), 6.51, 6.55 (2s,
1H). Anal. Calcd for C19H26O4N2: C, 65.88; H, 7.56; N, 8.09.
Found: C, 65.85; H, 7.60; N, 8.09.
N-P yr r olo En a m id e 56c. This material was prepared in
a fashion identical to that for N-pyrrolo enamide 56a described
above (method B), using 194 mg (0.45 mmol) of hydrazide 55c
in 50 mL of THF, and 2.75 mL (2.75 mmol) of 1.0 M TBAF in
THF. After the mixture was heated reflux for 2 h, workup
and purification by preparative TLC (silica gel, 500 µm, 30%
EtOAc/hexanes) gave 148 mg (76%) of 56c as a colorless gum:
Rf 0.77 (40% EtOAc/hexanes); [R]25 ) -18.20° (c 15, MeOH);
D
1H NMR (CDCl3) δ (two atropisomers) 1.26 (d, J ) 6.2 Hz,
3H), 1.45 (d, J ) 7.6 Hz, 3H), 1.73 (m, 4H), 2.51 (m, 2H), 2.75-
3.00 (m, 4H), 3.76 (s, 3H), 3.80 (m, 1H), 3.92 (t, J ) 1.2 Hz,
1H), 4.17 (t, J ) 1.2 Hz, 1H), 4.52 (d, 1H), 4.60 (d, 1H), 6.40
(s, 1H), 7.33 (m, 5H). Anal. Calcd for C25H30N2O4: C, 71.01;
H, 7.19; N, 6.63. Found: C, 70.83; H, 7.16; N, 6.57.
Z-63b: pale yellow foam; Rf 0.30 (40% EtOAc/hexanes);
[R]25D ) -20.83° (c 8.21, MeOH); IR (CH2Cl2) 3437, 2931, 2821,
1732, 1686, 1591, 1497, 1455, 1366, 1298, 1238, 1189, 1083,
N-P yr r olo En a m id e 56d . This material was prepared in
a fashion identical to that for N-pyrrolo enamide 56a described
above (method B), using 125 mg (0.46 mmol) of hydrazide 55c
in 15 mL of THF and 2.73 mL (2.73 mmol) of 1.0 M TBAF in
THF. After the mixture was heated at reflux for 1 h, workup
and purification by preparative TLC (silica gel, 1000 µm, 40%
EtOAc/hexanes) gave 110 mg (88%) of 56d as a colorless gum,
which crystallized from EtOAc/hexane as a colorless solid: mp
167-68 °C; Rf 0.40 (40% EtOAc/hexanes); IR (CH2Cl2) 2940,
2858, 2253, 1745, 1697, 1575, 1605, 1455, 1402, 1308, 1241,
1
1018, 956, 809 cm-1; H NMR (CDCl3) δ 1.18 (d, J ) 6.2 Hz,
3H), 1.34 (d, J ) 7.36 Hz, 3H), 1.75 (m, 4H), 2.41 (m, 2H),
2.62 (m, 1H), 2.78 (m, 2H), 2.98 (m, 1H), 3.39 (s, 3H), 3.58
(dq, 1H), 3.82 (s, 3H), 5.33 (d, J ) 1.28 Hz, 1H), 8.26 (br s,
1H), 8.97 (br s, 1H); MS (EIMS) m/z 346 (M+), 314, 270, 255,
244, 212, 170, 115, 84; (CIMS) 347 (M + 1)+; HRMS calcd for
C19H26O4N2 346.1892, found 346.1880. Anal. Calcd for
C19H26O4N2: C, 65.88; H, 7.56; N, 8.09. Found: C, 65.89; H,
7.60; N, 8.08.
1
1189, 1102, 958, 911, 829, 760 cm-1; H NMR (CDCl3) δ 1.72
E-63b: yellow foam; Rf 0.15 (40% EtOAc/hexanes); [R]25
D
(m, 4H), 2.52 (m, 2H), 2.60-2.95 (m, 6H), 3.74 (s, 3H), 3.83
(d, J ) 1.8 Hz, 1H), 4.15 (d, J )1.8 Hz, 1H), 6.56 (s, 1H); 13C
NMR (CDCl3) δ 173.17, 159.99, 145.55, 130.10, 123.26, 119.97,
115.32, 84.47, 50.79, 27.33, 23.76, 22.90, 22.80, 21.94, 21.49;
MS (EIMS) m/z 274 (M+•). Anal. Calcd for C15H18O3N2: C,
65.68; H, 6.61; N,10.21. Found: C, 65.54; H, 6.61; N, 10.12.
This compound was also prepared in 71% yield by following
method A (vide supra).
) -14.11° (c 5.1, MeOH); IR (CH2Cl2) 4314, 3260, 3060, 2988,
1723, 1662, 1391 cm-1 1H NMR (CDCl3) δ 1.25 (d, J ) 7.6
;
Hz, 3H), 1.28 (d, J ) 7.6 Hz, 3H), 1.74 (m, 4H), 2.31 (m, 1H),
2.44 (m, 2H), 2.78 (m, 2H), 2.85 (m, 1H), 3.35 (m, 1H), 3.40 (s,
3H), 3.80 (s, 3H), 5.82 (s, 1H), 7.35 (br s, 1H), 10.61 (br s, 1H);
MS (EIMS) m/z 346 (M
+), 314, 270, 255, 244, 212, 170, 115,
84; (CIMS) m/z 347 (M + 1)+; HRMS calcd for C19H26O4N2
346.1898, found 346.1894.
P h otolysis of N-P yr r olo En a m id e 56a (f 29c, 32b,
E-63a , Z-63a ). Photolysis of 251 mg (0.83 mmol) of N-pyrrolo
enamide 56a for 16 h at -10 °C (300 nm, piperylene), by
following the general procedure described above, afforded 98
mg (39%) of 63a as a 47:51 E/ Z mixture, 18 mg (7%) of
recovered 56a , 41 mg (16%) of pyrrole 32b, and 32 mg (13%)
of 1,5-isomer 29c (not shown; cf. Scheme 5). Purification was
accomplished by preparative TLC (silica gel).
29d : pale yellow foam; Rf 0.42 (40% EtOAc/hexanes); [R]25
D
) -11.75° (c 9.7, MeOH); IR (CH2Cl2) 3431, 3061, 2974, 2937,
2859, 2826, 1727, 1690, 1593, 1509, 1382, 1330, 1259 cm-1
;
1H NMR (CDCl3) δ 1.18 (d, J ) 6.2 Hz, 3H), 1.34 (d, J ) 7.3
Hz, 3H), 1.73 (m, 4H), 2.30 (m, 2H), 2.70 (m, 1H), 2.83 (m,
2H), 2.90 (m, 1H), 3.41 (s, 3H), 3.60 (dq, 1H), 3.84 (s, 3H), 4.28
(dt, J ) 1.2 Hz, 2H), 8.72 (br s, 1H).
P h otolysis of N-P yr r olo En a m id e 56d (f 32b, E-63d ,
Z-63d ). Photolysis of 150 mg (0.55 mmol) of N-pyrrolo
enamide 56d for 36 h at -10 °C (300 nm, piperylene), by
following the general procedure described above (rigorous
exclusion of air), afforded 90.3 mg (60%) of 63d as a 1:1 E/ Z
mixture, 30 mg (20%) of recovered 56d , and 12 mg (8%) of
E-63a : yellow foam; Rf 0.2 (30% EtOAc/hexanes); [R]25
)
D
38.04° (c 3.13, MeOH); 1H NMR (CDCl3) δ 1.21 (d, J ) 7.2 Hz,
3H), 1.28 (d, J ) 7.3 Hz, 3H), 1.71 (m, 4H), 2.28 (dq, J ) 3.2
Hz, 1H), 2.38 (m, 2H), 2.75 (m, 2H), 2.89 (m, 1H), 3.80 (s, 3H),
5.67 (s, 1H), 8.61 (br s, 1H), 8.91 (br s, 1H); 13C NMR (CDCl3)