H. Tamiaki et al. / Tetrahedron 72 (2016) 3477e3489
3485
s, NHꢂ2); IR (film)
n
¼3430 (OeH), 1736 (172-C]O), 1695 cmꢁ1 (13-
172-COOCH3), 3.43/42 (3H, s, 2-CH3), 3.22 (3H, s, 7-CH3), 2.773/765
(1H, d, J¼3 Hz, OH), 2.71e2.65, 2.61e2.50, 2.35e2.22 (1Hþ1Hþ2H,
m, 17-CH2CH2), 1.82 (3H, s, 32-CH3), 1.81/80 (3H, d, J¼7 Hz, 18-CH3),
1.69 (3H, t, J¼8 Hz, 81-CH3), 0.38, e1.79 (each 1H, s, NHꢂ2); IR
C]O); HRMS (APCI) found: m/z 595.3279, calcd for C36H43N4O4:
MHþ, 595.3280; see also its spectral data in Ref. 13.
4.3.4. Methyl 32,32-ethylene-bacteriopheophorbide-d (2f) [3-
C*H(OH)cycloPr]. Black solid; mp 121e123 ꢀC; VIS (CH2Cl2)
lmax¼663 (relative intensity, 0.49), 606 (0.08), 537 (0.10), 506
(film)
n
¼3450 (OeH), 1736 (172-C]O), 1695 cmꢁ1 (13-C]O);
HRMS (APCI) found: m/z 593.3122, calcd for C36H41N4O4: MHþ,
593.3122.
(0.10), 410 nm (1.00); 1H NMR (CDCl3)
d¼9.69/67 (1H, s, 10-H), 9.45
(1H, s, 5-H), 8.52/51 (1H, s, 20-H), 5.51/50 (1H, d, J¼9 Hz, 3-CH),
5.24/19, 5.10/05 (each 1H, d, J¼20 Hz, 131-CH2), 4.45 (1H, dq, J¼2,
7.5 Hz, 18-H), 4.25 (1H, m, 17-H), 3.67 (2H, q, J¼8 Hz, 8-CH2), 3.63
(3H, s, 12-CH3), 3.604/598 (3H, s, 172-COOCH3), 3.416/407 (3H, s, 2-
CH3), 3.24 (3H, s, 7-CH3), 2.77/76 (1H, br, 31-OH), 2.71e2.61,
2.58e2.48, 2.31e2.21 (1Hþ1Hþ2H, m, 17-CH2CH2), 2.13e2.03 (1H,
m, 31-CH), 1.78/77 (3H, d, J¼7.5 Hz, 18-CH3), 1.67 (3H, t, J¼8 Hz, 81-
CH3), 0.98e0.84, 0.70e0.63, 0.60e0.53 (2Hþ1Hþ1H, m, 32-
4.3.8. Methyl 32-methylidyne-bacteriopheophorbide-d (2k) [3-
C*H(OH)C^CH]. Black solid; mp 158e160 ꢀC; VIS (CH2Cl2)
lmax¼665 (relative intensity, 0.51), 607 (0.08), 537 (0.09), 507
(0.10), 411 nm (1.00); 1H NMR (CDCl3)
d
¼9.80/75 (1H, s, 10-H), 9.36
(1H, s, 5-H), 8.56/55 (1H, s, 20-H), 6.95/92 (1H, br, 3-CH), 5.14/12,
5.01/00 (each 1H, d, J¼20 Hz,131-CH2), 4.43 (1H, br q, J¼7 Hz,18-H),
4.15 (1H, br t, J¼7 Hz, 17-H), 3.65 (2H, q, J¼7.5 Hz, 8-CH2), 3.62 (3H,
s, 12-CH3), 3.56 (3H, s, 172-COOCH3), 3.52/50 (3H, s, 2-CH3), 3.26
(3H, s, 7-CH3), 2.941/938 (1H, d, J¼1 Hz, 32hCH), 2.63e2.50,
2.31e2.13 (each 2H, m, 17-CH2CH2), 1.76/74 (3H, d, J¼7 Hz, 18-CH3),
1.66 (3H, t, J¼7.5 Hz, 81-CH3), 0.00, e2.01 (each 1H, s, NHꢂ2); IR
CH2ꢂ2), 0.32, e1.81 (each 1H, s, NHꢂ2); IR (film) ¼3440 (OeH),
n
1736 (172-C]O), 1694 cmꢁ1 (13-C]O); HRMS (APCI) found: m/z
593.3124, calcd for C36H41N4O4: MHþ, 593.3122.
(film)
n
¼3430 (OeH), 2115 (C^C), 1734 (172-C]O), 1690 cmꢁ1 (13-
4.3.5. Methyl 32-methylene-bacteriopheophorbide-d (2g) [3-
C*H(OH)CH]CH2]. Black solid; mp 132e135 ꢀC; VIS (CH2Cl2)
lmax¼663 (relative intensity, 0.50), 606 (0.07), 536 (0.09), 506
C]O); HRMS (APCI) found: m/z 577.2809, calcd for C35H37N4O4:
MHþ, 577.2809; see also its spectral data in Ref. 28.
(0.09), 410 nm (1.00); 1H NMR (CDCl3)
d
¼9.68/67 (1H, s, 10-H), 9.52
4.3.9. Methyl 32-ethylidyne-bacteriopheophorbide-d (2l) [3-C*H(OH)
ChCMe]. Black solid; mp 125e127 ꢀC; VIS (CH2Cl2) lmax¼666
(relative intensity, 0.53), 609 (0.07), 537 (0.09), 507 (0.09), 410 nm
(1H, s, 5-H), 8.55/54 (1H, s, 20-H), 6.76e6.67 (2H, m, 3-CHCH), 5.72
(1H, d, J¼16 Hz, 32¼CH trans to C32eH), 5.44 (1H, s, J¼9 Hz, 32¼CH
cis to C32eH), 5.26/25, 5.11/10 (each, 1H, d, J¼20 Hz, 131-CH2), 4.48
(1H, br q, J¼7 Hz, 18-H), 4.29 (1H, br d, J¼7 Hz, 17-H), 3.70 (2H, q,
J¼7.5 Hz, 8-CH2), 3.67 (3H, s, 12-CH3), 3.61/60 (3H, s, 172-COOCH3),
3.42/41 (3H, s, 2-CH3), 3.24 (3H, s, 7-CH3), 2.76 (1H, br s, OH),
2.72e2.64, 2.61e2.50, 2.34e2.22 (1Hþ1Hþ2H, m, 17-CH2CH2),
1.81/79 (3H, d, J¼7 Hz, 18-CH3), 1.69 (3H, t, J¼7.5 Hz, 81-CH3), 0.33,
(1.00); 1H NMR (CDCl3)
d¼9.85/81 (1H, s,10-H), 9.43/42 (1H, s, 5-H),
8.56/55 (1H, s, 20-H), 6.90/88 (1H, s, 3-CH), 5.22/17, 5.08/03 (each
1H, d, J¼20 Hz, 131-CH2), 4.41 (1H, m, 18-H), 4.23 (1H, m, 17-H), 3.67
(2H, q, J¼8 Hz, 8-CH2), 3.62 (3H, s, 12-CH3), 3.61 (3H, s, 172-
COOCH3), 3.50/48 (3H, s, 2-CH3), 3.27 (3H, s, 7-CH3), 2.92 (1H, s, 31-
OH), 2.71e2.59, 2.58e2.53, 2.33e2.17 (1Hþ1Hþ2H, m, 17-CH2CH2),
2.01 (3H, s, 33-CH3), 1.78/76 (3H, d, J¼7 Hz, 18-CH3), 1.68 (3H, t,
e1.81 (each 1H, s, NHꢂ2); IR (film)
n
¼3450 (OeH), 1736 (172-C]O),
1690 cmꢁ1 (13-C]O); HRMS (APCI) found: m/z 579.2966, calcd for
J¼7 Hz, 81-CH3), 0.25, e1.92 (each 1H, s, NHꢂ2); IR (film)
¼3440
n
C
35H39N4O4: MHþ, 579.2966.
(OeH), 2226 (C^C), 1736 (172-C]O), 1694 cmꢁ1 (13-C]O);
HRMS (APCI) found: m/z 591.2966, calcd for C36H39N4O4: MHþ,
591.2964.
4.3.6. Methyl 32-cis/trans-ethylidene-bacteriopheophorbide-d (2h/i)
[3-C*H(OH)-cis/trans-CH¼CHMe¼3/7]. Black solid; mp 115e117 ꢀC;
VIS (CH2Cl2) lmax¼662 (relative intensity, 0.47), 606 (0.08), 536
4.3.10. Methyl 32-phenylmethylidyne-bacteriopheophorbide-d (2m)
[3-C*H(OH)ChCPh]. Black solid; mp 140e141 ꢀC; VIS (CH2Cl2)
lmax¼666 (relative intensity, 0.54), 608 (0.08), 537 (0.10), 506
(0.10), 506 (0.10), 410 nm (1.00); 1H NMR (CDCl3)
d
¼9.674/645 (1H-
trans, s, 10-H), 9.654/631 (1H-cis, s, 10-H), 9.432 (1H-trans, s, 5-H),
9.427 (1H-cis, s, 5-H), 8.51 (1H-trans, s, 20-H), 8.50 (1H-cis, s, 20-H),
7.04/02 (1H-cis, d, J¼8 Hz, 3-CH), 6.66/64 (1H-trans, d, J¼8 Hz, 3-
CH), 6.56e6.47 (1H-cis, m, 31-CH), 6.43e6.34 (1H-trans, m, 31-
CH), 6.09 (1H-trans, dq, J¼15, 7 Hz, 32¼CH), 5.78 (1H-cis, dq, J¼11,
7 Hz, 32¼CH), 5.22/20, 5.07/06 (each 1H-trans, d, J¼20 Hz, 131-CH2),
5.21, 5.07 (each 1H-cis, d, J¼20 Hz, 131-CH2), 4.45 (1H, q, J¼7 Hz, 18-
H), 4.24 (1H, m, 17-H), 3.67 (2H, q, J¼8 Hz, 8-CH2), 3.62 (3H, s, 172-
COOCH3), 3.610 (3H-cis, s,12-CH3), 3.607 (3H-trans, s,12-CH3), 3.44/
43 (3H-cis, s, 2-CH3), 3.39/38 (3H-trans, s, 2-CH3), 3.234 (3H-cis, s,
7-CH3), 3.227 (3H-trans, s, 7-CH3), 2.80e2.47, 2.36e2.17 (3Hþ2H,
m, 31-OH, 17-CH2CH2), 2.09e1.97, 1.83e1.73 (3H, m, 33-CH3), 1.79
(3H-trans, d, J¼7 Hz, 18-CH3), 1.76 (3H-cis, d, J¼7 Hz, 18-CH3), 1.68
(3H, t, J¼8 Hz, 81-CH3), 0.28, e1.85 (each 1H, s, NHꢂ2); IR
(0.10), 411 nm (1.00); 1H NMR (CDCl3)
d
¼9.93/92 (1H, s, 10-H), 9.52
(1H, s, 5-H), 8.62/61 (1H, s, 20-H), 7.52e7.50 (2H, m, o-H of 33-Ph),
7.31e7.30 (3H, m, m-, p-H of 33-Ph), 7.18/17 (1H, s, 3-CH), 5.27/22,
5.12/07 (each 1H, d, J¼20 Hz, 131-CH2), 4.41 (1H, dq, J¼2, 7 Hz, 18-
H), 4.18 (1H, br t, J¼9 Hz, 17-H), 3.70 (2H, q, J¼8 Hz, 8-CH2), 3.66
(3H, s, 12-CH3), 3.612/607 (3H, s, 172-COOCH3), 3.573/565 (3H, s, 2-
CH3), 3.253/248 (3H, s, 7-CH3), 2.96 (1H, s, 31-OH), 2.74e2.65,
2.59e2.51, 2.36e2.24 (1Hþ1Hþ2H, m, 17-CH2CH2), 1.82/80 (3H, d,
J¼7 Hz, 18-CH3), 1.71 (3H, t, J¼7 Hz, 81-CH3), 0.25, e1.82 (each 1H, s,
NHꢂ2); IR (film)
n
¼3420 (OeH), 2233 (C^C), 1736 (172-C]O),
1697 cmꢁ1 (13-C]O); HRMS (APCI) found: m/z 653.3123, calcd for
C
41H41N4O4: MHþ, 653.3122.
(film)
n
¼3440 (OeH), 1736 (172-C]O), 1694 cmꢁ1 (13-C]O);
4.3.11. Methyl 31-demethyl-31-phenyl-bacteriopheophorbide-d (2n)
[3-C*H(OH)Ph]. Black solid; mp 138e140 ꢀC; VIS (CH2Cl2) lmax¼663
(relative intensity, 0.50), 607 (0.08), 537 (0.09), 507 (0.10), 411 nm
HRMS (APCI) found: m/z 593.3123, calcd for C36H41N4O4: MHþ,
593.3122.
(1.00); 1H NMR (CDCl3)
d
¼9.67 (1H, s, 10-H), 9.49 (1H, s, 5-H), 8.50
4.3.7. Methyl 32-methyl-32-methylene-bacteriopheophorbide-d (2j)
[3-C*H(OH)CMe¼CH2]. Black solid; mp 131e133 ꢀC; VIS (CH2Cl2)
lmax¼663 (relative intensity, 0.50), 606 (0.08), 537 (0.09), 506
(1H, s, 20-H), 7.73/72 (2H, d, J¼8 Hz, o-H of 31-Ph), 7.36 (2H, t,
J¼8 Hz, m-H of 31-Ph), 7.36/32 (1H, s, 3-CH), 7.28 (1H, t, J¼8 Hz, p-H
of 31-Ph), 5.14/11, 5.02/01 (each 1H, d, J¼20 Hz, 131-CH2), 4.41 (1H,
m, 18-H), 4.18 (1H, br t, J¼9 Hz, 17-H), 3.63/62 (3H, s, 12-CH3), 3.61
(2H, q, J¼8 Hz, 8-CH2), 3.56/55 (3H, s, 172-COOCH3), 3.38/37 (3H, s,
2-CH3), 3.10/08 (3H, s, 7-CH3), 2.63e2.49, 2.28e2.14 (each 2H, m,
17-CH2CH2), 1.76/74 (3H, d, J¼7 Hz, 18-CH3), 1.64/63 (3H, t, J¼8 Hz,
(0.09), 410 nm (1.00); 1H NMR (CDCl3)
d
¼9.76/75 (1H, s,10-H), 9.53/
52 (1H, s, 5-H), 8.56/55 (1H, s, 20-H), 6.59 (1H, br, 3-CH), 5.85, 5.32
(each 1H, br s, 32¼CH2), 5.27/26, 5.11 (each 1H, d, J¼20 Hz,131-CH2),
4.49/48 (1H, dq, J¼2, 7 Hz, 18-H), 4.30/29 (1H, dt, J¼9, 2 Hz, 17-H),
3.70 (2H, q, J¼8 Hz, 8-CH2), 3.68 (3H, s, 12-CH3), 3.608/606 (3H, s,
81-CH3), 0.08, e1.94/96 (each 1H, s, NHꢂ2); IR (film)
¼3450 (OeH),
n