PAPER
Synthesis of Coscinamide B
2013
washed with H2O and dried (Na2SO4). The solvent was distilled off
and the residue was crystallised from EtOAc–petroleum ether to
furnish 5 (2.92 g, 88%) as reddish brown crystals; mp 198–200 °C.
The filtrate was concentrated and the residue was purified by pre-
parative TLC on silica gel (benzene) to furnish 8 as light orange
flakes (0.168 g, 55%); mp 204–206 °C (CH2Cl2–petroleum ether)
and 9 as yellow needles (52 mg, 15%); mp 222–224 °C (CH2Cl2–
petroleum ether).
IR (KBr): 3388, 3354, 3278, 1662, 1618, 1504, 1436, 1234, 738
cm–1.
8
1H NMR (DMSO-d6): d = 2.941 (t, 2 H, J = 7.5 Hz, H-8), 3.506 (dt,
2 H, J = 7, 7 Hz, H-9), 6.967 (t, 1 H, J = 7.5 Hz, H-5), 7.051 (td, 1
H, J = 7.5, 1 Hz, H-6), 7.18 (d, 1 H, J = 2 Hz, H-2), 7.229 (td, 1 H,
J = 7, 2 Hz, H-5¢), 7.248 (td, 1 H, J = 7, 2 Hz, H-6¢), 7.327 (d, 1 H,
J = 8 Hz, H-7), 7.5–7.537 (m, 1 H, H-7¢), 7.585 (d, 1 H, J = 7.5 Hz,
H-4), 8.2–8.24 (m, 1 H, H-4¢), 8.75 (d, 1 H, J = 3 Hz, H-2¢) , 8.786
(t, 1 H, J = 5.5 Hz, NHCO), 10.803 (br s, 1 H, NH-1), 12.208 (br s,
1 H, NH-1¢).
IR (Nujol): 3337, 1686, 1646, 1175, 764, 724 cm–1.
1H NMR (CDCl3): d= 6.504 (d, 1 H, J = 15 Hz), 7.312 and 7.371 (t
each, 1 H, J = 7.5 Hz), 7.412, 7.449 and 7.512 (t each, 2 H, J = 7.5
Hz), 7.527 and 7.542 (t each, 1 H, J = 7.5 Hz), 7.601 (m, 1 H), 7.611
(s, 1 H), 7.743 (d, 1 H, J = 7.5 Hz), 7.9 (d, 2 H, J = 7.5 Hz), 7.95–
8.08 (m, 4 H), 8.363 (d, 1 H, J = 7.5 Hz), 9.164 (d, 1 H, J = 10.5
Hz), 9.461 (s, 1 H).
13C NMR (CDCl3): d = 108.0, 122.2 (both olefinic CH), 113.7,
114.2, 120.7, 123.2, 123.7, 124.2, 125.6, 125.7, 126.6, 127.2 (2 ×),
127.7 (2 ×), 129.7 (2 ×), 130.1 (2 ×), 134.3, 135.1, 139.1 (ArCH),
116.4, 119.1, 128.4, 129.0, 134.7, 135.9, 137.8, 138.4 (ArC), 158.2
(NHCO), 180.9 (ArCO).
13C NMR (DMSO-d6): d = 25.7 (CH2-8), 40.2 (CH2-9), 112.2 (CH-
7), 113.4 (CH-7¢), 119.13 and 119.19 (CH-4, 5), 121.8 (CH-6),
122.1 (CH-4¢), 123.3 (CH-2), 123.5 (CH-5¢), 124.2 (CH-6¢), 139.3
(CH-2¢), 112.4 (C-3), 113.0 (C-3¢), 127.1 (C-3¢a), 128.0 (C-3a),
137.1 (2 × C-7a, 7¢a), 164.3 (NHCO), 183.0 (ArCO).
MS: m/z (%) = 331 (M+, 31), 144 (100), 143 (98), 130 (60), 116
MS: m/z (%) = 609 (M+, 34), 284 (100), 141 (26), 77 (44).
(15), 89 (9), 77 (3).
HRMS: m/z calcd for C32H23N3O6S2: 609.1029; found: 609.1033
Anal. Calcd for C20H17N3O2: C, 72.50; H, 5.17; N, 12.68. Found: C,
72.54; H, 5.18; N, 12.65.
(M+).
9
1,1¢-Bis(benzenesulfonyl)dihydrocoscinamide B (6)
IR (Nujol): 3350, 1699, 1653, 1182, 731 cm–1.
To a solution 5 (1.66 g, 5 mmol) in CH2Cl2 (50 mL) was added
BnEt3NCl (23 mg, 0.10 mmol, 2 mol%), followed by powdered
NaOH (0.6 g, 15 mmol), and the mixture was stirred at r.t. for 1 h.
Benzenesulfonyl chloride (1.92 mL, 15 mmol) was then added to
this suspension and the mixture was stirred at r.t. for another 1 h.
The reaction mixture was poured into H2O and extracted with
CH2Cl2 (3 × 20 mL). The CH2Cl2 extract was dried (Na2SO4) and
evaporated. The residue was crystallised from CH2Cl2–petroleum
ether to furnish 6 (2.72 g, 89%) as a white amorphous solid; mp
162–164 °C.
1H NMR (CDCl3): d = 7.349 and 7.401 (t each, 1 H, J = 7.5 Hz),
7.416, 7.488 and 7.519 (t each, 2 H, J = 7.5 Hz), 7.580 and 7.618 (t
each, 1 H, J = 7.5 Hz), 7.747 (d, 1 H, J = 11 Hz), 7.822 (s, 1 H),
7.846 (d, 1 H, J = 8 Hz), 7.936 (d, 2 H, J = 8 Hz), 7.955–8.058 (m,
4 H), 8.388 (d, 1 H, J = 7.5 Hz), 9.42 (s, 1 H), 9.507 (d, 1 H, J = 11
Hz).
13C NMR (CDCl3): d = 121.4 (=CH), 113.7, 114.3, 120.9, 123.2,
124.5, 125.8, 126.0, 126.7, 127.1, 127.3 (2 ×), 127.7 (2 ×), 129.9 (2
×), 130.1 (2 ×), 134.6, 135.2, 138.9 (ArCH), 102.8 (=CBr) 116.3,
120.7, 127.5, 128.4, 134.7, 135.8, 137.7, 138.2 (ArC), 158.2 (NH-
CO), 180.1 (ArCO).
MS: m/z (%) = 689 (37), 687 (M+, 34), 608 (100), 468 (45), 351
(27), 326 (66), 284 (13), 141 (16), 77 (91).
HRMS: m/z calcd for C32H22Br79N3NaO6S2: 710.0031; found:
710.0035 (M + Na) +; m/z calcd for C32H22Br81N3NaO6S2:
712.0010; found: 712.0021 (M + Na) +.
IR (Nujol): 3270, 1692, 1653, 1520, 1175, 1135, 976, 751 cm–1.
1H NMR (CDCl3): d = 3.009 (t, 2 H, J = 7 Hz, H-8), 3.711 (dt, 2 H,
J = 7, 7 Hz, H-9), 7.267 (t, 1 H, J = 7.5 Hz, H-5), 7.342 (t, 1 H,
J = 7.5 Hz, H-6), 7.387 (t, 1 H, J = 7.5 Hz, H-5¢), 7.402 (t, 2 H,
J = 7.5 Hz, H-3¢¢¢, 5¢¢¢), 7.417 (t, 1 H, J = 7.5 Hz, H-6¢), 7.43 (t, 1 H,
J = 7.5 Hz, CONH), 7.463 (m, 1 H, H-4¢¢¢), 7.504 [t, 2 H (out of 3
H), J = 7.5 Hz, H-3¢¢, 5¢¢], 7.504 [s, 1 H (out of 3 H), H-2], 7.542 (d,
1 H, J = 7.5 Hz, H-4), 7.597 (t, 1 H, J = 7.5 Hz, H-4¢¢), 7.873 (d, 2
H, J = 7.5 Hz, H-2¢¢¢, 6¢¢¢), 7.986–8.05 (m, 4 H, H-7, 7¢, 2¢¢, 6¢¢), 8.34
(d, 1 H, J = 7 Hz, H-4¢), 9.444 (s, 1 H, H-2¢).
13C NMR (CDCl3): d = 25.4 (CH2-8), 38.9 (CH2-9), 113.6 (CH-7¢),
114.2 (CH-7), 119.7 (CH-4), 123.1 (CH-4¢), 123.8 and 123.9 (CH-
2, 5), 125.4 (CH-6), 125.6 (CH-5¢), 126.4 (CH-6¢), 127.1 (2 ×, CH-
2¢¢¢, 6¢¢¢), 127.7 (2 ×, CH-2¢¢, 6¢¢), 129.7 (2 ×, CH-3¢¢¢, 5¢¢¢), 130.1 (2
×, CH-3¢¢, 5¢¢), 134.1 (CH-4¢¢¢), 135.0 (CH-4¢¢), 138.9 (CH-2¢),
116.5 (C-3¢), 119.8 (C-3), 128.5 (C-3¢a), 130.8 (C-3a), 134.6 (C-
7¢a), 135.7 (C-7a), 137.8 (C-2¢¢), 138.4 (C-2¢¢¢), 161.5 (NHCO),
181.9 (ArCO).
1,1¢-Bis(benzenesulfonyl)-8-bromodihydrocoscinamide B (7)
To a solution of 6 (0.2 g, 0.32 mmol) in CCl4 (40 mL) was added
NBS (63 mg, 0.35 mmol), followed by benzoyl peroxide (5 mg),
and the mixture was refluxed for 3 h, when the solution, as before,
slowly became yellow. After workup as before, followed by purifi-
cation by preparative TLC on silica gel (EtOAc–benzene, 1:9), fur-
nished 7 as a yellowish brown solid (88 mg, 39%); mp 158–160 °C
along with a mixture (TLC) of 8 and 9 (76 mg) which were not fur-
ther separated.
7
MS: m/z (%) = 611 (M+, 21), 284 (75), 283 (100), 70 (13), 141 (16),
77 (18).
IR (Nujol): 3356, 1692, 1653, 1527, 1454, 1175, 970, 751 cm–1.
1H NMR (DMSO-d6): d = 3.527 (ddd, 1 H, J = 13, 6.5, 6.5 Hz, H-
9), 3.662 (ddd, 1 H, J = 12, 6.5, 5.5 Hz, H-9), 5.064 (dd, 1 H, J = 11,
5.5 Hz, H-8), 7.256 (t, 1 H, J = 7.5 Hz, H-5), 7.327 (t, 1 H, J = 7.5
Hz, H-6), 7.43 (t, 1 H, J = 7.5 Hz, H-5¢), 7.455 (t, 2 H, J = 7.5 Hz,
H-3¢¢¢, 5¢¢¢), 7.469 (t, 1 H, J = 7.5 Hz, H-6¢), 7.541 (t, 1 H, J = 7.5
Hz, H-4¢¢), 7.628 (t, 2 H, J = 7.5 Hz, H-3¢¢, 5¢¢), 7.729 (s, 1 H, H-2),
7.744 (t, 1 H, J = 7.5 Hz, H-4¢¢¢), 7.764 (d, 1 H, J = 7.5 Hz, H-4),
7.917 (d, 3 H, J = 8 Hz, H-7, 2¢¢, 6¢¢), 7.983 (d, 1 H, J = 8 Hz, H-7¢),
8.121 (d, 2 H, J = 7.5 Hz, H-2¢¢¢, 6¢¢¢), 8.242 (d, 1 H, J = 7.5 Hz, H-
4¢), 8.921(dd, 1 H, J = 5.5, 5.5 Hz, CONH), 9.125 (s, 1 H, H-2¢).
Anal. Calcd for C32H25N3O6S2: C, 62.84; H, 4.12; N, 6.87. Found:
C, 62.76; H, 4.14; N, 6.85
1,1¢-Bis(benzenesulfonyl)coscinamide B (8) and 8-Bromo-1,1¢-
bis(benzenesulfonyl)coscinamide B (9)
To a solution of 6 (0.306 g, 0.5 mmol) in CCl4 (50 mL) was added
NBS (0.1 g, 0.55 mmol) and benzoyl peroxide (6 mg), and the mix-
ture was refluxed for 8 h when the solution gradually turned yellow.
It was then cooled and the precipitated succinimide was filtered off.
Synthesis 2003, No. 13, 2011–2014 © Thieme Stuttgart · New York