5 S. Hashiguchi, A. Kawada and H. Natsugari, J. Chem. Soc., Perkin
Trans. 1, 1991, 2435.
0.60 mmol) added and the mixture stirred for 2 h. After removal
of the resin by filtration, and washing with DCM (2 × 10 mL), the
solvent was removed from the combined filtrate and washings in
vacuo to afford the title compound 84 as a pale yellow oil (32 mg,
78%, 4″Z:4″E > 95:5); []2D2 +41.5 (c = 0.3, CHCl3); max (film)
3291 (N–H), 2979 (C–H), 1694, 1683, 1651, 1645 (CO carba-
mate, CO amide, CN), 1614 (CC), 1595 (CC), 1532 (amide
II); H (400 MHz, CDCl3) 1.31 (3H, d, J = 6.8, CH3CHN), 1.42
(9H, s, C(CH3)3), 1.58 (3H, s, CH3CCH3), 1.66 (3H, s, CH3CCH3),
1.71–1.92 (2H, m, CHCH2CH), 1.86 (3H, d, J = 7.2, CH3CHCH),
2.38–2.47 (4H, m, CH2CO, CH2CN), 3.48 (2H, m, CH2N), 3.75
(1H, m, CH3CHN), 3.92 (1H, m, CHO), 4.03 (1H, m, CH2CHCH2),
4.75 (4H, br s, NH), 5.75 (1H, br s, NH), 5.88 (1H, dq, J = 10.6,
7.1, CH3CHCH), 6.05 (1H, d, J = 14.7, CHCHCO), 6.15 (1H,
m, CH3CHCH), 7.63 (1H, dd, J = 14.2, 11.8, CHCHCO); C
(125 MHz, CDCl3) 13.8 (CH3CHCH), 21.3 (CH3CHN), 25.9
(CH3CCH3), 27.0 (CH3CCH3), 28.3 (C(CH3)3), 36.2 (CH2CN),
37.4 (CH2N), 38.0 (CHCH2CH), 40.7 (CH2CO), 46.3
(CH2CHCH2), 57.8 (CH3CHN), 79.3 (CHO), 96.0 (C(CH3)2), 122.5
(CHCHCO), 127.4 (CH3CHCH), 134.8 (CH3CHCH), 136.7
(CHCHCO), 155.5 (CO carbamate), 163.7 (CHCHCO),
166.0 (CNH), 171.0 (CH2CO); m/z (ESI) 480 (MH+, 100%);
HRMS (ESI) C24H42N5O5+ requires 480.3186; found 480.3189.
6 For examples see: D. Socha, M. Jurczak and M. Chmielewski,
Tetrahedron Lett., 1995, 36, 135; S. De Bernardo, J. P. Tengi, G. Sasso
and M. Weigele, Tetrahedron Lett., 1988, 29, 4077.
7 For examples, see: S. Shibihara, S. Kondo, K. Maeda, H. Umezawa
and M. Ohno, J. Am. Chem. Soc., 1972, 94, 4353; D. Tanner and
P. Somfai, Tetrahedron Lett., 1988, 29, 2373; H. Iida, K. Kasahara
and C. Kibayashi, J. Am. Chem. Soc., 1986, 108, 4647; K. Kasahara,
H. Iida and C. Kibayashi, J. Org. Chem., 1989, 54, 2225; U. Schmidt,
F. Stäbler and L. Lieberknecht, Synthesis, 1992, 482; R. P. Jain and
R. M. Williams, J. Org. Chem., 2002, 67, 6361.
8 S. Hashiguchi, A. Kawada and H. Natsugari, Synthesis, 1992, 403.
9 S. G. Davies and O. Ichihara, Tetrahedron: Asymmetry, 1991, 2,
183.
10 S. D. Bull, S. G. Davies, S. Delgado-Ballester, M. Gianotti, P. M. Kelly,
L. J. Kotchie, M. Laderas and A. D. Smith, J. Chem. Soc., Perkin Trans.
1, 2001, 3112; S. D. Bull, S. G. Davies and A. D. Smith, J. Chem. Soc.,
Perkin Trans. 1, 2001, 2931; S. D. Bull, S. G. Davies, M. Gianotti,
P. M. Kelly, E. D. Savory and A. D. Smith, J. Chem. Soc., Perkin Trans.
1, 2002, 1858.
11 S. G. Davies, O. Ichihara and I. A. S. Walters, Synlett, 1993, 7, 461;
S. G. Davies, O. Ichihara, I. Lenoir and I. A. S. Walters, J. Chem.
Soc., Perkin Trans. 1, 1994, 1411; M. E. Bunnage, S. G. Davies,
C. J. Goodwin and O. Ichihara, Tetrahedron, 1994, 50, 3975;
S. G. Davies and O. Ichihara, Tetrahedron: Asymmetry, 1996, 7, 1919;
S. G. Davies, C. J. R. Hedgecock and J. M. McKenna, Tetrahedron:
Asymmetry, 1995, 6, 827; A. Chippindale, S. G. Davies, K. Iwamoto,
R. M. Parkin, C. A. P. Smethurst, A. D. Smith and H. Rodriguez-Solla,
Tetrahedron, 2003, 59, 3253; M. E. Bunnage, A. J. Burke, S. G. Davies,
N. L. Millican, R. L. Nicholson, P. M. Roberts and A. D. Smith, Org.
Biomol. Chem., 2003, 1, 3708.
12 S. Bailey, S. G. Davies,A. D. Smith and J. M. Withey, Chem. Commun.,
2002, 2910; M. E. Bunnage, A. M. Chippendale, S. G. Davies,
R. M. Parkin, A. D. Smith and J. M. Withey, Org. Biomol. Chem., 2003,
1, 3698; S. G. Davies, D. Díez, M. M. El Hammouni, N. M. Garrido,
A. C. Garner, M. J. C. Long, R. M. Morrison, A. D. Smith, M. J. Sweet
and J. M. Withey, Chem. Commun., 2003, 2410.
13 S. G. Davies and G. D. Smyth, Tetrahedron: Asymmetry, 1996, 7,
1001; S. G. Davies and G. D. Smyth, Tetrahedron: Asymmetry, 1996,
7, 1005; S. G. Davies and G. D. Smyth, J. Chem. Soc., Perkin Trans.
1, 1996, 2467; S. G. Davies, A. C. Garner, R. L. Nicholson, J. Osborne,
E. D. Savory and A. D. Smith, Chem. Commun., 2003, 2134.
14 S. G. Davies and O. Ichihara, Tetrahedron Lett., 1999, 40, 9313;
S. G. Davies, R. J. Kelly and A. J. Price Mortimer, Chem. Commun.,
2003, 2132.
Sperabillin B hydrochloride 2. To a stirred solution of amidine
84 (29 mg, 0.0605 mmol) in DCM (3 mL) under Ar, was added
TFA(1 mL) drop-wise. The resulting mixture was stirred for 30 min
and the solvent removed in vacuo. The resulting crude product was
1
4″Z:4″E > 95:5 by H NMR spectroscopic analysis. Purification
by preparative HPLC and concentration in vacuo of the fractions
absorbing at = 260 nm followed by passage of the residue through
Amberlite IRA-402 (H2O), and removal of the volatile material in
vacuo afforded sperabillin B hydrochloride 2 as a colourless foam
(15 mg, 60%, 4″Z:4″E 93:7); []2D2 +48.3 (c = 0.24, H2O) {lit.2
[]D +56.0 (c = 1.0, H2O)}; max (KBr disc) 3269, 3068 (N–H, O–H),
1692, 1654 (CO amide, CN), 1618 (CC), 1609 (CC), 1546
(amide II); H (500 MHz, D2O) 1.10 (3H, d, J = 6.6, CH3CHN),
1.61–1.74 (2H, m, CHCH2CH), 1.77 (3H, d, J = 7.2, CH3CHCH),
2.53–2.60 (2H, m, CH2CN), 2.62 (2H, d, J = 6.7, CH2CO)
3.41–3.49 (2H, m, CH2N) 3.72–3.78 (2H, m, CH2CHCH2, CHO),
3.92 (1H, qd, J = 6.7, 3.8, CH3CHNH), 5.91 (1H, dq, J = 10.7,
7.4, CH3CHCH), 5.97 (1H, d, J = 15.2, CHCHCO), 6.12
(1H, appt t, J = 11.2, CH3CHCH), 7.45 (1H, dd, J = 15.2, 11.7,
CHCHCO); C (125 MHz, D2O) 13.6 (CH3CHCH), 16.4
(CH3CHN), 35.0 (CH2CN), 36.6 (CH2N, CHCH2CH), 37.5
(CH2CO), 46.7 (CH2CHCH2), 49.8 (CH3CHN), 70.0 (CHO),
122.8 (CHCHCO), 127.1 (CH3CHCH), 136.9, 137.0
(CH3CHCH, CHCHCO), 169.2, 172.2 (CNH, CH2CO,
CHCHCO); m/z (ESI) 340 (MH+, 100%), 253 (30), 246 (60),
15 N. Yasuda, Y. Hsiao, M. S. Jensen, N. R. Rivera, C. Yang, K. M. Wells,
J. Yau, M. Palucki, L. Tan, P. G. Dormer, R. P. Volante, D. L. Hughes
and P. J. Reider, J. Org. Chem., 2004, 69, 1959.
16 O. P. Vig, M. L. Sharma, A. Sabharwal, R. Gupta and M. L. Huq,
J. Indian Chem. Soc., 1990, 67, 34.
17 C. Binet Du Jassonneix and J. Y. Lallemand, Bull. Soc. Chim. Fr., 1977,
1223.
18 P. Grenouillet, D. Neibecker and I. Tkatchenko, Fr. Demande, FR
86-4644 19860327.
19 S. G. Davies and O. Ichihara, Tetrahedron Lett., 1998, 39, 6045.
20 S. G. Davies and D. R. Fenwick, Chem. Commun., 1995, 1109.
21 S. D. Bull, S. G. Davies, G. Fenton, A. W. Mulvaney, R. S. Prasad and
A. D. Smith, Chem. Commun., 2000, 337; S. D. Bull, S. G. Davies,
G. Fenton, A. W. Mulvaney, R. S. Prasad and A. D. Smith, J. Chem.
Soc., Perkin Trans. 1, 2000, 3765.
+
242 (60), 239 (40), 212 (37), 191 (40); HRMS (ESI) C16H30N5O3
requires 340.2349; found 340.2349.
22 S. D. Bull, S. G. Davies, P. M. Roberts, E. D. Savory and A. D. Smith,
Tetrahedron, 2002, 58, 4629.
Acknowledgements
23 J. F. Costello, S. G. Davies and O. Ichihara, Tetrahedron: Asymmetry,
1994, 5, 3919.
24 S. G. Davies, K. Iwamoto, C. A. P. Smethurst, A. D. Smith and
H. Rodriguez-Solla, Synlett, 2002, 7, 1146.
The authors wish to thank the EPSRC (A. J. P. M.) and
Rhône-Poulenc Rôrer (R. J. K.) for funding and New College, Ox-
ford, for a Junior Research Fellowship (A. D. S.).
25 F. GarroHelion, A. Merzouk and F. Guibe, J. Org. Chem., 1993, 58,
6109.
26 B. C. Laguzza and B. Ganem, Tetrahedron Lett., 1981, 22, 1483.
27 S. G. Davies, D. R. Fenwick and O. Ichihara, Tetrahedron: Asymmetry,
1997, 8, 3387.
28 M. M. Joullie, P. C. Wang and J. E. Semple, J. Am. Chem. Soc., 1980,
102, 887; S. Y. Chen and M. M. Joullie, J. Org. Chem., 1984, 49, 1769;
J. E. Semple, P. C. Wang, Z. Lysenko and M. M. Joullie, J. Am. Chem.
Soc., 1980, 102, 7505.
29 For selected examples see: T. A. Foglia and D. Swern, J. Org. Chem.,
1969, 34, 1680; Y. Takemoto, J. Takeuchi, E. Matsui and C. Iwata,
Synlett, 1995, 737; S. G. Davies, G. D. Smyth and A. M. Chippindale,
J. Chem. Soc., Perkin Trans. 1, 1999, 3089; D. L. Comins andA. L. Wil-
liams, Tetrahedron Lett., 2000, 41, 2839.
References and notes
1 S. Harada and H. Ono, Eur. Pat. Appl., 1986, EP 206068; N. Katayama,
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1992, 45, 10.
2 T. Hida, S. Tsubotani, Y. Funabashi, H. Ono and S. Harada, Bull. Chem.
Soc. Jpn., 1993, 66, 863.
3 Polymers of sperabillins A and B, formed by radical reaction of their
hexa-2,4-dienoyl groups, also show anti-tumour activity in vitro and
in vivo: T. Hida, S. Tsubotani, A. Hori, M. Murakami, H. Natsugari,
Y. Kozai and S. Harada, Chem. Pharm. Bull., 1993, 41, 889.
4 M. Hamada, T. Takeuchi, S. Kondo, Y. Ikeda, H. Naganawa, K. Maeda,
Y. Okami and H. Umezawa, J. Antibiot., 1970, 23, 170.
2 6 4 8
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 2 6 3 0 – 2 6 4 9