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M. Zöllinger et al.
LETTER
(16) (a) Burgess, E. M.; Penton, H. R.; Taylor, E. A. J. Org.
paper on the isolation of dibromophakellstatin, the
absolute configuration had been determined by X-ray
crystal structure analysis.3 Optical activity data have been
Chem. 1973, 38, 26. (b) Burgess, E. M.; Penton, H. R.;
Taylor, E. A. J. Am. Chem. Soc. 1970, 92, 5224.
(17) Appel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 801.
(18) Compound (+)-16: [a]D25 +46.1 (c 1.2 mg/10.0 mL, MeOH).
TLC (silica, EtOAc): Rf = 0.83. 1H NMR (600 MHz,
CDCl3): d = 1.40 (t, 3 H, 3J = 7.1 Hz, OCH2CH3), 2.42 (s,
3 H, ArCH3), 2.90–3.00 (m, 2 H, CCH2), 3.63 (dd, 1 H,
2J = 11.7 Hz, 3J = 9.9 Hz, NCHH), 4.12–4.18 (m, 1 H,
CHBr), 4.42 (dq, 1 H, 2J = 11.5 Hz, 3J = 7.1 Hz, OCHH),
4.44 (dq, 1 H, 2J = 11.5 Hz, 3J = 7.1 Hz, OCHH), 4.53 (dd, 1
H, 2J = 11.7 Hz, 3J = 7.5 Hz, NCHH), 6.05 (s, 1 H, NCHN),
6.36 (dd, 1 H, 3J = 3.6, 3.1 Hz, CHCHCHN), 6.87 (dd, 1 H,
3J = 2.7 Hz, 4J = 1.6 Hz, CHCHCHN), 7.07 (dd, 1 H,
3J = 3.9 Hz, 4J = 1.5 Hz, CHCHCHN), 7.22 [d, 2 H, 3J = 8.3
Hz, MeC(CH)2], 7.61 [d, 2 H, 3J = 8.3 Hz, O2SC(CH)2].
13C NMR (150 MHz, CDCl3): d = 14.1 (OCH2CH3), 21.9
(PhCH3), 35.5 (CHBr), 41.7 (CCH2), 53.5 (NCH2), 65.2
(OCH2), 66.3 (NCHN), 83.5 (CCH2), 112.1 (CHCHCHN),
115.3 (CHCHCHN), 123.0 (CHCHCHN), 123.4
reported by Romo et al. {(–)-1: [a]D25 –70.4; (+)-1: [a]D
25
+68.7}.5
References and Notes
(1) Al-Mourabit, A.; Potier, P. Eur. J. Org. Chem. 2001, 237.
(2) (a) Hoffmann, H.; Lindel, T. Synthesis 2003, 1753.
(b) Jacquot, D. E. N.; Lindel, T. Curr. Org. Chem. 2005, 9,
1551.
(3) Pettit, G. R.; McNulty, J.; Herald, D. L.; Doubek, D. L.;
Chapuis, J. C.; Schmidt, J. M.; Tackett, L. P.; Boyd, M. R.
J. Nat. Prod. 1997, 60, 180.
(4) For example, (–)-1 exhibits an IC50 of 0.7 mM against the
glioblastoma cancer cell line CNXF 498NL, while (+)-1 was
inactive. See: Zöllinger, M.; Kelter, G.; Fiebig, H.-H.;
Lindel, T. Bioorg. Med. Chem. Lett. 2007, 17, 346.
(5) Poullennec, K. G.; Romo, D. J. Am. Chem. Soc. 2003, 125,
6344.
(CCHCHCHN), 129.4 [2 C, O2SC(CH)2], 129.5
[MeC(CH)2], 129.9 [2 C, MeC(CH)2], 146.9 [SO2C(CH)2],
149.0 [O(CO)N], 151.0 [N(CO)N], 154.2 [(CO)N]. MS
(ESI+, FTMS): m/z (%) = 553/555 (100/94.5) [M + H+].
HRMS (ESI+): m/z calcd for [C21H2179BrN4O7S + H]:
553.0393; found: 553.0375.
(6) Jacquot, D. E. N.; Zöllinger, M.; Lindel, T. Angew. Chem.
Int. Ed. 2005, 44, 2295.
(7) Wiese, K. J.; Yakushijin, K.; Horne, D. A. Tetrahedron Lett.
2002, 43, 5135.
(19) Reduction of secondary alkyl bromides by SmI2 has rarely
been reported: (a) Inanaga, J.; Ishikawa, M.; Yamaguchi, M.
Chem. Lett. 1987, 1485. (b) Ogawa, A.; Nanke, T.; Takami,
N.; Sumino, Y.; Ryu, I.; Sonoda, N. Chem. Lett. 1994, 379.
(20) Compound 17 had also been obtained as the (+)-enantiomer
by Romo (ref. 5) and as the racemate by Austin (ref. 9).
(21) Compound (–)-1: [a]D20 –75.7 (c 0.14 mg/mL, MeOH). TLC
(silica, MeOH–CHCl3, 1:9): Rf = 0.52. 1H NMR (600 MHz,
DMSO-d6): d = 1.95–2.00 (m, 1 H, NCHHCHH), 2.08–2.15
(m, 2 H, NCHHCHHCHH), 2.27–2.33 (m, 1 H,
(8) Feldman, K. S.; Skoumbourdis, A. P. Org. Lett. 2005, 7, 929.
(9) Chung, R.; Yu, E.; Incarvito, C. D.; Austin, D. J. Org. Lett.
2004, 6, 3881.
(10) Lu, J.; Tan, X.; Chen, C. J. Am. Chem. Soc. 2007, 129, 7768.
(11) Zöllinger, M.; Mayer, P.; Lindel, T. J. Org. Chem. 2006, 71,
9431.
(12) Compound 4 can be obtained by alkaline hydrolysis of the
corresponding trichloromethylketone. See: Bailey, D. M.;
Johnson, R. E. J. Med. Chem. 1973, 16, 1300.
(13) CCDC-623847 (12) and CCDC-623846 (15) contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via
NCHHCHHCHH), 3.40–3.45 (m, 1 H, NCHH), 3.54–3.57
(m, 1 H, NCHH), 5.98 (s, 1 H, NCHN), 6.91 (s, 1 H,
CBrCH), 7.97 (s, 1 H, NH), 8.26 (s, 1 H, NH). 13C NMR (150
MHz, DMSO-d6): d = 18.8 (NCH2CH2), 39.7 (CCH2), 44.1
(NCH2), 68.6 (NCHN), 78.9 (CCH2), 101.0 (CBrCH), 105.5
(NCBr), 113.7 (CBrCH), 125.3 (CBrCHC), 154.0
Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB21EZ, UK; fax: +44 (1223)336033; or
deposit@ccdc.cam.ac.uk].
[N(CO)N], 157.8 [N(CO)]. MS (ESI+, FTMS): m/z (%) =
389/391/393 (40.9/100/39.1) [M + H+]. CD (MeOH): lmax
(De) = 260 nm (–1.1, tr, sh), 233 (–2.7, tr.). HRMS
(ESI+): m/z calcd for [C11H1079Br2N4O2 + H+]: 388.9249;
found: 388.9255.
(14) (a) Lwowski, W.; Maricich, T. J. J. Am. Chem. Soc. 1963,
85, 1200. (b) Lwowski, W.; Maricich, T. J. J. Am. Chem.
Soc. 1965, 87, 3630.
(15) Fioravanti, S.; Loreto, M. A.; Pellacani, L.; Tardella, P. A.
J. Org. Chem. 1985, 50, 5365.
Synlett 2007, No. 17, 2756–2758 © Thieme Stuttgart · New York