PAPER
-(Triphenylphosphoranylidene)heptan-2-one (3)
Total Synthesis of (±)-Batzelladine K
2569
1
Anal. Calcd for C H O : C, 75.63; H, 9.97. Found: C, 75.91; H,
1
4
22
2
A 1.6 M soln of BuLi in hexane (11.5 mL, 18.9 mmol) was added
10.09.
dropwise to a cooled (–78 °C) soln of 2 (5 g, 15.7 mmol) in THF
(250 mL), resulting in the formation of a deep red color. The mix-
(±)-Batzelladine K (1)
ture was stirred for 30 min, and then BuI (2.15 mL, 18.8 mmol) was
added dropwise. The resulting mixture was then allowed to stir at
To a cooled (0 °C) soln of 6 (200 mg, 0.9 mmol) in DMF (5 mL)
was added guanidine (7; 53 mg, 0.9 mmol) in DMF (1 mL), and the
mixture was allowed to stir at 25 °C for 5 h. The reaction mixture
2
5 °C for 12 h. After evaporation of the THF, the resulting red oil
was dissolved in EtOAc (30 mL) and the soln was washed with H O
was cooled again at 0 °C and MeOH (5 mL) and H O (2 mL) were
2
2
(
2 × 50 mL); the organic layer was dried over Na SO and subse-
added, followed by NaBH (200 mg, 5.4 mmol). The mixture was
2
4
4
quently concentrated in vacuo to give phosphorane 3 as a viscous
oil.
then stirred at 25 °C overnight; the MeOH was evaporated in vacuo
and the reaction mixture was diluted with CH Cl (15 mL), fol-
2
2
lowed by 2 M aq HCI (5 mL). The organic layer was separated and
Yield: 5.8 g (98%).
the aqueous layer was washed with CH Cl (3 × 10 mL). The com-
2
2
–
1
IR (KBr): 3282, 1715, 1566, 1429 cm .
bined organic layer was washed with H O (3 × 40 mL) and brine
2
1
(2 × 40 mL), then dried over Na SO , and concentrated in vacuo to
H NMR (400 MHz, CDCl ): d = 0.89 (t, J = 6.8 Hz, 3 H), 1.34 (m,
2
4
3
give a slightly yellow oil, which upon column chromatography (sil-
4
7
6
H), 1.66 (quin, J = 7.6, 15.2 Hz, 2 H), 2.30 (t, J = 7.6 Hz, 2 H),
.42–7.48 (m, 6 H, ArH), 7.52–7.55 (m, 3 H, ArH), 7.61–7.67 (m,
H, ArH); methine H not observed.
ica gel, CHCl –MeOH, gradient) afforded 1 as a yellow semisolid.
3
Yield: 55 mg (25%).
1
3
C NMR (100 MHz, CDCl ): d = 14.1, 22.6, 26.9, 33.0, 41.6,
1
3
H NMR (400 MHz, CDCl ): d = 0.90 (t, J = 6.56 Hz, 3 H), 1.32 (d,
3
1
1
28.4, 128.5, 128.7, 128.8, 129.0, 131.90, 131.93, 131.95, 133.9,
32.0, 132.0, 132.1, 133.0, 133.1.
J = 6.2 Hz, 3 H), 1.25 (m, 2 H), 1.30 (m, 6 H), 1.54 (m, 1 H), 1.62
m, 1 H), 1.70 (m, 2 H), 2.22 (m, 2 H), 2.26 (m, 2 H), 3.39 (m, 1 H),
3.54 (m, 1 H), 3.68 (m, 2 H).
(
MS (CI): m/z = 375 [M + 1]+.
1
3
C NMR (100 MHz, CDCl ): d = 14.0, 20.5, 22.6, 25.0, 30.3, 30.4,
Anal. Calcd for C H OP: C, 80.19; H, 7.27. Found: C, 80.38; H,
3
25
27
3
1.4, 34.0, 34.7, 36.5, 45.7, 50.1, 55.7, 55.8, 162.5.
7
.56.
MS (CI): m/z = 250 [M + 1]+.
(
E)-6-Oxoundec-4-enal (5)
+
HRMS (ESI ): m/z calcd for C H N [M + H]: 250.2283; found:
1
5
28
3
Freshly prepared succinaldehyde (4; 1.8 g, 21 mmol) was added to
2
50.2261.
a soln of 3 (2 g, 5.3 mmol) in CH Cl (15 mL) and the resulting soln
2
2
was stirred at 25 °C for 24 h. The soln was then washed with H O
2
(
2 × 30 mL) to remove excess succinaldehyde and concentrated in
Acknowledgment
vacuo; this gave the crude product, which was subjected to column
chromatography (silica gel, hexane–EtOAc, gradient); this gave
product 5 as a slightly yellow oil.
The authors thank the Department of Biotechnology, Ministry of
Science and Technology, Government of India for the financial sup-
port for this project (grant no. BT/PR7020/Med/14/930/2005).
Yield: 660 mg (68%).
–
1
IR (KBr): 3188, 1730, 1628, 1556 cm .
1
References
H NMR (400 MHz, CDCl ): d = 0.88 (t, J = 7.12 Hz, 3 H), 1.30 (m,
3
4
H), 1.59 (quin, J = 7.36, 14.7 Hz, 2 H), 2.53 (m, 4 H), 2.67 (t, 6.0
(
1) (a) Berlinck, R. G. S. Nat. Prod. Rep. 1996, 13, 377.
Hz, 2 H), 6.10 (d, J = 15.9 Hz, 1 H), 6.78 (dt, J = 6.2, 15.8 Hz, 1 H),
9
(
b) Berlinck, R. G. S. Nat. Prod. Rep. 1999, 16, 339.
.88 (s, 1 H).
(
c) Berlinck, R. G. S. Nat. Prod. Rep. 2002, 19, 617.
1
3
C NMR (100 MHz, CDCl ): d = 13.9, 22.4, 23.8, 24.5, 31.4, 40.3,
(d) Berlinck, R. G. S.; Kossuga, M. H. Nat. Prod. Rep. 2005,
22, 516. (e) Berlinck, R. G. S.; Burtoloso, A. C. B.; Kossuga,
M. H. Nat. Prod. Rep. 2008, 25, 919. (f) Heys, L.; Moore,
C. G.; Murphy, P. J. Chem. Soc. Rev. 2000, 29, 57.
3
4
1.9, 130.9, 143.9, 200.3, 200.4.
MS (CI): m/z = 183 [M + 1]+.
Anal. Calcd for C H O : C, 72.49; H, 9.95. Found: C, 72.71; H,
1
(2) Patil, A. D.; Kumar, N. V.; Kokke, W. C.; Bean, M. F.;
Freyer, A. J.; Brosse, C. D.; Mai, S.; Truneh, A.; Faulkner,
D. J.; Carté, B.; Breen, A. L.; Hertzberg, R. P.; Johnson, R.
K.; Westley, J. W.; Potts, B. C. M. J. Org. Chem. 1995, 60,
11
18
2
0.19.
(
3E,7E)-Tetradeca-3,7-diene-2,9-dione (6)
Compound 2 (400 mg, 1.25 mmol) was added to a soln of 5 (230
1182.
mg, 1.25 mmol) in CH Cl (10 mL) at 25 °C, and the soln was
stirred for 24 h. The CH Cl soln was concentrated in vacuo to give
the crude product, which upon column chromatography (silica gel,
hexane–EtOAc, gradient) yielded 6 as a colorless oil.
(3) Patil, A. D.; Freyer, A. J.; Taylor, P. B.; Carte, B.; Zuber, G.;
Johnson, R. K.; Faulkner, D. J. J. Org. Chem. 1997, 62,
1814.
2
2
2
2
(
4) Gallimore, W. A.; Kelly, M.; Scheuer, P. J. J. Nat. Prod.
005, 68, 1420.
2
Yield: 200 mg (71%).
(
5) Hua, H. M.; Peng, J.; Dunbar, D. C.; Schinazi, R. F.;
Andrews, A. G. D. C.; Cuevas, C.; Garcia-Fernandez, L. F.;
Kelly, M.; Hamann, M. T. Tetrahedron 2007, 63, 11179.
–
1
IR (KBr): 3302, 1727, 1694, 1491, 1372 cm .
1
H NMR (400 MHz, CDCl ): d = 0.89 (t, J = 6.8 Hz, 3 H), 1.31 (m,
3
4
2
H), 1.60 (quin, J = 7.4, 15 Hz, 2 H), 2.23 (s, 3 H), 2.41 (m, 4 H),
.50 (t, J = 7.4 Hz, 2 H), 6.11 (d, J = 8.4 Hz, 1 H), 6.13 (d, J = 9.6
(6) (a) Snider, B. B.; Chen, J.; Patil, A. D.; Freyer, A. J.
Tetrahedron Lett. 1996, 37, 6977. (b) Rama Rao, A. V.;
Gurjar, M. K.; Vasudevan, J. J. Chem. Soc., Chem. Commun.
1995, 1369. (c) Black, G. P.; Murphy, P. J.; Walshe, N. D.
A.; Hibbs, D. E.; Hursthouse, M. B.; Abdul Malik, K. M.
Tetrahedron Lett. 1996, 37, 6943. (d) Elliott, M. C.; Long,
M. S. Tetrahedron Lett. 2002, 43, 9191. (e) Elliott, M. C.;
Long, M. S. Org. Biomol. Chem. 2004, 2, 2003. (f) Black,
G. P.; Murphy, P. J.; Thornhill, A. J.; Walshe, N. D. A.;
Hz, 1 H), 6.75–6.81 (m, 2 H).
1
3
C NMR (100 MHz, CDCl ): d = 13.9, 22.4, 23.6, 27.0, 30.6, 30.7,
3
3
1.4, 40.4, 130.9, 131.9, 144.4, 145.8, 198.3, 200.5.
MS (CI): m/z = 223 [M + 1]+.
Synthesis 2010, No. 15, 2567–2570 © Thieme Stuttgart · New York