400 J ournal of Natural Products, 2004, Vol. 67, No. 3
Stritzke et al.
+5.5 (c 3.25, diethyl ether); 1H NMR data match published
data;25 13C NMR (CDCl3, 100 MHz) δ 174.2 (C, C-1), 60.2 (CH2,
OCH2), 34.0 (CH, C-4), 32.2 (CH2), 31.5 (CH2), 29.2 (CH2), 18.8
(CH3, 4-CH3), 14.3 (CH3, CH3CH2O), 11.3 (CH3, C-6); EIMS
m/z 158 [M]+ (<1), 129 (16), 113 (35) 102 (11), 101 (100), 95
(35), 83 (24), 74 (16), 73 (33), 71 (17), 70 (28), 69 (22), 61 (15),
60 (19), 57 (23), 56 (16), 55 (40), 45 (12), 43 (36), 42 (11), 41
(39), 39 (14).
(+)-(R)-2-(4-Met h ylp en t yl)cycloh exa n on e (R-4). See
method B using 1-bromo-5-methylpentane as starting material
to give 262 mg (63%) of R-4 as a colorless oil: [R]25 +2.1 (c
D
1
2.23, diethyl ether); H NMR (CDCl3, 400 MHz) δ 2.36-2.31
(1H, m), 2.30-2.22 (1H, m), 2.21-2.16 (1H, m), 2.07-2.01 (1H,
m), 1.99-1.92 (1H, m), 1.82-1.75 (1H, m), 1.73-1.65 (1H, m),
1.64-1.54 (2H, m), 1.51-1.41 (1H, m), 1.34-1.30 (1H, m),
1.25-1.04 (5H, m), 0.79 (6H, d, J ) 6.6 Hz); 13C NMR (CDCl3,
100 MHz) δ 213.6 (C, C-1), 50.8 (CH, C-2), 42.0 (CH2, C-6),
39.1 (CH2), 33.8 (CH2), 29.6 (CH2), 28.0 (CH2), 27.9 (CH), 24.9
(CH2), 24.8 (CH2), 22.61 (CH3), 22.56 (CH3); EIMS m/z 182 [M]+
(4), 111 (10), 98 (100), 97 (12), 83 (19), 70 (12), 55 (19), 41 (20).
(+)-(S)-4-Meth ylh exa n ol. To a suspension of LiAlH4 (42
mg, 1.1 mmol) in diethyl ether (2 mL) was added dropwise
S-8 (320 mg, 2 mmol) in diethyl ether (1 mL). After stirring 1
h at room temperature, the reaction mixture was heated to
reflux for 3 h. Ice water (2 mL) was added, the solution was
extracted three times with diethyl ether, and the combined
organic extracts were dried with MgSO4. The product was
obtained almost quantitatively after evaporation of the solvent.
2-(4-Meth ylp en tyl)cycloh exa n on e (4). See method A
starting with 1-bromo-5-methylpentane to give 87 mg (44%)
of 4 as a colorless oil: see R-3 for NMR and MS data.
No further purification was necessary. [R]25 +4.7 (c 6.50,
10-Meth yl-6-u n d eca n olid e (1). See method C starting
with 4 to give 26 mg (55%) of 1 as a colorless oil: see R-1 for
NMR and MS data. GC experiments on chiral stationary
cyclodextrin phase delivered the following retention times (120
°C isothermal for 3 min, then with 0.5 °C/min to 170 °C): tRS-1
) 34.01 min, tRR-1 ) 34.65 min.
D
diethyl ether), ref [R]25 +7.64 (c 4.01, CHCl3); for NMR and
D
MS data, see ref 21.
(S)-1-Br om o-4-m eth ylh exa n e (S-7). According to the
method of Sonnett,22 (S)-4-methylhexanol was transformed
into its bromide to give 550 mg (73%) of S-7 as a colorless oil.
For NMR and MS data see 7.
(-)-(R)-10-Meth yl-6-u n d eca n olid e (R-1). See method D
using R-3 as starting reagent to give 163 mg (75%) of R-1 as
(+)-(2R,4′S)-2-(4-Meth ylh exyl)cycloh exa n on e (2R,4′S-
5). See method B. The bromide S-7 was used as starting
material to give 71 mg (66%) of 2R,4′S-5 as a colorless oil:
[R]25D +16.2 (c 2.19, diethyl ether); 1H NMR (CDCl3, 400 MHz)
δ 2.41-2.36 (1H, m, H-6), 2.34-2.29 (2H, m) 2.12-2.08 (1H,
m), 2.04-1.97 (1H, m), 1.88-1.04 (13H, m), 0.88-0.83 (6H,
m); 13C NMR (CDCl3, 100 MHz) δ 213.6 (C, C-1), 50.8 (CH,
C-2), 41.9 (CH2, C-6), 36.7 (CH2), 34.3 (CH), 33.8 (CH2), 29.7
(CH2), 29.4 (CH2), 28.0 (CH2), 24.8 (CH2), 24.6 (CH2), 19.1
(CH3), 11.4 (CH3); EIMS m/z 196 [M]+ (3), 111 (10), 98 (100),
97 (11), 83 (16), 55 (18), 41 (18).
a colorless oil: [R]25 -1.2 (c 3.20, diethyl ether); 1H NMR
D
(CDCl3, 400 MHz) δ 4.23 (1H, dt, J ) 8.0 Hz, J ) 4.2 Hz, H-6),
2.70-2.56 (2H, m, H-2), 2.00-1.84 (3H, m), 1.77-1.24 (8H,
m), 1.18-1.23 (2H, m, H-9), 0.87 (6H, d, J ) 6.6 Hz, 10-CH3,
H-12); 13C NMR δ 175.8 (C, C-1), 80.6 (CH, C-6), 38.7 (CH2,
C-9), 36.7 (CH2, C-7), 34.9 (CH2, C-2), 34.6 (CH2, C-5), 28.3
(CH2, C-3), 27.9 (CH, C-10), 23.2 (CH2, C-8), 23.1 (CH2, C-4),
22.6 (CH3, C-11), 22.52 (CH3, 10-CH3); EIMS m/z 198 [M]+
(<1), 113 (36), 95 (14), 85 (100), 84 (64), 83 (14), 70 (17), 69
(30), 68 (11), 67 (37), 57 (20), 56 (57), 55 (85), 43 (36), 42 (14),
(+)-(2R,4′RS)-2-(4-Meth ylh exyl)cycloh exa n on e (2R-5).
See method B. Racemic 7 was used as starting material to give
200 mg (61%) of 2R-5 as a colorless oil. For NMR and MS data
41 (55), 39 (17); HREIMS 198.1612 (calcd for
C12H22O2,
198.1620); ee ) 93%.
8-Meth yl-4-d od eca n olid e. EIMS m/z 166 [M - 18]+ (2),
155 (5), 137 (14), 128 (9), 127 (6), 110 (13), 109 (12), 100 (13),
95 (18), 85 (100), 83 (15), 70 (34), 69 (18), 57 (21), 56 (14), 55
(29), 43 (15), 42 (9), 41 (33).
see (2R,4′S)-5. [R]25 +9.5 (c 0.22, diethyl ether).
D
(2RS,4′S)-2-(4-Meth ylh exyl)cycloh exa n on e (4′S-5). See
method A. The bromide (S)-7 was used as alkylation agent to
give 12 mg (38%) of 4′S-5 as a colorless oil. For NMR and MS
data see 2R,4′S-5.
2-(4-Meth ylh exyl)cycloh exa n on e (5). See method A.
Racemic 7 was used as starting material to give 4 mg (32%)
of 5 as a colorless oil. For NMR and MS data see 2R,4′S-5.
10-Meth yl-6-d od eca n olid e (2). See method C starting
from racemic 5 to give 4 mg (87%) of 2 as a colorless oil. For
NMR and MS data see 6R,10S-2. GC experiments on a chiral
stationary cyclodextrin phase delivered the following retention
times (120 °C, 3 min isothermal, then with 0.5 °C/min to 170
Ack n ow led gm en t. This work was financed by a grant
from the Volkswagenstiftung within the Lower Saxony Coop-
erative Research Project of Marine Biotechnology. Financial
support by the Fonds der Chemischen Industrie is gratefully
acknowledged.
Refer en ces a n d Notes
°C): tR6R,10R-2 ) 54.88 min, tR6R,10S-2 ) 55.43 min, tR6S,10R-2
)
(1) Maskey, R. P.; Helmke, E.; Laatsch, H. J . Antibiot. 2002, 55, 1031-
1035, and previous articles of this series.
(2) J ensen, P. R.; Fenical, W. In Drugs From the Sea; Fusetani, N., Ed.;
Karger: Basel, 2000; pp 6-29.
tR6R,10S-2 ) 57.74 min.
(-)-(6R,10S)-10-Meth yl-6-d od eca n olid e (6R,10S-2). See
method C starting with 2R,4′S-5 to give 49 mg (66%) of 6R,-
(3) Blunt, J . W.; Copp, B. R.; Munro, M. H. G.; Northcote, P. T.; Prinsep,
M. R. Nat. Prod. Rep. 2003, 20, 1-48. Faulkner, D. J . Nat. Prod.
Rep. 2002, 19, 1-48, and previous reviews of this series.
(4) Mu¨ller, K.-D.; Husmann, H.; Nalik, H. P.; Schomburg, G. Chro-
matographia 1990, 30, 245-248.
10S-2 as a colorless oil: [R]25 -20.1 (c 2.01, diethyl ether);
D
1H NMR (CDCl3, 400 MHz) δ 4.23 (1H, dt, J ) 8.1 Hz, J ) 4.1
Hz, H-6), 2.70-2.57 (2H, m, H-2), 1.96-1.88 (3H, m), 1.75-
1.08 (12H, m), 0.85 (3H, d, J ) 5,7 Hz, 10-CH3), 0.85 (3H, t, J
) 7.4 Hz, H-12); 13C NMR (CDCl3, 100 MHz) δ 175.8 (C, C-1),
80.4 (CH, C-6), 36.8 (CH2, C-7), 36.3 (CH2, C-9), 35.0 (CH2,
C-2), 34.6 (CH2, C-5), 34.3 (CH, C-10), 29.3 (CH2, C-11), 28.3
(CH2, C-4), 23.1 (CH2, C-3), 23.0 (CH2, C-8), 19.2 (CH3, 10-
CH3), 11.4 (CH3, C-12); EIMS m/z 212 [M]+ (<1), 113 (32), 95
(17), 85 (100), 84 (66), 83 (24), 81 (16), 71 (12), 70 (55), 69 (37),
68 (12), 67 (41), 57 (29), 56 (43), 55 (96), 43 (23), 42 (14), 41
(63), 39 (18); HREIMS m/z 212.1774 (calcd for C13H24O2,
212.1776); ee > 94%, dr ) 94/6.
(5) Leonhardt, B. A.; DeVilbiss, E. D. J . Chromatogr. 1985, 322, 484-
490.
(6) Meyers, A. I.; Williams, D. R.; Erickson, G. W.; White, S.; Druelinger,
M. J . Am. Chem. Soc. 1981, 103, 3081-3087.
(7) Bolm, C.; Luong, T. K. K.; Beckmann, O. In Asymmetric Oxidation
Reactions; Katsuki, T., Ed.; Oxford University Press: Oxford, 2001;
pp 147-152.
(8) Bergmann, J .; Loefstedt, C.; Ivanov, V. D.; Francke, W. Eur. J . Org.
Chem 2001, 3175-3180.
(9) Krapcho, A. P. Synthesis 1982, 805-822.
(10) Thakar, K. A.; Pathak, U. S. J . Indian Chem. Soc. 1965, 42, 109-
111.
(-)-(6R,10RS)-10-Met h yl-6-d od eca n olid e (6R-2). See
method C starting with 2R-5 to give 160 mg (89%) of 6R-2 as
(11) Stewart, J . D.; Reed, K. W.; Zhu, J .; Chen, G.; Kayser, M. M. J . Org.
Chem. 1996, 61, 7652-7653.
a colorless oil: [R]25 -33.4 (c 3.40, diethyl ether); for NMR
(12) Torrenegra, R.; Pedrozo, J . A.; Robles, J .; Fuentes, O. Phytochemistry
1990, 29, 305-306.
D
and MS data see 2; ee ) 91%.
(13) Tang, Y.-Q.; Sattler, I.; Thiericke, R.; Grabley, S.; Feng, X.-Z. J .
Antibiot. 2000, 53, 934-943.
(+)-(6RS,10S)-10-Meth yl-6-d od eca n olid e (10S-2). See
method C starting with 10S-5 to give 8 mg (82%) of 10S-2 as
a colorless oil: [R]25D +8.8 (c 0.69, diethyl ether); for NMR and
MS data see 2; ee > 99%.
(14) MacLachlan, L. K.; Taylor, D. A. H. Phytochemistry 1982, 21, 1701-
1704.
(15) Ko¨nig, W. A. Chirality 1998, 499-504.