An Efficient Alternative Synthesis of (+)-(6S,7S)-7-Hydroxy-6,11-cyclofarnes-3(15)-en-2-one, the (S)-Enantiomer of the Antibacterial Sesquiterpene from Premna oligotricha

Article abstract of DOI:10.1081/SCC-120027252

The title compound has been synthesized from optically active lactone derived from (S)-(+)-Wieland-Miescher ketone analogue employing solid-state Baeyer-Villiger reaction.

Full text of DOI:10.1081/SCC-120027252

This article was downloaded by: [University Of Pittsburgh]
On: 11 November 2014, At: 19:29
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer
House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
An Efficient Alternative Synthesis of
(+)‐(6S,7S)‐7‐Hydroxy‐6,11‐cyclofarnes‐3(15)‐en‐2‐one,
the (S)‐Enantiomer of the Antibacterial
Sesquiterpene from Premna oligotricha
Masato Nozawa a , Takashi Hoshi b , Toshio Suzuki b & Hisahiro Hagiwara a
a Graduate School of Science and Technology , Niigata University , Ikarashi‐2, Niigata,
950‐2181, Japan
b Faculty of Engineering , Niigata University , Niigata, Japan
Published online: 16 Aug 2006.
To cite this article: Masato Nozawa , Takashi Hoshi , Toshio Suzuki & Hisahiro Hagiwara (2004) An Efficient Alternative
Synthesis of (+)‐(6S,7S)‐7‐Hydroxy‐6,11‐cyclofarnes‐3(15)‐en‐2‐one, the (S)‐Enantiomer of the Antibacterial Sesquiterpene
from Premna oligotricha , Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:1, 187-195, DOI: 10.1081/SCC-120027252
To link to this article: http://dx.doi.org/10.1081/SCC-120027252
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of
the Content. Any opinions and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied
upon and should be independently verified with primary sources of information. Taylor and Francis shall
not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other
liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 1, pp. 187–195, 2004
An Efficient Alternative Synthesis of
(1)-(6S,7S)-7-Hydroxy-6,11-cyclofarnes-
3(15)-en-2-one, the (S)-Enantiomer of the
Antibacterial Sesquiterpene from
Premna oligotricha
Masato Nozawa,1 Takashi Hoshi,2 Toshio Suzuki,2
and Hisahiro Hagiwara1,
*
1Graduate School of Science and Technology, Niigata University,
Niigata, Japan
2Faculty of Engineering, Niigata University, Niigata, Japan
ABSTRACT
The title compound has been synthesized from optically active lactone
derived from (S)-(þ)-Wieland–Miescher ketone analogue employing
solid-state Baeyer–Villiger reaction.
Key Words: Premna oligotricha; Wieland–Miescher ketone; Baeyer–
Villiger reaction.
*
Correspondence: Hisahiro Hagiwara, Graduate School of Science and Technology,
Niigata University, Ikarashi-2, Niigata 950-2181, Japan; Fax: þ81-25-262-7368;
E-mail: hagiwara@gs.niigata-u.ac.jp.
187
DOI: 10.1081/SCC-120027252
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

188
Nozawa et al.
Premna oligotricha Baker (Verbenaceae) involves several biologically
active terpenoids[1,2] and flavonoids,[3] of which some have pronounced anti-
bacterial activity. In 1993, Waterman and his co-workers reported isolation of
novel sesquiterpenoid, 7-hydroxy-6,11-cyclofarnes-3(15)-en-2-one 1[1] from
antibiotic fraction of ethanol extract of aerial parts of the plant as a minor
constituent (Fig. 1). The compound exhibits weak antibacterial activity against
a range of Gram-positive bacteria. The relative stereochemistries of C-6 and
C-7 of the natural product 1 were initially assigned by NOESY measurement
to be 6Rꢀ,7Sꢀ as shown in the structure 3. However the proposed relative
stereochemistry was corrected by Mori et al.,[4] to be 6Rꢀ,7Rꢀ as shown in the
structure 1 by the total synthesis of racemic 1 and 3. Subsequently, they
synthesized the (S)-enantiomer 2, an antipode of the natural product 1, thereby
establishing the absolute stereochemistry of 1 to be 6R,7R.[5]
Optically pure Wieland–Miescher ketone analogue 7 has been a very
useful starting material for numerous natural products[6–10] since our disclo-
sure of an improved synthetic procedure of 7.[11] Our ongoing efforts in
Figure 1.

Antibacterial Sesquiterpene from Premna oligotricha
189
Scheme 1.
enantioselective total syntheses of several terpenoids starting from 7 enabled
the first total syntheses of cyclofarnesane sesquiterpenoids, 4 and 5,
employing solid state Baeyer–Villiger reaction as the key reaction[12,13] (Sch.
1). This protocol offered good solution for construction of substituted
cyclofarnesane framework which is not enantioselectively accessible by usual
means, owing to conformational flexibility of cyclohexane ring. Low optical
purity (38% op) of (S)-enantiomer 2 in the previous total synthesis by Mori
et al.[5] exemplifies such difficulty in enantiocontrol in the synthesis.
Based on our previous synthetic results along with our interest on
synthetic study of the constituents of P. oligotricha,[14] we delineate herein an
alternative enantioselective total synthesis of 2 (Sch. 2).
Synthesis has started from the common precursor 10 for total syntheses of
4-(20-hydroxy-20,60,60-trimethylcyclohexyl)-2-methylbutanoic acid 4[13] or
chapechoderin A 6,[15] which was prepared from optically pure (S)-(þ)-
Wieland–Miescher ketone analogue 7 in six steps. Solid state Baeyer–
Villiger reaction was achieved in the presence of sodium hydrogencarbonate
according to the modified procedure by Uenishi et al.[16] and was found to be
accelerated to finish in shorter period of time (1.5 h) to give lactone 11 in
slightly better yield (93%) than our previous procedure.[13] Since aldol
condensation of enolate of the lactone 11 with acetaldehyde resulted in
recovery, the lactone 11 was hydrolysed to afford hydroxy-acid which was
treated with diazomethane to give hydroxy-ester 12 quantitatively. Aldol
condensation of the ester enolate of 12 with acetaldehyde furnished b-
hydroxyester 13 in 74% yield as a mixture of diastereomers. Then, the
hydroxy-ester 13 was reduced with lithium aluminum hydride to give in 97%

190
Nozawa et al.
Scheme 2. Reagents and conditions; (i) MCPBA, NaHCO3, 1.5 h, 93%; (ii) NaOH,
EtOH, room temp., 2.3 h then CH2N2, quant.; (iii) LDA, THF, HMPA, acetaldehyde,
2788C, 74%; (iv) LAH, Et2O, 97%; (v) TsCl, DMAP, Et3N, CH2Cl2, 62%; (vi)
DMSO, Et3N, SO3-pyridine, CH2Cl2, 98%; (vii), DBU, toluene, room temp., 86%.
yield triol 14 which was transformed into tosylate 15 in 62% yield. An attempt
of selective oxidation of secondary alcohol of the triol 14 by NBS failed.[4]
Oxidation of the tosylate 15 by SO3-pyridine complex afforded keto-tosylate
16 in 98% yield. b-Elimination of tosyloxy group was observed partially on

Antibacterial Sesquiterpene from Premna oligotricha
191
prolonged treatment to give target compound 2. Then the keto-tosylate 16 was
treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to complete enantio-
selective total synthesis of 2 in 86% yield. The spectral data were completely
identical with those reported in the literature except sign of optical rotational
value [a]D þ 18.4 (c 0.15, CHCl3) flit.1 [a]D 2 17 (c 0.1, CHCl3)g.
In summary, we have completed enantioselective total synthesis of 2, in 7
steps in 35% overall yield from the known decalone 10 in better enantio-
selectivity and overall yield than previous work.[5]
EXPERIMENTAL
General
Mp was determined with a Yanaco MP hot-stage apparatus and is
uncorrected. IR spectra were recorded on a Shimadzu FT/IR-4200 spectro-
photometer in carbon tetrachloride unless otherwise indicated. 1H-NMR
spectra were obtained for solutions in deuteriochloroform with Varian Gemini
200H (200 MHz) and Unity 500 plus (500 MHz) instruments with tetra-
methylsilane as internal standard. J-values are in Hz. 13C-NMR spectra were
obtained for solutions in deuteriochloroform with Varian Gemini 200H
(50 MHz) and Unity 500 plus (125 MHz) instruments. Mass spectral data were
obtained with a JEOL GC-Mate spectrometer. Specific rotations were
measured with a Horiba SEPA-200 spectrophotometer for solutions in
methanol unless otherwise indicated. Medium pressure LC (MPLC) were
carried out on Hitachi LC system.
(1S,7S)-1,8,8-Trimethyl-2-oxabicyclo[5.4.0]undecan-3-one (11). To a
solution of ketone 10 (81 mg, 0.42 mmol) and MCPBA (80%; 183 mg,
0.85 mmol) in CH2Cl2 (1 cm3) was added finely ground NaHCO3 (56 mg,
0.66 mmol) and then the suspension was evaporated to dryness at room
temperature in 1.5 h. The resulting mixture was dissolved in ethyl acetate and
the organic layer was washed successively with water and brine. The organic
layer was dried over anhydrous Na2SO4 and evaporated to dryness. MPLC
purification of the residue (ethyl acetate-n-hexane 2 : 1) gave lactones 11
(82 mg, 93%) as a white solid; [a]2D0 2 72.1 (c 0.62); m.p. 40 ꢀ 428C; nmax
/
cm21 2960, 2870, 1779, 1725 and 1551; d
˙ (200 MHz) 0.81 (3H, s), 0.99 (3H,
s), 1.51 (3H, s), 1.1–1.8 (8H, m), 1.88–2.08 (3H, m), 2.56 (1H, dd like) and
2.75 (1H, dd like); dC (50 MHz) 19.5 (t), 21.3 (q), 21.8 (q), 23.9 (t), 25.8 (t),
32.6 (q), 35.3 (s), 37.0 (t), 41.6 (t), 42.4 (t), 54.3 (d), 85.6 (s) and 175.4 (s); m/z
(EI) 210.1615 (3.2%, Mþ, C13H22O2 requires 210.1620), 195 (14), 58 (31) and
43 (100).

192
Nozawa et al.
Methyl
4-[(1S,2S)-2-hydroxy-2,6,6-trimethylcyclohexyl]butanoate
(12). A solution of the lactone 11 (85 mg, 0.40 mmol) in EtOH (9.9 cm3)
and 2N aq. sodium hydroxide (2.0 cm3) was stirred at room temperature for
2.3 h. The reaction was quenched by addition of dil. aq. hydrochloric acid.
After extraction with ethyl acetate (ꢁ3), the combined organic layer was
washed with brine (ꢁ1) and water and dried over anhydrous Na2SO4.
Evaporation of the solvent provided crude carboxylic acid (114 mg).
A solution of the carboxylic acid (114 mg) in diethyl ether (2.5 cm3) was
treated with an ethereal solution of diazomethane at 08C until the yellow
colour persisted. Evaporation of diethyl ether followed by MPLC purification
of the residue (ethyl acetate-n-hexane 2 : 1) provided ester 12 (97 mg, 100% in
two steps) as a colourless oil; [a]2D0 þ 9.8 (c 0.60); nmax/cm21 2950, 1742,
1366 and 1379; d (200 MHz) 0.80 (3H, s), 0.94 (3H, s), 1.16 (3H, s), 1.1–1.9
(12H, m), 2.34 (2H, t, J 7.1) and 3.67 (3H, s); dC (50 MHz) 20.5 (t), 21.3 (q),
23.4 (q), 25.8 (t), 27.9 (t), 32.8 (q), 34.5 (t), 35.4 (s), 41.5 (t), 43.3 (t), 51.5 (q),
57.2 (d), 74.1 (s) and 174.4 (s) ; m/z (EI) 224.1775 (29.5%, Mþ 2 H2O,
C14H24O2 requires 224.1776), 209 (100), 168 (94), 123 (80) and 109 (78).
Methyl 2-[2-(1S,2S)-(2-hydroxy-2,6,6-trimethylcyclohexyl)ethyl]-3-
hydroxybutanoate (13). To
a stirred solution of diisopropylamine
(0.69 cm3, 4.9 mmol) in THF (1.0 cm3) was added an n-hexane solution
(1.57 M) of n-butyllithium (3.1 cm3, 4.9 mmol) at 08C under nitrogen
atmosphere. After being stirred for 30 min, a solution of ester 12 (118 mg,
0.49 mmol) in THF (1.0 cm3) was added at 2788C and stirring was continued
for 30 min. Subsequently, HMPA (0.34 cm3, 2.0 mmol) was added at 2788C.
After being stirred at for 30 min, acetaldehyde (0.14 cm3, 2.5 mmol) was
added at 2788C and the resulting solution was stirred at 2788C for 2.5 h. The
reaction was quenched by addition of aq. ammonium chloride and product was
extracted with ethyl acetate ( ꢁ 3). The combined organic layer was washed
with water and brine. After drying over anhydrous Na2SO4, evaporation of the
solvent followed by MPLC purification of the residue (ethyl acetate-n-hexane
3 : 1) gave diastereomeric diols, 13-1 and 13-2 as an inseparable mixture
(67 mg, 48%), 13-3 (18 mg, 13%) and 13-4 (19 mg, 14%) as colourless oil in
the order of elution.
Diols 13-1 and 13-2 had (200 MHz) 0.78 (3H, s), 0.916 and 0.925 (total
3H, s), 1.15 and 1.17 (total 3H, s), 1.19 and 1.22 (total 3H, d, J 6.5 and 6.6),
1.00–2.01 (13H, m), 2.45 (1H, m), 3.72 and 3.73 (total 3H, s), and 4.00 (1H,
m); dC(50 MHz) 20.4 (t), 20.7 (q), 21.2 (q), 21.4 (q), 23.4 (q), 23.5 (t), 23.7 (t),
30.4 (t), 31.6 (t), 32.7 (q), 35.3 (s), 35.4 (s), 41.4 (t), 41.5 (t), 43.2 (t), 43.5 (t),
51.6 (q), 52.7 (d), 53.1 (d), 56.8 (d), 67.8 (d), 68.1 (d), 74.1 (s), 74.4 (s), 175.4
(s) and 175.9 (s).
Diol 13-3 had [a]D20 þ 43.1 (c 0.126); nmax/cm21 3616, 3360, 2950,
1736, 1366 and 1379; dH(200 MHz) 0.79 (3H, s), 0.93 (3H, s), 1.15 (3H, s),

Antibacterial Sesquiterpene from Premna oligotricha
193
1.19 (3H, d, J 6.3), 1.00–1.90 (13H, m), 2.45 (1H, m), 3.73 (3H, s) and 3.98
(1H, m)
Diol 13-4 had [a]2D0 þ 80.2 (c 0.096); nmax/cm21 3603, 3400, 2951, 1721
and 1379; d˙(200 MHz) 0.79 (3H, s), 0.91 (3H, s), 1.15 (3H, s), 1.23 (3H, d, J
6.3), 1.00–1.90 (13H, m), 2.43 (1H, m), 3.73 (3H, s) and 3.93 (1H, m); m/z
(EI) 268.2041 (4.8%, Mþ 2 H2O, C16H28O3 requires 268.2038), 123 (100),
95 (86), 81 (97) and 79 (74).
2-[2-((1S,2S)-2-Hydroxy-2,6,6-trimethylcyclohexyl)ethyl]butane-1,3-
diol (14). To a solution of the diols 13-1 and 13-2 (29 mg, 0.10 mmol) in
anhydrous diethyl ether (10 cm3) was added lithium aluminium hydride
(23 mg, 0.60 mmol) at 08C under nitrogen atmosphere. After being stirred for
2 h, the reaction mixture was quenched by cautious addition of aq. ammonium
chloride. Filtration through anhydrous Na2SO4 followed by evaporation of
diethyl ether provided triol 14 an inseparable diastereomeric mixture (26 mg,
97%) as a colourless oil.
Compound 14 had nmax/cm21 3312, 2992, 2896, 1091, 1075 and 918;
d˙(200 MHz) 0.77 (3H, s), 0.88 (3H, s), 1.17 and 1.19 (total 3H, s), 1.16 and
1.32 (total 3H, d, J 5.6 and 6.5), 0.53–1.90 (11H, m), 1.94–2.50 (1H, m),
3.60–4.30 (3H, m) and 4.68–5.60 (3H, br m); dC(50 MHz) 20.0 (q), 20.4 (t),
20.5 (t), 21.0 (q), 21.4 (q), 22.3 (q), 22.5 (q), 23.3 (t), 23.5 (t), 26.5 (t), 32.2 (q),
34.3 (t), 35.7 (s), 41.2 (t), 42.4 (t), 42.7 (t), 45.2 (d), 45.4 (d), 58.4 (d), 58.7 (d),
59.8 (t), 65.1 (t), 73.5 (d), 73.6 (d) and 74.4 (s); m/z (EI) 240.2090 (1.2%,
Mþ 2 H2O, C15H28O2 requires 240.2089), 123 (38), 109 (100), 95 (48) and 81
(58).
2-[2-((1S,2S)-2-Hydroxy-2,6,6-trimethylcyclohexyl)ethyl]-3-hydroxy-
butyl 4-methylbenzenesulfonate (15). To a solution of the triols 14 (9 mg,
0.03 mmol) in anhydrous dichloromethane (1 cm3), was added anhydrous
triethylamine (0.12 cm3) and p-toluenesulfonyl chloride (34 mg, 0.18 mmol) at
room temperature. After being stirred at room temperature for 13 h, the
organic layer was diluted with ethyl acetate and passed through a short column
of silica-gel. Evaporation of the solvent followed by MPLC purification of the
residue (ethyl acetate) gave a diastereomeric tosylates 15-1 (4 mg, 30%) and
15-2 (5 mg, 32%) as colourless oils in the order of elution.
Less polar tosylate 15-1 had [a]2D0 2 6.3 (c 0.511); nmax/cm21 3568,
3440, 2944, 1599 and 1462; d˙(200 MHz) 0.77 (3H, s), 0.89 (3H, s), 1.14 (3H,
s), 1.16 (3H, d, J 7.12), 1.05–1.80 (14H, m), 2.45 (3H, s), 3.83 (1H, quint, J
6.24), 4.13 (1H, dd, J 9.85 and 4.76), 4.21 (1H, dd, J 9.85 and 4.52), 7.34 (2H,
d, J 8.06) and 7.80 (2H, d, J 8.34); dC(125 MHz) 20.4 (t), 20.8 (q), 21.2 (q),
21.6 (q), 23.4 (t), 23.4 (q), 29.8 (t), 32.7 (q), 35.4 (s), 41.5 (t), 43.4 (t), 45.4 (d),
56.9 (d), 67.6 (d), 70.0 (t), 74.2 (s), 127.9 (d), 129.8 (d), 132.9 (s) and 144.7
(s); m/z (EI) 412.2271 (0.3%, Mþ, C22H36O5S requires 412.2283), 109 (98),
95 (92), 91 (100) and 81 (98).

194
Nozawa et al.
More polar tosylate 15-2 had [a]2D0 2 6.2 (c 1.052); nmax/cm21 3408,
2934, 1599 and 1462; d˙(200 MHz) 0.76 (3H, s), 0.88 (3H, s), 1.14 (3H, s),
1.15 (3H, d, J 6.4), 1.05–1.80 (14H, m), 2.45 (3H, s), 3.88 (1H, quint
like), 4.04 (1H, dd, J 5.29 and 9.81), 4.13 (1H, dd, J 6.05 and 9.78), 7.35
(2H, d, J 8.06) and 7.80 (2H, d, J 8.34); dC(50 MHz) 20.5 (t), 20.5 (q), 21.2 (q),
21.7 (q), 22.9 (t), 23.4 (q), 29.2 (t), 32.7 (q), 35.3 (s), 41.4 (t), 43.4 (t), 45.1
(d), 57.2 (d), 67.1 (d), 70.6 (t), 74.4 (s), 127.9 (d), 129.9 (d), 132.8 (s)
and 144.8 (s).
2-[2-((1S,2S)-2-Hydroxy-2,6,6-trimethylcyclohexyl)ethyl]-3-oxobutyl
4-methylbenzenesulfonate (16). To a solution of the less polar tosylate
15-2 (16 mg, 0.039 mmol) in anhydrous dichloromethane (1.4 cm3),
DMSO (0.20 cm3, 2.8 mmol) and triethylamine (0.077 cm3, 0.55 mmol)
were added at room temperature. Subsequently SO3-Py (54 mg, 0.34 mmol)
was added at 08C and the reaction mixture was stirred at room temperature
for 0.7 h. The resulting mixture was diluted with ethyl acetate and the organic
layer was washed successively with water and brine and dried over
anhydrous Na2SO4. Evaporation of the solvent followed by MPLC
purification of the residue (ethyl acetate) provided 16 (16 mg, 98%) as
a colourless oil which had [a]2D0 þ 9.5 (c 1.140); nmax/cm21 3540, 2944,
1721, 1599, 1460, 1372, 1190, 1179, 1100, 970 and 666; d˙(200 MHz)
0.75 (3H, s), 0.87 (3H, s), 1.12 (3H, s), 1.00–1.80 (12H, m), 2.18 (3H, s),
2.45 (3H, s), 2.93 (1H, quint like), 4.09 (1H, dd, J 9.4 and 5.3), 4.17 (1 H,
dd, J 9.2 and 7.3), 7.35 (2H, d, J 8.5) and 7.77 (2H, d, J 8.4); dC(50 MHz)
20.5 (t), 21.1 (q), 21.7 (q), 23.0 (t), 23.4 (q), 29.8 (q), 30.8 (t), 32.7 (q),
35.4 (s), 41.4 (t), 43.8 (t), 51.8 (d), 57.0 (d), 69.5 (t), 74.1 (s), 127.9 (d),
129.8 (d), 132.5 (s), 144.9 (s) and 208.8 (s); m/z (EI) 392.1951 (0.11%,
Mþ 2 H2O, C22H32O4S requires 392.2021), 150 (60), 94 (64), 81 (63)
and 43 (100).
(1)-(6S,7S)-7-Hydroxy-6,11-cyclofarnes-3(15)-en-2-one 5 3-[2-((2S)-
2-hydroxy-2,6,6-trimethylcyclohexyl)ethyl]but-3-en-2-one (2). To a sol-
ution of 16 (16 mg, 0.038 mmol) in toluene (0.45 cm3), DBU (0.0068 cm3,
0.045 mmol) was added 08C, and the reaction mixture was stirred at room
temperature for 4.5 h. The solution was diluted with ethyl acetate and passed
through a short column of silica-gel (ethyl acetate). Evaporation of the solvent
followed by MPLC purification of the residue (ethyl acetate) gave enone 2
(7.8 mg, 86%) as a colourless oil which had [a]2D0 þ 18.4(c 0.152,
CHCl3)flit.1[a]D 2 17 (c 0.1, CHCl3)g; nmax/cm21 3517, 2963, 1680, 1462,
1366 and 1101; d˙(500 MHz) 0.78 (3H, s), 0.95 (3H, s), 1.17 (3H, s), 1.18–1.61
(8H, m), 1.75 (1H, m), 1.85 (1H, br s), 2.34 (3H, s), 2.35 (1H, m), 2.46 (1H,
dddd, J 14.2, 10.8, 4.9 and 1.2), 5.82 (1H, s) and 6.00 (1H, s); dC(125 MHz)
20.4, 21.2, 23.4, 25.5, 25.9, 32.7, 34.2, 35.4, 41.5, 43.0, 56.9, 74.1, 125.3,
149.8 and 200.3.

Antibacterial Sesquiterpene from Premna oligotricha
195
REFERENCES
1. Habtemariam, S.; Gray, A.I.; Waterman, P.G. J. Natural Prod. 1993, 56,
140.
2. Habtemariam, S.; Gray, A.I.; Waterman, P.G. Planta Med. 1992, 58, 109.
3. Habtemariam, S.; Gray, A.I.; Waterman, P.G. Z. Naturforsch 1992, 47b,
144.
4. Yajima, A.; Takikawa, H.; Mori, K. Liebigs Ann. 1996, 891.
5. Horiuchi, S.; Takikawa, H.; Mori, K. Eur. J. Org. Chem. 1998, 2851.
6. Zhang, F.; Danishefsky, S.J. Angew. Chem. Int. Ed. Engl. 2002, 41, 1434.
7. Almstead, J.K.; Demuth, T.P., Jr.; Ledoussal, B. Tetrahedron: Astmmetry
1998, 9, 3179.
8. Corey, E.J.; Roberts, B.E. J. Am. Chem. Soc. 1997, 119, 12425.
9. Hagiwara, H.; Kamat, V.P. Recent Res. Devel. in Org. & Bioorg. Chem.
1997, 1, 25.
10. Corey, E.J.; Virgil, S.C. J. Am. Chem. Soc. 1990, 112, 6429.
11. Hagiwara, H.; Uda, H. J. Org. Chem. 1988, 53, 2308.
12. Hagiwara, H.; Nagatomo, H.; Yoshii, F.; Hoshi, T.; Suzuki, T.; Ando, M.
J. Chem. Soc., Perkin Transactions 1 2000, 2645.
13. Hagiwara, H.; Nagatomo, H.; Kazayama, S.; Sakai, H.; Hoshi, T.;
Suzuki, T.; Ando, M. ibid. 1999, 457.
14. Hagiwara, H.; Inome, K.; Uda, H. ibid. 1995, 757.
15. Hagiwara, H.; Takeuchi, F.; Hoshi, T.; Suzuki, T.; Ando, M. Tetrahedron
Lett. 2001, 42, 7629.
16. Yakura, T.; Kitano, T.; Ikeda, M.; Uenishi, J. ibid. 2002, 43, 6925.
Received in Japan July 3, 2003