Biotransformation of cedrol by Curvularia lunata ATCC 12017

Dwight O. Collins, Paul B. Reese *

Department of Chemistry, University of the West Indies, Mona, Kingston 7, Jamaica
Received 22 June 2000; received in revised form 28 September 2000
Dedicated to Dr Earle V. Roberts in celebration of his service of over 30 years to the Chemistry Department,
University of the West Indies, Mona Campus.
Abstract
Bioconversion of cedrol (1) with the Curvularia lunata was investigated in two dierent growth media. Five products were obtained
in potato dextrose broth, whereas nine compounds were produced in a mediumcontaining beef extract. Only three of the metabolites:
3b-hydroxycedrol (2), 3a-hydroxycedrol (3) and 12-hydroxycedrol (4) were common to both media. They were also obtained as the
major products in each case. Three new derivatives have also been identied. #2001 Elsevier Science Ltd. All rights reserved.
Keywords: Curvularia lunata ATCC 12017; Cedrol; Biotransformation; Hydroxylation; Cedrane; Sesquiterpene
1. Introduction
Curvularia lunata is a deuteromycete best known in
chemistry for the 11b-hydroxylation of steroids (Hol-
land, 1992). Strain ATCC 12017 (synonyms: IMI 61535,
CBS 215.54, NRRL 2380) has been used previously to
eect the biotransformation of eudesmane (Garcia-
Granados et al., 1991) and aromadendrane (de Lima et
al., 1999) sesquiterpenes as well as the diterpene sclareol
(Kouzi and McChesney, 1990; Aranda et al., 1991).
The sesquiterpene cedrol (1) is isolated from the
volatile oil of Juniperus sp. Odiferous analogues of this
compound have potential as high value products in the
perfume industry. This terpene has been biotransformed
by several microorganisms previously including Asper-
gillus niger (Wang et al., 1972), Beauveria sulfurescens
(Lamare et al., 1987), Cephalosporium aphidicola (Han-
son and Nasir, 1993), Glomerella cingulata (Miyazawa et
al., 1995) and Mucor plumbeus (Fraga et al., 1996).
Extensive transformations of 1 have also been carried
out by Abraham (Abraham et al., 1987) using Rhizopus
stolonifer, Streptomyces bikiniensis, Verticillium tenerum,
Streptoverticillium reticuli and Corynespora cassicola.
Maatooq (Matooq et al., 1993), using Streptomyces griseus
and Bacillus cereus, also produced several hydroxycedrane
derivatives. No report of the biotransformation of 1 using
C. lunata, however, has been encountered.
In an ongoing programme to examine the metabolism
of terpenes by fungi (Hanson et al., 1994; Buchanan and
Reese, 2000), 1 was fed to C. lunata. The microorganism
was cultivated in two dierent liquid media previously
used in biotransformation studies with this fungus, viz,
potato dextrose broth (PDB; Chen and Wey, 1990), and
a beef extract medium (BEM; Garcia-Granados et al.,
1991). Five known products were obtained from growth
in PDB. Metabolismof 1 was, however, more extensive in
BEM, resulting in the isolation of nine analogues, three in
common with those from PDB. In addition three new
derivatives: 7-hydroxycedrol (10), 2,12-dihydroxycedrol
(11) and 7,12-dihydroxycedrol (12) were obtained.
2. Results and discussion
Incubation of cedrol (1) with C. lunata for 14 days in
PDB resulted in the production of 3b-hydroxycedrol (2),
3a-hydroxycedrol (3), 12-hydroxycedrol (4), 3b-hydro-
xycedrene (6) and 3-oxocedrol (7). Transformation of 1
with C. lunata in BEM gave 2-hydroxycedrol (5), 4b-
hydroxycedrol (8), 10b-hydroxycedrol (9), 7-hydro-
xycedrol (10), 2,12-dihydroxycedrol (11) and 7,12-dihy-
droxycedrol (12) in addition to the major metabolites 2,
3 and 4. The known compounds 29 were identied by
0031-9422/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved.
PI I : S0031- 9422( 00) 00412- X
Phytochemistry 56 (2001) 417421
www.elsevier.com/locate/phytochem
* Corresponding author. Tel.: +876-9271910; fax: +876-9771835.
E-mail address: pbreese@uwimona.edu.jm (P.B. Reese).
comparison of their spectral data with that in the lit-
erature (Hanson and Nasir, 1993 [2, 4, 6, 7]; Fraga et
al., 1996 [2, 3, 4, 5]; Abraham et al., 1987 [2, 3, 4, 5, 8,
9]; Miyazawa et al., 1995 [2, 3, 4]; Matooq et al., 1993
[2, 3, 4, 5, 8, 9]; Lamare et al., 1987 [3]) (Fig. 1).
Data from the HREIMS of 10 suggested a molecular
formula of C
15
H
26
O
2
([M]
+
=238.1930) which indicated
the presence of an additional hydroxyl group in the
molecule. The
13
C NMR spectrum revealed that inser-
tion of the new hydroxyl group (
C
85.1) occurred
simultaneously with the disappearance of a methine.
Finally, downeld shifts in resonances of the adjacent
carbons (C-6, C-8 and C-11) justied the positioning of
the new hydroxyl group at C-7.
The structure of 2,12-dihydroxycedrol (11) followed
from the
1
H NMR spectrum that contained two doub-
lets (
H
3.52, J=11.0; 3.64, J=11.0 Hz) that were char-
acteristic of a primary alcohol. The methyl doublet of
the starting material was also absent. The
13
C NMR
spectrum contained a CH
2
O signal at 66.7 that was
therefore assigned to C-12. A third hydroxyl group was
identied in this isomer, notably borne by a non-pro-
tonated carbon atom (
C
83.7). The carbon shifts seen
within the molecule bore a striking resemblance to
those of 5 with hydroxylation having occurred at C-2.
Compound 11 was thus assigned as the 2,12-dihydroxy
derivative.
The methyl doublet of the substrate was also missing
from the
1
H NMR spectrum of 12 pointing to hydro-
xylation having occurred at C-12. This C-12 methyl
group was replaced by an oxygen bearing methylene (
C
63.6) in the
13
C NMR spectrum. The presence of a third
hydroxyl function was conrmed by HREIMS that gave
a molecular formula of C
15
H
26
O
3
([M]
+
=254.1881).
This hydroxyl group was borne on a non-protonated
carbon (C-7). A comparison of the carbon resonance
values of this metabolite with both 4 and 10 veried
congener 12 as 7,12-dihydroxycedrol.
Bioconversion reactions of cedrol in PDB were more
regioselective. The oxidation reactions occurred at only
two centres, C-3 and -12. The hydroxylases developed
by the fungus in BEM, however, appeared to be less
selective with hydroxylation occurring at C-2, -3, -4, -7,
-10 and -12. Preliminary molecular modeling studies on
11 and 12 indicate that both metabolites may have resul-
ted from a single enzyme system. Both compounds could
Fig. 1. Cedrol and biotransformation products.
418 D.O. Collins, P.B. Reese / Phytochemistry 56 (2001) 417421
have been obtained because the rigid bridged system of
the substrate may have two possible orientations in the
active site of the enzyme. This idea of a triangular rela-
tionship between binding and hydroxylation sites within
enzymes is not new (Holland, 1983; Lamare and Fur-
stoss, 1990) and in fact, cedrol (1) has been used by
Fraga (Fraga et al., 1996) to map the three dimensional
topology of enzyme systems in Mucor plumbeus.
In summary cedrol was biotransformed by C. lunata,
growing in PDB, to ve known compounds. When the
microorganism was grown on a BEM the sesquiterpene
was converted to nine analogues, three of which were iso-
lated from the other fermentation. Three of the metabo-
lites, however, have not been reported previously.
3. Experimental
Cedrol (1) was obtained commercially from the May-
bridge Chemical Company, UK. Column chromato-
graphy was performed with Kieselgel silica (4063 mm).
Compounds on thin layer chromatography (TLC)
plates were visualised by the use of the ammonium
molybdate/sulphuric acid spray reagent followed by
heating at 120

C. IR data was acquired on a Perkin

Elmer FTIR Paragon 1000 instrument using KBr disks.
Optical rotations were acquired on a Perkin Elmer 241
polarimeter. High resolution electron impact mass
spectrometry (HREIMS) was done on a Kratos MS50
instrument at an ionising voltage of 70 eV.
1
H and
13
C
NMR spectra were generated in deuterated chloroform
at 200 and 50 MHz respectively using a Bruker AC200
instrument. Tetramethylsilane (TMS) was used as the
internal standard.
13
C NMR assignments are listed in
Table 1. C. lunata ATCC 12017 was obtained from the
American Type Culture Collection, Rockville, MD, USA.
The fungus was maintained on PDA slants. PDB was
comprised of potato dextrose broth (24 g l
1
; Chen and
Wey, 1990). BEM was composed of peptone (1 g l
1
),
yeast extract (1 g l
1
), beef extract (1 g l
1
) and glucose
(5 g l
1
) in water (Garcia-Granados et al., 1991). One
14-day-old slant was used to inoculate four 500 ml con-
ical asks each containing 125 ml of liquid medium. The
asks were incubated at 200 rpm at 27

C. An EtOAc
solution (2 ml) containing 10% of the total mass of the
substrate was fed 24 h after inoculation. The remaining
20, 30 and 40% of the substrate was fed at 36, 48 and
60 h after inoculation respectively. The fermentation
was allowed to proceed for 10 days after the last feed.
The pH was measured and the mycelium was ltered
from the broth. Broth extraction utilised EtOAc
(3500 ml). The mycelium was homogenised in EtOAc.
The extracts were dried with sodium sulphate, con-
centrated in vacuo, and analysed by TLC.
Cedrol (1) (1 g) was fed to C. lunata in 20 asks of each
medium as outlined above. After incubation the fungus
was harvested to give broth extracts (0.818 and 0.883 g)
and mycelial extracts (0.442 and 0.540 g) from PDB and
BEMrespectively. The pHat the end of each fermentation
was 6.5. Analysis of both extracts by TLC indicated the
presence of biotransformed compounds. The broth and
mycelial extracts of each fermentation were combined and
subjected to column chromatography using increasing
concentrations of EtOAc in petrol. Untransformed
cedrol was recovered (PDB, 555 mg; BEM, 337 mg).
Three new metabolites, 10, 11 and 12, were obtained
Table 1
C-13 NMR chemical shifts for cedranes 112
Compounds
1 2 3 4 5 6 7 8 9 10 11 12
C-1 52.0 50.7 52.7 53.2 57.5 52.0 52.6 52.9 60.0 49.3 58.4 48.5
C-2 41.4 50.1 46.0 50.3 79.6 45.8 48.4 38.0 38.1 42.3 83.7 51.1
C-3 37.0 81.4 79.9 32.1 36.5 79.0 220.0 46.7 34.5 36.4 36.5 30.6
C-4 25.3 32.1 32.7 25.8 21.5 33.2 35.9 73.5 23.8 26.5 22.0 26.9
C-5 61.0 52.6 61.4 61.1 59.1 56.8 58.2 61.4 53.4 57.2 59.2 57.0
C-6 43.4 42.6 42.9 43.0 44.9 47.4 44.1 45.1 44.1 45.6 44.2 45.0
C-7 56.5 60.9 54.2 57.4 53.5 55.0 52.3 63.0 59.7 85.1 54.2 85.3
C-8 75.1 74.8 74.9 75.0 74.9 140.2 74.2 74.9 74.7 77.2 74.9 77.7
C-9 35.3 35.3 35.0 34.9 35.6 119.0 35.2 34.7 43.5 34.8 35.7 34.5
C-10 31.6 34.2 33.9 30.8 30.0 39.9 34.4 31.6 71.5 31.3 29.3 31.3
C-11 41.9 43.1 42.4 42.5 41.2 40.9 37.7 42.7 35.0 45.5 37.8 46.1
C-12 15.5 12.4 9.6 63.7 24.3 9.4 8.9 15.3 15.4 15.2 66.7 63.6
C-13 27.6 29.5 27.4 27.4 28.4 26.0 27.8 30.1 28.6 25.4 28.4 25.2
C-14 28.9 27.3 29.1 29.0 27.5 27.4 30.0 28.5 29.3 24.7 27.5 24.8
C-15 30.2 30.2 29.7 30.1 30.3 24.7 30.1 30.6 32.4 26.1 30.2 25.2
D.O. Collins, P.B. Reese / Phytochemistry 56 (2001) 417421 419
from the extracts of the fermentation in BEM. They
were eluted in solutions of 3, 5 and 10% EtOAc in pet-
rol respectively.
3.1. 3-Hydroxycedrol (2) (PDB, 78 mg; BEM, 84 mg)
Cubes from MeOH; m.p. 147148

C, []
25
D
: +3.41

(c=3.8, CHCl
3
) [lit. m.p. 149.5152.4

C, []
20
D
: +3.21

(c=1.0, CHCl
3
) (Miyazawa et al., 1995)]; IR
max
cm
1
:
3280 (OH);
1
H NMR: 0.91 (3H, d, J=7.3 Hz, H-12),
1.01 (3H, s, H-14), 1.26 (3H, s, H-13), 1.34 (3H, s, H-
15), 1.64 (1H, m, w/2=3.7 Hz, H-4), 1.90 (1H, m, w/
2=7.0 Hz, H-11), 2.17 (1H, m, w/2=3.7 Hz, H-5), 4.29
(1H, q, J=4.1 Hz, H-3).
3.2. 3-Hydroxycedrol (3) (PDB, 24 mg; BEM, 56 mg)
Needles from MeOH; m.p. 161162

C, []
25
D
: +13.62

(c=7.8, CHCl
3
) [lit. m.p. 159.5162.7

C, []
20
D
: +12.87

(c=1.0, CHCl
3
) (Miyazawa et al., 1995)]; IR
max
cm
1
:
3331 (OH);
1
H NMR: 0.96 (3H, d, J=7.0 Hz, H-12),
1.03 (3H, s, H-14), 1.26 (3H, s, H-13), 1.34 (3H, s, H-
15), 1.80 (1H, m, w/2=11.0 Hz, H-4), 3.61 (1H, ddd,
J=5.1, 9.8, 10.1 Hz, H-3).
3.3. 12-Hydroxycedrol (4) (PBD, 156 mg; BEM, 368 mg)
Needles from EtOH; m.p. 121122

C, []
25
D
: +8.00

(c=13.7, CHCl
3
) [lit. m.p. 124.9127.2

C, []
20
D
: +9.78

(c=1.0, CHCl
3
) (Miyazawa et al., 1995)]; IR
max
cm
1
:
3317 (OH);
1
H NMR: 1.01 (3H, s, H-14), 1.26 (3H, s,
H-15), 1.33 (3H, s, H-13), 1.50 (1H, m, w/2=3.5 Hz, H-
4), 3.49 (1H, m, w/2=12.9 Hz, H-12), 3.68 (1H, m, w/
2=12.9 Hz, H-12).
3.4. 2-Hydroxycedrol (5) (BEM, 24 mg)
Oil; []
25
D
: +10.52

(c=12.9, CHCl
3
) [lit. m.p.137

C,
[]
D
: +10.6

(c=1.0, CHCl
3
) (Abraham et al., 1987)];
IR
max
cm
1
: 3472 (OH);
1
H NMR: 1.05 (3H, s, H-
15), 1.18 (3H, s, H-14), 1.28 (3H, s, H-13), 1.30 (3H, s,
H-12), 1.52 (1H, m, w/2=5.9 Hz, H-9), 1.61 (1H, m, w/
2=5.9 Hz, H-10), 1.77 (1H, m, w/2=7.5 Hz, H-3), 1.80
(3H, m, w/2=7.5 Hz, H-4), 1.86 (1H, m, w/2=4.0 Hz,
H-11).
3.5. 3-Hydroxycedrene (6) (PDB, 39 mg)
Oil; []
25
D
: 35.22

(c=13.3, CHCl
3
) [lit. oil. (Hanson
and Nasir, 1993)]; IR
max
cm
1
: 3400 (OH), 1466;
1
H
NMR: 0.89 (3H, d, J=7.3 Hz, H-12), 0.96 (3H, s, H-
14), 1.04 (3H, s, H-13), 1.41 (1H, m, w/2=3.0 Hz, H-2),
1.62 (1H, m, w/2=3.0 Hz, H-3), 1.67 (3H, dd, J=1.5,
3.8 Hz, H-15), 1.76 (1H, m, w/2=4.5 Hz, H-7), 1.83
(1H, d, J=7.3 Hz, H-2), 1.90 (1H, d, J=2.5 Hz, H-5),
4.34 (1H, q, J=5.0 Hz, H-3), 5.21 (1H, bs, H-9).
3.6. 3-Oxocedrol (7) (PDB, 21 mg)
Cubes from EtOH; m.p. 9496

C, []
25
D
: 28.10

(c=3.5, CHCl
3
) [lit. m.p. 113114

C (Hanson and
Nasir, 1993)]; IR
max
cm
1
: 3460 (OH), 1731 (CO);
1
H
NMR: 0.96 (3H, d, J=1.6 Hz, H-14), 1.00 (3H, d,
J=7.6 Hz, H-12), 1.30 (3H, s, H-13), 1.31 (1H, m, w/
2=1.9 Hz, H-11), 1.35 (1H, m, w/2=1.9 Hz, H-11), 1.40
(1H, s, H-10), 1.41 (3H, s, H-15), 1.57 (1H, m, w/
2=7.0 Hz, H-7), 1.78 (1H, m, w/2=3.8 Hz, H-10), 2.10
(1H, d, J=7.3 Hz, H-2), 2.18 (1H, d, J=1.0 Hz, H-5),
2.28 (1H, d, J=5.7 Hz, H-4), 2.37 (1H, m, w/2=8.9 Hz,
H-4).
3.7. 4-Hydroxycedrol (8) (BEM, 17 mg)
Oil; []
25
D
: +5.19

(c=1.9, CHCl
3
) [lit. m.p. 118

C,
[]
D
: +5.9

(c=1.0, CHCl
3
) (Abraham et al., 1987)]; IR

max
cm
1
: 3340 (OH);
1
H NMR: 0.92 (3H, d,
J=7.0 Hz, H-12), 1.26 (3H, s, H-15), 1.35 (3H, s, H-14),
1.41 (3H, s, H-13), 4.31 (1H, ddd, J=2.9, 6.3, 6.6 Hz,
H-4).
3.8. 10-Hydroxycedrol (9) (BEM, 60 mg)
Cubes from EtOH; m.p. 9394

C, []
25
D
: 9.52

(c=26.5, CHCl
3
) [lit. m.p. 88

C, []
D
: 9.8

(c=1.0,
CHCl
3
) (Abraham et al., 1987)]; IR
max
cm
1
: 3416
(OH);
1
H NMR: 0.91 (3H, d, J=6.6 Hz, H-12), 1.02
(3H, s, H-14), 1.27 (3H, s, H-13), 1.36 (1H, d,
J=10.1 Hz, H-11), 1.45 (3H, s, H-15), 1.59 (1H, t,
J=10.1 Hz, H-7), 1.72 (1H, m, w/2=6.2 Hz, H-5), 1.80
(1H, m, w/2=4.1 Hz, H-9), 1.89 (1H, m, w/2=4.1 Hz,
H-3), 1.95 (1H, m, w/2=4.1 Hz, H-2), 3.95 (1H, d,
J=4.8 Hz, H-10).
3.9. 7-Hydroxycedrol (10) (BEM, 3 mg)
Oil; []
25
D
: +14.53

(c=1.1, CHCl
3
); EIMS m/z
238.1930 ([M]
+
, C
15
H
26
O
2
, 238.1932), 193.1590 (64),
165.1277 (30), 154.0991 (22); IR
max
cm
1
: 3566 (OH);
1
H NMR: 0.88 (3H, d, J=7.0 Hz, H-12), 0.97 (3H, s,
H-14), 1.21 (3H, s, H-13), 1.35 (3H, s, H-15), 1.40 (1H,
m, w/2=5.3 Hz, H-11), 1.62 (1H, m, w/2=4.0 Hz, H-2),
1.80 (1H, m, w/2=5.3 Hz, H-11), 2.35 (1H, m, w/
2=7.6 Hz, H-5).
3.10. 2,12-Dihydroxycedrol (11) (BEM, 13 mg)
Oil; []
25
D
: +10.42

(c=3.5, CHCl
3
); EIMS m/z
254.1884 ([M]
+
, C
15
H
26
O
3
, 254.1882), 223.1699 (100),
165.1281 (30), 147.1178 (49); IR
max
cm
1
: 3453 (OH);
1
H NMR: 1.01 (3H, s, H-15), 1.27 (3H, s, H-14), 1.31
(3H, s, H-13), 1.59 (1H, m, w/2=6.7 Hz, H-9), 1.73 (1H,
m, w/2=4.2 Hz, H-4), 3.52 (1H, d, J=11.0 Hz, H-12),
3.64 (1H, d, J=11.0 Hz, H-12).
420 D.O. Collins, P.B. Reese / Phytochemistry 56 (2001) 417421
3.11. 7,12-Dihydroxycedrol (12) (BEM, 10 mg)
Oil; []
25
D
: +8.90

(c=2.7, CHCl
3
); EIMS m/z
254.1881 ([M]
+
, C
15
H
26
O
3
, 254.365), 236.1775 (94),
165.1277 (20), 147.1179 (21); IR
max
cm
1
: 3416 (OH);
1
H NMR: 0.98 (3H, s, H-14), 1.22 (3H, s, H-13), 1.35
(3H, s, H-15), 1.47 (1H, m, w/2=3.2 Hz, H-3), 1.62 (1H,
m, w/2=3.2 Hz, H-2), 1.71 (1H, d, J=2.2 Hz, H-11),
1.75 (1H, t, J=1.6 Hz, H-5), 3.54 (1H, dd, J=7.3,
11.4 Hz, H-12), 3.67 (1H, dd, J=6.6, 11.1 Hz, H-12).
Acknowledgements
This work was supported in part by funds secured
under the University of the West Indies/Interamerican
Development Bank (UWI/IDB) Programme. D.O.C.
thanks the University of the West Indies for the grant-
ing of a Postgraduate Scholarship. The authors are
grateful to Professor John C. Vederas (University of
Alberta) for arranging mass spectral analyses. Optical
rotations were measured at the Bureau of Standards,
Kingston. Fermentations were carried out in the Bio-
technology Centre, UWI.
References
Abraham, W., Washausen, P., Kieslich, K., 1987. Microbial hydro-
xylation of cedrol and cedrene. Z. Naturforsch. 42, 414419.
Aranda, G., El Kortbi, M.S., Lallemand, J.-Y., Neuman, A., Ham-
moumi, A., Facon, I., Azerad, R., 1991. Microbial transformation
of diterpenes: hydroxylation of sclareol, manool and derivatives by
Mucor plumbeus. Tetrahedron 47, 83398350.
Buchanan, G.O., Reese, P.B., 2000. Biotransformation of cadinane
sesquiterpenes by Beauveria bassiana ATCC 7159. Phytochemistry
54, 3945.
Chen, K.C., Wey, H.C., 1990. Dissolution-enzyme kinetics of 11b-
hydroxylation of cortexolone by Curvularia lunata. Enz. Microb.
Technol. 12, 616621.
de Lima, D.P., Carnell, A.J., Roberts, S.M., 1999. Microbial trans-
formation of (+)-10,14-dihydroxy-allo-aromadendrane and ()-
allo-aromadendrone. J. Chem. Res., Synop., 396397
Fraga, B.M., Guillermo, R., Hanson, J.R., Truneh, A., 1996. Bio-
transformation of cedrol and related compounds by Mucor plum-
beus. Phytochemistry 42, 15831586.
Garcia-Granados, A., Martinez, A., Onorato, M.E., Rivas, F., Arias,
J.M., 1991. Chemical-microbiological synthesis of 6b-eudesmano-
lides by Curvularia lunata cultures from eudesmanes with functions
at C-1 and C-6. Tetrahedron 47, 91102.
Hanson, J.R., Nasir, H., 1993. Biotransformation of the sesquiterpenoid
cedrol by Cephalosporium aphidicola. Phytochemistry 33, 835837.
Hanson, J.R., Reese, P.B., Takahashi, J.A., Wilson, M.R., 1994. Bio-
transformation of some stemodane diterpenoids by Cephalosporium
aphidicola. Phytochemistry 36, 13911393.
Holland, H.L., 1983. The mechanism of the microbial hydroxylation
of steroids. Chem. Soc. Rev. 11, 371395.
Holland, H.L., 1992. Organic Synthesis With Oxidative Enzymes.
VCH, New York, pp. 8695.
Kouzi, S.A., McChesney, J.D., 1990. Microbial metabolism of the
diterpene sclareol: oxidation of the A ring by Septomyxa anis.
Helv. Chim. Acta 73, 21572164.
Lamare, V., Fourneron, J.D., Furstoss, R., 1987. Microbial transfor-
mations 9. Biohydroxylation of alpha-cedrene and cedrol. Synthesis
of an odoriferous minor component of cedar wood essential oil.
Tetrahedron Lett. 28, 62696272.
Lamare, V., Furstoss, R., 1990. Biotransformation of sesquiterpenes.
Tetrahedron 46, 41094132.
Matooq, G., El-Sharkawy, S., A, M.S., Rosazza, J.P.N., 1993.
Microbial transformations of cedrol. J. Nat. Prod. 56, 10391050.
Miyazawa, M., Nankai, H., Kameoka, H., 1995. Biotransformation of
(+)-cedrol by plant pathogenic fungus, Glomerella cingulata. Phy-
tochemistry 40, 6972.
Wang, K.C., Ho, L.Y., Cheng, Y.S., 1972. Microbial oxidation of ter-
penes. I. Hydroxylation of cedrol. J. Chin. Biochem. Soc. 1, 5355.
D.O. Collins, P.B. Reese / Phytochemistry 56 (2001) 417421 421