Synthesis of phenol abietane diterpenes based on the oxidative radical cyclization utilizing the Mn(OAc)3/Ac2O system

Article abstract of DOI:10.1055/s-2007-985586

A new route to phenol abietane diterpenes from trans-communic acid is reported. The key step is the transformation of a β-ketoester into the corresponding O-acetylsalicilate, via a manganese(III)-based oxidative free-radical cyclization carried out in Ac₂O. Utilizing this, the first synthesis of (-)-sugikurojin A has been achieved. The immunosuppressor 19-hydroxyferruginol has also been synthesized. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-985586

LETTER
2425
Synthesis of Phenol Abietane Diterpenes Based on the Oxidative Radical
Cyclization Utilizing the Mn(OAc)3/Ac2O System
S
ynthesis of Phe
n
nol
A
bietan
r
e
Diterpe
i
ne
s
que Alvarez-Manzaneda,*a Rachid Chahboun,a Eduardo Cabrera,a Esteban Alvarez,a
Ramón Alvarez-Manzaneda,b Mohammed Lachkar,c Ibtissam Messouric
a
Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Biotecnología, Universidad de Granada, 18071 Granada, Spain
Fax +34(958)248089; E-mail: eamr@ugr.es
b
c
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Almería, 04120 Almería, Spain
Departement de Biologie, Unité des Substances Naturelles, Faculté de Médecine et Pharmacie, Université Mohammed V-Suissi,
Rabat, Morocco
Received 31 May 2007
O
OH
Abstract: A new route to phenol abietane diterpenes from trans-
communic acid is reported. The key step is the transformation of a
b-ketoester into the corresponding O-acetylsalicilate, via a manga-
nese(III)-based oxidative free-radical cyclization carried out in
Ac2O. Utilizing this, the first synthesis of (–)-sugikurojin A has
been achieved. The immunosuppressor 19-hydroxyferruginol has
also been synthesized.
HO
R1
O
O
R2
R2
R
R
R
O
3
4 R = H; R1 = OH; R2,R2 = O
5 R = COOH; R1,R2 = H
6 R = CH2OH; R1,R2 = H
1 R,R = H
2 R,R = O
Key words: enantiospecific synthesis, abietane diterpenoids,
phenols
16
R1
OH
R2
Abietane diterpenes comprise an important group of
secondary metabolites, which are widespread in the
vegetable kingdom. In recent years interest in this type of
terpenoids has increased, as a result of the isolation of
compounds, mainly phenols and related derivatives,
showing remarkable biological activities.1 As representa-
tive examples we might cite (–)-12-deoxyroyleanone (1),
an antileishmanial agent,2,3 and cryptoquinone (2), which
shows cytotoxic activity against mouse lymphoid
neoplasm (P388) cells.4 Other relevant oxidized abietane
diterpenes are taxodione (3)5,6 and salvinolone (4),7 which
are active against methicillin-resistant Staphylococcus
aureus (MRSA) and vancomycin-resistant Enterococcus
(VRE). Recently, the isolation of 6,7-dehydro-19-hy-
droxyferruginol (sugikurojin A, 10), a new diterpene from
Cryptomeria japonica, has been reported;8 very recent
studies have revealed that 19-hydroxyferruginol (11)9 is a
target for tolerance after transplantation and in auto-
immune diseases (Figure 1).10
15
11
17
1
14
O
6
HOH2C
O
COOH
18
19
O
12
7 R1 = OH; R2 = H
8 R1 = R2 = H
9 R1 = H; R2 = OH
10
11 6,7-dihydro
Figure 1 Some representative oxygenated abietane diterpenes.
these, compounds 1 and 5–9 were synthesized from this
diterpene.3a,18
Following our research into the synthesis of phenol abiet-
ane diterpenes, we are now interested in developing a new
route to C-18 functionalized abietane, such as the recently
isolated sugikurojin A (10) and the bioactive 6,7-dihydro-
derivative 11, starting from trans-communic acid (17), a
labdane diterpene very abundant in some species of
Juniperus19 and Cupressus.20 Scheme 1 shows the
planned synthetic strategy. The key step is the elaboration
of the aromatic C ring, which will be accomplished via an
oxidative free-radical cyclization of a suitable unsaturated
b-ketoester; thus, compound 15, obtained from aldehyde
16, will be transformed into aromatic ester 14. The iso-
propyl group of the abietane skeleton will be introduced
through the methoxycarbonyl group, providing the 15-hy-
droxy derivative 13. After removing the 15-hydroxy
group, via cationic reduction or dehydration–hydrogena-
tion processes, deprotecting the phenol and reducing the
ester group, the bioactive 19-hydroxyferruginol (11) will
Despite the interest in this type of compound, few synthe-
ses have been described, most of them being total synthe-
ses involving polyene cascade cyclizations,11 Diels–Alder
cycloadditions,12 electrophilic cyclizations,13 Robinson
annulation14 and domino acylation–cycloalkylation.15
Enantioselective syntheses of these compounds have also
been reported, in most cases starting from podocarpic9,16
and abietic acid.3a,b,6,17 During the last few years, our
group has reported new procedures to introduce oxygen-
ated functions on the C ring of abietic acid (12); utilizing
SYNLETT 2007, No. 15, pp 2425–2429
1
7
.0
9
.2
0
0
7
Advanced online publication: 16.08.2007
DOI: 10.1055/s-2007-985586; Art ID: D16807ST
© Georg Thieme Verlag Stuttgart · New York

2426
E. Alvarez-Manzaneda et al.
LETTER
OP
OP
OH
corresponding alkyl salycilates, via manganese(III)-based
oxidative free-radical cyclizations; the use of Mn(OAc)3
and LiCl in acetic acid has been described to minimize the
overoxidation of cyclization products, improving the
yield of end compounds.23 However, a complex mixture
of compounds was obtained when ketoester 15 was
oxidized under these conditions. These results, which can
be attributed to the overoxidation of resulting phenol, in-
cited us to essay a reaction medium, such as Ac2O, which
could simultaneously act as the solvent and as the reagent
to protect the phenolic hydroxyl group. We have found
that the treatment of compound 15 with 4 equivalents of
Mn(OAc)3·2H2O and 3 equivalents of LiCl in Ac2O at 120
°C for 12 hours affords the methyl O-acetyl salycilate 22
in 74% yield.24 A possible mechanism for this trans-
formation is postulated in Scheme 3. Compound 22 could
be formed after acetylation of an intermediate manga-
nese(III) enolate.
OH
COOMe
COOMe
14
COOMe
CH2OH
13
10
11 6,7-dihydro
O
COOMe
CHO
COOMe
COOH
COOMe
15
17
16
Scheme 1 Retrosynthetic analysis of compounds 10 and 11.
O
O
O
COOMe
MnIII
COOMe
MnIII
COOMe
be obtained. The D6 double bond of sugikurojin A (10)
will be created after elimination of a suitable 7-hydroxy
derivative obtained after benzylic oxidation.
+
The synthesis of ketoester 15 is depicted in Scheme 2.
Epoxidation of methyl ester 18 gave a mixture of dia-
stereomeric 12,13-epoxiderivatives 19 and 20,21 which
was converted into aldehyde 16 by treatment with HIO4 in
THF at room temperature.22 Treatment of compound 16
with MeMgBr (1 equiv) and further oxidation with Jones
reagent gave methylketone 21, which was converted into
b-ketoester 15 after treatment with Me2CO3 and NaH in
benzene.
– H+
15
MnIII
O
O
OAc
O
O
COOMe
OMe
MnIII
OMe
Ac2O
MnIII
OAc
OAc
OAc
Next, the construction of the aromatic C ring was under-
taken. Snider et al. have reported the transformation of
unsaturated b-ketoesters, such as compound 15, into the
COOMe
MnIII
COOMe
COOMe
– H+
+
O
22
Scheme 3 A tentative mechanism for the formation of
compound 22
b
a
COOH
COOMe
Scheme 4 shows the transformation of bicyclic ketoester
1525 into the bioactive 19-hydroxyferruginol (11), via the
O-acetyl salycilate 22. Treatment of this compound with
MeMgBr in excess afforded the abietane phenol 23. When
this compound was treated with Et3SiH and CF3COOH
the 15-hydroxy group was removed, producing the silyl
ether 24. It should be noted that small quantities of phenol
25 were also obtained when the reaction conditions were
not completely anhydrous. Refluxing of compound 24
with LiAlH4 in THF caused reduction of the ester group
and simultaneous deprotection of the silyl ether, affording
19-hydroxyferruginol (11).
COOMe
17
19 (12R,13R)
20 (12S,13S)
18
c
O
O
COOMe
f
CHO
d,e
COOMe
COOMe
COOMe
15
21
16
Scheme 2 Reagents and conditions: (a) CH2N2, Et2O, r.t., 10 min
(97%); (b) MCPBA, NaHCO3, CH2Cl2, 0 °C to r.t., 12 h (87%);
(c) HIO4, THF, –10 °C, 1 h (83%); (d) MeMgBr, Et2O, 0 °C (96%);
(e) Jones reagent, acetone, 0 °C, 15 min (92%); (f) Me2CO3, NaH,
benzene, 3 h (89%).
The synthesis of sugikurojin A (10) starting from silyl
ether 24 is shown in Scheme 5. Heating of this compound
with Na2CrO4 and NaOAc in Ac2O–AcOH led to the
Synlett 2007, No. 15, 2425–2429 © Thieme Stuttgart · New York

LETTER
Synthesis of Phenol Abietane Diterpenes
2427
under the reduction conditions, and consequently the D7
double bond of compound 10 should be probably formed
by elimination of the aluminum oxide complex, favored
by its secondary and benzylic character. Spectroscopic
properties of compound 10 were identical to those re-
ported in the literature for the natural product,8 but the op-
tical rotation of our synthetic compound was [a]D25 –29.2
{c 0.92, CHCl3; lit.8 [a]D25 +32.8 (c 0.39, CHCl3)}.
OAc
OH
O
OH
COOMe
COOMe
a
b
COOMe
COOMe
23
COOMe
22
15
c
In summary, a new route to phenolic abietane diterpenes
from trans-communic acid (17), via a manganese(III)-
based oxidative free-radical cyclization in Ac2O of a
suitable unsaturated b-ketoester, is described. This new
procedure, by which A-ring-functionalized diterpenes can
be prepared, has been utilized to carry out the first synthe-
sis of (–)-sugikurojin A (10). The bioactive 19-hydroxy-
ferruginol (11) was also prepared.
OR
OH
d
COOMe
CH2OH
11
24 R = SiEt3
25 R = H
Acknowledgment
Scheme 4 Reagents and conditions: (a) Mn(OAc)3 (4 equiv), LiCl
(3 equiv), Ac2O, 120 °C, 12 h (74%); (b) MeMgBr (excess), Et2O,
0 °C, 15 min (92%); (c) Et3SiH, CF3COOH, CH2Cl2, –40 °C, 30 min
(87%); (d) LiAlH4, THF, r.t. to reflux, 12 h (95%).
The authors thank Ministerio de Ciencia y Tecnologia (Project
CTQ2006-12697) and Junta de Andalucia for financial support.
References and Notes
OSiEt3
OH
OSiEt3
(1) For some references on the biological activities, see:
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a
b
O
COOMe
CH2OH
COOMe
26
27 ∆5
10
24
c
f
Phytochemistry 1994, 35, 539. (f) Batista, O.; Simoes, M.
F.; Duarte, A.; Valdivia, M. L.; De La Torre, M. C.;
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OH
OAc
OAc
d
e
O
COOMe
25
COOMe
COOMe
28
29
Scheme 5 Reagents and conditions: (a) Na2CrO4, NaOAc, Ac2O,
AcOH, 70 °C, 3 h (83%); (b) LiAlH4, THF, r.t. to reflux, 12 h (98%);
(c) TBAF, THF, r.t., 20 min (94%); (d) Ac2O, pyridine, r.t., 24 h
(93%); (e) Jones reagent, acetone, r.t., 2 d (76%); (f) LiAlH4, THF,
r.t., 10 h (88%).
corresponding 7-oxoderivative 26; the a,b-unsaturated
ketone 27 was also obtained when the oxidation time was
prolonged. Refluxing of compound 26 with LiAlH4 in
THF gave directly sugikurojin A (10).
An alternative route to hydroxy phenol 10 from silyl de-
rivative 24, which prevents the overoxidation to a,b-un-
saturated ketones, such as 27, involves the removal of
silyl group and the further acetylation to obtain the ace-
toxyester 28, which was then transformed into sugikurojin
A (10) under the same reaction conditions utilized for
compound 26. It must be emphasized that benzylic alco-
hols derived from ketones 26 and 29 never were isolated
Synlett 2007, No. 15, 2425–2429 © Thieme Stuttgart · New York

2428
E. Alvarez-Manzaneda et al.
LETTER
(10) Takei, M.; Umeyama, A.; Arihara, S. Biochem. Biophys.
Res. Commun. 2005, 337, 730.
(11) Harring, S. R.; Livinghouse, T. Tetrahedron Lett. 1989, 30,
1499.
Selected Data
Compound 15: [a]D25 +13.6 (c 0.9, CHCl3). 1H NMR (500
MHz, CDCl3): d = 0.52 (3 H, s), 1.05 (1 H, ddd, J = 13.4,
13.4, 4.1 Hz), 1.14 (1 H, ddd, J = 13.2, 13.2, 4.1 Hz), 1.19 (3
H, s), 1.41 (1 H, dd, J = 12.5, 2.7 Hz), 1.51 (1 H, dt, J = 14.1,
3.1 Hz), 1.59 (1 H, m), 1.77 (1 H, ddd, J = 17.6, 13.4, 4.2
Hz), 1.81 (1 H, dt, J = 13.8, 3,6 Hz), 1.95–2.10 (2 H, m),
2.17 (1 H, br d, J = 12.6 Hz), 2.36–2.44 (2 H, m), 2.61 (1 H,
dd, J = 17.5, 3.3 Hz), 2.71 (1 H, dd, J = 17.5, 10.2 Hz), 3.43
(1 H, d, J = 15.4 Hz), 3.47 (1 H, d, J = 15.4 Hz), 3.61 (3 H,
s), 3.72 (3 H, s), 4.34 (1 H, br s), 4.77 (1 H, br s). 13C NMR
(125 MHz, CDCl3): d = 38.3 (C-1), 20.1 (C-2), 39.5 (C-3),
44.5 (C-4), 50.7 (C-5), 26.0 (C-6), 38.1 (C-7), 148.5 (C-8),
56.2 (C-9), 39.7 (C-10), 39.8 (C-11), 202.3 (C-12), 49.3 (C-
13), 106.8 (C-14), 29.0 (C-15), 177.8 (C-16, COOCH3), 13.1
(C-17), 167.9 (COOCH3), 51.4 (COOCH3), 52.5
(12) (a) Engler, T. A.; Sampath, U.; Naganathan, S.; Vander
Velde, D.; Takusagawa, F. J. Org. Chem. 1989, 54, 5712.
(b) Zambrano, J. L.; Rosales, V.; Nakano, T. Tetrahedron
Lett. 2003, 44, 1859.
(13) (a) Banik, B. K.; Ghosh, S.; Ghatak, V. R. Tetrahedron
1988, 44, 6947. (b) Majetich, G.; Siesel, D. Synlett 1995,
559. (c) Majetich, G.; Liu, S.; Fang, J.; Siesel, D.; Zhang, Y.
J. Org. Chem. 1997, 62, 6928. (d) Tada, M.; Nishiiri, S.;
Zhixiang, Y.; Imai, Y.; Tajima, S.; Okazaki, N.; Kitano, Y.;
Chiba, K. J. Chem. Soc., Perkin Trans. 1 2000, 2657.
(14) Shishido, K.; Got, K.; Miyoshi, S.; Takaishi, Y.; Shibuya, M.
J. Org. Chem. 1994, 59, 406.
(15) Bhar, S. S.; Ramana, M. M. V. J. Org. Chem. 2004, 69,
8935.
(16) Bendell, J. G.; Cambie, R. C.; Rutledge, P. S.; Woodgate, P.
D. Aust. J. Chem. 1993, 46, 1825.
(COOCH3).
Compound 22: [a]D25 +64.5 (c 1.1, CHCl3). 1H NMR (400
MHz, CDCl3): d = 1.01 (3 H, s), 1.07 (1 H, ddd, J = 13.6,
13.6, 4.1 Hz), 1.27 (3 H, s), 1.41 (1 H, ddd, J = 13.3, 13.3,
4.1 Hz), 1.51 (1 H, dd, J = 12.2, 1.4 Hz), 1.63 (1 H, m), 1.90–
2.07 (2 H, m), 2.18 (1 H, m), 2.28 (1 H, br d, J = 13.7 Hz),
2.31 (3 H, s), 2.77 (1 H, ddd, J = 16.9, 12.7, 6.4 Hz), 2.94 (1
H, dd, J = 16.9, 4.5 Hz), 3.65 (3 H, s), 3.82 (3 H, s), 6.94 (1
H, s), 7.69 (1 H, s). 13C NMR (100 MHz, CDCl3): d = 37.7
(C-1), 20.0 (C-2), 39.1 (C-3), 44.2 (C-4), 51.5 (C-5), 20.9
(C-6), 31.5 (C-7), 133.6 (C-8), 148.8 (C-9), 39.2 (C-10),
120.8 (C-11), 154.9 (C-12), 120.2 (C-13), 132.7 (C-14),
170.1 (COOCH3), 28.6 (C-16), 177.8 (COOCH3), 23.0 (C-
20), 52.2 (COOCH3), 52.3 (COOCH3), 21.2 (OCOCH3),
165.2 (OCOCH3).
(17) (a) Tahara, A.; Akita, H. Chem. Pharm. Bull. 1975, 23, 197.
(b) Gigante, B.; Santos, C.; Silva, A. M.; Curto, M. J. M.;
Nascimento, M. S. J.; Pinto, E.; Pedro, M.; Cerqueira, F.;
Pinto, M. M.; Duarte, M. P.; Laires, A.; Rueff, J.; Gonçalves,
J.; Pegado, M. I.; Valdeira, M. L. Bioorg. Med. Chem. 2003,
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Lachkar, M.; Dahdouh, A.; Lara, A.; Messouri, I.
Tetrahedron Lett. 2006, 47, 2577. (b) Alvarez-Manzaneda,
E.; Chahboun, R.; Cabrera, E.; Alvarez, E.; Alvarez-
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2007, 48, 989.
Compound 23: [a]D25 +48.4 (c 0.6, CHCl3). 1H NMR (400
MHz, CDCl3): d = 1.00 (3 H, s), 1.06 (1 H, ddd, J = 13.7,
13.7, 4.4 Hz), 1.26 (3 H, s), 1.37 (1 H, ddd, J = 13.2, 13.2,
3.8 Hz), 1.50 (1 H, d, J = 12.1 Hz), 1.63 (3 H, s), 1.66 (3 H,
s), 1.86–2.04 (3 H, m), 2.09 (1 H, s), 2.12–2.23 (2 H, m),
2.27 (1 H, d, J = 13.4 Hz), 2.68 (1 H, ddd, J = 16.3, 12.7, 6.0
Hz), 2.79 (1 H, dd, J = 16.3, 4.9 Hz), 3.64 (3 H, s), 6.73 (1
H, s), 6.77 (1 H, s). 13C NMR (100 MHz, CDCl3): d = 37.9
(C-1), 20.2 (C-2), 39.5 (C-3), 44.2 (C-4), 51.5 (C-5), 21.4
(C-6), 31.6 (C-7), 126.4 (C-8), 149.2 (C-9), 38.5 (C-10),
114.4 (C-11), 153.7 (C-12), 129.0 (C-13), 125.9 (C-14), 75.9
(C-15), 30.5 (C-16), 30.6 (C-17), 28.3 (C-18), 178.2 (C-19),
23.0 (C-20), 53.1 (COOCH3).
(19) Pascual Teresa, J. de; San Feliciano, A.; Miguel del Corral,
J. M.; Barrero, A. F. Phytochemistry 1983, 22, 300.
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1964, 348.
(21) The epoxidation of ester 18 to give compounds 19 and 20
was previously described by Barrero et al., who reported a
40% yield for this transformation. See: Barrero, A. F.;
Quintana, R.; Altarejos, J. Tetrahedron 1991, 47, 4441.
(22) Aldehyde 16 was obtained by the same procedure from the
mixture of 12R,13S- and 12S,13R-epoxy derivatives,
resulting from the epoxidation of methyl cis-communate.
See: Barrero, A. F.; Sánchez, J. F.; Elmerabet, J.; Jimenez-
Gonzalez, D.; Macías, F. A.; Simonet, A. M. Tetrahedron
1999, 55, 7289.
(23) Snider, B. B.; Patricia, J. J. J. Org. Chem. 1989, 54, 38.
(24) Typical Procedure for Radical Cyclization
Strictly deoxygenated Ac2O (20 mL) was added to a mixture
of manganese(III) acetate dihydrate (3.21 g, 12 mmol) and
LiCl (365 mg, 8.6 mmol) under argon atmosphere, and the
resulting suspension was stirred at r.t. for 15 min. Then, a
solution of b-ketoester (15, 1 g, 2.86 mmol) in deoxygenated
Ac2O (20 mL) was added, and the mixture was stirred at
reflux for 9 h, at which time TLC showed no starting
material. The reaction mixture was cooled to 0 °C, and
then quenched with H2O (10 mL). After stirring for 10 min,
t-BuOMe (120 mL) was added and the reaction mixture was
stirred for an additional 10 min. The mixture was washed
with H2O (10 × 30 mL) and brine (3 × 20 mL). The dried
organic layer was evaporated and the residue was directly
purified by flash chromatography (hexane–t-BuOMe, 7:3) to
yield 22 (0.82 g, 74%) as a yellow syrup.
Compound 24: [a]D25 +30.8 (c 0.8, CHCl3). 1H NMR (500
MHz, CDCl3): d = 0.77 (6 H, q, J = 7.9 Hz), 1.01 (9 H, t,
J = 7.9 Hz), 1.02 (3 H, s), 1.08 (1 H, ddd, J = 14.0, 14.0, 4.1
Hz), 1.18 (3 H, d, J = 6.9 Hz), 1.19 (3 H, d, J = 6.9 Hz), 1.27
(3 H, s), 1.41 (1 H, ddd, J = 13.4, 13.4, 3.9 Hz), 1.54 (1 H, d,
J = 12.0 Hz), 1.64 (1 H, br d, J = 14.0 Hz), 1.90–2.01 (2 H,
m), 2.13 (1 H, br d, J = 14.1 Hz), 2.17 (1 H, dd, J = 13.6, 5.7
Hz), 2.28 (1 H, br d, J = 13.4 Hz), 2.73 (1 H, ddd, J = 16.3,
12.6, 5.9 Hz), 2.83 (1 H, dd, J = 16.3, 5.0 Hz), 3.21 (1 H,
sept, J = 6.9 Hz), 3.66 (3 H, s), 6.65 (1 H, s), 6.82 (1 H, s).
13C NMR (125 MHz, CDCl3): d = 37.9 (C-1), 20.3 (C-2),
39.7 (C-3), 44.2 (C-4), 51.4 (C-5), 21.5 (C-6), 31.6 (C-7),
127.6 (C-8), 146.1 (C-9), 38.3 (C-10), 115.1 (C-11), 151.2
(C-12), 136.2 (C-13), 126.6 (C-14), 26.9 (C-15), 23.0 (C-
16), 23.1 (C-17), 28.7 (C-18), 178.1 (C-19), 23.2 (C-20),
53.0 (COOCH3), 5.7 (SiCH2CH3), 7.0 (SiCH2CH3).
Compound 25: [a]D25 +72.6 (c 0.6, CHCl3). 1H NMR (400
MHz, CDCl3): d = 1.01 (3 H, s), 1.07 (1 H, ddd, J = 13.6,
13.6, 4.1 Hz), 1.22 (3 H, d, J = 6.9 Hz), 1.23 (3 H, d, J = 6.9
Hz), 1.26 (3 H, s), 1.39 (1 H, ddd, J = 13.3, 13.3, 4.1 Hz),
1.52 (1 H, d, J = 12.1 Hz), 1.61 (1 H, m), 1.80–2.05 (2 H, m),
2.16 (2 H, m), 2.27 (1 H, br d, J = 13.3 Hz), 2.71 (1 H, ddd,
J = 16.4, 12.7, 5.9 Hz), 2.83 (1 H, dd, J = 16.4, 5.3 Hz), 3.11
(25) Spectroscopic properties of natural terpenoids (10 and 11)
were identical to those reported in the literature. All new
compounds were fully characterized spectroscopically and
had satisfactory high-resolution mass spectroscopy data.
Synlett 2007, No. 15, 2425–2429 © Thieme Stuttgart · New York

LETTER
(1 H, sept, J = 6.9 Hz), 3.65 (3 H, s), 4.54 (1 H, br s), 6.63 (1
Synthesis of Phenol Abietane Diterpenes
2429
1.53 (1 H, d, J = 12.1 Hz), 1.60 (1 H, br d, J = 14.2 Hz),
1.90–2.05 (2 H, m), 2.13–2.21 (2 H, m), 2.28 (1 H, m), 2.29
(3 H, s), 2.77 (1 H, ddd, J = 16.7, 12.7, 6.2 Hz), 2.88 (1 H,
dd, J = 16.7, 5.9 Hz), 2.91 (1 H, sept, J = 6.8 Hz), 3.65 (3 H,
s), 6.65 (1 H, s), 6.84 (1 H, s). 13C NMR (100 MHz, CDCl3):
d = 37.8 (C-1), 20.1 (C-2), 39.5 (C-3), 44.2 (C-4), 51.4 (C-
5), 21.2 (C-6), 31.8 (C-7), 133.4 (C-8), 146.5 (C-9), 38.5 (C-
10), 119.3 (C-11), 146.9 (C-12), 137.2 (C-13), 127.2 (C-14),
27.4 (C-15), 23.1 (C-16), 23.2 (C-17), 28.7 (C-18), 178.0 (C-
19), 23.2 (C-20), 52.7 (COOCH3), 21.1 (OCOCH3), 170.1
(OCOCH3).
H, s), 6.83 (1 H, s). 13C NMR (100 MHz, CDCl3): d = 37.9
(C-1), 20.2 (C-2), 39.6 (C-3), 44.2 (C-4), 51.4 (C-5), 21.4
(C-6), 31.6 (C-7), 127.7 (C-8), 146.7 (C-9), 38.4 (C-10),
112.2 (C-11), 151.1 (C-12), 132.0 (C-13), 126.9 (C-14), 27.0
(C-15), 22.7 (C-16), 22.9 (C-17), 28.9 (C-18), 178.2 (C-19),
23.1 (C-20), 53.0 (COOCH3).
Compound 26: 1H NMR (400 MHz, CDCl3): d = 0.80 (6 H,
q, J = 7.9 Hz), 1.01 (9 H, t, J = 7.9 Hz), 1.08 (3 H, s), 1.13 (1
H, ddd, J = 13.6, 13.6, 4.1 Hz), 1.19 (3 H, d, J = 6.9 Hz),
1.21 (3 H, d, J = 6.9 Hz), 1.25 (3 H, s), 1.51 (1 H, ddd,
J = 13.3, 13.3, 4.1 Hz), 1.60 (1 H, m), 1.70 (1 H, br d,
J = 14.2 Hz), 2.03 (2 H, m), 2.20 (1 H, br d, J = 12.8 Hz),
2.31 (1 H, br d, J = 13.6 Hz), 2.92 (1 H, dd, J = 17.5, 2.1 Hz),
3.13 (1 H, dd, J = 17.5, 14.6 Hz), 3.21 (1 H, sept, J = 6.9
Hz), 3.69 (3 H, s), 6.72 (1 H, s), 7.91 (1 H, s). 13C NMR (125
MHz, CDCl3): d = 37.7 (C-1), 19.9 (C-2), 38.7 (C-3), 44.1
(C-4), 50.5 (C-5), 37.7 (C-6), 197.3 (C-7), 137.7 (C-8),
154.2 (C-9), 38.5 (C-10), 113.8 (C-11), 158.8 (C-12), 128.2
(C-13), 126.1 (C-14), 27.2 (C-15), 22.6 (C-16), 22.7 (C-17),
28.2 (C-18), 177.3 (C-19), 21.5 (C-20), 53.0 (COOCH3), 5.6
(SiCH2CH3), 6.8 (SiCH2CH3).
Compound 29: [a]D25 +53.3 (c 0.9, CHCl3). 1H NMR (400
MHz, CDCl3): d = 1.11 (3 H, s), 1.20 (3 H, d, J = 6.8 Hz),
1.22 (3 H, d, J = 6.8 Hz), 1.25 (3 H, s), 1.53 (1 H, ddd,
J = 13.1, 13.1, 4.1 Hz), 1.68 (1 H, m), 1.98 (1 H, dt, J = 10.6,
3.6 Hz), 2.06 (1 H, dd, J = 14.5, 3.3 Hz), 2.26 (1 H, br d,
J = 14.6 Hz), 2.33 (3 H, s), 2.98 (1 H, m), 2.97 (1 H, ddd,
J = 17.9, 6.7, 3.3 Hz), 3.00 (1 H, sept, J = 6.8 Hz), 3.21 (1 H,
dd, J = 17.9, 14.5 Hz), 3.69 (3 H, s), 7.02 (1 H, s), 8.01 (1 H,
s). 13C NMR (100 MHz, CDCl3): d = 37.7 (C-1), 19.7 (C-2),
38.6 (C-3), 44.1 (C-4), 50.3 (C-5), 37.6 (C-6), 198.2 (C-7),
139.0 (C-8), 153.0 (C-9), 38.7 (C-10), 119.1 (C-11), 153.6
(C-12), 128.9 (C-13), 126.5 (C-14), 27.3 (C-15), 22.9 (C-
16), 23.0 (C-17), 27.5 (C-18), 177.2 (C-19), 21.6 (C-20),
51.8 (COOCH3), 177.2 (COOCH3), 21.2 (OCOCH3), 169.3
(OCOCH3).
Compound 28: [a]D25 +36.0 (c 0.4, CHCl3). 1H NMR (400
MHz, CDCl3): d = 1.02 (3 H, s), 1.07 (1 H, ddd, J = 13.6,
13.6, 4.2 Hz), 1.18 (3 H, d, J = 6.9 Hz), 1.19 (3 H, d, J = 6.8
Hz), 1.27 (3 H, s), 1.39 (1 H, ddd, J = 13.4, 13.4, 3.8 Hz),
Synlett 2007, No. 15, 2425–2429 © Thieme Stuttgart · New York

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