Synthesis of (+)-hanagokenol A, (+)-fortunins E, G, H, and (-)-sugikurojin A from abietic acid

Article abstract of DOI:10.1055/s-0030-1258226

A series of 12-hydroxy-substituted abietane diterpenes, functionalized on C19 or C18, have been synthesized starting from 18-hydroxyferruginol. The first synthesis of antibacterial hanagokenol A and fortunins E, G, and H, and a new procedure for preparing

Full text of DOI:10.1055/s-0030-1258226

PAPER
3493
Synthesis of (+)-Hanagokenol A, (+)-Fortunins E, G, H, and (–)-Sugikurojin A
from Abietic Acid
(
+)-Hanagokeno
n
l
A
,
(
+)-For
r
tunins
E
i
,
G
,
H
,
qand (–)-Sugi
u
kurojin
A
e Alvarez-Manzaneda,*a Rachid Chahboun,a Esteban Alvarez,a Jose M. Ramos,a Juan J. Guardia,a
Ibtissam Messouri,a Ikram Chayboun,a Ahmed I. Mansour,b Abdelaziz Dahdouhb
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
Laboratoire de Chimie Organique Appliquée, Département de Chimie, Faculté des Sciences, Université Abdelmalek Essaâdi,
b
Tetouan, Morocco
Received 28 May 2010; revised 13 July 2010
Diels–Alder cycloadditions,14 electrophilic cyclizations,15
Abstract: A series of 12-hydroxy-substituted abietane diterpenes,
Robinson annulations,16 and domino acylation–cyclo-
functionalized on C19 or C18, have been synthesized starting from
18-hydroxyferruginol. The first synthesis of antibacterial hanago-
kenol A and fortunins E, G, and H, and a new procedure for prepar-
alkylations.17 Diastereoselective syntheses of these com-
pounds have also been reported, in most cases starting
ing sugikurojin A and the immunosuppressive 19-hydroxy- from podocarpic18 and abietic acid. The introduction of an
ferruginol are reported.
oxygenated function on C12 of the latter compound has
been undertaken utilizing different procedures, such as the
preparation of an iron complex,19 the electrochemical ox-
idation of the methyl ester,20 or the Baeyer–Villiger oxi-
dation of the 12-acetyl derivative of dehydroabietic acid.21
Our group has reported a new procedure for this purpose,
which was used for the synthesis of compounds 5 and 6
and others.22 The preparation of C19-functionalized abie-
tane diterpenes, such as compounds 1–4, has been
achieved most frequently by starting from natural C19
functionalized precursors.23 In a previous paper, we com-
municated the synthesis of sugikurojin A (3) and 19-hy-
droxyferruginol (4) from the labdane diterpene trans-
communic acid, via manganese(III)-based oxidative free
radical cyclization.24
Key words: antibiotics, diastereoselectivity, phenols, terpenoids,
oxidation
Oxygenated abietane diterpenes, especially phenols and
quinones, are interesting metabolites due to the wide
range of valuable biological activity exhibited by some of
them. Representative examples of such derivatives are
taxodione1 and salvinolone,2 which are active against
methicillin-resistant Staphylococcus aureus (MRSA) and
vancomycin-resistant Enterococcus (VRE), two bacteria
that are increasingly found in hospitals worldwide. Anoth-
er significant oxidized abietane diterpene is 6a-hydroxy-
sugiol, which strongly inhibits various human tumors and
oncogen-transformed cells.3 Abietane phenols functional-
ized at C19, even though they are not very abundant, have
also been found in nature. Examples of these include lam-
bertic acid (1)4 and 12-hydroxyabieta-8,11,13-trien-19-al
(2);5 the isolation of 6,7-dehydro-19-hydroxyferruginol
(sugikurojin A, 3), a new diterpene from Cryptomeria
japonica, was recently reported,6 and very recent studies
have revealed that 19-hydroxyferruginol (4)7 is a target
for tolerance after transplantation and in autoimmune dis-
eases.8 Abietane phenols bearing a functional group on
C18 are most frequently found in natural sources, e.g. 12-
hydroxydehydroabietic acid (5),9 and the gastroprotective
18-hydroxyferruginol (6).10 Recently, the MRSA and
VRE antibacterial hanagokenol A (7) was isolated from
Cladonia rangiferina.11 More recently, fortunins E (9), G
(10), and H (8) were isolated from the bark of Cladonia
fortunei.12 The biological activity of compounds 8–10 has
not yet been investigated.
The synthesis of the scarce C19-functionalized abietane
diterpenes starting from the abundant C18-functionalized
abietane diterpenes appears to be of interest. Only two
16
OH
OH
OH
15
11
17
1
14
9
5
3
7
O
H
H
18
H
O
R
19
R
7
1 R = COOH
2 R = CHO
5 R = COOH
6 R = CH2OH
3 R = CH2OH
6,7-dehydro
4 R = CH2OH
OH
OAc
OH
In spite of the interest of this type of compound, few syn-
theses have been reported, and most of these have been
total syntheses, including polyene cascade cyclizations,13
O
OH
OH
H
H
H
OH
OAc
O
OH
OAc
SYNTHESIS 2010, No. 20, pp 3493–3503
x
x.
x
x
.
2
0
1
0
8
9
10
Advanced online publication: 20.08.2010
DOI: 10.1055/s-0030-1258226; Art ID: T12010SS
© Georg Thieme Verlag Stuttgart · New York
Figure 1 Bioactive abietane diterpenes and related compounds

3494
E. Alvarez-Manzaneda et al.
PAPER
OR
OBn
OH
LiAlH4, THF, 0 °C
r.t., 2 h (93%)
PCC, CH2Cl2
r.t., 1 h (71%)
CH2OH
R = H
CHO
COOMe
6
11
K2CO3, BnBr
acetone, reflux
12 h (80%)
13
12 R = Bn
MCPBA, CH2Cl2
reflux, 4 h (72%)
OBn
OBn
OBn
1) BH3⋅THF
collidine, reflux
18 h (88%)
r.t., 15 h
2) NaOH, EtOH
30% H2O2
HOH2C
H
OCHO
r.t., 4 h (75%)
14
15
16
PCC, CH2Cl2
r.t., 1 h (76%)
OBn
OBn
OH
H2, Pd/C
MeI, t-BuOK
MeOH, r.t., 1 h
(97%)
THF, r.t., 1 h
(88%)
OHC
OHC
H
OHC
17
18
2
Scheme 1 Synthesis of aldehyde 2 from hydroxy ester 11
procedures, based on oxidative decarboxylations, have ry.27 The key step is the transformation of a formate into
been reported to achieve this goal; however, they exhibit- an exocyclic alkene with complete regioselectivity.
ed low regioselectivity25 or they were tedious and expen-
The synthesis of 12-hydroxyabieta-8,11,13-trien-19-al (2)
from hydroxy ester 11 is depicted in Scheme 1. Treatment
of aldehyde 13 with m-chloroperoxybenzoic acid in re-
fluxing dichloromethane for four hours gave formate 14,
sive.26 We report in this paper a new procedure that avoids
these problems starting from methyl 12-hydroxydehydro-
abietate (11), which is easily prepared from abietic
acid,21,22 utilizing methodology developed in our laborato-
which after heating at 170 °C in collidine for 18 hours was
OBn
OBn
OH
H2, Pd/C
NaBH4, EtOH
r.t., 2 h (95%)
MeOH, r.t., 1 h
(97%)
HOH2C
HOH2C
OHC
19
18
4
Ac2O, DMAP
pyridine, r.t., 2 h (91%)
OR
OBn
OH
CrO3, AcOH
LiAlH4, THF
r.t., 2 h
(79%)
0 °C, 30 min
(69%)
O
AcOH2C
AcOH2C
HOH2C
20
3
21 R = Bn
22 R = H
H2, Pd/C, MeOH
r.t., 40 min (82%)
Scheme 2 Synthesis of compounds 3 and 4 from aldehyde 18
Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York

PAPER
(+)-Hanagokenol A, (+)-Fortunins E, G, H, and (–)-Sugikurojin A
3495
OBn
OBn
OBn
TsCl, DMAP
CrO3, AcOH
0 °C, 3 h
(73%)
pyridine, r.t.
2 h (83%)
O
CH2OTs
24
CH2OTs
23
CH2OH
12
isopropenyl acetate
TsOH, reflux, 3 h
(99%)
OBn
OBn
OBn
MCPBA
K2CO3, MeOH
CH2Cl2, r.t.
20 min (94%)
r.t., 30 min
(85%)
O
OAc
O
CH2OTs
O
OAc
OTs
26
27
25
H2, Pd/C
MeOH, r.t.
30 min (90%)
NaBH4, EtOH
0 °C, 45 min
(83%)
OH
OBn
OH
H2, Pd/C
MeOH, r.t., 2 h
(87%)
OH
OH
O
O
O
O
8
7
28
Scheme 3 Synthesis of hanagokenol A (7) and fortunin H (8) from alcohol 12
transformed into exocyclic olefin 15. Hydroboration–oxi- gokenol A (7). The treatment of ketone 27 with sodium
dation of this substrate afforded alcohol 16, which was borohydride gave alcohol 28, which after debenzylation
then oxidized to give intermediate aldehyde 17. Treatment afforded fortunin H (8); this compound was also directly
of this with iodomethane in the presence of potassium obtained when hydrogenation of compound 27 was pro-
tert-butoxide led to aldehyde 18, which was finally con- longed for four hours. Compounds 7 and 8 have spectro-
verted into aldehyde 2.
scopic properties identical to those reported in the
literature.11,12
Aldehyde 18 is also an adequate precursor for the synthe-
sis of sugikurojin A (3) and 19-hydroxyferruginol (4) The synthesis of fortunins E (9) and G (10) is depicted in
(Scheme 2). Reduction of the aldehyde group and depro- Scheme 4. The key intermediate was the triacetoxy ketone
tection of the phenol hydroxy group gave compound 4. On 32, resulting from the treatment of enol acetate 31 with m-
the other hand, acetylation of alcohol 19 and subsequent chloroperoxybenzoic acid. Saponification of compound
treatment with chromium(VI) oxide gave ketone 21, 32 with potassium carbonate in methanol at room temper-
which after hydrogenation and reduction with lithium alu- ature afforded compound 9. Treatment of triacetyl deriva-
minum hydride afforded diol 3.
tive 32 with sodium borohydride in ethanol at –20 °C gave
fortunin G (10). The spectroscopic properties of com-
pounds 9 and 10 were identical to those reported in the lit-
erature.12
Next, the synthesis of the recently reported antimicrobial
hanagokenol A (7) and fortunins E (9), G (10), and H (8),
which have not previously been synthesized, was under-
taken. These C18 functionalized abietane diterpenes were In summary, a new and efficient procedure for this synthe-
synthesized from 18-hydroxyferruginol (6) or from its sis of C19-functionalized abietane diterpenes from the
benzyl derivative 12. Scheme 3 shows the synthesis of corresponding natural abundant C18-functionalized de-
compounds 7 and 8 starting from alcohol 12. The oxida- rivatives has been developed; utilizing this, sugikurojin A
tion of tosylate 23 with chromium(VI) oxide in acetic acid (3) and the immunosupressive 4 have been synthesized
gave ketone 24, which was then converted into the enol from abietic acid. Moreover, the first synthesis of antimi-
acetate 25. Treatment of this compound with m-chloro- crobial hanagokenol A (7) and fortunins E (9), G (10), and
peroxybenzoic acid afforded acetoxy ketone 26, which af- H (8) starting from 18-hydroxyferruginol (6) has been
ter treatment with potassium carbonate in methanol at achieved.
room temperature and further hydrogenation led to hana-
Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York

3496
E. Alvarez-Manzaneda et al.
PAPER
OAc
OAc
OR
isopropenyl acetate
CrO3, AcOH
TsOH, reflux
3 h (97%)
0 °C, 3 h
(75%)
O
OAc
CH2OAc
CH2OAc
31
CH2OR
Ac2O, DMAP
pyridine, r.t., 2 h
(81%)
6
R = H
MCPBA, CH2Cl2, r.t.
20 min (91%)
30
29 R = Ac
OH
OAc
OAc
K2CO3, MeOH
r.t., 12 h (77%)
NaBH4, EtOH
–20 °C, 5 h
(79%)
O
OH
O
OH
OAc
OAc
OH
OAc
10
OAc
32
9
Scheme 4 Synthesis of fortunins E (9) and G (10) from phenol 6
CH2Cl2 was dried over CaH2. Toluene, THF, and benzene were
dried over Na. MeOH was distilled from Mg at 1 bar. DMF and
EtOH were dried over 4 Å molecular sieves. Reactions were moni-
tored for the disappearance of starting material by TLC. Separations
were carried out by conventional column chromatography on silica
gel 60 (230–400 mesh) using hexane–t-BuOMe mixtures of in-
creasing polarity. IR spectra were obtained using a Perkin Elmer
Spectrum models 782 and 983G spectrophotometers with samples
between NaCl plates or as KBr pellets. 1H or 13C NMR spectra were
recorded on a Varian 500 spectrometer. The signals of the 13C NMR
were assigned utilizing DEPT experiments and on the basis of liter-
ature data. Interchangeable assignments are indicated by * or **.
HRMS were obtained on a trisector WG AutoSpecQ spectrometer.
FAB spectra acquisition was performed with a 10000 resolution and
a relative error of 5 ppm. Microanalytical data for C and H were de-
termined on a Fisons Carlo Erba EA 1108 analyzer.
(d, J = 11.1 Hz, 1 H), 3.33 (h, J = 6.9 Hz, 1 H), 3.48 (d, J = 11.1 Hz,
1 H), 5.05 (s, 2 H), 6.79 (s, 1 H), 6.87 (s, 1 H), 7.31 (t, J = 7.3 Hz, 1
H), 7.39 (t, J = 7.52 Hz, 2 H), 7.45 (d, J = 7.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 37.9 (C1), 19.1 (C2)*, 38.6 (C3),
49.5 (C4), 44.1 (C5), 18.8 (C6)*, 29.6 (C7), 134.7 (C8), 147.9 (C9),
37.1 (C10), 108.6 (C11), 154.1 (C12), 138.0 (C13), 126.6 (C14),
26.7 (C15), 22.8 (C16)**, 23.0 (C17)**, 72.3 (C18), 17.5 (C19),
25.3 (C20), 70.4 (CH2OBn), 127.2 (COBn), 127.3 (2 CHOBn),
127.7 (CHOBn), 128.5 (2 CHOBn).
HRMS (FAB): m/z [M + Na]+ calcd for C27H36O2Na: 415.2613;
found: 415.2605.
Anal. Calcd for C27H36O2: C, 82.61; H, 9.24. Found: C, 82.35; H,
9.27.
12-(Benzyloxy)abieta-8,11,13-trien-18-al (13)
PCC (6.26 g, 29.04 mmol) was added to a stirred soln of 12 (6.26 g,
15.95 mmol) in anhyd CH2Cl2 (80 mL) and the mixture was stirred
at r.t. under an argon atmosphere for 1 h (TLC monitoring). The re-
action was worked up by the addition of CH2Cl2 (40 mL) and the re-
sulting mixture was filtered through a silica gel pad and washed
with hexane–t-BuOMe (1:4, 150 mL). Removal of the solvent under
vacuum afforded 13 (4.42 g, 71%) as a yellow oil. Flash chromatog-
raphy of 13 (131 mg) (silica gel, 15% t-BuOMe–hexanes) gave pure
13 (122 mg).
18-Hydroxyferruginol (6)
LiAlH4 (1.59 g, 39.7 mmol) was added at 0 °C to a stirred soln of
11 (11.3 g, 37.8 mmol) in anhyd THF (150 mL) and the mixture was
stirred at r.t. under an argon atmosphere for 2 h. Then, 2 M HCl (50
mL) was added slowly at 0 °C and the solvent was removed. t-
BuOMe (80 mL) was added and the layers were fractionated. The
organic layer was washed with brine (3 × 30 mL), dried (anhyd
Na2SO4), and concentrated to give 6 (10.6 g, 93%) as a colorless oil.
[a]D25 +30.6 (c 0.1, CHCl3).
IR (film): 1725, 1499, 1459, 1379, 1248, 1028, 696 cm–1.
12-(Benzyloxy)abieta-8,11,13-trien-18-ol (12)
To a soln of 6 (9.48 g, 31.4 mmol) in acetone (100 mL) was added
K2CO3 (6.49 g, 47.03 mmol) and the mixture was stirred at r.t. for
15 min. Then BnBr (7.4 mL, 47.03 mmol) was added and the mix-
ture was stirred at reflux for 12 h. The solvent was evaporated and
the crude mixture was poured into t-BuOMe–H2O (5:1, 120 mL).
The organic phase was washed with H2O (2 × 30 mL) and brine
(3 × 30 mL) and dried (Na2SO4). The solvent evaporated to give a
crude product that was purified by flash chromatography (silica gel,
40% t-BuOMe–hexanes) to give pure 12 (9.85 g, 80%) as a yellow
oil.
1H NMR (500 MHz, CDCl3): d = 1.16 (s, 3 H), 1.19 (d, J = 6.9 Hz,
3 H), 1.20–1.30 (m, 2 H), 1.22 (d, J = 6.9 Hz, 3 H), 1.26 (s, 3 H),
1.43–1.50 (m, 2 H), 1.76–1.85 (m, 3 H), 1.90 (dd, J = 12.4, 1.8 Hz,
1 H), 2.26 (br d, J = 13.0 Hz, 1 H), 2.82 (d, J = 4.4 Hz, 1 H), 2.84
(d, J = 4.2 Hz, 1 H), 3.33 (h, J = 6.9 Hz, 1 H), 5.05 (s, 2 H), 6.77 (s,
1 H), 6.88 (s, 1 H), 7.32 (t, J = 7.2 Hz, 1 H), 7.39 (t, J = 7.6 Hz, 2
H), 7.45 (d, J = 7.1 Hz, 2 H), 9.26 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 32.1 (C1), 17.8 (C2), 38.0 (C3),
49.9 (C4), 43.0 (C5), 21.5 (C6), 29.8 (C7), 135.2 (C8), 146.7 (C9),
36.7 (C10), 108.0 (C11), 154.2 (C12), 137.8 (C13), 126.8 (C14),
26.7 (C15), 22.7 (C16)*, 22.9 (C17)*, 206.2 (C18), 14.0 (C19), 25.0
(C20), 70.3 (CH2OBn), 126.8 (COBn), 127.2 (2 CHOBn), 127.6
(CHOBn), 128.5 (2 CHOBn).
[a]D25 +30.5 (c 0.03, CHCl3).
IR (film): 3378, 2928, 2868, 1612, 1499, 1380, 1246, 1216, 1028,
756, 697 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.89 (s, 3 H), 1.21 (d, J = 6.9 Hz,
3 H), 1.22 (s, 3 H), 1.23 (d, J = 6.9 Hz, 3 H), 1.36–1.54 (m, 4 H),
1.62–1.84 (m, 4 H), 2.21 (d, J = 12.5 Hz, 1 H), 2.82 (m, 2 H), 3.23
HRMS (FAB): m/z [M + Na]+ calcd for C27H34O2Na: 413.2457;
found: 413.2436.
Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York

PAPER
(+)-Hanagokenol A, (+)-Fortunins E, G, H, and (–)-Sugikurojin A
3497
Anal. Calcd for C27H34O2: C, 83.03; H, 8.77. Found: C, 83.35; H,
8.71.
Anal. Calcd for C26H32O: C, 86.62; H, 8.95. Found: C, 86.39; H,
9.00.
12-(Benzyloxy)-4a-(formyloxy)-18-norabieta-8,11,13-triene
(14)
12-(Benzyloxy)-18-norabieta-8,11,13-trien-19-ol (16)
1 M BH3·THF (8 mL, 8 mmol) was added to a soln of 15 (1.57 g,
4.36 mmol) in anhyd THF (10 mL) at –10 °C under an argon atmo-
sphere and the mixture was stirred at r.t. for 15 h (TLC monitoring).
Then, EtOH (2 mL), 4 M NaOH in EtOH (2 mL), and 30% H2O2 (3
mL) were added and the mixture was stirred at r.t. for 4 h. The sol-
vent was evaporated and t-BuOMe (120 mL) was added. The organ-
ic layer was washed with H2O (3 × 20 mL) and brine (2 × 20 mL)
and dried (anhyd Na2SO4). Removal of the solvent under vacuum
afforded a crude product that was purified by flash chromatography
column (silica gel, 30% t-BuOMe–hexanes), affording 16 (1.24 g,
75%) as a yellow colorless syrup. Flash chromatography of 16 (227
mg) (silica gel, 25% t-BuOMe–hexanes) gave pure 16 (213 mg).
Solid MCPBA (2.59 g, 10.45 mmol) and NaHCO3 (874 mg, 10.45
mmol) in CH2Cl2 (170 mL) were added to a soln of 13 (2.04 g, 5.23
mmol) in CH2Cl2 (180 mL) and the mixture was stirred under reflux
for 4 h. Removal of the solvent under vacuum afforded a crude
product and t-BuOMe–H2O (120: 40 mL) was added. The layers
were fractionated, the organic phase was washed with sat. NaHCO3
(10 × 30 mL) and brine (2 × 30 mL), dried (Na2SO4), and concen-
trated to give 14 (1.53 g, 72%) as yellow oil. Flash chromatography
of 14 (200 mg) (silica gel, 15% t-BuOMe–hexanes) gave pure 14
(187 mg).
[a]D25 +19.6 (c 0.15, CHCl3).
[a]D25 +71.2 (c 0.14, CHCl3).
IR (film): 1719, 1499, 1459, 1381, 1249, 1201, 1182, 1131, 1102,
1027, 736 cm–1.
IR (film): 3374, 1611, 1499, 1458, 1406, 1319, 1241, 1168, 1027,
755, 696 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.18 (s, 3 H), 1.21 (d, J = 6.9 Hz,
3 H), 1.23 (d, J = 6.9 Hz, 3 H), 1.46 (m, 1 H), 1.57 (s, 3 H), 1.67–
1.76 (m, 3 H), 1.80 (m, 1 H), 1.98 (dd, J = 12.4, 1.8 Hz, 1 H), 2.05
(br dd, J = 13.8, 6.5 Hz, 1 H), 2.17 (br d, J = 12.2 Hz, 1 H), 2.64 (dd,
J = 8.4, 2.6 Hz, 1 H), 2.83–2.89 (m, 2 H), 3.33 (h, J = 6.9 Hz, 1 H),
5.05 (s, 2 H), 6.75 (s, 1 H), 6.89 (s, 1 H), 7.31 (t, J = 7.3 Hz, 1 H),
7.39 (t, J = 7.3 Hz, 2 H), 7.44 (t, J = 7.0 Hz, 2 H), 8.08 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 37.8 (C1), 18.7 (C2), 38.2 (C3),
87.2 (C4), 49.8 (C5), 20.2 (C6), 29.5 (C7), 135.4 (C8), 146.6 (C9),
38.8 (C10), 108.6 (C11), 154.5 (C12), 138.0 (C13), 126.9 (C14),
26.9 (C15), 22.8 (C16)*, 23.0 (C17)*, 20.1 (C19), 24.7 (C20), 160.5
(COCHO), 70.7 (CH2OBn), 127.1 (COBn), 127.3 (2 CHOBn),
128.6 (2 CHOBn).
1H NMR (500 MHz, CDCl3): d = 1.04 (s, 3 H), 1.22 (d, J = 6.9 Hz,
3 H), 1.23 (d, J = 6.9 Hz, 3 H), 1.30–1.45 (m, 3 H), 1.61–1.67 (m, 2
H), 1.72 (m, 1 H), 1.83 (m, 1 H), 1.89–1.95 (m, 2 H), 1.98 (br d,
J = 13.1 Hz, 1 H), 2.19 (br d, J = 11.7 Hz, 1 H), 2.83–2.87 (m, 2 H),
3.33 (h, J = 6.9 Hz, 1 H), 3.72 (dd, J = 10.3, 3.0 Hz, 1 H), 3.77 (d,
J = 10.3 Hz, 1 H), 5.05 (s, 2 H), 6.77 (s, 1 H), 6.88 (s, 1 H), 7.32 (t,
J = 7.3 Hz, 1 H), 7.39 (t, J = 7.5 Hz, 2 H), 7.45 (t, J = 7.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 38.7 (C1), 18.3 (C2), 27.7 (C3),
44.1 (C4), 44.6 (C5), 24.6 (C6), 29.9 (C7), 134.9 (C8), 146.7 (C9),
37.3 (C10), 108.5 (C11), 154.2 (C12), 137.9 (C13), 126.7 (C14),
26.7 (C15), 22.7 (C16)*, 22.9 (C17)*, 61.8 (C19), 25.1 (C20), 70.4
(CH2OBn), 127.1 (COBn), 127.1 (2 CHOBn), 127.6 (CHOBn),
128.4 (2 CHOBn).
HRMS (FAB): m/z [M + Na]+ calcd for C27H34O3Na: 429.2406;
found: 429.2418.
HRMS (FAB): m/z [M + Na]+ calcd for C26H34O2Na: 401.2457;
found: 401.2433.
Anal. Calcd for C27H34O3: C, 79.76; H, 8.43. Found: C, 79.92; H,
8.48.
Anal. Calcd for C26H34O2: C, 82.49; H, 9.05. Found: C, 82.62; H,
9.09.
12-(Benzyloxy)-4-methylene-18,19-dinorabieta-8,11,13-triene
(15)
12-(Benzyloxy)-18-norabieta-8,11,13-trien-19-al (17)
A soln of 14 (2.44 g, 6.0 mmol) in collidine (10 mL) was stirred un-
der reflux for 18 h (TLC monitoring). The mixture was cooled to r.t.
and t-BuOMe (80 mL) was added; the black soln was washed with
2 M HCl (5 × 25 mL) and brine. The organic layer was dried and
concentrated under reduced pressure to afford 15 (1.91 g, 88%).
Flash chromatography of 15 (83 mg) (silica gel, 5% t-BuOMe–hex-
anes) gave pure 15 (77 mg).
PCC (700 mg, 3.25 mmol) was added to a stirred soln of 16 (650
mg, 1.72 mmol) in anhyd CH2Cl2 (40 mL) and the mixture was
stirred at r.t. under an argon atmosphere for 1 h (TLC monitoring).
Following the same workup used for 13, 17 (489 mg, 76%) was ob-
tained as a colorless syrup. Flash chromatography of 17 (47 mg)
(silica gel, 15% t-BuOMe–hexanes) gave pure 17 (39 mg).
[a]D25 +108.6 (c 0.09, CHCl3).
[a]D25 +63.5 (c 0.21, CHCl3).
IR (film): 1499, 1459, 1409, 1324, 1250, 1189, 1028, 887, 735 cm–1.
IR (film): 1716, 1501, 1455, 1315, 1251, 1235, 1205, 1028, 889,
737, 696 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.00 (s, 3 H), 1.22 (d, J = 6.9 Hz,
3 H), 1.24 (d, J = 6.9 Hz, 3 H), 1.56 (ddd, J = 13.0, 13.0, 4.5 Hz, 1
H), 1.70–1.86 (m, 4 H), 2.06 (ddd, J = 13.4, 13.4, 5.5 Hz, 1 H),
2.17–2.22 (m, 2 H), 2.38 (br d, J = 12.8 Hz, 1 H), 2.84 (d, J = 4.4
Hz, 1 H), 2.86 (d, J = 4.0 Hz, 1 H), 3.34 (h, J = 6.9 Hz, 1 H), 4.60
(s, 1 H), 4.85 (s, 1 H), 5.06 (s, 2 H), 6.83 (s, 1 H), 6.92 (s, 1 H), 7.32
(t, J = 7.3 Hz, 1 H), 7.39 (t, J = 7.5 Hz, 2 H), 7.45 (d, J = 7.4 Hz, 2
H).
13C NMR (125 MHz, CDCl3): d = 36.4 (C1), 21.5 (C2), 38.5 (C3),
150.7 (C4), 47.9 (C5), 23.0 (C6), 29.3 (C7), 134.9 (C8), 145.2 (C9),
39.5 (C10), 109.1 (C11), 154.1 (C12), 137.9 (C13), 126.8 (C14),
23.8 (C15), 22.7 (C16)*, 22.8 (C17)*, 106.4 (C19), 22.9 (C20), 70.3
(CH2OBn), 126.1 (COBn), 127.2 (2 CHOBn), 127.6 (CHOBn),
128.4 (2 CHOBn).
1H NMR (500 MHz, CDCl3): d = 1.03 (s, 3 H), 1.22 (d, J = 6.9 Hz,
3 H), 1.23 (d, J = 6.9 Hz, 3 H), 1.27–1.44 (m, 2 H), 1.64–1.79 (m, 2
H), 1.94 (m, 1 H), 2.11 (ddd, J = 11.3, 5.5, 2.0 Hz, 1 H), 2.18 (br d,
J = 13.4 Hz, 1 H), 2.29 (m, 1 H), 2.39 (br d, J = 13.4 Hz, 1 H), 2.46
(t, J = 4.9 Hz, 1 H), 2.90–2.92 (m, 2 H), 3.34 (h, J = 6.9 Hz, 1 H),
5.05 (s, 2 H), 6.77 (s, 1 H), 6.91 (s, 1 H), 7.31 (t, J = 7.3 Hz, 1 H),
7.39 (t, J = 7.5 Hz, 2 H), 7.44 (d, J = 7.1 Hz, 2 H), 10.03 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 38.3 (C1), 19.2 (C2), 24.9 (C3),
52.4 (C4), 45.1 (C5), 24.4 (C6), 30.2 (C7), 135.4 (C8), 145.3 (C9),
37.9 (C10), 108.7 (C11), 154.4 (C12), 137.9 (C13), 126.9 (C14),
26.8 (C15), 22.7 (C16)*, 22.8 (C17)*, 204.5 (C19), 23.5 (C20), 70.5
(CH2OBn), 126.8 (COBn), 127.3 (2 CHOBn), 127.7 (CHOBn),
128.5 (2 CHOBn).
HRMS (FAB): m/z [M + Na]+ calcd for C26H32O2Na: 399.2300;
found: 399.2989.
HRMS (FAB): m/z [M + Na]+ calcd for C26H32ONa: 383.2351;
found: 383.2346.
Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York

3498
E. Alvarez-Manzaneda et al.
PAPER
Anal. Calcd for C26H32O2: C, 82.94; H, 8.57. Found: C, 83.06; H,
8.57.
13C NMR (125 MHz, CDCl3): d = 35.3 (C1), 19.1 (C2)*, 39.0 (C3),
38.7 (C4), 51.4 (C5), 19.4 (C6)*, 30.4 (C7), 134.8 (C8), 147.7 (C9),
37.8 (C10), 108.3 (C11), 154.2 (C12), 137.9 (C13), 126.5 (C14),
26.7 (C15), 22.7 (C16)**, 22.9 (C17)**, 26.8 (C18), 65.4 (C19),
25.6 (C20), 70.3 (CH2OBn), 126.9 (COBn), 127.2 (2 CHOBn),
127.6 (CHOBn), 128.4 (2 CHOBn).
12-(Benzyloxy)abieta-8,11,13-trien-19-al (18)
To a soln of 17 (685 mg, 1.82 mmol) in anhyd THF (60 mL) was
added t-BuOK (267 mg, 2.38 mmol) and the resulting brown soln
was stirred for 5 min. Then MeI (450 mg, 3.17 mmol) was added
and the mixture was stirred for 1 h (TLC monitoring). The solvent
was removed in vacuo and t-BuOMe–H2O (70:25, 105 mL) was
added to the crude product and the layers were fractionated. The or-
ganic phase was washed with H2O and brine and dried (Na2SO4).
Removal of the solvent under vacuum afforded 18 (624 mg, 88%)
as a colorless syrup. Flash chromatography of 18 (92 mg) (silica gel,
15% t-BuOMe–hexanes) gave pure 18 (84 mg).
HRMS (FAB): m/z [M + Na]+ calcd for C27H36O2Na: 415.2613;
found: 415.2607.
Anal. Calcd for C27H36O2: C, 82.61; H, 9.24. Found: C, 82.40; H,
9.19.
19-Hydroxyferruginol (4)
To a soln of 19 (173 mg, 0.44 mmol) in anhyd MeOH (8 mL) was
added 10% Pd/C (30 mg) and the mixture was stirred at r.t. under
H2 for 1 h. Filtration and concentration gave 4 (129 mg, 97%) as a
colorless syrup.
[a]D25 +64.9 (c 0.1, CHCl3).
IR (film): 1717, 1613, 1501, 1456, 1407, 1377, 1327, 1249, 1216,
1169, 1028, 897, 772, 736 cm–1.
19-Acetoxy-12-(benzyloxy)abieta-8,11,13-triene (20)
1H NMR (500 MHz, CDCl3): d = 1.05 (s, 3 H), 1.11 (s, 3 H), 1.21
(d, J = 6.9 Hz, 3 H), 1.23 (d, J = 6.9 Hz, 3 H), 1.40 (ddd, J = 13.4,
13.4, 3.9, 1 H), 1.61–1.69 (m, 2 H), 1.75 (m, 1 H), 2.00 (ddd,
J = 19.0, 12.8, 6.1 Hz, 1 H), 2.08–2.26 (m, 2 H), 2.83 (ddd, J = 16.5,
12.2, 6.5 Hz, 1 H), 2.92 (dd, J = 16.5, 5.1 Hz, 1 H), 3.33 (h, J = 6.9
Hz, 1 H), 5.04 (s, 2 H), 6.77 (s, 3 H), 6.90 (s, 1 H), 7.31 (t, J = 7.3
Hz, 1 H), 7.38 (t, J = 7.5 Hz, 2 H), 7.44 (t, J = 7.3 Hz, 2 H), 9.83 (s,
1 H).
13C NMR (125 MHz, CDCl3): d = 38.4 (C1), 19.0 (C2)*, 33.8 (C3),
48.6 (C4), 52.0 (C5), 19.2 (C6)*, 30.6 (C7), 135.1 (C8), 145.4 (C9),
38.1 (C10), 108.6 (C11), 154.2 (C12), 137.7 (C13), 126.6 (C14),
26.7 (C15), 22.7 (C16)**, 22.9 (C17)**, 24.0 (C18), 205.7 (C19),
24.2 (C20), 70.2 (CH2OBn), 126.7 (COBn), 127.1 (2 CHOBn),
127.6 (CHOBn), 128.5 (2 CHOBn).
To a soln of 19 (352 mg, 0.9 mmol) in pyridine (3 mL) was added
Ac2O (1.5 mL) and DMAP (50 mg, 0.4 mmol) and the mixture was
further stirred at r.t. for 2 h (TLC monitoring). The reaction was
quenched with H2O (5 mL) and the mixture was stirred for an addi-
tional 10 min. Then, it was diluted with t-BuOMe (50 mL), washed
with H2O (5 × 20 mL), 2 M HCl (5 × 20 mL), sat. NaHCO3 (3 × 20
mL), and brine (3 × 20 mL), and dried (anhyd Na2SO4). Removal of
the solvent under vacuum afforded 20 (355 mg, 91%) as a colorless
oil. Flash chromatography of 20 (55 mg) (silica gel, 10% t-BuOMe–
hexanes) gave pure 20 (48 mg).
[a]D25 +47.0 (c 0.15, CHCl3).
IR (film): 1736, 1647, 1500, 1458, 1376, 1242, 1029, 892, 847, 735,
696, 666 cm–1.
HRMS (FAB): m/z [M + Na]+ calcd for C27H34O2Na: 413.2457;
found: 413.2461.
1H NMR (500 MHz, CDCl3): d = 1.04 (s, 3 H), 1.05 (m, 1 H), 1.20
(s, 3 H), 1.21 (d, J = 7.0 Hz, 3 H), 1.22 (d, J = 7.0 Hz, 3 H), 1.42
(ddd, J = 12.9, 12.9, 4.4 Hz, 1 H), 1.51 (br d, J = 12.5 Hz, 1 H), 1.61
(m, 1 H), 1.66–1.76 (m, 2 H), 1.79 (br d, J = 14.8 Hz, 1 H), 1.99 (dd,
J = 12.9, 6.9 Hz, 1 H), 2.08 (s, 3 H), 2.24 (br d, J = 12.7 Hz, 1 H),
2.78 (ddd, J = 16.7, 11.7, 7.1 Hz, 1 H), 2.87 (dd, J = 16.7, 6.2 Hz, 1
H), 3.32 (h, J = 7.0 Hz, 1 H), 4.00 (d, J = 11.1 Hz, 1 H), 4.33 (d,
J = 11.1 Hz, 1 H), 5.05 (s, 2 H), 6.79 (s, 1 H), 6.89 (s, 1 H), 7.31 (t,
J = 7.3 Hz, 1 H), 7.38 (t, J = 7.5 Hz, 2 H), 7.44 (d, J = 7.6 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 36.0 (C1), 19.0 (C2)*, 38.9 (C3),
37.7 (C4), 51.4 (C5), 19.4 (C6)*, 30.4 (C7), 134.9 (C8), 147.4 (C9),
37.2 (C10), 108.3 (C11), 154.2 (C12), 137.9 (C13), 126.5 (C14),
26.6 (C15), 22.7 (C16)**, 22.9 (C17)**, 27.3 (C18), 67.0 (C19),
25.6 (C20), 21.0 (OCOCH3), 171.3 (OCOCH3), 70.3 (CH2OBn),
126.9 (COBn), 127.2 (2 CHOBn), 127.6 (CHOBn), 128.6 (2
CHOBn).
Anal. Calcd for C27H34O2: C, 82.84; H, 8.77. Found: C, 82.99; H,
8.81.
12-Hydroxyabieta-8,11,13-trien-19-al (2)
To a soln of 18 (220 mg, 0.56 mmol) in anhyd MeOH (8 mL) was
added 10% Pd/C (30 mg) and the mixture was stirred at r.t. under
H2 for 1 h. Filtration and concentration gave 2 (163 mg, 97%) as a
colorless syrup.
12-(Benzyloxy)abieta-8,11,13-trien-19-ol (19)
NaBH4 (70 mg, 1.84 mmol) was added to a stirred soln of 18 (380
mg, 0.97 mmol) in EtOH (10 mL) cooled at 0 °C and the mixture
was stirred at r.t. for 2 h (TLC monitoring). The reaction was
quenched with H2O (5 mL) and the solvent was evaporated. The
crude product was diluted with t-BuOMe (60 mL), washed with
H2O (2 × 20 mL) and brine (2 × 20 mL), and dried (Na2SO4). Re-
moval of the solvent under vacuum afforded 19 (363 mg, 95%).
Flash chromatography of 19 (64 mg) (silica gel, 25% t-BuOMe–
hexanes) gave pure 19 (59 mg).
HRMS (FAB): m/z [M + Na]+ calcd for C29H38O3Na: 457.2719;
found: 457.2721.
Anal. Calcd for C29H38O3: C, 80.14; H, 8.81. Found: C, 79.98; H,
8.77.
[a]D25 +36.9 (c 0.07, CHCl3).
19-Acetoxy-12-(benzyloxy)abieta-8,11,13-trien-7-one (21)
To a soln of 20 (348 mg, 0.8 mmol) in AcOH (8 mL) was added at
0 °C CrO3 (160 mg, 1.6 mmol) and the mixture was stirred at r.t. for
2 h (TLC monitoring). Then t-BuOMe–H2O (6:1, 70 mL) was added
to the crude product and the phases were shaken and separated. The
organic phase was washed with H2O (10 × 15 mL) and brine (3 × 30
mL) and dried (anhyd Na2SO4). Removal of the solvent under vac-
uum afforded 21 (284 mg, 79%) as a yellow oil. Flash chromatog-
raphy of 21 (82 mg) (silica gel, 20% t-BuOMe–hexanes) gave pure
21 (75 mg).
IR (film): 3377, 1613, 1499, 1456, 1407, 1378, 1325, 1246, 1217,
1027, 890, 804, 756, 736, 696 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.05 (s, 3 H), 1.17 (s, 3 H), 1.21
(d, J = 7.0 Hz, 3 H), 1.23 (d, J = 7.0 Hz, 3 H), 1.43 (ddd, J = 13.1,
13.1, 3.5 Hz, 1 H), 1.51 (br d, J = 12.6 Hz, 1 H), 1.60–1.73 (m, 4 H),
1.89 (br d, J = 13.6 Hz, 1 H), 1.97 (br dd, J = 13.0, 7.1 Hz, 1 H),
2.23 (br d, J = 12.6 Hz, 1 H), 2.74–2.85 (m, 2 H), 3.32 (h, J = 7.0
Hz, 1 H), 3.56 (d, J = 11.0 Hz, 1 H), 3.86 (d, J = 11.0 Hz, 1 H), 5.05
(s, 2 H), 6.80 (s, 1 H), 6.86 (s, 1 H), 7.31 (t, J = 7.1 Hz, 1 H), 7.38
(t, J = 7.6 Hz, 2 H), 7.45 (d, J = 7.3 Hz, 2 H).
[a]D25 +21.2 (c 0.15, CHCl3).
Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York

PAPER
(+)-Hanagokenol A, (+)-Fortunins E, G, H, and (–)-Sugikurojin A
3499
IR (film): 1737, 1673, 1601, 1498, 1457, 1374, 1259, 1242, 1178,
1029, 909, 850, 772, 697 cm–1.
and the mixture was stirred at r.t. for 2 h (TLC monitoring). The
mixture was cooled at 0 °C, H2O (20 mL) was added to quench the
reaction and t-BuOMe (100 mL) was added. The organic layer was
washed with 2 M HCl (5 × 20 mL), H2O (1 × 20 mL), and brine
(2 × 20 mL) and dried (Na2SO4). The solvent evaporated to give a
crude product which was purified by flash chromatography (silica
gel, 25% t-BuOMe–hexanes) to give pure 23 (11.39 g, 83%) as a
colorless oil.
1H NMR (500 MHz, CDCl3): d = 1.03 (s, 3 H), 1.06 (m, 1 H), 1.13
(ddd, J = 14.0, 14.0, 4.8 Hz, 1 H), 1.22 (d, J = 6.8 Hz, 3 H), 1.25 (d,
J = 6.8 Hz, 3 H), 1.26 (s, 3 H), 1.54 (ddd, J = 12.9, 12.9, 4.1 Hz, 1
H), 1.64–1.83 (m, 2 H), 2.01 (dd, J = 14.4, 3.4 Hz, 1 H), 2.09 (s, 3
H), 2.30 (br d, J = 12.8 Hz, 1 H), 2.65 (dd, J = 17.8, 14.4 Hz, 1 H),
2.80 (dd, J = 17.8, 3.4 Hz, 1 H), 3.33 (h, J = 6.8 Hz, 1 H), 4.04 (d,
J = 11.2 Hz, 1 H), 4.38 (d, J = 11.2 Hz, 1 H), 5.15 (s, 2 H), 6.82, (s,
1 H), 7.34 (t, J = 7.0 Hz, 1 H), 7.40 (t, J = 7.5 Hz, 2 H), 7.44 (d,
J = 6.8 Hz, 2 H), 7.92 (s, 1 H).
[a]D25 +46.3 (c 0.3, CHCl3).
IR (film): 1599, 1499, 1360, 1248, 1177, 1098, 1028, 966, 847, 759
cm–1.
13C NMR (125 MHz, CDCl3): d = 36.1 (C1), 18.6 (C2), 38.2 (C3),
38.0 (C4), 49.9 (C5), 35.9 (C6), 197.5 (C7), 135.8 (C8), 155.7 (C9),
36.8 (C10), 106.1 (C11), 160.8 (C12), 136.6 (C13), 125.8 (C14),
26.7 (C15), 22.4 (C16)*, 22.5 (C17)*, 26.8 (C18), 66.7 (C19), 23.8
(C20), 21.0 (OCOCH3), 171.2 (OCOCH3), 70.0 (CH2OBn), 123.9
(COBn), 127.2 (2 CHOBn), 128.1 (CHOBn), 128.6 (2 CHOBn).
1H NMR (500 MHz, CDCl3): d = 0.89 (s, 3 H), 1.18 (s, 3 H), 1.22
(d, J = 6.9 Hz, 3 H), 1.23 (d, J = 6.9 Hz, 3 H), 1.34–1.48 (m, 3 H),
1.50–1.78 (m, 5 H), 2.19 (br d, J = 12.6 Hz, 1 H), 2.47 (s, 3 H),
2.68–2.81 (m, 2 H), 3.34 (h, J = 6.9 Hz, 1 H), 3.63 (d, J = 9.3 Hz, 1
H), 3.83 (d, J = 9.3 Hz, 1 H), 5.04 (s, 2 H), 6.76 (s, 1 H), 6.86 (s, 1
H), 7.33 (d, J = 7.3 Hz, 1 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.39 (t,
J = 7.3 Hz, 2 H), 7.45 (d, J = 7.2 Hz, 2 H), 7.79 (d, J = 8.2 Hz, 2 H).
HRMS (FAB): m/z [M + Na]+ calcd for C29H36O4Na: 471.2511;
found: 471.2502.
13C NMR (125 MHz, CDCl3): d = 35.1 (C1), 18.4 (C2), 37.2 (C3),
38.1 (C4), 43.9 (C5), 19.2 (C6), 29.3 (C7), 134.9 (C8), 147.3 (C9),
37.7 (C10), 108.1 (C11), 154.2 (C12), 137.9 (C13), 126.6 (C14),
26.7 (C15), 22.8 (C16)*, 23.0 (C17)*, 77.8 (C18), 17.2 (C19), 25.2
(C20), 70.4 (CH2OBn), 126.9 (COBn), 127.2 (2 CHOBn), 127.7
(CHOBn), 128.0 (2 CHOBn), 133.1 (COTs), 128.5 (2 CHOTs),
129.9 (2 CHOTs), 144.7 (COTs), 21.7 (CH3-OTs).
Anal. Calcd for C29H36O4: C, 77.64; H, 8.09. Found: C, 77.85; H,
8.14.
19-Acetoxy-12-hydroxyabieta-8,11,13-trien-7-one (22)
To a soln of 21 (269 mg, 0.6 mmol) in anhyd MeOH (10 ml) was
added 10% Pd/C (60 mg) and the mixture was stirred at r.t. under
H2 for 40 min. Filtration and evaporation of the solvent yielded 22
(176 mg, 82%). Flash chromatography of 22 (35 mg) (silica gel,
35% t-BuOMe–hexanes) gave pure 22 (28 mg).
HRMS (FAB): m/z [M + Na]+ calcd for C34H42O4SNa: 569.2702;
found: 569.2694.
Anal. Calcd for C34H42O4S: C, 74.69; H, 7.74. Found: C, 74.90; H,
7.70.
[a]D25 +20.1 (c 0.2, CHCl3).
IR (film): 3283, 1737, 1655, 1596, 1571, 1459, 1374, 1303, 1267,
1177, 1035, 758 cm–1.
12-(Benzyloxy)-18-(tosyloxy)abieta-8,11,13-trien-7-one (24)
To a soln of 23 (8.26 g, 15.13 mmol) in AcOH (30 mL) at 0 °C was
added CrO3 (3.02 g, 30.22 mmol), and the mixture was stirred for 3
h (TLC monitoring). The mixture was poured into t-BuOMe–H2O
(6: 1, 140 mL). The organic layer was washed with H2O (10 × 40
mL), aq NaHCO3 (2 × 20 mL), and brine (2 × 20 mL), dried
(Na2SO4), and evaporated to give 24 (6.19 g, 73%) as a yellow oil.
Flash chromatography of 24 (282 mg) (silica gel, 25% t-BuOMe–
hexanes) gave pure 24 (271 mg).
1H NMR (500 MHz, CDCl3): d = 1.02 (s, 3 H), (ddd, J = 13.4, 13.4,
3.4 Hz, 1 H), 1.20 (s, 3 H), 1.24 (d, J = 6.8 Hz, 3 H), 1.25 (d, J = 6.8
Hz, 3 H), 1.54 (ddd, J = 13.0, 13.0, 3.9 Hz, 1 H), 1.63–1.74 (m, 2
H), 1.79 (br d, J = 14.6 Hz, 1 H), 2.00 (dd, J = 14.3, 3.4 Hz, 1 H),
2.09 (s, 3 H), 2.25 (br d, J = 12.5 Hz, 1 H), 2.66 (dd, J = 17.8, 14
Hz, 1 H), 2.80 (dd, J = 17.8, 3.4 Hz, 1 H), 3.17 (h, J = 6.8 Hz, 1 H),
4.03 (d, J = 11.1 Hz, 1 H), 4.37 (d, J = 11.1 Hz, 1 H), 6.47 (br s, 1
H), 6.74 (s, 1 H), 7.91 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 36.1 (C1), 18.6 (C2), 37.9 (C3),
37.8 (C4), 49.9 (C5), 35.9 (C6), 197.9 (C7), 133.2 (C8), 156.5 (C9),
36.8 (C10), 110.1 (C11), 158.9 (C12), 124.0 (C13), 126.7 (C14),
26.7 (C15), 22.3 (C16)*, 22.4 (C17)*, 27.0 (C18), 66.8 (C19), 23.6
(C20), 21.0 (OCOCH3), 171.3 (OCOCH3).
[a]D25 +27.8 (c 0.14, CHCl3).
IR (film): 2930, 1670, 1599, 1497, 1360, 1258, 1176, 1097, 969,
846, 756, 666 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.94 (s, 3 H), 1.19 (s, 3 H), 1.23
(d, J = 6.9 Hz, 3 H), 1.25 (d, J = 6.9 Hz, 3 H), 1.42–1.81 (m, 6 H),
2.11 (dd, J = 14.6, 3.7 Hz, 1 H), 2.20 (m, 1 H), 2.21 (dd, J = 17.8,
3.7 Hz, 1 H), 2.46 (s, 3 H), 3.34 (h, J = 6.9 Hz, 1 H), 3.59 (d, J = 9.7
Hz, 1 H), 3.64 (d, J = 9.7 Hz, 1 H), 5.15 (s, 2 H), 6.78 (s, 1 H), 7.45
(d, J = 8.3 Hz, 2 H), 7.34–2.46 (m, 5 H), 7.72 (d, J = 8.3 Hz, 2 H),
7.87 (s, 1 H).
HRMS (FAB): m/z [M + Na]+ calcd for C22H30O4Na: 381.2042;
found: 381.2029.
Anal. Calcd for C22H30O4: C, 73.71; H, 8.44. Found: C, 73.58; H,
8.43.
Sugikurojin A (3)
13C NMR (125 MHz, CDCl3): d = 35.4 (C1), 18.0 (C2), 37.1 (C3),
37.9 (C4), 42.6 (C5), 34.8 (C6), 196.9 (C7), 135.9 (C8), 155.5 (C9),
37.1 (C10), 105.8 (C11), 160.8 (C12), 136.7 (C13), 125.9 (C14),
26.8 (C15), 22.4 (C16)*, 22.6 (C17)*, 76.6 (C18), 17.1 (C19), 23.8
(C20), 70.1 (CH2OBn), 124.2 (COBn), 127.3 (2 CHOBn), 127.9
(CHOBn), 128.1 (2 CHOBn), 132.6 (COTs), 128.7 (2 CHOTs),
130.1 (2 CHOTs), 145.1 (COTs), 21.8 (CH3-OTs).
LiAlH4 (120 mg, 3.158 mmol) was added to a stirred soln of 22 (135
mg, 0.377 mmol) in anhyd THF (15 mL) at 0 °C and the mixture
was kept stirred under an argon atmosphere for 30 min. 2 M HCl
(0.5 mL) was added slowly at 0 °C and the mixture was stirred for
an additional 10 min. The solvent was removed in vacuo and the
crude product obtained was diluted with t-BuOMe–H2O (3:1, 40
mL), and the phases were shaken and separated. The organic phase
was washed with H2O and brine and dried (anhyd Na2SO4). Remov-
al of the solvent under vacuum afforded 3 (78 mg, 69%).
HRMS (FAB): m/z [M + Na]+ calcd for C34H40O5SNa: 583.2494;
found: 583.2503.
Anal. Calcd for C34H40O5S: C, 72.83; H, 7.19. Found: C, 72.68; H,
7.26.
12-(Benzyloxy)-18-(tosyloxy)abieta-8,11,13-triene (23)
To a soln of 12 (9.8 g, 25 mmol) in pyridine (40 mL) at 0 °C was
added TsCl (7.18 g, 37.65 mmol) and DMAP (100 mg, 0.8 mmol)
Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York

3500
E. Alvarez-Manzaneda et al.
PAPER
7-Acetoxy-12-(benzyloxy)-18-(tosyloxy)abieta-6,8,11,13-tetra-
ene (25)
HRMS (FAB): m/z [M + Na]+ calcd for C36H42O7SNa: 641.2549;
found: 641.2561.
To a soln of 24 (950 mg, 1.69 mmol) in isopropenyl acetate (8 mL)
was added TsOH·H2O (cat., 20 mg) and he mixture was refluxed for
3 h (TLC monitoring). The mixture was cooled to r.t. and quenched
with sat. aq NaHCO3 (1 mL) and extracted with t-BuOMe (3 × 60
mL). The combined organic layers were washed with sat. aq
NaHCO3 (3 × 10 mL) and brine (2 × 15 mL) and dried (Na2SO4).
The solvent was removed in vacuo to give a crude product that was
purified by flash chromatography to afford 25 (1.01 g, 99%) as a
yellow oil.
Anal. Calcd for C36H42O7S: C, 69.88; H, 6.84. Found: C, 70.01; H,
6.88.
18-(Benzyloxy)-6a,18-epoxyabieta-8,11,13-trien-7-one (27)
To a soln of 26 (332 mg, 0.537 mmol) in anhyd MeOH (10 mL) was
added K2CO3 (175 mg, 1.26 mmol) and the mixture was stirred at
r.t. for 30 min (TLC monitoring). MeOH was evaporated in vacuo
and the crude product was poured into t-BuOMe–H2O (3:1, 40 mL)
and washed with H2O (2 × 10 mL) and brine (10 mL). The organic
layer was dried (Na2SO4) and evaporated to give 27 (184 mg, 85%)
as a colorless syrup. Flash chromatography of 27 (42 mg) (silica gel,
25% t-BuOMe–hexanes) gave pure 27 (35 mg).
[a]D25 +42.1 (c 0.1, CHCl3).
IR (film): 3005, 2928, 2856, 1760, 1602, 1499, 1462, 1362, 1210,
1176, 967, 846, 757, 697, 667 cm–1.
[a]D25 +27.2 (c 0.2, CHCl3).
1H NMR (500 MHz, CDCl3): d = 1.02 (s, 3 H), 1.16 (s, 3 H), 1.21
(d, J = 6.9 Hz, 3 H), 1.22 (d, J = 6.9 Hz, 3 H), 1.25–1.80 (m, 5 H),
2.07 (br d, J = 12.6 Hz, 1 H), 2.28 (s, 3 H), 2.39 (d, J = 2.8 Hz, 1 H),
2.45 (s, 3 H), 3.33 (h, J = 6.9 Hz, 1 H), 3.66 (d, J = 9.7 Hz, 1 H),
3.68 (d, J = 9.7 Hz, 1 H), 5.06 (d, J = 12.1 Hz, 1 H), 5.08 (d,
J = 12.1 Hz, 1 H), 5.22 (d, J = 2.8 Hz, 1 H), 6.72 (s, 1 H), 6.78 (s, 1
H), 7.29 (d, J = 8.2 Hz, 2 H), 7.31 (d, J = 7.3 Hz, 1 H), 7.38 (t,
J = 7.3 Hz, 2 H), 7.45 (d, J = 7.2 Hz, 2 H), 7.73 (d, J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 34.4 (C1), 17.9 (C2), 35.3 (C3),
38.4 (C4), 44.6 (C5), 111.6 (C6), 146.1 (C7), 134.5 (C8), 147.3
(C9), 36.7 (C10), 106.3 (C11), 156.6 (C12), 137.4 (C13), 119.6
(C14), 26.8 (C15), 22.4 (C16)*, 22.9 (C17)*, 77.5 (C18), 18.0
(C19), 21.8 (C20), 70.3 (CH2OBn), 122.1 (COBn), 127.3 (2
CHOBn), 127.9 (CHOBn), 128.1 (2 CHOBn), 129.9 (2 CHOTs),
132.8 (COTs), 132.8 (2 CHOTs), 144.7 (COTs), 21.8 (CH3-OTs),
20.7 (OCOCH3), 169.3 (OCOCH3).
IR: 1693, 1600, 1492, 1465, 1251, 1176, 1082, 1024, 1008, 849,
755, 666, 755 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.22 (s, 3 H), 1.23 (d, J = 6.9 Hz,
3 H), 1.24 (d, J = 6.9 Hz, 3 H), 1.29 (s, 3 H), 1.40 (m, 1 H), 1.79–
1.9 (m, 4 H), 2.02 (d, J = 14.4 Hz, 1 H), 2.17 (br d, J = 13.3 Hz, 1
H), 3.33 (h, J = 6.9 Hz, 1 H), 3.5 (d, J = 7.4 Hz, 1 H), 3.81 (d,
J = 7.4 Hz, 1 H), 4.43 (d, J = 14.4 Hz, 1 H), 5.15 (s, 2 H), 6.74 (s, 1
H), 7.32–7.43 (m, 5 H), 7.97 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 34.9 (C1), 19.8 (C2), 38.3 (C3),
40.2 (C4), 56.6 (C5), 76.6 (C6), 196.2 (C7), 136.4 (C8), 154.8 (C9),
38.3 (C10), 107.1 (C11), 160.5 (C12), 136.6 (C13), 126.7 (C14),
26.9 (C15), 22.4 (C16)*, 22.6 (C17)*, 84.4 (C18), 18.4 (C19), 22.0
(C20), 70.1 (CH2OBn), 124.3 (COBn), 127.2 (2 CHOBn), 127.9
(CHOBn), 128.1 (2 CHOBn).
HRMS (FAB): m/z [M + Na]+ calcd for C27H32O3Na: 427.2249;
found: 427.2242.
HRMS (FAB): m/z [M + Na]+ calcd for C36H42O6SNa: 625.2600;
found: 625.2610.
Anal. Calcd for C27H32O3: C, 80.16; H, 7.97. Found: C, 80.35; H,
8.00.
Anal. Calcd for C36H42O6: C, 71.73; H, 7.02. Found: C, 71.56; H,
6.98.
Hanagokenol A (7)
6a-Acetoxy-12-(benzyloxy)-18-(tosyloxy)abieta-8,11,13-trien-7-
one (26)
To a soln of 27 (73 mg, 0.18 mmol) in anhyd MeOH (6 mL) was
added 10% Pd/C (30 mg) and the mixture was stirred at r.t. under
H2 for 30 min. Filtration and concentration gave 7 (51 mg, 90%) as
a white solid. Flash chromatography of 7 (22 mg) (silica gel, 40% t-
BuOMe–hexanes) gave pure 7 (15 mg).
[a]D25 +78.2 (c 0.15, MeOH) [Lit.11 +186 (c 0.18, MeOH)].
IR (KBr): 3374, 1761, 1709, 1613, 1588, 1032 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.23 (s, 3 H), 1.25–1.40 (m, 2 H),
1.26 (d, J = 6.9 Hz, 3 H), 1.263 (d, J = 6.9 Hz, 3 H), 1.31 (s, 3 H),
1.44 (ddd, J = 12.9, 12.9, 3.0 Hz, 1 H), 1.77–1.92 (m, 2 H), 2.02 (d,
J = 14.5 Hz, 1 H), 2.16 (m, 1 H), 3.14 (h, J = 6.9 Hz, 1 H), 3.5 (d,
J = 7.4 Hz, 1 H), 3.82 (d, J = 7.4 Hz, 1 H), 4.43 (d, J = 14.5 Hz, 1
H), 5.53 (br s, 1 H), 6.64 (s, 1 H), 7.97 (s, 1 H).
To a soln of 25 (400 mg, 0.66 mmol) in CH2Cl2 (10 mL) at 0 °C was
added MCPBA (115 mg, 0.67 mmol) (previously treated with sat.
aq NaHCO3 to remove 3-chlorobenzoic acid) and the mixture was
stirred at r.t. for 20 min (TLC monitoring). The mixture was cooled
to 0 °C, quenched with sat. aq Na2SO3 (1 mL), and stirred for an ad-
ditional 15 min. The solvent was evaporated and the crude product
was poured into t-BuOMe–H2O (60:15, 75 mL). The organic phase
was washed with sat. aq NaHCO3 (7 × 15 mL) and brine (2 × 15
mL), dried (Na2SO4), and concentrated to give 26 (382 mg, 94%) as
a yellow oil. Flash chromatography of 26 (59 mg) (silica gel, 20%
t-BuOMe–hexanes) gave pure 26 (51 mg).
[a]D25 +43.7 (c 0.1, CHCl3).
1H NMR (500 MHz, CDCl3): d = 1.03 (s, 3 H), 1.21 (d, J = 6.9 Hz,
3 H), 1.22 (d, J = 6.9 Hz, 3 H), 1.38 (s, 3 H), 1.49–1.61 (m, 3 H),
1.70–1.77 (m, 2 H), 1.97 (s, 3 H), 2.24 (br d, J = 12.3 Hz, 1 H), 2.39
(d, J = 13.1 Hz, 1 H), 2.42 (s, 3 H), 3.32 (h, J = 6.9 Hz, 1 H), 3.79
(d, J = 9.0 Hz, 1 H), 3.91 (d, J = 9.0 Hz, 1 H), 5.15 (s, 2 H), 5.81 (d,
J = 13.1 Hz, 1 H), 6.79 (s, 1 H), 7.32 (d, J = 8.3 Hz, 2 H), 7.33–7.45
(m, 5 H), 7.74 (d, J = 8.3 Hz, 2 H), 7.89 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 36.0 (C1), 17.7 (C2), 37.4 (C3),
39.7 (C4), 46.5 (C5), 78.9 (C6), 191.6 (C7), 136.5 (C8), 154.5 (C9),
37.8 (C10), 105.9 (C11), 161.3 (C12), 136.7 (C13), 126.6 (C14),
26.7 (C15), 22.3 (C16)*, 22.5 (C17)*, 74.6 (C18), 17.3 (C19), 25.3
(C20), 70.2 (CH2OBn), 122.3 (COBn), 127.2 (2 CHOBn), 128.0
(CHOBn), 128.2 (2 CHOBn), 128.8 (2 CHOTs), 129.9 (2 CHOTs),
133.3 (COTs), 144.7 (COTs), 21.6 (CH3-OTs), 20.9 (OCOCH3),
170.2 (OCOCH3).
13C NMR (125 MHz, CDCl3): d = 34.9 (C1), 19.8 (C2), 38.3 (C3),
40.1 (C4), 56.5 (C5), 72.8 (C6), 195.9 (C7), 133.5 (C8), 154.8 (C9),
37.9 (C10), 111.0 (C11), 158.1 (C12), 124.6 (C13), 127.5 (C14),
26.9 (C15), 22.3 (C16)*, 22.4 (C17)*, 84.3 (C18), 18.4 (C19), 22.0
(C20).
HRMS (FAB): m/z [M + Na]+ calcd for C20H26O3Na: 337.1780;
found: 337.1769.
Anal. Calcd for C20H26O3: C, 76.40; H, 8.33. Found: C, 76.22; H,
8.36.
12-(Benzyloxy)-6a,18-epoxyabieta-8,11,13-trien-7b-ol (28)
NaBH4 (32 mg, 0.84 mmol) was added to a soln of 27 (135 mg,
0.334 mmol) in EtOH (5 mL) and the mixture was stirred at 0 °C for
45 min (TLC monitoring). The reaction was quenched with H2O (1
Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York

PAPER
(+)-Hanagokenol A, (+)-Fortunins E, G, H, and (–)-Sugikurojin A
3501
mL) and t-BuOMe (20 mL) was added. The organic layer was
washed with H2O (3 × 8 mL) and brine (8 mL), dried (Na2SO4), and
concentrated to give 28 (112 mg, 83%) as a colorless oil. Flash chro-
matography of 28 (29 mg) (silica gel, 30% t-BuOMe–hexanes) gave
pure 28 (21 mg).
1H NMR (500 MHz, CDCl3): d = 0.93 (s, 3 H), 1.18 (d, J = 6.8 Hz,
3 H), 1.19 (d, J = 6.8 Hz, 3 H), 1.21 (s, 3 H), 1.6–1.81 (m, 8 H), 2.04
(s, 3 H), 2.19 (br d, J = 12.6 Hz, 1 H), 2.30 (s, 3 H), 2.70–2.88 (m,
2 H), 2.91 (h, J = 6.8 Hz, 1 H), 3.67 (d, J = 11.1 Hz, 1 H), 3.98 (d,
J = 11.1 Hz, 1 H), 6.83 (s, 1 H), 6.94 (s, 1 H).
[a]D25 +70.1 (c 0.2, CHCl3).
IR: 1498, 1456, 1255, 1175, 1089, 1028, 986, 903, 847, 759 cm–1.
13C NMR (125 MHz, CDCl3): d = 35.5 (C1), 18.5 (C2), 36.8 (C3),
38.3 (C4), 43.7 (C5), 19.0 (C6), 29.8 (C7), 133.0 (C8), 146.3 (C9),
37.6 (C10), 118.0 (C11), 148.4 (C12), 136.9 (C13), 127.1 (C14),
27.3 (C15), 23.08 (C16)*, 23.09 (C17)*, 72.3 (C18), 17.6 (C19),
25.3 (C20), 21.0 (2 OCOCH3), 171.1 (OCOCH3), 171.4 (OCOCH3).
HRMS (FAB): m/z [M + Na]+ calcd for C24H34O4Na: 409.2355;
found: 409.2361.
1H NMR (500 MHz, CDCl3): d = 1.18 (s, 3 H), 1.19 (s, 3 H), 1.23
(d, J = 6.9 Hz, 3 H), 1.24 (d, J = 6.9 Hz, 3 H), 1.33 (m, 1 H), 1.34
(ddd, J = 13.0, 13.0, 3.9 Hz, 1 H), 1.60 (d, J = 12.6 Hz, 1 H), 1.65–
1.95 (m, 3 H), 2.09 (br d, J = 12.8 Hz, 1 H), 3.35 (h, J = 6.9 Hz, 1
H), 3.45 (d, J = 7.3 Hz, 1 H), 3.74 (d, J = 7.3 Hz, 1 H), 3.97 (dd,
J = 12.6, 7.1 Hz, 1 H), 4.70 (d, J = 7.1 Hz, 1 H), 5.07 (s, 2 H), 6.67
(s, 1 H), 7.32 (d, J = 7.3 Hz, 1 H), 7.38 (t, J = 7.3 Hz, 2 H), 7.45 (d,
J = 7.2 Hz, 2 H), 7.47 (s, 1 H).
Anal. Calcd for C24H34O4: C, 74.58; H, 8.87. Found: C, 74.74; H,
8.92.
12,18-Diacetoxyabieta-8,11,13-trien-7-one (30)
13C NMR (125 MHz, CDCl3): d = 35.2 (C1), 20.0 (C2), 38.6 (C3),
40.0 (C4), 54.7 (C5), 78.7 (C6), 72.8 (C7), 136.0 (C8), 146.8 (C9),
38.0 (C10), 108.0 (C11), 155.6 (C12), 137.6 (C13), 125.7 (C14),
27.0 (C15), 22.7 (C16)*, 22.8 (C17)*, 84.0 (C18), 19.0 (C19), 23.9
(C20), 70.1 (CH2OBn), 127.3 (2 CHOBn), 127.8 (CHOBn), 128.6
(2 CHOBn), 130.0 (COBn).
To a soln of 29 (6.9 g, 17.87 mmol) in AcOH (30 mL) at 0 °C, was
added CrO3 (3.66 g, 36.6 mmol), and the mixture was stirred for 3
h (TLC monitoring). The mixture was poured into t-BuOMe–H2O
(5:1, 120 mL). The organic phase was washed with H2O (10 × 40
mL), aq NaHCO3 (2 × 20 mL), and brine (2 × 20 mL), dried
(Na2SO4), and evaporated to give 30 (5.36 g, 75%) as a yellow oil.
Flash chromatography of 30 (352 mg) (silica gel, 20% t-BuOMe–
hexanes) gave pure 30 (341 mg).
HRMS (FAB): m/z [M + Na]+ calcd for C27H34O3Na: 429.2406;
found: 429.2401.
[a]D25 +17.3 (c 0.2, CHCl3).
Anal. Calcd for C27H34O3: C, 79.76; H, 8.43. Found: C, 79.91; H,
8.39.
IR (film): 1740, 1681, 1609, 1561, 1463, 1369, 1237, 1201, 1117,
1039, 909, 756 cm–1.
Fortunin H (8)
To a soln of 28 (219 mg, 0.54 mmol) in distilled MeOH (10 mL)
was added 10% Pd/C (150 mg) and the mixture was stirred at r.t. un-
der H2 for 2 h. Filtration and concentration gave 8 (148 mg, 87%) as
a yellow amorphous solid. Flash chromatography of 8 (32 mg) (sil-
ica gel, 50% t-BuOMe–hexanes) gave pure 8 (25 mg).
1H NMR (500 MHz, CDCl3): d = 0.97 (s, 3 H), 1.17 (d, J = 7.0 Hz,
3 H), 1.19 (d, J = 7.0 Hz, 3 H), 1.23 (s, 3 H), 1.39–1.56 (m, 3 H),
1.68–1.79 (m, 2 H), 1.99 (s, 3 H), 2.19–2.21 (m, 2 H), 2.31 (s, 3 H),
2.60–2.61 (m, 2 H), 2.96 (h, J = 7.0 Hz, 1 H), 3.67 (d, J = 11.3 Hz,
1 H), 3.80 (d, J = 11.3 Hz, 1 H), 6.97 (s, 1 H), 7.96 (s, 1 H).
[a]D25 +114.1 (c 0.15, CHCl3) [Lit.12 +108 (c 0.29, MeOH)].
13C NMR (125 MHz, CDCl3): d = 35.8 (C1), 18.0 (C2), 37.2 (C3),
37.7 (C4), 42.9 (C5), 35.1 (C6), 197.7 (C7), 128.9 (C8), 152.7 (C9),
36.6 (C10), 117.8 (C11), 154.7 (C12), 138.6 (C13), 126.5 (C14),
27.3 (C15), 22.73 (C16)*, 22.74 (C17)*, 71.3 (C18), 17.2 (C19),
23.8 (C20), 20.9 (2 OCOCH3), 169.9 (OCOCH3), 171.0 (OCOCH3).
HRMS (FAB): m/z [M + Na]+ calcd for C24H32O5Na: 423.2147;
found: 423.2156.
1H NMR (500 MHz, CDCl3): d = 1.21 (s, 3 H), 1.25 (s, 3 H), 1.25–
1.40 (m, 2 H), 1.25 (d, J = 6.8 Hz, 3 H), 1.26 (d, J = 6.8 Hz, 3 H),
1.60 (d, J = 12.6 Hz, 1 H), 1.66–1.92 (m, 3 H), 2.08 (br d, J = 12.7
Hz, 1 H), 3.13 (h, J = 6.8 Hz, 1 H), 3.46 (d, J = 7.2 Hz, 1 H), 3.76
(d, J = 7.2 Hz, 1 H), 3.99 (dd, J = 12.6, 7.1 Hz, 1 H), 4.69 (d, J = 7.1
Hz, 1 H), 6.56 (s, 1 H), 7.44 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 35.2 (C1), 20.0 (C2), 38.6 (C3),
40.0 (C4), 54.6 (C5), 78.8 (C6), 76.6 (C7), 133.0 (C8), 147.2 (C9),
37.7 (C10), 111.2 (C11), 152.7 (C12), 1128.6 (C13), 126.1 (C14),
27.1 (C15), 22.6 (C16)*, 22.7 (C17)*, 83.9 (C18), 19.0 (C19), 23.9
(C20).
Anal. Calcd for C24H32O5: C, 71.97; H, 8.05. Found: C, 72.23; H,
8.11.
7,12,18-Triacetoxyabieta-6,8,11,13-tetraene (31)
To a soln of 30 (791 mg, 1.98 mmol) in isopropenyl acetate (8 mL)
was added TsOH·H2O (cat. 20 mg). The mixture was refluxed for 3
h, cooled to r.t., and quenched with sat. NaHCO3. The mixture was
extracted with t-BuOMe (3 × 60 mL) and the combined organic lay-
ers were washed with sat. aq NaHCO3 (3 × 10 mL), brine (2 × 15
mL), and dried (Na2SO4). The soln was evaporated in vacuo and the
residue was purified by flash chromatography to afford 31 (848 mg,
97%) as yellow oil.
Anal. Calcd for C20H28O3: C, 75.91; H, 8.92. Found: C, 76.07; H,
8.86.
12,18-Diacetoxyabieta-8,11,13-triene (29)
To a soln of 6 (6.83, 22.6 mmol) in pyridine (40 ml) at 0 °C was add-
ed Ac2O (20 mL) and DMAP (100 mg, 0.8 mmol) and the mixture
was stirred at r.t. for 2 h (TLC monitoring). The mixture was cooled
to 0 °C, H2O (15 mL) was added to quench the reaction, and the
mixture was stirred for an additional 20 min. Then it was diluted
with t-BuOMe (100 mL) and washed with 2 M HCl (5 × 20 mL),
H2O (1 × 20 mL), sat. aq NaHCO3 (5 × 20 mL), and brine (2 × 20
mL). The organic layer was dried (Na2SO4), and the solvent evapo-
rated to give 29 (7.07 g, 81%) as a colorless syrup. Flash chroma-
tography of 29 (640 mg) (silica gel, 15% t-BuOMe–hexanes) gave
pure 29 (626 mg).
[a]D25 +25.6 (c 0.2, CHCl3).
IR (film): 1761, 1739, 1656, 1491, 1464, 1369, 1205, 1103, 1038,
912, 757 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.05 (s, 3 H), 1.17 (d, J = 7.0 Hz,
3 H), 1.19 (d, J = 7.0 Hz, 3 H), 1.22 (s, 3 H), 1.42 (m, 1 H), 1.45 (dd,
J = 9.8, 3.7 Hz, 1 H), 1.61 (ddd, J = 12.3, 12.3, 3.7 Hz, 1 H), 1.69–
1.85 (m, 2 H), 2.03 (s, 3 H), 2.09 (br d, J = 12.6 Hz, 1 H), 2.28 (s, 3
H), 2.31 (s, 3 H), 2.59 (d, J = 2.8 Hz, 1 H), 2.96 (h, J = 7.0 Hz, 1 H),
3.74 (d, J = 11.3 Hz, 1 H), 3.86 (d, J = 11.3 Hz, 1 H), 5.6 (d, J = 2.8
Hz, 1 H), 6.79 (s, 1 H), 7.06 (s, 1 H).
[a]D25 +21.2 (c 0.17, CHCl3).
IR (film): 1739, 1498, 1463, 1369, 1239, 1219, 1037, 914, 757 cm–1.
Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York

3502
E. Alvarez-Manzaneda et al.
PAPER
13C NMR (125 MHz, CDCl3): d = 34.6 (C1), 18.0 (C2), 35.2 (C3),
38.2 (C4), 44.5 (C5), 115.1 (C6), 145.4 (C7), 127.5 (C8), 147.4
(C9), 36.1 (C10), 116.6 (C11), 148.3 (C12), 137.2 (C13), 119.8
(C14), 27.3 (C15), 22.7 (C16)*, 22.9 (C17)*, 71.5 (C18), 18.4
(C19), 21.0 (C20), 20.8 (OCOCH3), 20.9 (2 OCOCH3), 169.1
(OCOCH3), 169.6 (OCOCH3), 171.0 (OCOCH3).
37.5 (C10), 110.0 (C11), 161.1 (C12), 120.4 (C13), 127.1 (C14),
26.9 (C15), 22.1 (C16)*, 22.3 (C17)*, 74.6 (C18), 17.4 (C19), 25.0
(C20).
HRMS (FAB): m/z [M + Na]+ calcd for C20H28O4Na: 355.1885;
found: 355.1883.
Anal. Calcd for C20H28O4: C, 72.26; H, 8.49. Found: C, 72.40; H,
8.51.
HRMS (FAB): m/z [M + Na]+ calcd for C26H34O6Na: 465.2253;
found: 465.2248.
Anal. Calcd for C26H34O6: C, 70.56; H, 7.74. Found: C, 70.35; H,
7.73.
Fortunin G (10)
To a soln of 32 (100 mg, 0.218 mmol) in anhyd EtOH (10 mL), at
–20 C was added NaBH4 (25 mg, 0.6 mmol) and the mixture was
stirred at –20 °C for 5 h (TLC monitoring). The reaction was
quenched with H2O (3 mL) and the solvent was evaporated to give
a crude product that was diluted with t-BuOMe and washed with
H2O (3 × 15 mL) and brine (2 × 15 mL). The organic layer was
dried (Na2SO4), and concentrated to give 10 (79 mg, 79%) as a yel-
low amorphous solid. Flash chromatography of 10 (28 mg) (silica
gel, 50% t-BuOMe–hexanes) gave pure 10 (19 mg).
6a,12,18-Triacetoxyabieta-8,11,13-trien-7-one (32)
To a soln of 31 (800 mg, 1.81 mmol) in CH2Cl2 (10 mL) at 0 °C was
added MCPBA (331 mg, 1.93 mmol), previously treated with
NaHCO3, and the mixture was stirred at r.t. for 20 min (TLC moni-
toring). The mixture was cooled at 0 °C and quenched with sat. aq
Na2SO3 (5 mL) and stirred for an additional 5 min. The CH2Cl2 was
evaporated and the mixture was poured into t-BuOMe–H2O (4:1, 75
mL). The organic phase was washed with sat. aq NaHCO3 (3 × 15
mL) and brine (5 × 15 mL), dried (Na2SO4), and concentrated to
give 32 (754 mg, 91%) as a yellow oil. Flash chromatography of 32
(91 mg) (silica gel, 20% t-BuOMe–hexanes) gave pure 32 (84 mg).
[a]D25 +36.5 (c 0.2, CHCl3) [Lit.12 +38 (c 0.18, CHCl3)].
IR (KBr): 3460, 1738, 1605, 1469, 1372, 1238, 1040, 913, 757
cm–1.
1H NMR (500 MHz, CDCl3): d = 0.99 (s, 3 H), 1.18 (d, J = 6.5 Hz,
3 H), 1.19 (d, J = 6.5 Hz, 3 H), 1.35 (s, 3 H), 1.39–1.74 (m, 7 H),
2.04 (s, 3 H), 2.12 (d, J = 11.8 Hz, 1 H), 2.15 (s, 3 H), 2.30 (s, 3 H),
2.93 (h, J = 6.9 Hz, 1 H), 3.55 (d, J = 10.8 Hz, 1 H), 4.15 (d,
J = 10.8 Hz, 1 H), 4.59 (d, J = 5.1 Hz, 1 H), 5.39 (dd, J = 11.8, 5.2
Hz, 1 H), 6.83 (s, 1 H), 7.37 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 37.1 (C1), 17.8 (C2), 38.2 (C3),
39.2 (C4), 45.3 (C5), 78.4 (C6), 76.2 (C7), 133.0 (C8), 147.4 (C9),
36.4 (C10), 117.1 (C11), 147.9 (C12), 138.3 (C13), 127.2 (C14),
27.3 (C15), 22.9 (C16)*, 23.0 (C17)*, 73.7 (C18), 17.9 (C19), 26.0
(C20), 20.8 (OCOCH3), 20.9 (OCOCH3), 21.5 (OCOCH3), 169.6
(OCOCH3), 170.1 (OCOCH3), 172.5 (OCOCH3).
[a]D25 +57.6 (c 0.2, CHCl3).
IR (film): 3016, 2964, 2937, 2874, 1746, 1695, 1612, 1566, 1467,
1372, 1236, 1199, 117, 1041, 926, 907, 756 cm–1.
1 H NMR (500 MHz, CDCl3): d = 1.06 (s, 3 H), 1.19 (d, J = 6.8 Hz,
3 H), 1.21 (d, J = 6.8 Hz, 3 H), 1.43 (m, 1 H), 1.43 (s, 3 H), 1.58–
1.82 (m, 4 H), 2.01 (s, 3 H), 2.21 (s, 3 H), 2.26 (br d, J = 12.3 Hz, 1
H), 2.34 (s, 3 H), 2.59 (d, J = 13.2 Hz, 1 H), 2.98 (h, J = 6.8 Hz, 1
H), 3.65 (d, J = 10.9 Hz, 1 H), 4.12 (d, J = 10.9 Hz, 1 H), 5.87 (d,
J = 13.2 Hz, 1 H), 7.03 (s, 1 H), 7.99 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 36.7 (C1), 17.8 (C2), 37.8 (C3),
39.3 (C4), 45.7 (C5), 74.6 (C6), 192.6 (C7), 139.4 (C8), 153.2 (C9),
36.7 (C10), 117.8 (C11), 153.7 (C12), 127.3 (C13), 127.3 (C14),
27.3 (C15), 22.7 (C16), 22.7 (C17), 73.3 (C18), 17.7 (C19), 25.5
(C20), 20.95 (OCOCH3), 20.98 (OCOCH3), 21.0 (OCOCH3), 169.1
(OCOCH3), 170.4 (OCOCH3), 171.0 (OCOCH3).
HRMS (FAB): m/z [M + Na]+ calcd for C26H36O7Na: 483.2359;
found: 483.2366.
Anal. Calcd for C26H36O7: C, 67.80; H, 7.88. Found: C, 68.02; H,
7.84.
HRMS (FAB): m/z [M + Na]+ calcd for C26H34O7Na: 481.2202;
found: 481.2198.
Acknowledgment
Anal. Calcd for C26H34O7: C, 68.10; H, 7.47. Found: C, 67.91; H,
7.51.
The authors thank the Regional Government of Andalucia (Project
P07-FQM-03101 and aids to the group FQM-348) for financial sup-
port. I. C. thanks the Spanish Agency for the International Develop-
ment and Cooperation (AECID) for a predoctoral grant.
Fortunin E (9)
To a soln of 32 (140 mg, 0.3 mmol) in distilled MeOH (8 mL) was
added K2CO3 (169 mg, 1.2 mmol) and the mixture was stirred at r.t.
for 12 h (TLC monitoring). The reaction was quenched by slow ad-
dition of 2 M HCl (3 mL) at 0 °C, then MeOH was evaporated and
the crude product was poured into MEK–H2O (5:1, 60 mL). The or-
ganic layer was washed with H2O (4 × 15 mL) and brine (2 × 15
mL), dried (Na2SO4), and evaporated to give 9 (76 mg, 77%) as an
amorphous solid. Flash chromatography of 9 (32 mg) (silica gel,
70% t-BuOMe–hexanes) gave pure 9 (26 mg).
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Synthesis 2010, No. 20, 3493–3503 © Thieme Stuttgart · New York