Chemical transformations of phyllocladane (=13β-kaurane) diterpenoids

Article abstract of DOI:10.1002/hlca.200390043

Earlier phytochemical work on Plectranthus ambiguus (Lamiaceae) afforded a series of tetracyclic phyllocladane-type (=13β-kaurane) diterpenoids (see 1a-f). In the course of investigations concerning the reaction behavior of this rare natural-products, a new constituent of P. ambiguus was isolated, (2S,3R,16R)-phyllocladane-2,3,16,17-tetrol 2,3-diacetate (1g), and another eighteen new phyllocladanes were prepared by chemical transformations and characterized. The main constituent 1b of P. ambiguus was chemically transformed to the known natural diterpenoid calliterpenone (=(16R)-16,17-dihydroxyphyllocladan-3-one; 2) thus unambiguously establishing its structure (Scheme 1). Epimerization at C(16) via the epoxy derivative 20 yielded 16-epicalliterpenone (21), 17-hydroxyphylloclad-15-ene-3-one (22), and (16R)-3-oxophyllocladan-17-al (23) (Scheme 6). Comparing this reaction sequence with the corresponding one starting from diastereoisomeric (16R)-16,17-dihydroxy-ent-kauran-3-one (=abbeokutone; 27) showed basically the same outcome (Scheme 7). Furthermore, three new C(16)-substituted ent-kauran-3-ones were characterized. Reliable spectroscopic arguments for the determination of the configuration at C(16) in phyllocladanes and kauranes as well as for the differentiation of the diastereoisomeric skeletons are presented.

Full text of DOI:10.1002/hlca.200390043

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Helvetica Chimica Acta Vol. 86 (2003)
Chemical Transformations of Phyllocladane (ˆ13b-Kaurane) Diterpenoids
by Gui Liu, Ralph M¸ller, and Peter R¸edi*
Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
Earlier phytochemical work on Plectranthus ambiguus (Lamiaceae) afforded a series of tetracyclic
phyllocladane-type (ˆ13b-kaurane) diterpenoids (see 1a f). In the course of investigations concerning the
reaction behavior of this rare natural-products, a new constituent of P. ambiguus was isolated, (2S,3R,16R)-
phyllocladane-2,3,16,17-tetrol 2,3-diacetate (1g), and another eighteen new phyllocladanes were prepared by
chemical transformations and characterized. The main constituent 1b of P. ambiguus was chemically
transformed to the known natural diterpenoid calliterpenone (ˆ(16R)-16,17-dihydroxyphyllocladan-3-one;
2) thus unambiguously establishing its structure (Scheme 1). Epimerization at C(16) via the epoxy derivative 20
yielded 16-epicalliterpenone (21), 17-hydroxyphylloclad-15-ene-3-one (22), and (16R)-3-oxophyllocladan-17-al
(23) (Scheme 6). Comparing this reaction sequence with the corresponding one starting from diastereoisomeric
(16R)-16,17-dihydroxy-ent-kauran-3-one (ˆabbeokutone; 27) showed basically the same outcome (Scheme 7).
Furthermore, three new C(16)-substituted ent-kauran-3-ones were characterized.
Reliable spectroscopic arguments for the determination of the configuration at C(16) in phyllocladanes and
kauranes as well as for the differentiation of the diastereoisomeric skeletons are presented.
1. Introduction. In connection with our research program concerning the isolation
and synthesis of genuine constituents of African and Asian Lamiaceae species of the
genera Coleus, Plectranthus, and Solenostemon with respect to antioxidants, inhibitors
of the arachidonate metabolism, and allergens [1], we had reported on the isolation and
structure elucidation of a series of tetracyclic diterpenoids of the phyllocladane-type
(ˆ13b-kaurane) from Plectranthus ambiguus, i.e. 1a f [2].
OR3
OH
OH
OH
OCOMe
OH
13
20
16
R1
R2
1
4
O
O
19
18
MeOCO
2
3
1a R1 = R3 = H, R2 = OCOMe
b
c
d
e
f
R1 = OCOCH=C(Me)2, R2 = OCOMe, R3 = H
R1 = OCOCH2C(Me)2, R2 = OCOMe, R3 = H
R1 = OCOCH=C(Me)2, R2 = R3 = OCOMe
R1 = OCOCH2C(Me)2, R2 = R3 = OCOMe
R1 = OCOCH=C(Me)2, R2 = O, R3 = H
R1 = R2 = OCOMe, R3 = H
g
Phyllocladane-type diterpenoids are very rare in nature as by far most of the
tetracyclic diterpenoids belong to the diastereoisomeric ent-kaurane series. The scarcity
of relevant data of phyllocladanes and the fact that misinterpretations and confusion

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421
concerning the correct denomination exist in the current literature1) prompted us to
confirm the structures of the new natural products, which were based only on
spectroscopic data. Therefore, the main constituent 1b of P. ambiguus was chemically
transformed to the known natural diterpenoid (16R)-16,17-dihydroxyphyllocladan-3-
one (ˆcalliterpenone; 2) from Callicarpa macrophylla [3]2)3). Earlier we had isolated
the closely related (16R)-17,19-bis(acetyloxy)-16-hydroxyphyllocladan-3-one (3) from
Plectranthus purpuratus [5]. The constitution of 3 had been established by X-ray-
analysis and the absolute configuration assigned by CD spectroscopy. Therefore, the
successful chemical conversion of 3 to calliterpenone (2) assures an additional,
independent confirmation of the structure of 1b.
In the course of our investigations, a new natural product, (2S,3R,16R)-phyllocla-
dane-2,3,16,17-tetrol 2,3-diacetate (1g), was isolated, and the chemical transformations
of 1a f yielded a series of new phyllocladanes. Thus, the actual number of
representatives of this skeletal type is significantly increased4). In this report, we give
a full account of these interconversions, which yielded also some unexpected results
[7]. Moreover, reliable spectroscopic arguments for the determination of the
configuration at C(16) in phyllocladanes and kauranes as well as for the differentiation
of such diastereoisomers are presented.
Because of the continuing confusion and to clear any inconsistencies and
discrepancies concerning the denomination and the nomenclature, the correct
skeletons and a part of the semisystematic numbering (C(19) is always axial!) are
depicted in Fig. 15).
2. Results and Discussion. 2.1. Transformation of 1b and 3 into Calliterpenone (2).
First, 1b was protected by forming the acetonide 4 [2] (Scheme 1), which was then
treated with LiAlH4 to yield the 2a,3a-diol 5. Tosylation of 5 furnished exclusively the
mono-tosylate 6. Subsequently, reaction of 6 with LiAlH4 afforded the unexpected 3b-
hydroxy acetonide 7 [7], which was oxidized with pyridinium chlorochromate (PCC)
1
)
)
For recent examples of inadequacies, see, e.g. [3].
2
The history of the structure elucidation of calliterpenone (2) is typical of the problems encountered with
these diastereoisomeric skeletons. Originally, an erroneous ent-kaurane structure had been assigned to 2
[4a]. It was revised in terms of a phyllocladane by chemical transformations [4b], and the revision was
confirmed including the determination of the absolute configuration [4c]. Later the relative configuration
was verified again by X-ray-analysis [4d].
Although the most straightforward route to ketone 2 is a simple transformation of the minor compound
1a, the main constitutent 1b was chosen since it allowed broader studies of the chemical reactivity of such
phyllocladanes.
3
)
4
5
)
Only eleven phyllocladanes had been characterized [4][6] when the structures of 3 [5] and, later, 1a f [2]
were disclosed.
)
An alternative, applicable name for −phyllocladane× is −13b-kaurane×. The term indicates the relative
position of the 5-membered ring D (C(15)ÀC(16)) on the same side as the C(10)ÀC(20) bond.
Unfortunately, the skeletons are sometimes not differentiated; in particular, phyllocladanes are mixed up
with ent-kauranes. Moreover, as the prefix −ent× inverts all the following descriptors, the enantiomer of
(2S,3R,16R)-phyllocladane-2,3,16,17-tetrol 2,3-diacetate (ˆ(2S,3R,16R)-13b-kaurane-2,3,16,17-tetrol 2,3-
diacetate; 1g) must be called either ent-(2S,3R,16R)-phyllocladane-2,3,16,17-tetrol 2,3-diacetate (ˆent-
(2S,3R,16R)-13b-kaurane-2,3,16,17-tetrol 2,3-diacetate; ent-1g) or (2R,3S,16S)-ent-phyllocladane-2,3,16,17-
tetrol 2,3-diacetate (ˆ(2R,3S,16S)-13a-ent-kauran-2,3,16,17-tetrol 2,3-diacetate; ent-1g).

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Helvetica Chimica Acta Vol. 86 (2003)
Fig. 1. Structures corresponding to the names phyllocladane (A), ent-phyllocladane (B), kaurane (C), and ent-
aurane (D). Note that Chem. Abstr. designates D with (16S) configuration as kaurane, this name implying
(5b,8a,9b,10a,13a,16b) configuration as defined by Chem. Abstr.; the Chem. Abstr. name of A with (16S)
configuration is thus (5a,9a,10b)-kaurane, and that of B with (16S) configuration is (8b,13b)-kaurane.
Scheme 1
OH
OH
O
HO
HO
O
a)
b)
O
O
MeOCO
1b
4
5
OH
OH
TsO
HO
c)
b)
d)e)
HO
O
2
6
7
a) Acetone, anh. CuSO4, refl.; 95%. b) LiAlH4, THF, r.t.; 4 (94%); 7 (90%). c) TsCl, pyridine, r.t.; 92%. d)
PCC, NaOAc, CH2Cl2, r.t. e) 2% H2SO4, MeOH, 708; 91% (d) and e)).
and then hydrolyzed to the 16,17-dihydroxy ketone 2 (calliterpenone). Comparison of
semisynthetic 2 with authentic calliterpenone (2) showed both compounds to be
1
identical (TLC, m.p., mixed m.p., [a]D, CD, IR, H- and 13C-NMR, MS).
A very similar route was followed for transforming 3 to calliterpenone (2)
(Scheme 2). As ketone 3 is prone to retro-aldol reactions, the most unefficient step in
the sequence was the neat removal of the acetate groups to yield the trihydroxy ketone
8. The tosylate 10, prepared from the correspondig acetonide 9, was then treated with
LiAlH4 to afford the 3b-hydroxy acetonide 7, identical to that derived from 6. It is
remarkable that the analogous reduction of a related tosylate without the 3-oxo group
yielded only traces of the desired hydrocarbon as the nucleophilic reaction almost

Helvetica Chimica Acta Vol. 86 (2003)
423
Scheme 2
OH
O
OH
O
a)
b)
3
O
O
OH
OH
8
9
c)
d)
e)f)
2
O
HO
OTs
10
7
a) 5 % HSO4, EtOH, r.t.; 33%. b) Acetone, anh. CuSO4, refl.; 89%. c) TsCl, pyridine, r.t.; 88%. d) LiAlH4,
2
THF, r.t.; 84%. e) PCC, NaOAc, CH2Cl2, r.t. f) 2% H2SO4, MeOH, 708, 3 h; 83% (e) and f)).>
exclusively took place at the S-atom [6d]. This fact demonstrates that the reactivity of
ring A in such diterpenoids strongly depends on its conformation. Usual oxidation and
hydrolysis of the acetal yielded calliterpenone (2), identical in every respect to both the
natural sample and that obtained from 1b.
2.2. retro-Aldol Reaction of 3. The natural product 3 was mentioned to undergo
retro-aldol cleavage easily. This was exemplified by the basic hydrolysis leading to the
19-nor compound 11a as well as by the attempted reduction according to Huang-
Minlon to give 11b (Scheme 3). The equatorial position of the remaining Me(18) group
was established from its original orientation and by the coupling characteristics of 11a
(see Exper. Part). Both the unfavorable 1,3-diaxial interaction of the CH2OAc group
with Me(20) and its stereoelectronically optimal arrangement with the C(3) carbonyl
group are the driving forces for the retro-aldol reaction.
Scheme 3
OH
OAc
OH
2N KOH
OH
EtOH
R
O
11a R = O
R = H2
Huang-Minlon
3
OAc
b
2.3. Transformation of the 2a,3a-Dioxy-Substituted Derivative 6 to the 3b-Hydroxy
Compound 7. The unexpected one-pot transformation 6 ! 7 (Scheme 1) appears to
proceed via an elimination yielding an enol(ate) and stereospecific reduction of the

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Helvetica Chimica Acta Vol. 86 (2003)
corresponding ketone. However, loss of TsOH in terms of an E2 mechanism is only
feasible when ring A adopts the boat conformation; moreover, HÀC(3) is less acidic
than HÀC(2) and is not expected to be abstracted primarily. But an alternative
mechanism can be formulated in terms of an electrocyclic elimination of TsOH and
hydride reduction from the less hindered −a-side×, as depicted in Scheme 4. Although
the stereoelectronic requirements for ideal orbital overlap are neither given in this
approach, an intramolecular six-membered ring transition state might be entropically
favored.
Scheme 4
Me
Me
H
H
R1
R2
Me
H
HO
Me
TsO
H
HO
Me
OTs
HO
Me
R1 = OTs, R2 = H
R1 = H, R2 = OH
O
O
S
H
Ar
HO
O
H
HO
O
H
HO
6
7
The proposed mechanisms were supported to some extent by the fact that 6 reacted
with LiAlD4 to generate exclusively the (3a-D) compound 12 and by the reactivity of
the bis(methanesulfonate) derivative 13. The results obtained from the reaction of 13
with LiAlH4 (Scheme 5) seem to support the E2 mechanism: The predominant product
is the 2b-alcohol 14 which, is easily formed from the favorable chair conformation,
whereas the 3b-alcohol 7 that would be generated from the disfavored boat form or by
the cyclic mechanism is only a minor product. Moreover, a minor amount of the starting
diol 5 is regenerated due to nucleophilic reaction at the S-atom of the methanesulfonate
groups. A full account on the elucidation of the mechanism is reported in the following
paper [7].
With regard to the characterization of further potential phyllocladane-type natural
product, (2R,3S,16R)-phyllocladane-2,3,16,17-tetrol (15), (3S,16R)-phyllocladane-
3,16,17-triol (18)6), (2R,16R)-phyllocladane-2,16,17-triol (16), and (16R)-16,17-trihy-
droxyphyllocladan-2-one (17) were prepared from 57), 7, and 14 by hydrolysis and/or
oxidation (Scheme 5 and Exper. Part)8).
2.4. Epimerization of Calliterpenone (2). Inversion of the configuration at C(16) of
2 was attempted by the route depicted in Scheme 6. The tosylate 19 was treated under
6
)
The (3S,16R)-phyllocladanetriol 18 has been obtained by either microbiological or NaBH4 reduction of 2
[3b]. The structure depicted in [3b] is a kaurane (see Fig. 1), and the physical data are not consistent.
The tetrol 15 was also prepared from natural 1b by LiAlH4 reduction (see Exper. Part).
Until now, these compounds have not been isolated from natural sources.
7
8
)
)

Helvetica Chimica Acta Vol. 86 (2003)
425
Scheme 5
TsO
HO
LiAlD4
HO
D
6
12
HO
HO
MsO
MsO
HO
b)
a)
+
+
5
HO
13
14
c)
7
5
c)
18
c)
15
d),c)
16,17
a) MeSO2Cl, pyridine, r.t.; 88%. b) LiAlH4, THF, r.t.; 5 (10%), 7 (10%), 14 (65%). c) 2% H2SO4, MeOH, 708.
d) PCC, NaOAc, CH2Cl2, r.t.
basic conditions to yield the epoxyphyllocladanone 20, which was opened by dilute acid
(5% H2SO4/H2O) to afford the desired (16S)-epimer 21, besides the regenerated
epimeric calliterpenone (2) and the elimination product 17-hydroxyphylloclad-15-en-3-
one (22) as the main products.
When epoxy derivative 20 was treated with 60% HClO4/H2O [8], the main product
was (16R)-3-oxophyllocladan-17-al (23) besides 22 and traces of 2 and its (16S)-epimer
21. Upon standing in solution, 23 was spontaneously oxidized to (16R)-3-oxophyllo-
cladan-17-oic acid (24).

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 6
R
b)
O
OH
O
O
20
2
R = OH
a)
19 R = OTs
25 R = Cl
f)
R1
R2
c) or d)
H
26a R1 = H, R2 = Cl
26b R1 = Cl, R2 = H
OH
CHO
COOH
e)
+
+
OH +
2
OH
H
H
H
H
21
22
23
24
a) TsCl, pyridine, r.t.; 91%. b) K2CO3, MeOH, r.t.; 91%. c) 60% HClO4, THF, r.t.; 2 and 21 (trace), 22 (4%), 23
(60%). d) 5 % HSO4, THF, r.t.; 2 (42%), 21 (5%), 22 (30%), 23 (0%). e) CDCl3/O2 (71%). f) TsCl, pyridine,
2
refl.; 25 (87%), 26a/26b (11%).
The structure of the substituted-ring-D moiety of 20 24 was supported by corresponding 1H- and
13C-NMR data (see Exper. Part). The (16R)-configuration of 23 was established by the chemical shift and
coupling characteristics of HÀC(17): It appeared at d 9.65( d, 3J(17,16) ˆ 1.7 Hz). HÀC(17) was reported to
resonate at d 9.45as a s in (16S)-phyllocladan-17-al [9]9).
All attempts to improve the yield of 16-epicalliterpenone (21; (16S)) were not
satisfactory, obviously due to the fact that the required backside attack of the
nucleophile (H2O) is sterically hindered10).
2.5. Chlorophyllocladanones 25, 26a, and 26b. In the course of the attempted
preparation of tosylate 19, unexpected reaction products were found (Scheme 6).
When 2 was treated with excess p-toluenesulfonyl chloride in pyridine under reflux, the
main compounds were (16R)-17-chloro-16-hydroxyphyllocladan-3-one (25) and the
9
)
Reaction of 2 with borontrifluoride etherate was reported to yield (16S)-3-oxophyllocladan-17-al [10].
However, the 1H-NMR data show HÀC(17) at d 9.6 (d, 3J ˆ 2 Hz), and there is no comment on the
determination of the configuration at C(16). Therefore, our report presents the first unambiguous
characterization of 23.
Under acidic conditions, the protonated epoxy moiety can either react by an SN1 or SN2 mechanism. In SN1
mechanisms, which favor tertiary C-atoms, attack is expected at the more highly substituted C-atom. When
protonated epoxides react by the SN2 mechanism, attack is usually at the more highly substituted position.
In neutral or basic solution, attack of the nucleophile will rather take place at the less highly substituted C-
atom [8].
10
)

Helvetica Chimica Acta Vol. 86 (2003)
427
(16E)- and (16Z)-17-chlorophylloclad-16-en-3-ones (26a and 26b, resp.) as an
unseparable (E)/(Z)-mixture (2 :1). Their structures were established by their MS
and NMR data (see Exper. Part).
2.6. Epimerization of (16R)-16,17-Dihydroxy-ent-kauran-3-one (27). To compare
the reactivities of phyllocladane- and kaurane-type diterpenoids, the ent-kauranone 27
(abbeokutone) [11] was subjected to the same series of reactions (Scheme 7). The
tosylate 28 yielded the epoxy-ent-kauranone 2911), which was opened by dilute acid
(5% H2SO4/H2O) to furnish the expected (16S)-epimer 3012) and 17-hydroxy-ent-kaur-
15-en-3-one (31)11). The predominant products were abbeokutone (27), (16R)-3-oxo-
ent-kauran-17-al (32a) and (16S)-3-oxo-ent-kauran-17-al (32b) as a ca. 1:1 mixture13).
Scheme 7
OR
OH
O
b)
c)
O
O
29
27 R = H
28 R = Ts
a)
OH
OH
CHO
+
+
OH
+
27
H
H
H
30
31
32a/32b
a) TsCl, pyridine, r.t.; 95%. b) K2CO3, MeOH, r.t.; 95%. c) 5 % HSO4, THF, r.t.; 27 (4%), 30 (38%), 31 (22%),
2
32a/32b (33%).
In the 1H-NMR spectrum of 32a, HÀC(17) appeared at d 9.67 (d, 3J(17,16) ˆ 1.7 Hz), and that of 32b at d
9.89 (s, HÀC(17)). As HÀC(17) of (16R)-3-oxo-ent-kauran-17-al was reported to resonate at d 9.65( d,
3J(17,16) ˆ 1.2 Hz) [13], the respective assignments are consistent (see also the argumentation for 23)14).
2.7. New Phyllocladane-Type Diterpenoids. The (2S,3R,16R)-phyllocladane-
2,3,16,17-tetrol 2,3-diacetate (1g) was detected in a fraction from Plectranthus
ambiguus containing 1f, and its structure was assigned by 1H-NMR data. Acetalization
of the mother liquor of 1f resulted in an easy separation of the acetonide of 1g, which
11
)
)
(16R)-16,17-Epoxy-ent-kauran-3-one (29) and 17-hydroxy-ent-kaur-15-en-3-one (31) are new compounds
and characterized for the first time.
The 16-epiabbeokutone (30; (16S)) has been isolated first from Euphorbia sieboldiana [12a], later from
Homalanthus acuminatus [12b], Sapium rigidifolium [12c], and Euphorbia portulacoides together with its
17-acetate [12d].
12
13
14
)
)
(16S)-3-Oxo-ent-kauran-17-al (32b) is a new compound, whereas (16R)-3-oxo-ent-kauran-17-al (32a) has
been characterized as a reaction product of (16R)-17-hydroxy-ent-kauran-3-one [13].
Due to the enhanced flexibility of the kaurane skeleton (see below), the couplings between HÀC(16),
CH2(15), etc., are not resolved.

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Helvetica Chimica Acta Vol. 86 (2003)
was carefully hydrolyzed to afford the unknown genuine compound 1g (for data, see
Exper. Part). Further proof for the structure was obtained by the preparation of 1g
from 1b via 5 (see Scheme 1), acetylation, and selective hydrolysis.
In addition to the new compounds 8 (Sect. 2.1 and Scheme 2) and 15 18 (Sect. 2.3
and Scheme 5), three further new phyllocladane derivatives were prepared, in view of
the characterization of potential natural products: reduction of 1a, 1f, and 8 afforded
33, 34, and 35, respectively (Formulae in Sect. 2.3).
The data of the nineteen new phyllocladanes 1g, 8, 11a, 11b, 15 18, 20 26a,b, and
33 35 and of the three new ent-kauran-3-ones 29, 31, and 32b are presented in the
Exper. Part.
2.8. Determination of the Configuration at C(16) of Phyllocladane-and Kaurane-
16,17-diols. From the ent-kaurane series, it is known that the configuration at C(16)
1
can be determined by using the H- and 13C-NMR-data of the 16,17-dihydroxy-ent-
kauran-3-ones 27 and 30 and of the ent-kauran-16,17-diols 36 and 37 [12a,b][14]:
In the (16R)-series (see 27 and 36), CH2(17) and C(16) are deshielded (Dd ca. ‡ 0.3
and ca. ‡ 2 ppm, resp.), whereas C(17) is shielded (Dd ca. À4 ppm) with respect to the
(16S)-diastereoisomers (see 30 and 37) (Dd ˆ d(16R) À d(16S); see Fig. 2). Compar-
ing the spectral data of calliterpenone (2; (16R)) with that of the new 16-
epicalliterpenone (21; (16S)) now established that the same set of arguments is valid
in the phyllocladane series (Fig. 2). In addition, it seems to apply also to the
corresponding 17-(acetyloxy) derivatives as shown for the relevant pair 3 (d (16R); 4.19
and 4.26 and (16S)-17-(acetyloxy)-16-hydroxy-ent-kauran-3-one [12d] (d 3.91 and
4.05).
2.9. NMR-Spectroscopic Differentiation between Phyllocladanes and Kauranes.
Differences were worked out on very closely related compounds such as the
phyllocladane-type calliterpenone (2) and the ent-kaurane-type abbeokutone (27)
(see Fig. 2). A general feature that fundamentally differentiates the diastereoisomers is
the enhanced flexibility of the kaurane skeleton, a fact that generally results in well-
resolved 1H-NMR spectra of the phyllocladanes compared to the ent-kauranes. Thus, in
2
calliterpenone (2), CH2(2) appears as a complex ABXY system at d 2.38 (ddd, J ˆ
3
3
2
15.8 Hz, J(2eq,1ax) ˆ 7.1, J(2eq,1eq) ˆ 4.1, HeqÀC(2)) and 2.52 (ddd, J ˆ 15.8 Hz,
3J(2ax,1ax) ˆ 10.8, 3J(2ax,1eq) ˆ 7.2, HaxÀC(2)), but in abbeokutone (27), CH2(2) is a
dd at d 2.47 (2 H, 3J ˆ 8.6, 6.3 Hz). Moreover, in the ent-kaurane derivative 27, Me(18)
and Me(20) are indistinguishable (s at d 1.09 (6 H)), whereas they appear as 2 s at
d 1.08 (Me(18)) and 1.03 (Me(20)) in 2. A further example is (16R)-3-oxophyllocladan-
17-al (23), which afforded easily interpretable spectra, whereas the corresponding
(16R)- and (16S)-3-oxo-ent-kauran-17-als (32a/32b) showed only poorly resolved
ones14).
Concerning the relevance of 13C-NMR data, Wenkert and co-workers stated in an
early paper that only the chemical shifts of C(14), C(16), and C(20) are of relevant
diagnostic value for the differentiation between phyllocladanes and kauranes [15].
However, as only phylloclad-15-ene and phylloclad-16-ene (38) could be directly
compared with ent-kaur-16-ene (39) at that time, the significance might be moderate.
The availability of recent data now clearly supports this statement (Fig. 2). In addition,
also C(13) is shielded in the phyllocladane series (Dd ca. À 2 ppm); but this shielding
intereferes in the 16,17-dioxy compounds where the influence of the O-substituents is

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3.65/3.79
65.4
39.6
48.4
43.9
48.0
OH
82.5
OH
14.8
14.7
84.4
OH
OH
69.9
44.5
3.40/3.50
44.5
O
O
2
21
3.67/3.79
66.3 OH
40.9
37.8
45.3
52.8
OH
79.7
17.6
17.8
81.7
36.9
OH
69.8 OH
3.41/3.49
52.2
O
O
27
30
3.65/3.80
66.2 OH
40.8
38.3
45.5
OH
79.7
17.7
17.6
81.6
37.2
OH
OH
69.8
3.37/3.51
52.8
53.4
36
37
42.7
50.4
44.2
15.1
17.6
39.9
41.5
49.2
38 a)
39 a)
Fig. 2. Diagnostic relevant NMR chemical shifts (CDCl3) of selected phyllocladanes and ent-kauranes. 1H-NMR
a)
at 400 MHz, 13C-NMR at 100.6 MHz. Values taken from [15].
predominant, and it is only reliable when closely related pairs (e.g., 2/27 and 38/39) are
compared15). However, the most-significant value is C(20): Due to the absence of the
extra d-effect from C(12), the angular Me(20) group is shielded in the phyllocladanes
and resonates at exceptionally high field (d ca. 15)16).
15
)
)
C(13) is an additional probe for the configuration at C(16) in the 16,17-dioxy-substituted compounds as it
is shielded in the (16S) series (Dd ca. À 4 ppm).
16
It was the crucial argument that enabled the discovery of the new phyllocladanes 1a f. Before discarding
the not antioxidant fraction of P. ambiguus [2], its 13C-NMR indicated a particular Me group at high field.

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Helvetica Chimica Acta Vol. 86 (2003)
In recent times, a similar attempt has been made to correlate spectral data and
configurational assignments of kauranoids [3c,d]. But the reports are a source of
confusion of terms, compound types, and inconsistent conclusions17).
3. Remark. Our recent investigations significantly increased the number of new
phyllocladanes. Contrary to the situation in the kauranes, where the ent-series is
predominant (ca. 95%), all phyllocladanes hitherto known belong to the −normal×
series, as no single enantiomer has been evidenced. −hoffmanniaketone×, a tetracyclic
diterpenoid isolated from Hoffmannia strigillosa, together with its 17-(acetyloxy)
derivative, was originally assigned the structure of (16R)-16,17-dihydroxy-ent-phyllo-
cladan-3-one (ent-2) [16], and the absolute configuration was based on chiroptical data.
However, thorough spectral comparison with calliterpenone (2) clearly showed the
identity of the two compounds, including their congruent CD spectra18). As a
consequence, the constituent of Hoffmannia strigillosa is calliterpenone (2) and the
name −hoffmanniaketone× has to be withdrawn from the literature.
The authors are indebted to the Swiss National Science Foundation for the financial support and to the
analytical department of our institute for the MS and the AMX-600 and DRX-600 NMR spectra. Thanks are due
to Prof. Dr. T. Komori, Osaka, Japan, for the generous gift of valuable reference samples.
Experimental Part
1. General. TLC: Merck-60F254 silica gel plates; detection by UV254 light or by spraying with −mostain×
solution ((NH4)6Mo7O24 ¥ 4 H2O (40 g), Ce(SO4)2 (0.8 g), 10% H2SO4 soln. (800 ml)) and heating (blue spots).
Column chromatography (CC): Merck silica gel 60 (40 63 mm). M.p.: Mettler FP 5/52; not corrected. [a]D:
Perkin-Elmer-241-MC polarimeter with thermostat B. Braun Thermomix 1441; 10-cm cell. UV: Perkin-Elmer-
Lambda-9-UV/VIS/NIR spectrophotometer; lmax (log e) in nm. CD: JASCO-J-500A spectropolarimeter; l
(De) in nm. IR: Perkin-Elmer-1600-FT-IR spectrometer; in cmÀ1. 1H- and 13C-NMR: Bruker-AC-300 or -ARX-
300 (300 and 75.4 MHz, resp.), -AMX-400 (400 and 100.6 MHz, resp.), -DRX-500 (500 and 125.7 MHz, resp.), -
AMX-600 or -DRX-600 (600 and 150.9 MHz, resp.) spectrometers; chemical shifts d in ppm rel. to the assigned
solvent (Me4Si ˆ 0 ppm), coupling constants J in Hz; all assignments are based on extensive interpretations of
1H,1H-COSY, DEPT90, DEPT135, 13C,1H-COSY (HSQC), and 13C,1H-long-range (HMBC) experiments; spin-
systems are interpreted according to 1st-order approximation, although in several complex cases significant AB
character shows higher-order spectra; HbÀC(15) specifies the H-atom pointing to C(20). GC/MS: Hewlett-
Packard HP-5980 series II (GC), HP-5971 MSD (mass-selective detector, EI; 70 eV), column HP-5, 25 mÂ
0.2 mm, 0.33 m; injector at 1808, detector at 3308; temp. program: 1508 (2 min), 1008 ! 2408 (rate 308/min), 2908
(5min). MS: Varian MAT 112s and Varian MAT 90 for electron impact (EI; 70 eV); Varian MAT 7011 and
Finnigan MAT SSQ 700 for chemical ionization (CI) with NH3, unless otherwise stated; Finnigan MAT TSQ
7000 for electrospray ionization (ESI).
2. Extraction of P. ambiguus: Phyllocladanes 1a g. Air-dried leaves and stems of P. ambiguus (500 g) were
extracted with hexane (3 l) at r.t. (20 h) and then re-extracted (4Â) with Et2O (each 2.5l, 16 h). The hexane
extract was evaporated to give a green semi-solid (6 g, 1.71%). CC (hexane/AcOEt 1:1) yielded 1b (330 mg), 1c
(170 mg), and the inseparable ca. 6 :1 mixture 1d/1e (390 mg). Analogous treatment of the Et2O extract
afforded a green gum (18 g, 3.6%) which was purified by CC (hexane/AcOEt 1:1) to yield Fractions A
(containing 1a d) and B (containing further 1b and 1c). After further CC and crystallization according to [2],
17
)
)
Unfortunately, the correct structure of 16-epiabbeokutone (30; (16S)) [12a] was erroneously revised due to
the misapplication of the authors× own arguments [3c].
The CD spectrum of calliterpenone (2) shows a positive Cotton effect at 289 nm. This can be rationalized
by the established anti-octant effect for the 8b-methyl group in 3-oxo triterpenes [17], see also [4c].
18

Helvetica Chimica Acta Vol. 86 (2003)
431
the following amounts of pure known compounds were isolated: 1a (520 mg, 0.1%), 1b (2.77 g, 0.55%), 1c
(1.45g, 0.29%), 1d/1e ca. 6 :1 (390 mg, 0.08%), and 1f (1.35g, 0.27%) 19).
(2S,3R,16R)-Phyllocladane-2,3,16,17-tetrol 2,3-Diacetate (1g). The mother liquor of 1f contained an
additional, unseparable genuine compound that was supposed to be a phyllocladane-2,3,16,17-tetrol diacetate
according to 1H-NMR. Preparation of the 16,17-acetonide (acetone, anh. CuSO4, see Exper. 7) from the mother
liquor of 1f allowed the CC separation (toluene/AcOEt 12 :1) of the new compound as an acetonide: 1H-NMR
(300 MHz, CDCl3): 5.21 (ddd, 3J(2,1ax) ˆ 12.5, 3J(2,1eq) ˆ 4.5, 3J(2,3) ˆ 2.8, HÀC(2)); 4.96 (d, 3J(2,3) ˆ 2.8,
HÀC(3)); 4.07, 3.90 (AB, 2J ˆ 8.6, CH2(17)); 2.25( dd, 2J ˆ 14.5, 4J(15b,14ax) ˆ 2.0, HbÀC(15)); 2.12, 1.97 (each
s, 2 COMe); 1.38, 1.35(each s, Me2C(O)2); 0.99, 0.98, 0.86 (each s, Me(18), Me(19), Me(20)).
The soln. of the acetonide (20 mg) in THF (0.5ml) and 2% H 2SO4 soln. (0.5ml) was stirred at r.t. (20 h).
Workup and CC (hexane/AcOEt 10 :1) of the residue gave 1g (10 mg, 41%). Colorless viscous oil. [a]2D0 ˆ À2.6
(c ˆ 0.43, CHCl3). IR (CHCl3): 3568, 2942, 2875, 1734, 1457, 1375, 1261, 1156, 1034, 865, 806. 1H-NMR
(500 MHz, CDCl3): 5.21 (ddd, 3J(2,1ax) ˆ 12.5, 3J(2,1eq) ˆ 4.5, 3J(2,3) ˆ 2.8, HÀC(2)); 4.96 (d, 3J(3,2) ˆ 2.8,
HÀC(3)); 3.77, 3.62 (AB, 2J ˆ 8.9, CH2(17)); 2.12, 1.97 (each s, 2 COMe); 1.00 (s, Me(20)); 0.98 (s, Me(18)); 0.87
(s, Me(19)). 13C-NMR (125.7 MHZ, CDCl3): 170.8, 170.7 (COMe); 84.7 (C(16)); 68.2 (C(2)); 65.8 (C(17)); 56.5
(C(9)); 50.5 (C(5)); 48.6 (C(14)); 45.2 (C(15)); 44.1 (C(13)); 43.8 (C(8)); 41.2 (C(7)); 39.2 (C(10)); 38.3 (C(4));
38.1 (C(1)); 28.2 (C18)); 26.8 (C(12)); 21.9 (C(19)); 21.3, 21.2 (COMe); 19.6 (2C, C(6), C(11)); 15.9 (C(20)).
‡
ESI-MS (MeOH/CH2Cl2/NaI): 445(100, [ M ‡ Na] ).
An identical compound 1g was also obtained from 1b via 5 (see below) after acetylation and hydrolysis. The
real content of 1g in P. ambiguus could not be determined; it is estimated to be ca. 60 mg (0.01%).
3. (2R,3S,16R)-16,17-(Isopropylidenedioxy)phyllocladane-2,3-diol 3-Acetate 2-(3-Methylbut-2-enoate) (4).
Preparation from 1b and physical data, see [2].
4. (2R,3S,16R)-16,17-(Isopropylidenedioxy)phyllocladane-2,3-diol (5). LiAlH4 (100 mg) was added to a
soln. of 4 (61 mg) in abs. THF (8 ml) and stirred at r.t. (20 min). Then, EtOH and H2O were added and some dil.
H2SO4 soln. to dissolve the precipitate. The soln. was extracted with Et2O, the org. phase washed with H2O, dried
(MgSO4), and evaporated, and the residue purified by CC (CH2Cl2/MeOH 24 :1) to yield a white solid that was
crystallized from Et2O/CH2Cl2: 5 (43 mg, 94%). White flakes. M.p. 188 1908. IR (KBr): 3200 3600 (br.), 2980,
2938, 2860, 1556, 1540, 1454, 1382, 1370, 1250, 1214, 1148, 1065, 1035, 992, 945, 926, 890, 860, 842, 806, 715, 670,
618. 1H-NMR (300 MHz, CDCl3): 4.07, 3.90 (AB, 2J ˆ 8.6, CH2(17)); 3.98 (ddd, 3J(2ax,1ax) ˆ 12.4, 3J(2ax,1eq) ˆ
2
4
4.5, 3J(2ax,3eq) ˆ 2.7, HaxÀC(2)); 3.42 (d, 3J(3eq,2ax) ˆ 2.7, HeqÀC(3)); 2.24 (dd, J ˆ 12.4, J(15b,14a) ˆ 2.0,
HbÀC(15)); 1.38, 1.34 (each s, Me2C(O)2); 1.01 (s, Me(20)); 0.91 (s, Me(18)); 0.85( s, Me(19)). CI-MS (2-
‡
‡
‡
methylpropane): 379 (37, [M ‡ H] ), 362 (23), 361 (85, [M ‡ H À H2O] ), 343 (16, [361 À H2O] ), 304 (17),
‡
‡
303 (100, [361 À acetone] ), 286 (16), 285(70, [343 À acetone] ), 273 (15).
5. (2R,3S,16R)-16,17-(Isopropylidenedioxy)phyllocladane-2,3-diol 2-(4-Methylbenzenesulfonate) (6). TsCl
(95mg) was added to a soln. of 5 (70 mg) in abs. pyridine (4 ml). The mixture was stirred at r.t. (24 h), then H2O
was added. The mixture was extracted with Et2O, the org. phase washed with H2O, dried (MgSO4), and
evaporated, and the residue separated by CC (hexane/AcOEt 1:1): 6 (93 mg, 94%). White solid. M.p. 81 848.
IR (KBr): 3300 3600 (br.), 2985, 2935, 2870, 1600, 1560, 1545, 1455, 1370, 1245, 1215, 1190, 1180, 1125, 1100,
1060, 1000, 930, 920, 900, 840, 815, 745, 665. 1H-NMR (300 MHz, CDCl3): 7.81, 7.37 (AA'BB', J ˆ 8.2, arom. H);
4.86 (ddd, 3J(2ax,1ax) ˆ 9.4, 3J(2ax,1eq) ˆ 7.2, 3J(2ax,3eq) ˆ 2.5, HaxÀC(2)); 3.46 (d, 3J(3eq,2ax) ˆ 2.5,
HeqÀC(3)); 4.05, 3.88 (AB, 2J ˆ 8.6, CH2(17)); 2.47 (s, MeC6H4); 1.38, 1.34 (each s, Me2C(O)2); 0.97 (s,
.
‡
‡
Me(20)); 0.85( s, Me(18)); 0.80 (s, Me(19)). EI-MS: 532 (0.6, M ), 517 (6, [M À Me] ), 436 (7), 346 (9), 345
‡
(33, [517 À TsOH] ), 331 (7), 289 (27), 285(62), 267 (11), 159 (13), 147 (22), 145(16), 137 (12), 135(15), 133
(22), 131 (11), 123 (16), 121 (20), 119 (20), 117 (11), 114 (13), 109 (27), 107 (32), 105(25), 43 (100).
6. (16R)-16,17,19-Trihydroxyphyllocladan-3-one (8). A soln. of the natural product 3 (100 mg) in EtOH
(5ml) and 5% H 2SO4 soln. (5ml) was stirred at r.t. (15h). As TLC still showed starting material, the mixture
was refluxed at ca. 708 (4 h). H2O was added, the mixture extracted with Et2O, the org. phase washed with H2O,
dried (MgSO4), and evaporated, and the white solid separated by CC (CH2Cl2/MeOH 24 :1 ! 9 :1): 8 (26 mg,
33%). Colorless prisms (from CH2Cl2/MeOH). M.p. 162 1648. [a]2D0 ˆ À4.4 (c ˆ 0.3, MeOH). IR (KBr):
3200 3500 (br.), 2930, 2850, 1705, 1455, 1435, 1385, 1315, 1260, 1190, 1130, 1095, 1070, 1045, 980, 916, 875, 750,
715, 690, 640. 1H-NMR (300 MHz, CD3OD): 4.00, 3.46 (AB, 2J ˆ 11.3, CH2(19)); 3.70, 3.58 (AB, 2J ˆ 8.5,
CH2(17)); 2.71 (ddd, 2J ˆ 15.1, 3J(2ax,1ax) ˆ 13.4, 3J(2ax,1eq) ˆ 6.4, HaxÀC(2)); 2.25( ddd, 2J ˆ 15.1,
3J(2eq,1ax) ˆ 5.2, 3J(2eq,1eq) ˆ 3.0, HeqÀC(2)); 1.14 (s, Me(18)); 1.12 (s, Me(20)). CI-MS: 35
4 (42,
19
)
The yield of 1f could be improved as compared to the reported value (0.13%) [2].

432
Helvetica Chimica Acta Vol. 86 (2003)
.
‡
‡
‡
[M ‡ NH4] ), 337 (9), 336 (30, M ), 325(23), 324 (100), 323 (14, [ M ‡ NH4 À CH2OH] ), 322 (26, [M ‡
‡
‡
‡
NH4 À MeOH] ), 306 (23, [324 À H2O] ), 292 (19, [324 À MeOH] ).
7. (16R)-19-Hydroxy-16,17-(isopropylidenedioxy)phyllocladan-3-one (9). To a soln. of 9 (32 mg) in abs.
acetone (4 ml) anh. CuSO4 (50 mg) was added and the mixture refluxed under N2 (6 h). The CuSO4 was filtered
off, the filtrate evaporated, and the residue purified by CC (CH2Cl2/MeOH 100 :1 ! 9 :1): 9 (23 mg, 89%).
Colorless solid. M.p. 212 2148. 1H-NMR (300 MHz, CDCl3): 4.07, 3.91 (AB, 2J ˆ 8.6, CH2(17)); 3.92, 3.42 (AB,
2J ˆ 11.2, CH2(19)); 2.92 (br. s, OHÀC(19)); 2.57 (ddd, 2J ˆ 16.1, 3J(2ax,1ax) ˆ 9.1, 3J(2ax,1eq) ˆ 4.8,
HaxÀC(2)); 2.40 (ddd, 2J ˆ 16.1, 3J(2eq,1ax) ˆ 3J(2eq,1eq) ˆ 8, HeqÀC(2)); 2.18 (dd, 2J ˆ 14.5, 4J(15b,14a) ˆ
2.0, HbÀC(15)); 2.01 (m, HÀC(13)); 1.39, 1.35(each s, Me2C(O)2); 1.26 (s, Me(18)); 0.91 (s, Me(20)). CI-MS (2-
‡
‡
methylpropane): 377 (100, [M ‡ H] ), 361 (8), 320 (17), 319 (80, [M ‡ H À acetone] ), 306 (9), 271 (5).
8. (16R)-16,17-(Isopropylidenedioxy)-19-{[(4-methylphenyl)sulfonyl]oxy}phyllocladan-3-one (10). A soln.
of TsCl (40 mg) and 9 (15mg) in abs. pyridine (2 ml) was stirred at r.t. (15h). Then, H 2O was added, the mixture
extracted with Et2O, the org. phase washed with H2O, dried (MgSO4), and evaporated, and the residue
separated by CC (CH2Cl2): 10 (19 mg, 86%). White solid. M.p. 60 648. 1H-NMR (300 MHz, CDCl3): 7.75, 7.35
(AA'BB', J ˆ 8.2, arom. H), 4.31, 3.98 (AB, 2J ˆ 10, CH2(19)); 4.07, 3.90 (AB, 2J ˆ 8.6, CH2(17)); 2.46 (s,
2
MeC6H4); 2.37 (m, CH2(2)); 2.19 (dd, J ˆ 14.5, 4J(15b,14a) < 1, HbÀC(15)); 2.00 (m, HÀC(13)); 1.41, 1.36
.
‡
‡
(each s, Me2C(O)2); 1.08 (s, Me(18)); 0.94 (s, Me(20)). EI-MS: 530 (2, M ), 515 (7, [M À Me] ), 283 (22), 137
(11), 121 (15), 91 (10).
9. (3S,16R)-16,17-(Isopropylidenedioxy)phyllocladan-3-ol (7). To a soln. of 6 (70 mg) in abs. THF (5ml)
was added LiAlH4 (60 mg). The mixture was stirred at r.t. under N2 (1 h). Workup as described in Exper. 4 and
CC (CH2Cl2) yielded 7 (43 mg, 90%). White solid.
An identical compound 7 (11 mg, 84%) was isolated after analogous treatment of 10 (18 mg) with LiAlH4
(20 mg). M.p. 151 1538. IR (KBr): 3500, 2985, 2940, 2860, 1558, 1540, 1455, 1382, 1368, 1250, 1212, 1150, 1105,
2
1056, 1032, 1012, 982, 916, 890, 858, 842, 805, 735, 715. 1H-NMR (400 MHz, CDCl3): 4.06, 3.90 (AB, J ˆ 8.6,
CH2(17)); 3.20 (dd, 3J(3,2ax) ˆ 10.9, 3J(3,2eq) ˆ 4.4, HÀC(3)); 2.25( dd, 2J ˆ 14.6, 4J(15b,14a) ˆ 2.2,
HbÀC(15)); 1.99 (m, HÀC(13)); 1.39, 1.34 (each s, Me2C(O)2); 0.98 (s, Me(18)); 0.87 (s, Me(20)); 0.77 (s,
Me(19)). 1H-NMR (400 MHz, C5D5N): 4.16, 4.00 (AB, 2J ˆ 8.6, CH2(17)); 3.45( m, w1/2 ˆ 25, HÀC(3)); 2.28 (dd,
4
2
2J ˆ 14.4, J(15b,14a) ˆ 2.0, HbÀC(15)); 2.07 (m, HÀC(13)); 1.71 (d, J ˆ 14.4, HaÀC(13)); 1.51, 1.44 (each s,
.
‡
Me2C(O)2); 1.22 (s, Me(18)); 1.04 (s, Me(19)); 0.88 (s, Me(20)). EI-MS: 362 (4, M ), 348 (15), 347 (84, [M À
‡
‡
‡
‡
Me] ), 329 (7, [347 À H2O] ), 287 (10, [M À OH À acetone] ), 269 (100, [287 À H2O] ), 161 (17), 147 (18), 135
(22), 121 (19), 109 (19), 107 (19), 105(17).
10. (16R)-16,17-Dihydroxyphyllocladan-3-one (ˆCalliterpenone; 2). A soln. of 7 (31 mg) in abs. CH2Cl2
(0.5ml) was added in one portion to a well-stirred suspension of PCC (39 mg) and a trace of NaOAc in abs.
CH2Cl2 (0.5ml). The mixture was stirred at r.t. under dry N 2 (2.5h). Then, abs. Et 2O was added and the
supernatant liquid decanted from a black tar. The insoluble residue was washed with abs. Et2O (3Â), the
combined org. soln. passed through silica gel (Et2O), the solvent evaporated, and the white solid residue
subsequently dissolved in MeOH (3 ml) and 2% H2SO4 soln. (1 ml). The mixture was heated at ca. 708 (3 h).
After cooling to r.t., H2O was added, the mixture extracted with Et2O, the org. layer washed with H2O, dried
(MgSO4), and evaporated, and the white residue purified by CC (CH2Cl2 ! CH2Cl2/MeOH 100 :l): 2 (25mg,
91%). White needles (from MeOH).
An analogous treatment of 7 (13 mg) that was derived from 3 yielded 2 (9 mg, 83%). M.p. 156 1588.
[a]D20 ˆ ‡33.5( c ˆ 0.24, CHCl3). CD (MeOH, c ˆ 8.75¥ 10 À4 m): 235(0), 289 ( ‡0.62), 315(0), 321 ( À0.06), 340
(0). IR (KBr): 3450 3400 (br.), 3330, 2970, 2930, 2860, 1705, 1558, 1540, 1480, 1454, 1438, 1415, 1385,1350,
1315, 1248, 1208, 1192, 1162, 1138, 1130, 1118, 1095, 1072, 1054, 1035, 1020, 1005, 985, 962, 940, 918, 872, 836, 700,
1
2
2
3
672, 655. H-NMR (400 MHz, CDCl3): 3.79, 3.65( AB, J ˆ 10.9, CH2(17)); 2.52 (ddd, J ˆ 15.8, J(2ax,1ax) ˆ
10.8, 3J(2ax,1eq) ˆ 7.2, HaxÀC(2)); 2.38 (ddd, 2J ˆ 15.8, 3J(2eq,1ax) ˆ 7.1, 3J(2eq,1eq) ˆ 4.1, HeqÀC(2)); 2.12
2.04 (m, HbÀC(15), HeqÀC(14)); 1.94 1.83 (m, HeqÀC(1), HeqÀC(7), HeqÀC(12), HÀC(13)); 1.08 (s,
Me(18)); 1.03 (s, Me(20)); 1.00 (s, Me(19)). 13C-NMR (100.6 MHz, CDCl3): 217.8 (C(3)); 84.4 (C(16)); 65.4
(C(17)); 55.7, 55.2 (C(5), C(9)); 48.0 (C(14)); 47.3 (C(4)); 44.5 (C(15)); 43.9 (C(13)); 43.4 (C(8)); 40.6(C(7));
38.l (C(1)); 37.l (C(10)); 33.9 (C(2)); 26.7 (C(18)); 26.6 (C(12)); 21.5(C(19)); 21.2, 19.6 (C(6), C(11)); 14.7
‡
‡
(C(20)). CI-MS (2-methylpropane): 321 (74, [M ‡ H] ), 304 (17), 303 (100, [M ‡ H À H2O] ), 285(19, [303 À
‡
H2O] ).
Comparison of the dihydroxy ketones 2 derived from both 1b and 3 with an authentic sample of the natural
product calliterpenone (2) proved the compounds to be identical (TLC, m.p., mixed m.p., [a]D, CD, IR, 1H- and
13C-NMR, CI-MS).

Helvetica Chimica Acta Vol. 86 (2003)
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11. (16R)-16,17-Dihydroxy-19-norphyllocladan-3-one (11a). A soln. of 3 (22 mg) in EtOH (2.5ml) and 2 n
KOH (1 ml) was heated at 708 (3 h). Then, H2O was added, the mixture extracted with Et2O, the Et2O phase
washed with H2O, dried (MgSO4), and evaporated, and the residue purified by CC (CH2Cl2/MeOH 93 :7): 11a
(11 mg, 65%). White solid. M.p. 180 1838. [a]2D0 ˆ ‡16.7 (c ˆ 0.15, CHCl3). IR (KBr): 3200 3600 (br.), 2935,
2860, 1705, 1557, 1540, 1453, 1385, 1300, 1245, 1184, 1132, 1070, 1040, 1016, 980, 912, 870, 732, 675, 645. 1H-NMR
(400 MHz, CDC13): 3.79, 3.66 (AB, 2J ˆ 10.9, CH2(17)); 2.60 (dd, 3J(2ax,lax) ˆ 12.6, 3J(2ax,leq) ˆ 6.4,
HaxÀC(2)); 2.31 (dq, 3J(4,18) ˆ 6.4, 3J(4ax,5ax) ˆ 12.6, irradiation at d 0.92 (Me(18)) ! d, 3J(4ax,5ax) ˆ 12.1,
HaxÀC(4)); 1.14 (s, Me(20)); 0.92 (d, 3J (18,4) ˆ 6.4, irradiation at d 2.31 (HÀC(4)) ! s, Meeq(18)). 13C-NMR
(100.6 MHz, CDC13): 215.l (C(3)); 84.4 (C(16)); 65.6 (C(17)); 55.3 (C(9)); 54.4 (C(5)); 48.7(C(1)); 48.2
(C(14)); 44.9 (C(15)); 44.7 (C(4)); 44.0 (C(13)); 43.2(C(8)); 40.l (C(7)); 37.5(C(10)); 31.2 (C(18)); 26.7 (C(12));
‡
23.6 (C(6)); 20.2 (C(11)); 13.7 (C(2)); 11.5(C(20)). CI-MS (2-methylpropane): 307 (100, [ M ‡ H] ), 289 (48,
‡
[M ‡ H À H2O] ).
12. (16R)-19-Norphyllocladan-16,17-diol (11b). A mixture of 3 (10 mg), N2H4 ¥ H2O (212 mg), N2H4 ¥
2 HCl (50 mg), and ethylene glycol (1 g) was heated at 1608 (2.5h). Then, KOH (80 mg) was added, and the
temp. was raised gradually to 2108 to distill off the volatile substances. Then, the temp. was kept at 210 2158
(2.5h). After cooling, H 2O and dil. H2SO4 soln. were added. The mixture was extracted with Et2O, the Et2O
layer washed with H2O, dried (MgSO4), and evaporated, and the residue purified by CC (CH2Cl2): 11b (5mg,
72%). White flakes. M.p. 91 938. [a]2D0 ˆ ‡12.9 (c ˆ 0.26, CHCl3). IR (KBr): 3400, 3300, 2930, 2860, 2845, 1452,
1448, 1378, 1350, 1318, 1248, 1132, 1084, 1062, 1052, 1040, 1025, 1000, 968, 920, 874, 695, 685, 664. 1H-NMR
2
3
(300 MHz, CDC13): 3.78, 3.63 (AB, J ˆ 10.9, CH2(17)); 0.81 (s, Me(20)); 0.81 (d, J(4,18) ˆ 6.4, Me(18)). CI-
.
‡
‡
‡
MS: 310 (73, [M ‡ NH4] ), 293 (15), 292 (79, M ), 278 (9, [M ‡ NH4 À MeOH] ), 276 (10), 275(59, [ M ‡
‡
‡
‡
H À H2O] ), 274 (61, [M À H2O] ), 258 (20), 257 (100, [275 À H2O] ).
13. (3S,16R)-16,17-(Isopropylidenedioxy)[3-2H]phyllocladan-3-ol (12). LiAlD4 (20 mg) was added to a
soln. of 6 (24 mg) in abs. THF (3 ml) and the mixture stirred at r.t. under N2 (1.5h). Workup and CC as
described in Exper. 9 yielded 12 (15mg, 92%). White solid. M.p. 146 148 8. IR (KBr): 3510, 2980, 2938, 2864,
2140, 1556, 1540, 1455, 1434, 1380, 1368, 1246, 1210, 1148, 1105, 1058, 980, 955, 920, 895, 860, 840, 805, 715.
1H-NMR (300 MHz, CDCl3): 4.07, 3.9l (AB, 2J ˆ 8.6, CH2(17)); 2.25( dd, 2J ˆ 14.6, 4J(15b,14a) ˆ 2.2,
HbÀC(15)); 1.99 (m, HÀC(13)); 1.39, 1.35(each s, Me2C(O)2); 0.98 (s, Me(20)); 0.87 (s, Me(18)); 0.77 (s,
‡
‡
Me(19)). CI-MS (2-methylpropane): 364 (15, [M ‡ H] ), 346 (6, [M ‡ H À H2O] ), 323 (20), 306 (15, [M ‡
‡
‡
‡
H À acetone] ), 289 (16), 288 (100, [306 À H2O] ), 271 (11), 270 (72, [288 À H2O] ).
14. (2R,3S,16R)-16,17-(Isopropylidenedioxy)phyllocladane-2,3-diol 2,3-Bis(methanesulfonate) (13). Meth-
anesulfonyl chloride (160 ml) was added to a soln. of 5 (40 mg) in abs. pyridine (2 ml) and the mixture kept at r.t.
(40 h). Workup and CC as described in Exper. 5 yielded 13 (50 mg, 88%). White crystals. M.p. 103 1058.
1H-NMR (300 MHz, CDCl3): 5.05 (ddd, 3J(2,1ax) ˆ 12.4, 3J(2,1eq) ˆ 4.5, 3J(2,3) ˆ 2.6, HÀC(2)); 4.73 (d,
3J(3,2) ˆ 2.6, HÀC(3)); 4.07, 3.91 (AB, 2J ˆ 8.6, CH2(17)); 3.15, 3.08 (each s, 2 MeSO3); 1.39, 1.35(each s,
.
‡
‡
Me2C(O)2); 1.10 (s, Me(20)); 1.02 (s, Me(18), Me(19)). EI-MS: 534 (1.5, M ), 520 (6), 519 (22, [M À Me] ),
‡
327 (11, [519 À 2 MeSO3] ), 285(12), 267 (100), 185(10), 171 (14), 159 (14), 157 (10), 147 (15), 145(29), 135
(25), 133 (44), 131 (13), 121 (16), 119 (57), 114 (17), 109 (27), 107 (21), 105 (25).
15. (2R,16R)-16,17-(Isopropylidenedioxy)phyllocladan-2-ol (14). Treatment of 13 (50 mg) with LiAlH4
(100 mg) in abs. THF (5ml) as described in Exper. 9, workup, and CC (CH2Cl2 ! CH2Cl2/MeOH 100 :0.5)
afforded 5 (3.5mg, 10%), 7 (3.4 mg, 10%), and 14 (22 mg, 65%). 14: White crystals. M.p. 185 187 8. 1H-NMR
(300 MHz, CDCl3): 4.08 (m and A of AB, 2J ˆ 8.6, HÀC(2), HAÀC(17)); 3.92 (B of AB, 2J ˆ 8.6, HBÀC(17));
2.25( dd, 2J ˆ 14.5, 4J(15b,14a) ˆ 2.2, HbÀC(15)); 2.00 (m, HÀC(13)); 1.39, 1.35(each s, Me2C(O)2); 1.12 (s,
Me(20)); 0.99 (s, Me(18)); 0.92 (s, Me(19)). 1H-NMR (300 MHz, C5D5N): 4.33 (m, wl/2 ꢀ 12, HÀC(2)); 4.13, 3.98
(AB, 2J ˆ 8.6, CH2(17)); 2.30 (dd, 2J ˆ 14.4, 4J(15b,14a) ˆ 2.0, HbÀC(15)); 2.05 (m, HÀC(13)); 1.49, 1.42 (each s,
.
‡
Me2C(O)2); 1.29 (s, Me(20)); 1.17 (s, Me(19)); 0.93 (s, Me(18)). EI-MS: 362 (2, M ), 348 (10), 347 (53, [M À
‡
‡
Me] ), 329 (4, [347 À H2O] ), 305(3), 287 (11), 270 (12), 269 (65), 231 (4), 199 (3), 189 (9), 187 (8), 175(9),
173 (11), 161 (17), 159 (12), 149 14), 147 (27), 145 (16), 135 (29), 133 (21), 123 (17), 119 (22), 117 (11), 114 (19),
109 (28), 107 (28), 105(28), 104 (17), 43 (100).
16. Epimerization of Calliterpenone (2). (16R)-16-Hydroxy-17-{[(4-methylphenyl)sulfonyl]oxy}phyllocla-
dan-3-one (19). As described in Exper. 5, reaction of 2 (23 mg) with TsCl (70 mg) afforded 19 (31 mg, 91%).
White solid. M.p. 55 608. IR (KBr): 3480, 2930, 2870, 1695, 1600, 1455, 1388, 1360, 1302, 1190, 1178, 1100, 1050,
1020, 960, 930, 845, 820, 750, 665. 1H-NMR (300 MHz, CDCl3): 7.82, 7.37 (AA'BB', J ˆ 8.2, arom. H); 4.20, 4.07
(AB, 2J ˆ 9.7, CH2(17)); 2.47(s, MeC6H4); 2.37 (ddd, 2J ˆ 15.8, 3J(2ax,1ax) ˆ 7.1, 3J(2ax,1eq) ˆ 4.1, HaxÀC(2));
2
3
3
2.11 (ddd, J ˆ 15.8, J(2eq,1ax) ˆ 4.7, J(2eq,1eq) ˆ 2.3, HeqÀC(2)); 1.07 (s, Me(18)); 1.02 (s, Me(20)); 0.93 (s,

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‡
‡
Me(19)). CI-MS: 492 (100, [M ‡ NH4] ), 321 (15), 320 (75, [ M ‡ H À TsOH] ), 304 (8), 303 (36), 302 (15,
‡
‡
[320 À H2O] ), 285(18, [303 À H2O] ).
(16R)-16,17-Epoxyphyllocladan-3-one ( ˆ Epoxycalliterpenone; 20). A mixture of 19 (31 mg) in abs.
MeOH (4 ml) and anh. K2CO3 (13 mg) was stirred at r.t. (1 h). H2O was added, the mixture extracted with Et2O,
the org. phase washed with H2O, dried (MgSO4), and evaporated, and the white residue purified by CC (hexane/
CH2Cl2 1:3 ! 1:6): 20 (8 mg, 91%). White solid. M.p. 161 1638. [a]2D0 ˆ ‡8.3 (c ˆ 0.58, CHCl3). IR (KBr):
2940, 2920, 2850, 1702, 1455, 1385, 1365, 1265, 1205, 1145, 1110, 1078, 1020, 1000, 974, 945, 935, 900, 848, 805, 780,
725. 1H-NMR (300 MHz, CDCl3): 2.88, 2.81 (AB, 2J ˆ 4.7, CH2(17)); 2.53 (ddd, 2J ˆ 15.8, 3J(2ax,1ax) ˆ 10.4,
3J(2ax,1eq) ˆ 7.3, HaxÀC(2)); 2.41 (ddd, 2J ˆ 15.8, 3J(2eq,1ax) ˆ 7.3, 3J(2eq,1eq) ˆ 4.3, HeqÀC(2)); 2.31 (dd, 2J ˆ
4
14.5, J(15b,14a) ˆ 2.4, HbÀC(15)); 1.10 (s, Me(18)); 1.04 (s, Me(20)); 1.02 (s, Me(19)). CI-MS: 320 (47, [M ‡
.
‡
‡
‡
‡
NH4] ), 303 (92, [M ‡ H] ), 302 (16, M ), 286 (21), 285(100, [ M ‡ H À H2O] ), 109 (10).
Hydrolysis of 20: Products 2, 21, 22, and 23. The mixture of 20 (100 mg) and 5% H2SO4 soln. (4 ml) in THF
(20 ml) was stirred at r.t. (15h). After workup according to Exper. 24, the residue was separated by CC (CH2Cl2/
MeOH 99 :1): 22 (30 mg, 30%). Further elution with CH2Cl2/MeOH 95:5afforded calliterpenone ( 2; 45mg,
42%) and its (16S)-epimer 21 (5mg, 5%).
In a similar procedure, the mixture of 20 (42 mg) and 60% HClO4 soln. (0.5ml) in THF (2 ml) was stirred
at r.t. (32 h). After workup, the residue was separated by CC (CH2Cl2/MeOH 99 :1): 23 (25mg, 60%), 22
(1.7 mg, 4%), and traces of 2 and 21.
(16S)-16,17-Dihydroxyphyllocladan-3-one ( ˆ 16-Epicalliterpenone; 21): White needles (from CH2Cl2/
MeOH). M.p. 210 2128. CD (MeOH, c ˆ 8.16 ¥ 10À4 m): 235(0), 289 ( ‡0.58), 315 (0), 320 (À0.05), 337 (0). IR
(KBr): 3450 3400 (br.), 3330, 2985, 2932, 2860, 1704, 1560, 1542, 1478, 1454, 1440, 1415, 1385, 1348, 1315, 1248,
1210, 1190, 1165, 1138, 1130, 1120, 1095, 1072, 1054, 1035, 1020, 1005, 985, 962, 940, 918, 872, 836, 700, 672, 655.
1H-NMR (400 MHz, CDCl3): 3.50, 3.40 (AB, 2J ˆ 10.8, CH2(17)); 2.55 (ddd, 2J ˆ 15.8, 3J(2ax,1ax) ˆ 11.0,
3J(2ax,1eq) ˆ 7.3, HaxÀC(2)); 2.38 (ddd, 2J ˆ 15.8, 3J(2eq,1ax) ˆ 7.0, 3J(2eq,1eq) ˆ 4.0, HeqÀC(2)); 2.23 (s, OH);
1.08 (s, Me(18)); 1.05( s, Me(20)); 1.03 (s, Me(19)). 13C-NMR (100.6 MHz, CDCl3): 217.8 (C(3)); 82.5(C(16));
69.9 (C(17)); 56.2 (C(9)); 55.4 (C(5)); 48.4 (C(14)); 47.4 (C(4)); 44.5 (C(15)); 42.6 (C(8)); 41.0 (C(7)); 39.6
(C(13)); 38.3 (C(1)); 37.2 (C(10)); 34.1 (C(2)); 27.7 (C(12)); 26.7 (C(18)); 21.6 (C(19)); 21.2 (C(6)); 20.2
.
‡
‡
‡
(C(11)); 14.8 (C(20)). CI-MS: 338 (98, [M ‡ NH4] ), 321 (63, [M ‡ H] ), 320 (45, M ), 303 (100, [M ‡ H À
‡
‡
H2O] ), 285(51, [303 À H2O] ).
17-Hydroxyphylloclad-15-en-3-one (22): White crystals (from hexane/CH2Cl2). M.p. 165 166 8. [a]D20
ˆ
‡10.0 (c ˆ 0.52, CHCl3). IR (KBr): 3440, 2930, 2850, 1694, 1560, 1542, 1450, 1420, 1385, 1362, 1336, 1320, 1265,
1245, 1215, 1200, 1136, 1115, 1040, 1022, 995, 960, 915, 895, 875, 832, 735, 650. 1H-NMR (400 MHz, CDCl3): 5.68
(br. s, wl/2 ꢀ 4, HÀC(15)); 4.22 (d, 4J(17,15) ˆ 1.4, CH2(17)); 2.56 (ddd, 2J ˆ 15.6, 3J(2ax,1ax) ˆ 12.6,
3J(2ax,1eq) ˆ 6.6, HaxÀC(2)); 2.45( m, HÀC(13)); 2.31 (ddd, 2J ˆ 15.6, 3J(2eq,1ax) ˆ 5.8, 3J(2eq,1eq) ˆ 3.4,
HeqÀC(2)); 1.89 (ddd, 2J ˆ 13.3, 3J(1eq,2ax) ˆ 6.6, 3J(1eq,2eq) ˆ 3.4, HeqÀC(1)); 1.81 (ddd, 2J ˆ 9.8,
3J(14eq,13) ˆ 5.2, 4J(14eq,12eq) ˆ 2.0, HeqÀC(14)); 1.70 (dt, 2J ˆ 12.8, 3J(7eq,6ax) ˆ 3J(7eq,6eq) ˆ 3.1,
HeqÀC(7)); 1.21 (d, 2J ˆ 9.8, HaxÀC(14)); 1.12 (dd, 3J(9,11ax) ˆ 11.5, 3J(9,11eq) ˆ 4.5, HÀC(9)); 1.09 (s,
Me(18)); 1.06 (s, Me(19)); 0.93 (s, Me(20)). 13C-NMR (100.6 MHz, CDCl3): 217.4 (C(3)); 145.l (C(16)); 160.9
(C(15)); 61.2 (C(17)); 55.7 (C(5)); 54.5 (C(14)); 52.2 (C(9)); 47.6 (C(8)); 47.3 (C(4)); 39.5 (C(13)); 37.8 (C(7));
36.85(C(10)); 36.8 (C(1)); 34.3 (C(2)); 26.l (C(18)); 24.8 (C(12)); 21.8 (C(19)); 21.1 (C(11)); 19.4 (C(6)); 14.7
.
‡
‡
‡
(C(20)). CI-MS: 320 (63, [M ‡ NH4] ), 304 (22), 303 (100, [M ‡ H] ), 302 (41, M ), 301 (17), 287 (7), 286
(21), 285(100).
(16R)-3-Oxophyllocladan-17-al (23). White foam. IR (CHCl3): 2970, 2939, 2858, 1716, 1699, 1458, 1386,
1114. 1H-NMR (300 MHz, CDCl3): 9.65( d, 3J(17,16) ˆ 1.7, HÀC(17)); 2.61 (ddd, 3J (16,15b) ˆ 9.3, 3J(16,15a) ˆ
5.7, 3J(16,17) ˆ 1.7, HÀC(16)); 2.53 (ddd, 2J ˆ 15.8, 3J(2ax,1ax) ˆ 10.6, 3J(2ax,1eq) ˆ 7.3, HaxÀC(2)); 2.42 (m, q-
2
3
3
2
like, w1/2 ꢀ 10, HÀC(13)); 2.39 (ddd, J ˆ 15.8, J(2eq,1ax) ˆ 7.3, J(2eq,1eq) ˆ 4.2, HeqÀC(2)); 2.13 (ddd, J ˆ
13.6, 3J(15b,16) ˆ 9.3, 4J(15b,14ax) ˆ 2.3, HbÀC(15)); 1.93 (ddd, 2J ˆ 13.3, 3J(1eq,2ax) ˆ 7.3, 3J(1eq,2eq) ˆ 4.2,
HeqÀC(1)); 1.08 (s, Me(18)); 1.04 (s, Me(19), Me(20)). 13C-NMR (75.4 MHz, CDCl3): 217.5(C(3)); 203.0
(C(17)); 56.0 (C(16)); 55.8 (C(9)); 55.4 (C(5)); 47.9 (C(14)); 47.4 (C(4)); 44.5 (C(8)); 39.8 (C(7)); 38.4 (C(1));
37.2 (C(10)); 36.2 (C(13)); 34.0 (C(2)); 32.0 (2C, C(12), C(15)); 26.8 (C(18)); 21.5 (C(19)); 21.3 (C(11)); 20.0
‡
‡
(C(6)); 15.0 (C(20)). CI-MS: 320 (100, [M ‡ NH4] ), 303 (5, [M ‡ H] ).
(16R)-3-Oxophyllocladan-17-oic Acid (24). Aldehyde 23 (15mg) was left in CDCl 3 in an NMR tube for
several weeks at 48, until 1H-NMR showed the disappearance of the CHO signal. CC (CH2Cl2/MeOH 98 :2)
gave pure 24 (11.3 mg, 71%). Colorless viscous oil. IR (CHCl3): 3516, 3400 2500, 2974, 2939, 2858, 1701, 1459,
1386, 1280, 1130. 1H-NMR (300 MHz, CDCl3): 2.67 (dd, 3J(16,15b) ˆ 9.3, 3J(16,15a) ˆ 5.7, HÀC(16)); 2.53 (ddd,
2J ˆ 15.8, 3J(2ax,1ax) ˆ 10.6, 3J(2ax,1eq) ˆ 7.3, HaxÀC(2)); 2.42 (m, q-like, w1/2 ꢀ 10, HÀC(13)); 2.39 (ddd, 2J ˆ

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15.8, 3J(2eq,1ax) ˆ 7.3, 3J(2eq,1eq) ˆ 4.1, HeqÀC(2)); 2.32 (ddd, 2J ˆ 13.6, 3J(15b,16) ˆ 9.3, 4J(15b,14ax) ˆ 2.1,
HbÀC(15)); 1.92 (ddd, 2J ˆ 13.3, 3J(1eq,2ax) ˆ 7.3, 3J(1eq,2eq) ˆ 4.1, HeqÀC(1)); 1.08 (s, Me(18)); 1.03 (s,
Me(19), Me(20)). 13C-NMR (75.4 MHz, CDCl3): 217.7 (C(3)); 181.7 (C(17)); 55.7 (C(9)); 55.5 (C(5)); 48.4
(C(14)); 47.6 (C(16)); 47.4 (C(4)); 44.8 (C(8)); 39.8 (C(7)); 39.7 (C(13)); 38.4 (C(1)); 37.2 (C(10)); 36.6 (C(15));
34.1 (C(2)); 32.2 (C(12)); 26.8 (C(18)); 21.5(C(11)); 21.4 (C(19)); 19.7 (C(6)); 15.0 (C(20)). EI-MS: 290 (48,
‡
‡
[M À CO] ), 288 (100, [M À H2CO] ), 281 (31), 207 (54), 202 (59), 186 (91).
Chlorophyllocladanones 25 and 26a/26b. A soln. of TsCl (98 mg) and 2 (36 mg) in abs. pyridine (4 ml) was
refluxed (15h). Workup according to Exper. 5 and CC (CH2Cl2/MeOH 95:5) yielded 25 (33 mg, 87%) and an
(E/Z)-mixture 26a/26b 2 :1 (4 mg, 11%), both as colorless oils.
(16R)-17-Chloro-16-hydroxyphyllocladan-3-one ( ˆ 17-Chlorocalliterpenone; 25): IR (CHCl3): 3570, 2970,
2941, 2864, 1698, 1458, 1430, 1386, 1313, 1261, 1205, 1029. 1H-NMR (600 MHz, CDCl3): 3.86, 3.75( AB, 2J ˆ 11.0,
CH2(17)); 2.55 (ddd, 2J ˆ 15.8, 3J(2ax,1ax) ˆ 10.9, 3J(2ax,1eq) ˆ 7.4, Hax ÀC(2)); 2.39 (ddd, 2J ˆ 15.8,
3J(2eq,1ax) ˆ 6.8, 3J(2eq,1eq) ˆ 3.9, HeqÀC(2)); 2.19 (ddd, 2J ˆ 11.3, 3J(14eq,13) ˆ 4.6, 4J(14eq,12eq) ˆ 2.7,
HeqÀC(14)); 2.08 (dd, 2J ˆ 14.9, 4J(15b,14ax) ˆ 1.5, HbÀC(15)); 1.99 (m, q-like, w1/2 ꢀ 9, HÀC(13)); 1.89 (ddd,
2J ˆ 13.2, 3J(1eq,2ax) ˆ 7.4, 3J(1eq,2eq) ˆ 3.9, HeqÀC(1)); 1.10 (s, Me(18)); 1.05( s, Me(19)); 1.01 (s, Me(20)).
13C-NMR (150.9 MHz, CDCl3): 217.4 (C(3)); 83.2 (C(16)); 55.7 (C(9)); 55.3 (C(5)); 51.0 (C(17)); 47.8 (C(14));
47.7 (C(4)); 45.3 (C(15)); 44.9 (C(13)); 44.0 (C(8)); 40.5 (C(7)); 38.2 (C(1)); 37.1 (C(10)); 34.0 (C(2)); 26.8
‡
(C(18)); 26.5(C(12)); 21.6 (C(19)); 21.2 (C(11)); 19.8 (C(6)); 16.5(C(20)). CI-MS: 358 (29, [ M(37Cl) ‡ NH4] ),
.
‡
‡
‡
356 (100, [M(35Cl) ‡ NH4] ), 338 (5, M(35Cl) ), 320 (20, [M À H2O] ).
(16E)-and (16 Z)-17-Chlorophylloclad-16-en-3-ones (26a/26b): IR (CHCl3): 2977, 2938, 2858, 1698, 1493,
1445, 1385, 1250, 1112, 1073. 1H-NMR (300 MHz, CDCl3): (E)-isomer 26a20): 5.77 (m, q-like, w1/2 ꢀ 5,
2
4
HÀC(17)); 3.00 (m, q-like, w1/2 ꢀ 10, HÀC(13)); 2.76 (dd, J ˆ 15.2, J(15b,14ax) ˆ 1.4, HbÀC(15)); 2.52 (ddd,
2J ˆ 15.8, J(2ax,1ax) ˆ 10.6, J(2ax,1eq) ˆ 7.3, HaxÀC(2)); 2.39 (ddd, J ˆ 15.8, J(2eq,1ax) ˆ 7.3, J(2eq,1eq) ˆ
4.1, HeqÀC(2)); 1.96 1.84 (m, HeqÀC(1), HeqÀC(12), HaÀC(15)); 1.08 (s, Me(18)); 1.03 (s, Me(19)); 1.01 (s,
Me(20)). 13C-NMR (75.4 MHz, CDCl3): 217.4 (C(3)); 149.0 (C(16)); 106.5 (C(17)); 55.7 (C(9)); 55.3 (C(5));
49.2 (C(14)); 47.4 (C(4)); 43.8 (C(8)); 39.9 (2C, C(7), C(15)); 39.6 (C(13)); 38.2 (C(1)); 37.1 (C(10)); 34.0
(C(2)); 29.8 (C(12)); 26.7 (C(18)); 21.5(C(19)); 21.2 (C(11)); 19.8 (C(6)); 15.0 (C(20)); ( Z)-isomer) 26b 20): 5.77
(m, q-like, w1/2 ꢀ 5 , HÀC(17)); 2.82 (m, t-like, w1/2 ꢀ 6, HbÀC(15)); 2.66 (m, q-like, w1/2 ꢀ 10, HÀC(13)); 2.52
(ddd, 2J ˆ 15.8, 3J(2ax,1ax) ˆ 10.6, 3J(2ax,1eq) ˆ 7.3, HaxÀC(2)); 2.39 (ddd, 2J ˆ 15.8, 3J(2eq,1ax) ˆ 7.3,
3J(2eq,1eq) ˆ 4.1, HeqÀC(2)); 1.96 1.84 (m, HeqÀC(1), HeqÀC(12), HaÀC(15)); 1.09 (s, Me(18)); 1.05( s,
Me(19)); 1.04 (s, Me(20)). 13C-NMR (75.4 MHz, CDCl3): 217.4 (C(3)); 150.1 (C(16)); 106.6 (C(17)); 55.7
(C(9)); 55.3 (C(5)); 50.1 (C(14)); 47.4 (C(4)); 42.5 (C(8)); 41.5 (C(13)); 40.0 (C(7)); 39.0 (C(15)); 38.2 (C(1));
37.1 (C(10)); 34.0 (C(2)); 29.8 (C(12)); 26.7 (C(18)); 21.5(C(19)); 21.2 (C(11)); 19.8 (C(6)); 15.0 (C(20)). CI-
3
3
2
3
3
MS: 340 (33, [M(37Cl) ‡ NH4] ), 338 (100, [M(35Cl) ‡ NH4] ), 321 (5, [M(35Cl) ‡ H] ), 296 (6), 234 (29).
‡
‡
‡
17. Epimerization of (16R)-16,17-Dihydroxy-ent-kauran-3-one ( ˆ Abbeokutone; 27). Data of 27. CD
(MeOH, c ˆ 1.38 ¥ 10À4 m): 228 (0), 290 (À1.05), 319 (0), 323 (‡0.03), 340 (0). H-NMR (300 MHz, CDCl3):
1
3.79, 3.67 (AB, 2J ˆ 10.9, CH2(17)); 2.47 (dd, 3J ˆ 8.6, 6.3, CH2(2)); 2.08 (br. m, w1/2 ꢀ 15, HÀC(13)); 2.00 (dd,
2J ˆ 13.1, 3J ˆ 6.3, HeqÀC(1)); 1.92 (dd, 2J ˆ 11.9, 4J(15b,14ax) ˆ 2.6, HbÀC(15)); 1.08 (s, Me(18), Me(20)); 1.03
(s, Me(19)). 13C-NMR (100.6 MHz, CDCl3): 217.9 (C(3)); 81.7 (C(16)); 66.3 (C(17)); 55.4 (C(9)); 54.3 (C(5));
52.8 (C(15)); 47.2 (C(4)); 45.3 (C(13)); 44.4 (C(8)); 40.9 (C(7)); 39.2 (C(1)); 38.5 (C(10)); 36.9 (C(14)); 34.0
.
‡
(C(2)); 27.2 (C(18)); 26.0 (C(12)); 21.6 (C(6)); 20.9 (C(19)); 18.8 (C(11)); 17.8 (C(20)). EI-MS: 302 (< 5, M ),
‡
289 (100, [M À Me À H2O] ), 271 (20), 247 (6). Further physical data in [11c e].
(16R)-16-Hydroxy-17-{[(4-methylphenyl)sulfonyl]oxy})-ent-kauran-3-one (28). As described in Exper. 5,
reaction of 27 (10 mg) with TsCl (30 mg) and CC (hexane/Et2O 1:2) afforded 28 (14 mg, 95%). White foam.
1H-NMR (300 MHz, CDCl3): 7.81, 7.36 (AA'BB', J ˆ 8.1, arom. H); 4.19, 4.11 (AB, 2J ˆ 9.6, CH2(17)); 2.46 (dd,
3J ˆ 8.4, 6.6, CH2(2); s, MeC6H4); 2.08 (m, w1/2 ꢀ 12, HÀC(13)); 1.07 (s, Me(18)); 1.05( s, Me(20)); 1.01 (s,
Me(19)).
(16R)-16,17-Epoxy-ent-kauran-3-one (−Epoxyabbeokutone×; 29). As described in Exper. 16, reaction of 28
(14 mg) with anh. K2CO3 (14 mg) in MeOH (5ml) yielded 29 (9 mg, 95%). White tiny crystals. 1H-NMR
(300 MHz, CDCl3): 2.89, 2.82 (AB, 2J ˆ 4.7, CH2(17)); 2.49 (dd, 3J ˆ 8.6, 6.3, CH2(2)); 1.85( m, w1/2 ꢀ 12,
HÀC(13)); 1.09 (s, Me(18), Me(20)); 1.05( s, Me(19)).
20
)
The assignments are based on the respective shielding effects of the Cl-atom on HÀC(13) and CH2(15).
Moreover, assuming an E2 mechanism, the (E)-isomer is expected to be predominant due to a favored
conformation of 25.

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Helvetica Chimica Acta Vol. 86 (2003)
Hydrolysis of 29: Products 27, 30, 31, and 32a/32b. As described in Exper. 16, hydrolysis of 29 (9 mg) in
THF (2 ml) and 5% H2SO4 soln. (0.5ml) followed by CC (hexane/Et 2O 1:2 ! CH2Cl2/MeOH 95:5) gave
abbeokutone (27; 3.6 mg, 38%), the 16-epimer 30 (0.4 mg, 4%), 31 (2 mg, 22%), and 32a/32b (3 mg, 33%) as a
1:1 mixture of the 16-epimers.
(16S)-16,17-Dihydroxy-ent-kauran-3-one (ˆ16-Epiabbeokutone; 30). White foam. IR (CHCl3): 3024, 3016,
2935, 2869, 1698, 1459, 1386, 1228, 1158, 1114, 1051, 1019. 1H-NMR (300 MHz, CDCl3): 3.49, 3.41 (AB, 2J ˆ 10.8,
CH2(17)); 2.47 (dd, 3J ˆ 8.6, 3J ˆ 6.3, CH2(2)); 2.08 (m, w1/2 ꢀ 15, HÀC(13)); 2.00 (m, dd-like, w1/2 ꢀ 22, CH2(1));
1.92 (dd, 2J ˆ 11.9, 4J(15b,14ax) ˆ 2.6, HbÀC(15)); 1.08 (s, Me(18), Me(20)); 1.03 (s, Me(19)). 13C-NMR
(75.4 MHz, CDCl3): 217.9 (C(3)); 79.7 (C(16)); 69.8 (C(17)); 55.6 (C(5)); 54.3 (C(9)); 52.2 (C(15)); 47.1 (C(4));
43.3 (C(8)); 40.9 (C(13)); 40.7 (C(7)); 39.2 (C(1)); 38.5(C(10)); 37.8 (C(14)); 34.0 (C(2)); 27.2 (C(18)); 26.6
.
‡
(C(12)); 21.2 (C(6)); 20.9 (C(19)); 19.3 (C(11)); 17.6 (C(20)). EI-MS: 302 (5, M ), 289 (100, [M À Me À
‡
H2O] ), 271 (20), 247 (6). Further physical data in [12a,b].
17-Hydroxy-ent-kaur-15-en-3-one (31). White foam. IR (CHCl3): 3025, 2934, 2864, 1698, 1460, 1386, 1368,
1112, 1002. 1H-NMR (300 MHz, CDCl3): 5.38 (br. s, w1/2 ꢀ 4, HÀC(15)); 4.21 (br. s, w1/2 ꢀ 6, CH2(17)); 2.58 (m,
q-like, w1/2 ꢀ 11, HÀC(13)); 2.48 (m, td-like, CH2(2)); 2.04 (m, ddd-like, CH2(1)); 1.12 (s, Me(18)); 1.09 (s,
Me(20)); 1.03 (s, Me(19)). 13C-NMR (75.4 MHz, CDCl3): 217.9 (C(3)); 146.5(C(16)); 135.1 (C(15)); 61.3
(C(17)); 54.4 (C(5)); 48.7 (C(8)); 47.7 (C(9)); 47.3 (C(4)); 43.6 (C(7)); 41.1 (C(13)); 39.4 (C(1)); 38.7 (C(10));
38.3 (C(14)); 34.2 (C(2)); 27.1 (C(18)); 25.4 (C(12)); 21.0 (C(19)); 20.4 (C(6)); 19.2 (C(11)); 17.5 (C(20)). EI-
.
‡
MS: 302 (35, M ), 244 (14), 216 (27), 159 (27), 91 (100).
(16R)-and (16 S)-3-Oxo-ent-kauran-17-al (32a/32b). White foam. IR (CHCl3): 3027, 2935, 2864, 1701, 1460,
1385, 1114. 1H-NMR (300 MHz, CDCl3): 32a (16R): 9.67 (d, 3J(17,16) ˆ 1.7, HÀC(17)); 2.84 (m, HÀC(16)); 2.58
(m, HÀC(13)); 2.47 (m, td-like, CH2(2)); 2.00 (m, td-like, CH2(1)); 1.85( m, dd-like, CH2(15)); 1.08 (s, Me(18));
1.04 (s, Me(20)); 1.03 (s, Me(19)); 32b (16S): 9.89 (s, HÀC(17)); 2.77 (s, HÀC(16)); 2.58 (m, HÀC(13)); 2.47 (m,
td-like, CH2(2)); 2.00 (m, td-like, CH2(1)); 1.80 (m, dd-like, CH2(15)); 1.08 (s, Me(18)); 1.04 (s, Me(20)); 1.03 (s,
.
‡
Me(19)). EI-MS: 302 (40, M ), 244 (49), 216 (95), 187 (42), 159 (100).
18. Transformation of Derivatives into New Phyllocladanes. For the characterization as potential natural
products, the following compounds were prepared:
(2R,16R)-Phyllocladane-2,16,17-triol (16). As described in Exper. 10, acetonide 14 (14 mg) was hydrolyzed
with 2% H2SO4 soln. (2 ml), worked up, and purified by CC (CH2Cl2/MeOH 9 :1): 16 (12 mg, 96%). White solid.
M.p. 200 2048. [a]2D0 ˆ ‡44.8 (c ˆ 0.33, MeOH). IR (KBr): 3200 3600 (br.), 2930, 2860, 1460, 1455, 1385, 1366,
1
1200, 1125, 1072, 1035, 1000, 985, 965, 912, 870, 810, 678. H-NMR (300 MHz, (CD3)2CO): 3.42 (m, wl/2 ꢀ 10,
HÀC(2)); 3.68, 3.51 (AB, 2J ˆ 11.0, CH2(17)); 1.13 (s, Me(20)); 0.97 (s, Me(18)); 0.88 (s, Me(19)). CI-MS: 340
.
‡
‡
‡
(100, [M ‡ NH4] ), 323 (13), 322 (62, M ), 305(21), 304 (40, [ M À H2O] ), 288 (12), 287 (56, [M ‡ H À 2
‡
‡
H2O] ), 273 (5), 270 (9), 269 (44, [287 À H2O] ).
(16R)-16,17-Dihydroxyphyllocladan-2-one (17). Oxidation of 14 (24 mg) with PCC (32 mg), followed by
hydrolysis of the acetal, workup, and CC as described in Exper. 10 afforded 17 (17 mg, 79%). White crystals.
M.p. 174 1768. [a]2D0 ˆ ‡40.7 (c ˆ 0.41, CHCl3). IR (KBr): 3500. 3430, 2930, 2898, 2850, 1702, 1460, 1390, 1370,
1300, 1280, 1188, 1145, 1125, 1055, 1038, 1028, 1008, 985, 965, 916, 870, 802, 755, 725, 670, 660. 1H-NMR
(300 MHz, CDCl3): 3.79, 3.62 (AB, 2J ˆ l0.9, CH2(17)); 1.07 (s, Me(20)); 0.88 (s, Me(18), Me(19)). CI-MS: 338
‡
‡
(100, [M ‡ NH4] ), 321 (20, [M ‡ H] ).
(3S,16R)-Phyllocladane-3,16,17-triol (18). Hydrolysis of acetal 7 (10 mg) as described in Exper. 10 and CC
(CH2Cl2/MeOH, 90 :1) afforded 18 (9 mg, 100%). White crystals (from CH2Cl2/MeOH). M.p. 148 1508.
[a]2D0 ˆ ‡18.5( c ˆ 0.47, MeOH). IR (KBr): 3200 3600 (br.), 2930, 2860, 1454, 1436, 1382, 1368, 1348, 1305,
1255, 1205, 1128, 1088, 1074, 1032, 984, 918, 874, 855, 830, 745, 695, 642. 1H-NMR (300 MHz, (CD3)2CO): 3.66,
3.5l (AB, 2J ˆ 10.8, CH2(17)); 3.61 (dd, 3J(3,2ax) ˆ 9.5, 3J(3,2eq) ˆ 4.7, HÀC(3)); 0.96 (s, Me(18)); 0.89 (s,
‡
‡
‡
Me(20)); 0.75( s, Me(19)). CI-MS: 340 (100, [M ‡ NH4] ), 322 (7, M ), 304 (2, [M À H2O] ).
The following compounds were prepared by reaction with excess LiAlH4 in THF at r.t., workup, and CC
separation as described in Exper. 4.
(3R,16R)-Phyllocladane-3,16,17-triol (33). From the natural product 1a (10 mg), we obtained 33 (8 mg,
91%). White needles (from CH2Cl2/MeOH). M.p. 193 1968. [a]2D0 ˆ À3.9 (c ˆ 0.21, MeOH). IR (KBr): 3300
3500 (br.), 2930, 2860, 1450, 1435, 1385, 1350, 1315, 1305, 1245, 1205, 1195, 1146, 1128, 1095, 1078, 1055, 1042,
1008, 985, 938, 918, 874, 800, 685, 665, 618. 1H-NMR (300 MHz, (CD3)2CO): 3.68, 3.50 (AB, 2J ˆ 10.9, CH2(17));
3.3l (m, t-like, wl/2 ꢀ 7, H ÀC(3)); 0.9l (s, Me(20)); 0.90 (s, Me(18)); 0.80 (s, Me(19)). CI-MS: 340 (43, [M ‡
.
‡
‡
‡
‡
NH4] ), 323 (9), 322 (45, M ), 320 (6), 305(21), 304 (33, [ M À H2O] ), 288 (16), 287 (84, [M ‡ H À 2 H2O] ),
‡
270 (20), 269 (100, [287 À H2O] ), 248 (5).

Helvetica Chimica Acta Vol. 86 (2003)
437
(2R,3S,16R)-Phyllocladane-2,3,16,17-tetrol (15). From the natural product 1b (55 mg), we obtained 15
(24 mg, 60%). White crystalline solid. M.p. 246 2498. [a]2D0 ˆ ‡12.0 (c ˆ 0.35, MeOH). IR (KBr): 3500, 3390,
3290, 2945, 2870, 1558, 1540, 1450, 1380, 1350, 1325, 1305, 1295, 1285, 1255, 1212, 1195, 1150, 1130, 1085, 1075,
1
1040, 1010, 985, 952, 935, 915, 870, 830, 690, 620. H-NMR (300 MHz, CD3OD): 3.91 (m, w1/2 ꢀ 24, HÀC(2));
3.68, 3.54 (AB, 2J ˆ 11.3, CH2(17)); 3.30 (m, overlapping with the solvent peak, HÀC(3)); 0.97 (s, Me(18)); 0.95
1
2
(s, Me(20)); 0.85( s, Me(19)). H-NMR (400 MHz, C5D5N): 4.37 (m, wl/2 ꢀ 22, HÀC(2)); 4.18, 4.06 (AB, J ˆ
10.5, CH2(17)); 3.84 (d, 3J(3,2) ꢀ 1, HÀC(3)); 1.37 (s, Me(18)); 1.13 (s, Me(20)); 1.03 (s, Me(19)). CI-MS: 356
.
‡
‡
‡
(100, [M ‡ NH3] ), 339 (15), 338 (76, M ), 324 (9, [M ‡ NH3 À MeOH] ).
The same compound 15 (8.5mg, 95%) was also obtained after hydrolysis of acetal 5 (10 mg).
(2R,3R,16R)-Phyllocladane-2,3,16,17-tetrol (34). From the natural product 1f (25mg), we obtained 34
(14 mg, 70%). White crystalline solid (from MeOH). M.p. 225 228 8. [a]2D0 ˆ ‡7.8 (c ˆ 0.41, MeOH). IR (KBr):
3200 3600 (br.), 2940, 2870, 1558, 1540, 1460, 1385, 1305, 1250, 1190, 1050, 1030, 1000, 975, 915, 870, 755, 675.
1H-NMR (300 MHz, CD3OD): 3.67, 3.55 (AB, 2J ˆ 11.3, CH2(17)); 3.60 (ddd, 3J(2,1ax) ˆ 11.3, 3J(2,3) ˆ 9.6,
3J(2,1eq) ˆ 4.4, HÀC(2)); 2.89 (d, 3J(3,2) ˆ 9.6, HÀC(3)); 0.99 (s, Me(18)); 0.86 (s, Me(20)); 0.79 (s, Me(19)).
‡
‡
‡
‡
CI-MS: 356 (48, [M ‡ NH4] ), 339 (22), 338 (100, M ), 324 (5, [M ‡ NH4 À MeOH] ), 320 (5, [M À H2O] ),
‡
‡
303 (8, [M ‡ H À 2 H2O] ), 285(15, [303 À H2O] ).
(3S,16R)-Phyllocladane-3,16,17,19-tetrol (35). Trihydroxy ketone 8 (5mg) yielded 35 (2.5mg, 63%).
Amorphous white solid. 1H-NMR (300 MHz, CD3OD): 4.11, 3.46 (AB, 2J ˆ 11.2, CH2(19)); 3.68, 3.55 (AB, 2J ˆ
‡
11.3, CH2(17)); 3.52 (m, HÀC(3)); 1.18 (s, Me(18)); 0.89 (s, Me(20)). CI-MS: 356 (100, [M ‡ NH4] ), 338 (100,
‡
‡
M ), 324 (46, [M ‡ NH4 À MeOH] ), 323 (21).
(16R)-17,19-Bis(acetyloxy)-16-hydroxyphyllocladan-3-one (3). Revision of NMR Data21). 1H-NMR
(400 MHz, CDCl3): 4.60, 3.91 (AB, 2J ˆ 11.3, CH2(19)); 4.26, 4.19 (AB, 2J ˆ 11.3, CH2(17)); 2.73 (ddd, 2J ˆ
15.4, J(2ax,1ax) ˆ 13.7, 3J(2ax,1eq) ˆ 6.4, HaxÀC(2)); 2.33 (ddd, J ˆ 15.4, J(2eq,1ax) ˆ 5.1, J(2eq,1eq) ˆ 2.8,
HeqÀC(2)); 2.13, 2.00 (each s, 2 COMe); 1.16 (s, Me(20)); 1.13 (s, Me(18)). 13C-NMR (100.6 MHz, CDCl3): 212.8
(C(3)); 170.9, 170.95(2 COMe), 82.l (C(16)); 67.4 (C(17)); 65.8 (C(19)); 57.l (C(9)); 55.5 (C(5)); 51.5 (C(4));
47.6 (C(14)); 44.3 (C(15)); 44.1 (C(13)); 43.1 (C(8)); 40.7 (C(7)); 38.3 (C(1)); 36.9 (C(10)); 34.4 (C(2)); 26.3
(C(12)); 20.9 (C(11)); 20.6 (2C, COMe), 20.5(C(18)); 19.4 (C(6)); 14.6 (C(20)).
3
2
3
3
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21
)
Due to a calibration error, the NMR data of 3 are not correctly reported in [5].

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¬
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Received August 27, 2002