Synthesis of nitrogen-containing derivatives of (18α,19β)-19-Hydroxy-2,3-secooleanane-2,3,28-trioic Acid 28,19-Lactone

Article abstract of DOI:10.1002/hlca.201200492

The object of this study is the interaction of the cyclic anhydride 2 of (18α,19β)-19-hydroxy-2,3-secooleanane-2,3,28-trioic acid 28,19-lactone (1) with primary and secondary amines. It was shown that the products of steric control (the corresponding 2-amino-2-oxo-3-oic acids=2-amides) were formed solely upon the opening of the anhydride cycle by secondary amines (Scheme 2), whereas the interaction with primary amines yielded a mixture of isomeric amides (Scheme 10). In the latter case, the solvent provided a noticeable effect on the reaction selectivity, which was demonstrated in the case of 4-methoxybenzylamine. The interaction between the resulting 3-amides and oxalyl chloride yielded the corresponding cyclic imides, whereas under these conditions, 2-amides formed spiropyrrolidinetriones (Scheme 4). Copyright

Full text of DOI:10.1002/hlca.201200492

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Synthesis of Nitrogen-Containing Derivatives of (18a,19b)-19-Hydroxy-
2,3-secooleanane-2,3,28-trioic Acid 28,19-Lactone
by Andrey V. Shernyukov*, Ilya Ya. Mainagashev, Dina V. Korchagina, Alexander M. Genaev,
Nina I. Komarova, Nariman F. Salakhutdinov, and Genrikh A. Tolstikov
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of
Sciences, RU-630090 Novosibirsk
(fax: þ 73833309752; e-mail: andreysh@nioch.nsc.ru)
The object of this study is the interaction of the cyclic anhydride 2 of (18a,19b)-19-hydroxy-2,3-
secooleanane-2,3,28-trioic acid 28,19-lactone (1) with primary and secondary amines. It was shown that
the products of steric control (the corresponding 2-amino-2-oxo-3-oic acids ¼ 2-amides) were formed
solely upon the opening of the anhydride cycle by secondary amines (Scheme 2), whereas the interaction
with primary amines yielded a mixture of isomeric amides (Scheme 10). In the latter case, the solvent
provided a noticeable effect on the reaction selectivity, which was demonstrated in the case of 4-
methoxybenzylamine. The interaction between the resulting 3-amides and oxalyl chloride yielded the
corresponding cyclic imides, whereas under these conditions, 2-amides formed spiropyrrolidinetriones
(Scheme 4).
Introduction. – Pentacyclic triterpenoids of natural and semisynthetic origin are
attracting increasing attention as a result of the fact that these compounds can be
obtained from readily available sources, and are characterized by their high biological
activity [1][2]. The production of various ring-A-seco derivatives, which are charac-
terized by different biological activity [3 – 6], is an interesting application of the
targeted chemical transformation of these compounds. Further modification of seco
derivatives via the introduction of various pharmacophoric groups containing N-atoms
(from amides, ketoximes, nitrile groups) usually results in the enhancement or variation
of biological activity of the compounds obtained [7][8].
The data on 2,3-secooleananedioic acids and their cyclic anhydrides from the series
of pentacyclic triterpenoids have been published [9 – 12]; however, there seem to be no
data available on using them to produce amides and cyclic imides. The present study is
devoted to the production of N-containing derivatives of pentacyclic triterpenoids
based on (18a,19b)-19-hydroxy-2,3-secooleanane-2,3,28-trioic acid 28,19-lactone (1)
which is readily accessible from allobetuline (¼(3b,18a,19b)-19,28-epoxyoleanan-3-ol)
[13].
Results and Discussion. – In the case of dicarboxylic acids, in which the carboxylic
groups are spatially close to each other and can relatively easily form a cyclic anhydride,
the synthesis of amides is usually carried out both via a cyclic anhydride or via a
dicarbonyl dichloride. As reported earlier [14], the cyclic anhydride 2 can be obtained
in a 90% yield via treatment of compound 1 with a twofold excess of oxalyl chloride in
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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CH2Cl2. With DMF as a catalyst and increasing both the excess of oxalyl chloride (to
1:30) and the reaction time (to 96 h), mixtures of anhydride 2 and 2,3-secooleanane-
2,3-dioyl dichloride 3 were formed (Scheme 1), the amount of the latter being 25 – 56%
1
(by H-NMR). Dichloride 3 could be obtained in situ via interaction of 1 with a
fourfold excess of phosphorus pentachloride in boiling CH2Cl2 for 30 min. However,
compound 3 is unstable and could not be isolated from the mixture and used for further
reactions. Therefore, to produce amides and cyclic imides of dioic acid 1 in further
experiments, cyclic anhydride 2 was used as the starting material.
Scheme 1
The acylation of amines with anhydride 2 occurred smoothly at room temperature
in different solvents and did not require addition of catalysts, with the exception of
aniline (¼ benzenamine) and p-anisidine (¼4-methoxybenzenamine). For the latter
compounds, refluxing in dioxane was required to accelerate the reaction. The
interaction between cyclic anhydride 2 and secondary cyclic amines resulted solely in
the formation of amides 4 – 7 via the sterically less hindered carboxy center C(2) of the
initial acid 1 (Scheme 2).
Scheme 2
The formation of the mixtures of isomeric amic acids at both possible positions i.e.,
2-amino-2-oxo-3-oic acid or 3-amino-3-oxo-2-oic acid, was observed upon interaction
with primary amines. Since secondary amides are the major precursors of the
corresponding cyclic imides, it appeared promising to produce the latter compounds
without separation and isolation of the isomeric amic acids. Various methods of
producing the desired compounds generally used in synthetic practice were tested;
however, no efficient method could be found. Thus, when boiling the mixture of amic

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acids obtained via reactions with benzylamine (¼ benzenemethanamine), or 4-
methoxybenzyl amine (¼4-methoxybenzenemethanamine) in toluene with a Dean-
Stark trap or by the action of AcCl or Ac2O in boiling AcOH, no formation of the
targetted products was observed. The known noroleanone 8 [15] was isolated when
keeping the mixture of amic acids obtained from 2 and benzylamine at 130 – 2208 under
Ar (Scheme 3); yield of crude compound 8 (based on 2) was 44%. When boiling the
same mixture of amic acids in AcOH in the presence of P2O5, a fraction containing
cyclic imide 9 and the initial cyclic anhydride 2 was isolated after a chromatographic
1
separation, the ratio 9/2 being 72 :28 (by H-NMR). The formation of anhydride 2
is probably accounted for by the instability of the amide group under these con-
ditions.
Scheme 3
As reported earlier [16], the reaction of cyclic anhydride 2 and benzylamines and
subsequent treatment with oxalyl chloride (one-pot conditions) yielded compounds
with a triterpenoid noroleanone backbone, containing a spiropyrrolidinetrione frag-
ment. During this reaction, the residue of oxalyl chloride was incorporated into the
backbone as part of the pyrrolidinetrione moiety. It is known that pyrrolidinetriones
can be produced by condensation of alkyl oxalates with primary amides under the
action of alkali [17] or via the interaction of primary amides with oxalyl chloride [18 –
20]. In the latter case, when oxalyl chloride interacts with primary amides,
oxazolidinediones are initially formed, which are rather unstable compounds with
respect to nucleophilic agents and can easily isomerize to the corresponding
pyrrolidinetriones, even upon recrystallization from EtOH [20] or boiling in a
pyridine/EtOH mixture [21].
When studying the conversion described, the reaction of oxalyl chloride and
individual isomeric amic acids isolated chromatographically after the reaction of the
corresponding primary amines with anhydride 2 was investigated. Thus, the target
cyclic imides 14 – 17 were obtained with a 6 – 10-fold excess of oxalyl chloride from the
3-amino-3-oxo-2-oic acids (¼ 3-amides) 10 – 13 in 64 – 84% yields (Scheme 41)).
Spiropyrrolidinetriones 22 and 23 were formed in 76% and 74% yield, respectively,
by the reaction with 2-amino-2-oxo-3-oic acids (¼2-amides) 18 and 19. However, in the
case of 2-anilide derivatives 20 and 21, the reaction yielded a complex mixture of
compounds, from which spiropyrrolidinetriones 24 and 25 were isolated in 27% and
23% yield, respectively.
1
)
Arbitrary and/or trivial atom numberings; for systematic names, see Exper. Part.

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Scheme 4
The reactions of 2-[(4-methoxybenzyl)amino]-2-oxo-3-oic acid 19 and 2-(phenyl-
amino)-2-oxo-3-oic acid 21 with an excess of oxalyl chloride in CDCl3 were then carried
out directly in a NMR tube. In the case of anilide derivative 21, a mixture of compounds
was formed, its composition remaining virtually constant for a week, upon being kept in
the tube at room temperature. The major component 26 (Scheme 51)) was formed in ca.
80% yield; the corresponding spiropyrrolidinetrione was not observed. According to
the NMR data, exposing the resulting mixture to air yielded a small amount of
spiropyrrolidinetrione 25 and other compounds that contain the noroleanone backbone

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in their structure (and have the characteristic cyclopentanone 13C-signals in the d(C)
200 – 230 range).
Scheme 5
It is worthy of note that the barrier to rotation of the Ph substituent around the
N(2’)ꢀC(3’) of 26 can be determined from the temperature-dependent NMR spectra.
The rotational barrier estimated by the Eyring equation is equal to 14.6 kcal/mol at
þ 29.48. Comparatively high rotational barriers in cyclic and acyclic N,N-diacyl
derivatives of ortho-substituted aromatic amines have been observed before [22][23].
The dependence of the rotational barrier on the electron effects of the acyl group was
shown by Murakami and co-workers [24]. The presence of a relatively high barrier of
rotation of the phenyl substituent in compound 26 can be accounted for by the presence
of the strong p-acceptor C(¼O)Cl in the acyl group. Based on the analysis of the
NOESY 2D plot of 26, in which the cross-peaks HꢀC(1)/Me(25) and Me(24) in b-
position are present, the shown configuration of C(1) was proposed. The configuration
was also confirmed by comparing the experimental chemical shifts with the calculated
shifts that have the highest difference for both possible configurations of the
stereogenic center C(1).
When performing the reaction in an NMR tube with 2-[(4-methoxybenzyl)amino]-
2-oxo-3-oic acid 19, the formation of three intermediates and product 23 was observed
(Scheme 6), their ratio depending upon time (Scheme 6). Based on the analysis of 1D-
Scheme 6

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and 2D-NMR spectra (COSY, HMBC, HSQC) and comparing them with the spectra of
compound 26, the structures of compounds I-1 and I-2 were proposed. The structure of
the 2-amino-2-oxo-3-oyl chloride of the initial aminooxooic acid 19 was proposed for
compound I-1, the 2-amino-2-oxo moiety of I-1 being almost completely protonated
(broad s at d(H) 14.85). A structure similar to that of compound 26 was proposed for
compound I-2. Compound I-3 is probably not an intermediate but a by-product that
was formed at a noticeably lower rate, as attested to by its low amount that slowly
changed with time. Taking into account the high excess (ca. 20-fold) of oxalyl chloride
and neglecting the formation of compound I-3, calculations with the data of the table in
Scheme 6 can be made upon assumption of a kinetic scheme of two consecutive
k1
k2
irreversible reactions, I-1 ! I-2 ! 23. Thus, the variation of concentration of
compound I-1 in the mixture correlated well with a first-order reaction with the
kinetic rate constant k1 ¼ 3.9 · 10ꢀ5 sꢀ1. For the second reaction, the kinetic constant k2
was equal to 2.1 · 10ꢀ4 sꢀ1. Via substitution of these constants into the function of content
of the final product on time, which corresponds to the selected kinetic scheme, good
agreement with the data on the amount of compound 23 in the mixture was achieved.
To test whether spiropyrrolidinetriones can be obtained from the derivatives of
simple dicarboxylic acids, the model compound N-(4-methoxybenzyladipamic) acid
was treated with excess of oxalyl chloride in chloroform; however, in this case, a
complex mixture of products was formed. The use of the corresponding methyl ester 27
under the same conditions resulted in the formation of the corresponding oxazolidi-
nedione 28 in 38% yield (Scheme 7). When conducting this reaction in the presence of
Et3N, a violent reaction was observed, yielding a complex mixture of products from
which pyrrolidinetrione 29 was isolated in 11% yield. It should be noted that only the
Scheme 7

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enol form of this compound was observed in the NMR spectra (CDCl3). These data
attest the assumption of instability of the oxazolidinedione ring system in the presence
of nucleophiles, due to the presence of an ꢂactivatedꢃ ester group and leave open the
possibility of rearranging to the isomeric cyclic pyrrolidinetriones [20].
When methyl 2-(benzylamino)-2-oxo-3-oate 30, corresponding to the model methyl
ester 27, was treated with oxalyl chloride, oxazolidinedione 31 was obtained in 87%
yield (Scheme 7). Significantly broad signals were present in the NMR spectra of 31 at
room temperature, and three inter-exchanging compounds were observed in the NMR
spectra at 245 K. The quantum-chemical conformational analysis permitted the
reasonable assumption that these compounds were three conformers, formed upon
rotation around the C(5)ꢀC(4) bond. Compound 31 contains six bonds, around which
free rotation can take place. Based on the calculation results, this fact supposes the
existence of one major conformer and 28 other conformers, their population having the
capability to influence the NMR spectra. The fact that a conformational equilibrium
was observed in 31, unlike in other synthesized seco derivatives (e.g., 2-amides), can be
accounted for by the presence of a strong magnetically anisotropic Ph group in the
structure of 31. This magnetically anisotropic Ph group can adopt two positions: ꢂto the
backboneꢃ and ꢂfrom the backboneꢃ, resulting in an increased differentiation between
the chemical shifts of the exchanging signals and shifting the exchange boundaries
towards higher temperatures, due to the fact that the conformers have different
populations. Moreover, compound 31, as opposed to 2-amides, contains a COOMe
group, which is incapable of reducing the energy of the most stable conformer by
forming an intramolecular H-bond.
Hence, based on the published data on producing oxazolidinediones and
pyrrolidinetriones and the conversions shown above, the following reaction mechanism
of the formation of spiropyrrolidinetriones 22 – 25 can be proposed (Scheme 8): In a
first step, oxalyl chloride reacts with a 2-amino-2-oxo-3-oic acid to give 2-amino-2-oxo-
3-oyl chloride A wherein the amide moiety is protonated by HCl. Then the interaction
between A and oxalyl chloride results in the formation of oxazolidinedione B. The
reaction can then proceed via two pathways. The first one (Scheme 8, Path A) involves
the intramolecular acylation of B with ring opening via a hypothetical intermediate C
yielding D. The subsequent intramolecular acylation of the b-diketone moiety with the
oxalyl chloride moiety of D yields the desired spiropyrrolidinetrione F. The second
pathway (Scheme 8, Path B) involves the isomerization of the oxazolidinedione ring of
B into the pyrrolidinetrione ring with the formation of E, followed by intramolecular
acylation of the resulting b-diketone moiety with the acyl chloride moiety of E, which
also yields F. However, Path B is less viable when the reaction is run in a base-free
medium. A decrease in the yield of spiropyrrolidinetriones in the case of an aromatic
substituent at the amide N-atom, indicates that the barrier of the reaction D ! spiro-
pyrrolidinetrione F is higher in this case, as established by the fact that the reaction of
anilide derivative 21, as opposed to that of amide derivative 19, stopped at compound
26 (corresponding to compound D in Scheme 8) under conditions of the closed system
in an NMR tube (Scheme 5). Under the preparative conditions (the concentration of
HCl decreases because of its volatility), the formation of spiropyrrolidinetrione F from
D in the case of an aromatic substituent is likely to be accompanied by side reactions,
which results in the observed reduced yield.

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Scheme 8
It is worthy of note that when conducting the reaction between 2-amino-2-oxo-3-oic
acids and phosgene (Cl2C¼O) in THF, which is also used to obtain 2-amino-2-oxo-3-oyl
1
chlorides, complex mixtures of products were obtained. According to the H-NMR
data, these mixtures included compounds containing a 4-chlorobutoxy fragment, which
could be formed upon the opening of the solvent (THF) by the HCl formed. To verify
this assumption, in a model reaction, the secondary-amide derivative 4 was treated with
phosgene in THF, and indeed, compound 32 was isolated from the mixture
(Scheme 91)). A complex mixture of products was also formed in the reaction of 2-
amide derivatives and phosgene in CHCl3.
Scheme 9

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It was thus demonstrated that the reaction of oxalyl chloride and 2-amino-2-oxo-3-
oic acids derived from 2,3-secooleanane-2,3-dioic acids 1 may yield spiropyrrolidine-
triones, whereas 3-amino-3-oxo-2-oic acids form the corresponding cyclic imides under
these conditions. However, as mentioned above, the isolation of the individual amic
acids from the reaction mixture after treatment of cyclic anhydride 2 with primary
amines presents some difficulties (Scheme 101)). We now established that the solvent
used in this reaction has a considerable effect on the ratio of the formed isomeric amic
acids. To the best of our knowledge, no systematic study of the effect of solvents on the
acylation of amines with asymmetric cyclic anhydrides has been published yet. Thus a
series of experiments with different solvents was carried out for the model reaction of
Scheme 10

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Table 1. Ratio of Isomeric Amic Acids in the Product Mixtures Obtained from Anhydride 2 and (4-
Methoxybenzyl)aminea)
Entry
Solvent
Ratio 2-amide/3-amideb)
1c)
2d)
3e)
4
5
6f)
7
8
9
10
11g)
12
THF
THF
THF
THF
1,4-dioxane
THF
pyridine
MeCN
i-PrOH
DMF
AcOH
93 : 7 (13.3 : 1.0)
88 : 12 (7.3 : 1.0)
87: 13 (6.7: 1.0)
85 : 15 (5.7: 1.0)
85 : 15 (5.7: 1.0)
80 : 20 (3.8 : 1.0)
80 : 20 (4.0 : 1.0)
72 : 28 (2.6 : 1.0)
71 : 29 (2.4 : 1.0)
69 : 31 (2.2 : 1.0)
68 : 32 (2.1 : 1.0)
66 : 34 (1.9 : 1.0)
59 : 41 (1.4 : 1.0)
53 : 47 (1.1 : 1.0)
50 : 50 (1.0 : 1.0)
48 : 52 (1.0 : 1.1)
47: 53 (1.0 : 1.1)
39 : 61 (1.0 : 1.6)
38 : 62 (1.0 : 1.6)
38 : 62 (1.0 : 1.6)
34 : 66 (1.0 : 1.9)
CHCl3
13
14
15
CH2Cl2
benzene
EtOH
MeOH
MeOH
MeOH
MeOH
MeOH þ H2O (3 þ 2 ml)
MeOH
16d)
17c)
18e)
19
20h)
21f)
a) Reaction conditions: 0.10 mmol of 2, 0.15 mmol of (4-methoxybenzyl)amine, 3 ml of solvent, at r.t.
b) Ratio of 2-amide/3-amide (¼ 2-amino-2-oxo-3-oic acid/3-amino3-oxo-2-oic acid) as determined by
HPLC analysis. c) Reactions were carried out in the presence of 0.2 ml of Et3N. d) Reactions were carried
f
out in the presence of 0.2 ml of Bu3N. e) Catalytic amount of DMAP was added. ) Salt of amine and
dehydroabietic acid was used. g) At 608. h) Reflux.
anhydride 2 with (4-methoxybenzyl)amine, and the ratio of the isomeric amic acids (2-
amide/3-amide) was determined by HPLC (Table 1). In the majority of cases, the amic
acid resulting from attack at the sterically less hindered carboxy center C(2)
predominated in the solvents under study (Table 1, Entries 1 – 14). In THF or dioxane,
the ratio of the isomeric amic acids was 5.7 :1.0 in favor of the 2-amide (Entries 4 and 5).
In the case of benzene and EtOH, the ratio was close to 1:1 (Entries 14 and 15),
whereas in MeOH, the prevalence of the product resulting from attack at the sterically
more hidered carboxy center C(3) was observed (Entry 19). Within a series of alcohols,
the amount of 3-amide increased with increasing polarity of the solvent (Entries 9, 15,
and 19). The extreme ratios, obtained in MeOH and THF, were selected and the
influence of various additions on these ratios were examined. Thus, when a salt of (4-
methoxybenzyl)amine with dehydroabietic acid was acylated instead of the amine, a
slight increase in content of 3-amide was observed in both cases (Entries 6 and 21). The
addition of excess Et3N or Bu3N noticeably increased the content of 2-amide in both
cases (Entries 1 and 2, and 17 and 16). The addition of the catalytic amount of DMAP
had no considerable effect on the reaction selectivity (Entries 3 and 18). Thus, to
increase the content of 2-amide derivatives in the mixture, the reaction should be

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performed in THF or dioxane with Et3N added, whereas for a favored production of 3-
amide derivatives, a polar protic solvent (MeOH) is recommended.
This study was supported by the Program of Fundamental Research of the Presidium of the Russian
Academy of Sciences ꢂDevelopment of Methods for Obtaining Chemical Substances and Creating New
Materialsꢃ.
Experimental Part
1. General. Yields of products are given in the corresponding Schemes. Anal. and spectroscopic
studies were performed in the Chemical Service Center of collective use of the SB RAS. Column
chromatography (CC): silica gel Merck (60 – 200 mesh). TLC: Silufol silica-gel plates. HPLC: Milichrom-
A02 (EcoNova). M.p.: Kofler stage and Mettler-Toledo-FP-900 instrument. IR Spectra: Vector-22
1
instrument; in KBr; in cmꢀ1. H- and 13C-NMR Spectra: Bruker-DRX-500 (at 500.13 and 125.76 MHz,
resp.), AV-300 (at 300.13 MHz (1H)), AV-400 (at 400.13 and 100.78 MHz, resp.), and AV-600 instrument
(at 600.30 and 150.95 MHz, resp.); in CDCl3, (D6)DMSO, or CDCl3/(D6)DMSO 5 :1; d in ppm, J in Hz,
with CHCl3 as internal standard (d(H) 7.24, d(C) 76.90) or DMSO (d(H) 2.50, d(C) 39.50); assignments
on a routine basis by a combination of 1D and 2D experiments (COSY, COLOC, HSCQ, and HMBC),
most d(H) as overlapping m; 13C-NMR data in Tables 2 – 5; arbitrary and/or trivial atom numbering as
given in the Schemes1); Ha ¼ Haxial and He ¼ Hequatorial. MS: Thermo-Electron-DFS instrument; at 70 eV; in
m/z.
Quantum-Chemical Calculations. The initial set of conformers was obtained by using ChemAxonꢃs
Marvin (conformers plugin) [25] and Confab [26]; then structures were optimized by RM1 [27] with the
MOPAC2009 program [28] and by the density functional theory (DFT; functional PBE [29], basis L1
(L01 [30], cc-pVDZ analog), with the PRIRODA program [31]). The chemical shifts were calculated by
GIAO/DFT/PBE (basis L22 (L22, cc-pCVTZ analog), with the PRIRODA program. For quantum-
chemical calculations, we used the cluster of the Information Computation Center, Novosibirsk State
University. All results of calculations and selected NMR investigation are available from http://
limor1.nioch.nsc.ru/quant/conformers/shern/spiro/.
2.1. 2-Amino-2-oxooleanan-3-oic Acids 4 – 7. General Procedure. To a soln. of the cyclic anhydride 2
(1.00 mmol) in THF (7 – 10 ml) was added a soln. of the corresponding amine (1.05 – 1.10 mmol) in THF
(2 ml). After standing for 24 h, the mixture was extracted with CHCl3 and the extract washed with dil.
HCl soln. (pH 4 – 5), dried (MgSO4), and concentrated.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-13-
oxo-7-[2-oxo-2-(piperidin-1-yl)ethyl]-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid (4): IR: 1772
1
(lactone), 1695 (COOH), 1650 (CONR1R2). H-NMR (500 MHz, (D6)DMSO): 0.83 (s, Me(26)); 0.88
(s, Me(27)); 0.89 (s, Me(25)); 0.94 (s, Me(29), Me(30)); 1.11, 1.14 (2s, Me(23), Me(24)); 1.52 – 1.60 (m,
CH2(4’)); 1.62 – 1.71 (m, HeꢀC(12), HeꢀC(16), CH2(22)); 1.86 (d, J(18,13) ¼ 11.1, HꢀC(18)); 2.38 (s,
CH2(1)); 2.74 (dd, J(5a,6a) ¼ 12.0, J(5a,6e) ¼ 2.0, HaꢀC(5)); 2.95 (dd, J(9a,11a) ¼ 12.5, J(9a,11e) ¼ 2.3,
HaꢀC(9)); 3.30 – 3.51 (m, CH2(2’), CH2(6’)); 3.96 (s, HꢀC(19)); 11.71 (br. s, COOH); others 0.77 – 1.53.
Anal. calc. for C35H55NO5 (569.81): C 73.77, H 9.73, N 2.46; found: C 73.55, 73.58, H 9.74, 9.79, N 2.60,
2.62.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-7-[2-
(4-methylpiperazin-1-yl)-2-oxoethyl]-13-oxo-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid (5): M.p.
2058. IR: 1764 (lactone), 1726 (COOH), 1657 (CONR1R2). 1H-NMR (500 MHz, CDCl3): 0.85 (s,
Me(27)); 0.86 (s, Me(26)); 0.89 (s, Me(30)); 0.90 (s, Me(25)); 0.97 (s, Me(29)); 1.08 (s, Me(24)); 1.17 (s,
Me(23)); 0.84 – 0.92 (m, HaꢀC(12)); 1.52 – 1.58 (dm, 2J ¼ 12.8, HeꢀC(12)); 1.56 – 1.62 (dm, 2J ¼ 13.5,
HeꢀC(6)); 1.76 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.77 – 1.83 (dm, 2J ¼ 13.5, HeꢀC(16)); 1.95 – 2.04 (m,
HꢀC(3’), HꢀC(5’)); 2.22 (s, Me(7’)); 2.28, 2.31 (AB, J ¼ 18.1, CH2(1)); 2.72 – 2.87 (m, HꢀC(5), HꢀC(9),
HꢀC(3’) or HꢀC(5’), HꢀC(2’) or HꢀC(6’)); 3.02 – 3.12 (m, HꢀC(5’) or HꢀC(3’), HꢀC(6’) or HꢀC(2’));
3.68 (br. d, J ¼ 12.5, HꢀC(2’) or HꢀC(6’)); 3.86 (s, HꢀC(19)); 4.35 (br. d, J ¼ 12.5, HꢀC(6’) or HꢀC(2’));
others 1.13 – 1.52. HR-MS: 566.4061 ([M ꢀ H2O]þ, C35H54O4N2þ ; calc. 566.4184).

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Table 2. 13C-NMR Data (125 MHz) of Compounds 4 – 81). d in ppm.
C-Atom 4 (in (D6)DMSO) 5 (in CDCl3) 6 (in CDCl3/(D6)DMSO 5 : 1) 7 (in CDCl3) 8 (in CDCl3)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
38.9 (t)
168.8 (s)
180.1 (s)
46.0 (s)
46.6 (d)
20.9 (t)
32.2 (t)
39.8 (s)
40.9 (d)
42.1 (s)
21.0 (t)
26.0 (t)
35.9 (d)
39.7 (s)
27.4 (t)
25.0 (t)
45.4 (s)
45.5 (d)
38.5 (t)
169.5 (s)
184.0 (s)
45.3 (s)
47.9 (d)
19.2 (t)
32.5 (t)
40.3 (s)
41.3 (d)
43.0 (s)
21.9 (t)
26.4 (t)
36.1 (d)
40.2 (s)
27.8 (t)
25.3 (t)
46.0 (s)
46.5 (d)
85.7 (d)
33.4 (s)
32.2 (t)
31.7 (t)
30.9 (q)
21.3 (q)
21.5 (q)
15.2 (q)
13.8 (q)
179.6 (s)
28.6 (q)
23.8 (q)
44.2a) (t)
53.5b) (t)
–
38.2 (t)
168.9 (s)
181.8 (s)
44.5 (s)
47.5 (d)
18.9 (t)
32.1 (t)
39.9 (s)
40.2 (d)
42.1 (s)
21.1 (t)
26.1 (t)
35.6 (d)
39.7 (s)
27.4 (t)
25.0 (t)
45.5 (s)
46.0 (d)
85.4 (d)
33.0 (s)
31.8 (t)
39.1 (t)
170.4 (s)
183.9 (br. s)
46.3 (br. s)
47.6 (d)
20.5 (t)
32.6 (t)
40.4 (s)
41.7 (d)
42.9 (s)
21.7 (t)
26.5 (t)
36.0 (d)
40.1 (s)
27.8 (t)
25.4 (t)
46.0 (s)
46.5 (d)
85.7 (d)
33.4 (s)
32.2 (t)
31.7 (t)
55.6 (t)
224.0 (s)
–
45.7 (s)
59.5 (d)
17.8 (t)
33.2 (t)
41.3 (s)
49.4 (d)
41.2 (s)
23.6 (t)
26.1 (t)
35.9 (d)
40.0 (s)
27.8 (t)
25.4 (t)
46.0 (s)
46.6 (d)
85.9 (d)
33.4 (s)
32.2 (t)
31.8 (t)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
C(26)
C(27)
C(28)
C(29)
C(30)
C(2’)
C(3’)
C(4’)
C(5’)
C(6’)
C(7’)
C(8’)
84.9 (d)
33.0 (s)
32.0 (t)
30.8 (t)
31.3 (t)
25.5a) (q)
25.1a) (q)
20.5 (q)
29.9 (q)
21.1 (q)
20.5 (q)
15.0 (q)
13.3 (q)
179.4 (s)
28.2 (q)
23.3 (q)
41.5a) (br. t)
50.2 (br. t)
–
27.6 (br. q) 27.6 (q)
23.9 (br. q) 20.9 (q)
20.8 (q)
15.5 (q)
13.6 (q)
179.7 (s)
28.6 (q)
23.8 (q)
45.6a) (t)
66.8b) (t)
–
17.9 (q)
15.5 (q)
13.6 (q)
179.5 (s)
28.6 (q)
23.8 (q)
15.1 (q)
13.5 (q)
178.7 (s)
28.3 (q)
23.2 (q)
41.4b) (br. t)
25.8c) (br. t)
24.0 (t)
25.3c) (br. t)
ca. 39.7b) (br. t)
41.4b) (br. t)
25.8c) (br. t)
54.0b) (t)
39.8a) (t)
44.2 (q)
50.2 (br. t)
37.4a) (br. t)
51.3 (t)
66.3b) (t)
41.4a) (t)
8.9 (q)
a
c
)
b) ) Interchangeable signals.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-7-[2-(4-Ethylpiperazin-1-yl)-2-oxoethyl]hexadecahy-
dro-a8,a8,3,3,7,10a,10b-heptamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid (6):
1H-NMR (500 MHz, CDCl3): 0.81 (s, Me(26)); 0.84 (s, Me(27), Me(30)); 0.85 (s, Me(25)); 0.92 (s,
Me(29)); 1.03 (s, Me(24)); 1.10 (s, Me(23)); 1.33 (t, J(8’,7’) ¼ 7.0, Me(8’)); 1.72 (dt, 2J ¼ 13.8, J(16e,15) ¼
3.2, HeꢀC(16)); 1.74 (d, J(18,13) ¼ 11.1, HꢀC(18)); 2.18, 2.23 (AB, J ¼ 18.7, CH2(1)); 2.54 (dd, J(5,6a) ¼
11.8, J(5,6e) ¼ 2.2, HꢀC(5)); 2.98 (q, J(7’,8’) ¼ 7.0, CH2(7’)); 3.03 (dd, J(9,11a) ¼ 12.5, J(9,11e) ¼ 2.5,
HꢀC(9)); 3.83 (s, HꢀC(19)); signals of the piperazine moiety: 2.89 – 3.15 (m, 3 H); 3.15 – 3.30 (m, 1 H);
3.40 (br. s, 1 H); 3.53 – 3.70 (m, 2 H); 4.10 (br. s, 1 H); others 0.65 – 1.43. Anal. calc. for C36H58N2O5
(598.86): C 72.20, H 9.76, N 4.68; found: C 72.05, 72.11, H 9.73, 9.77, N 4.45, 4.55.

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Table 5. 13C-NMR Data (125 MHz, CDCl3) of Compounds 18, 10, 36, 11, 37, 12, and 131). d in ppm.
C-Atom 18 10 36 (major, minor) 11 (major, minor) 37 12 13
44.9 (t) 42.4, 43.2 (t) 44.1 (t) 44.9 (t) 44.9 (t)
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C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
44.8 (t)
44.8, 44.7 (t)
172.4, 172.3 (s)
182.3, 182.2 (s)
45.7, 45.7 (s)
49.6, 49.4 (d)
20.0, 20.0 (t)
32.5, 32.5 (t)
40.2, 40.2 (s)
44.1, 44.2 (d)
43.0, 43.0 (s)
22.1, 22.1 (t)
25.8, 25.8 (t)
36.2, 36.2 (d)
40.2, 40.2 (s)
27.7, 27.7 (t)
25.3, 25.3 (t)
46.0, 46.0 (s)
46.3, 46.3 (d)
85.8, 85.8 (d)
33.4, 33.4 (s)
32.2, 32.2 (t)
31.7, 31.7 (t)
31.3, 31.1 (q)
20.5, 20.4 (q)
20.3, 20.3 (q)
15.6, 15.6 (q)
13.4, 13.4 (q)
179.8, 179.8 (s)
28.6, 28.6 (q)
23.8, 23.8 (q)
43.9, 43.7 (t)
76.9, 76.8 (d)
28.7, 28.6 (t)
25.7, 25.6 (t)
68.1, 68.0 (t)
172.6 (s) 172.3 (s) 172.1, 172.1 (s)
183.7 (s) 182.3 (s) 182.8, 182.5 (s)
45.8 (s) 45.6 (s) 45.3, 45.6 (s)
49.2 (d) 49.5 (d) 50.2, 49.8 (d)
20.2 (t)
32.4 (t)
40.2 (s) 40.2 (s) 40.3, 40.3 (s)
43.7 (d) 44.2 (d) 42.2, 42.9 (d)
43.1 (s) 42.9 (s) 43.8, 43.1 (s)
22.3 (t)
26.0 (t)
36.2 (d) 36.2 (d) 36.1, 36.1 (d)
40.1 (s) 40.2 (s) 40.2, 40.2 (s)
27.6 (t)
25.4 (t)
46.0 (s) 46.0 (s) 46.0, 46.0 (s)
46.4 (d) 46.3 (d) 46.6, 46.5 (d)
85.8 (d) 85.8 (d) 85.8, 85.7 (d)
33.4 (s) 33.4 (s) 33.4, 33.4 (s)
32.2 (t)
31.7 (t)
172.2 (s) 172.2 (s)
183.2 (s) 182.3 (s)
45.8 (s) 45.7 (s)
49.2 (d) 49.5 (d)
172.2 (s)
183.0 (s)
45.6 (s)
49.7 (d)
20.0 (t)
32.5 (t)
19.9 (t)
32.4 (t)
19.2,19.7 (t)
33.0, 32.8 (t)
20.2 (t)
32.5 (t)
20.1 (t)
32.5 (t)
40.2 (s) 40.2a) (s) 40.3 (s)
C(9)
43.3 (d) 44.2 (d)
43.1 (s) 43.0 (s)
44.3 (d)
43.1 (s)
22.2 (t)
25.9 (t)
36.3 (d)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
C(21)
C(22)
C(23)
C(24)
C(25)
C(26)
C(27)
C(28)
C(29)
C(30)
C(31)
C(32)
C(33)
C(34)
C(35)
C(36)
22.1 (t)
25.8 (t)
21.9, 22.0 (t)
26.2, 26.1 (t)
22.2 (t)
26.0 (t)
22.1 (t)
25.8 (t)
36.1 (d) 36.2 (d)
40.2 (s) 40.2a) (s) 40.3 (s)
27.7 (t)
25.3 (t)
27.8, 27.7 (t)
25.4, 25.4 (t)
27.6 (t)
25.4 (t)
46.0 (s) 46.0 (s)
46.4 (d) 46.3 (d)
85.7 (d) 85.8 (d)
33.4 (s) 33.4 (s)
27.7 (t)
25.4 (t)
27.7 (t)
25.4 (t)
46.0 (s)
46.4 (d)
85.8 (d)
33.4 (s)
32.3 (t)
31.8 (t)
31.3 (q)
20.4 (q)
20.3 (q)
15.7 (q)
13.5 (q)
179.9 (s)
28.6 (q)
23.8 (q)
27.2 (q)
32.2 (t)
31.7 (t)
32.2, 32.2 (t)
31.8, 31.8 (t)
32.2 (t)
31.8 (t)
32.2 (t)
31.7 (t)
29.2 (q) 31.3 (q) 29.8, 29.4 (q)
22.2 (q) 20.2 (q) 21.2, 21.7 (q)
19.7 (q) 20.2 (q) 20.9, 20.3 (q)
15.6 (q) 15.6 (q) 15.7, 15.7 (q)
13.4 (q) 13.4 (q) 13.8, 13.6 (q)
179.9 (s) 179.9 (s) 179.8, 179.8 (s)
28.6 (q) 28.6 (q) 28.6, 28.6 (q)
23.9 (q) 23.8 (q) 23.8, 23.8 (q)
29.1 (q) 31.1 (q)
22.2 (q) 20.5 (q)
19.8 (q) 20.2 (q)
15.6 (q) 15.0 (q)
13.3 (q) 13.4 (q)
179.8 (s) 179.9 (s)
28.6 (q) 28.6 (q)
23.8 (q) 23.8 (q)
40.6 (t)
35.4 (t)
41.4 (t)
34.8 (t)
43.5, 43.2 (t)
76.7, 78.0 (d)
35.0 (t)
33.8 (t)
35.5 (t)
32.7 (t)
138.6 (s) 137.9 (s) 28.4, 28.8 (t)
128.5 (d) 128.5 (d) 25.6, 25.4 (t)
128.5 (d) 128.7 (d) 67.8, 67.9 (t)
126.4 (d) 126.8 (d)
173.1 (s) 172.8 (s)
51.8 (q) 51.9 (q)
a) Interchangeable signals.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-7-[2-(mor-
pholin-4-yl)-2-oxoethyl]-13-oxo-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid (7): 1H-NMR
(500 MHz, CDCl3): 0.86 (s, Me(26)); 0.87 (s, Me(27)); 0.89 (s, Me(30)); 0.90 (s, Me(25)); 0.97 (s,
Me(29)); 1.19 (s, Me(24)); 1.21 (s, Me(23)); 0.90 – 0.99 (m, HaꢀC(12)); 1.59 (dddd, 2J ¼ 12.8, J(12e,11a) ¼
4.2, J(12e,13a) ¼ 3.1, J(12e,11e) ¼ 2.8, HeꢀC(12)); 1.78 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.81 (ddd, 2J ¼ 13.7,
J(16e,15a) ¼ J(16e,15e) ¼ 3.4, HeꢀC(16)); 2.27, 2.39 (AB, J ¼ 17.9, CH2(1)); 2.71 (dd, J(5,6a) ¼ 9.3,
J(5,6e) ¼ 5.3, HꢀC(5)); 2.78 (dd, J(9,11a) ¼ 12.5, J(9,11e) ¼ 2.6, HꢀC(9)); 3.87 (s, HꢀC(19)); others
1.13 – 1.55. Anal. calc. for C34H53NO6 (571.79): C 71.42, H 9.34, N 2.45; found: C 71.53, 71.50, H 9.29, 9.31,
N 2.51, 2.47.

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2.2. Pyrolysis of an Amic Acid Mixture: (3aR,5aR,5bR,7aR,11R,11aR,11bR,13aR,13bR)-Octade-
cahydro-3,3,5a,5b,10,10,13b-heptamethyl-11,7a-(epoxymethano)-7aH-cyclopenta[a]chrysene-2,15(1H)-
dione (¼(18a,19b)-19-Hydroxy-3-oxo-2-noroleanan-28-oic Acid g-Lactone; 8). The amic acid mixture
obtained from anhydride 2 0.523 g (1.08 mmol) with benzylamine (0.121 g, 1.13 mmol) in THF (7 ml) was
heated under Ar at 130 – 2208 for 3 h. CC (SiO2, CH2Cl2/Et2O) and recrystallization from EtOH/CH2Cl2
gave 8 (0.213 g, 44% from 2). White powder. IR: 1757 (lactone), 1737 (CO). 1H-NMR (500 MHz,
CDCl3): 0.83 (d, J(25,1a) ¼ 1.2, Me(25)); 0.90 (s, Me(27)); 0.91 (s, Me(26)); 0.93 (s, Me(30)); 0.94 (s,
Me(24)); 0.98 (s, Me(23)); 1.00 (s, Me(29)); 1.04 (dddd, 2J ¼ J(12a,11a) ¼ J(12a,13) ¼ 12.8, J(12a,11e) ¼
4.2, HaꢀC(12)); 1.17 – 1.22 (m, HeꢀC(15)); 1.28 (ddm, 2J ¼ 13.0, J(11e,12a) ¼ 4.2, HeꢀC(11)); 1.63 (dddd,
2J ¼ 12.8, J(12e,11a) ¼ 4.5, J(12e,13a) ¼ 3.4, J(12e,11e) ¼ 2.8, HeꢀC(12)); 1.70 (dd, J(9a,11a) ¼ 12.6,
2
J(9a,11e) ¼ 3.2, HaꢀC(9)); 1.78 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.83 – 1.88 (m, HeꢀC(16)); 1.86 (dd, J ¼
2
15.8, J(1a,25) ¼ 1.2, HaꢀC(1)); 2.15 (d, J ¼ 15.8, HbꢀC(1)); 3.90 (s, HꢀC(19)); others 1.30 – 1.56. Anal.
calc. for C29H44O3 (440.66): C 79.04, H 10.06; found: C 78.79, 78.86, H 9.88, 9.99.
2.3. Cyclic Imides 14 – 17 and Spiro Derivatives 22 – 25: General Procedure. Oxalyl chloride (0.10 –
0.15 ml, 1.2 – 1.7 mmol) was added to a soln. of the corresponding amic acid (0.2 mmol) in THF (7 –
10 ml). After standing for 24 – 48 h, the solvent was evaporated and the residue subjected to CC
(SiO2, CH2Cl2/Et2O): 14 – 17 and 22 – 25.
(5aR,7aR,7bR,9aR,13R,13aR,13bR,15aR,15bR)-Octadecahydro-5,5,7a,7b,12,12,15b-heptamethyl-
3-(2-phenylethyl)-13,9a-(epoxymethano)-9aH-chryseno[1,2-d]azepine-2,4,17(1H,3H)-trione (14): M.p.
259.48. IR: 1772 (lactone), 1713, 1668 (CONRCO). 1H-NMR (500 MHz, CDCl3): 0.90 (s, Me(26),
Me(27)); 0.92 (s, Me(23)); 0.93 (s, Me(30)); 0.95 (s, Me(25)); 1.01 (s, Me(29)); 1.10 – 1.20 (m, HaꢀC(12),
HeꢀC(15)); 1.18 (s, Me(24)); 1.67 – 1.73 (dm, 2J ¼ 12.8, HeꢀC(12)); 1.74 – 1.82 (m, HeꢀC(11), HaꢀC(9));
1.81 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.86 (ddd, 2J ¼ 13.5, J(16e,15a) ¼ 3.5, J(16e,15e) ¼ 3.0, HeꢀC(16));
2
2
2
2.03 (d, J ¼ 13.3, HꢀC(1)); 2.79 (d, J ¼ 13.3, H’ꢀC(1)); 2.86 (ddd, J ¼ 13.4, J(32,31’) ¼ 8.3, J(32,31) ¼
5.7, HꢀC(32)); 2.93 (ddd, 2J ¼ 13.4, J(32’,31) ¼ 8.3, J(32’,31’) ¼ 7.5, H’ꢀC(32)); 3.76 (ddd, 2J ¼ 13.4,
J(31,32’) ¼ 8.3, J(31,32) ¼ 5.7, HꢀC(31)); 3.93 (s, HꢀC(19)); 3.95 (ddd, 2J ¼ 13.4, J(31’,32) ¼ 8.3,
J(31’,32’) ¼ 7.5, H’ꢀC(31)); 7.16 (tt, J(36,35) ¼ 7.0, J(36,34) ¼ 1.7, HꢀC(36)); 7.20 (br. d, J(34,35) ¼ 7.5,
HꢀC(34), HꢀC(38)); 7.24 (dd, J(35,34) ¼ 7.5, J(35,36) ¼ 7.0, HꢀC(35), HꢀC(37)); others 1.21 – 1.58.
Anal. calc. for C38H53NO4 (587.83): C 77.64, H 9.09, N 2.38; found: C 77.77, 77.48, H 9.10, 9.07, N 2.00, 2.02.
(5aR,7aR,7bR,9aR,13R,13aR,13bR,15aR,15bR)-Octadecahydro-5,5,7a,7b,12,12,15b-heptamethyl-
3-[(tetrahydrofuran-2-yl)methyl]-13,9a-(epoxymethano)-9aH-chryseno[1,2-d]azepine-2,4,17(1H,3H)-tri-
one (15): Spectra were recorded for a 1:1 mixture of diastereoisomers. IR: 1774 (lactone), 1747, 1689
(CONRCO). 1H-NMR (500 MHz, CDCl3): 0.86, 0.87 (2s, 2 Me(27)); 0.92 (s, 2 Me(26), 2 Me(30)); 0.98
(s, 2 Me(25)); 1.00 (s, 2 Me(29)); 1.08 – 1.19 (m, 2 HaꢀC(12), 2 HeꢀC(15)); 1.22, 1.23 (2s, 2 Me(24))); 1.26,
1.29 (2s, 2 Me(23)); 1.62 – 1.72 (m, 2 HeꢀC(12)); 1.79 (d, J(18,13) ¼ 11.1, 2 HꢀC(18)); 2.09, 2.10 (2d, 2J ¼
13.2, 2 HꢀC(1)); 2.79, 2.80 (2d, 2J ¼ 13.2, 2 H’ꢀC(1)); 3.45 (dd, 2J ¼ 13.4, J(31,32) ¼ 4.0, HꢀC(31)); 3.62 –
3.69 (m, 3 HꢀC(35)); 3.72 – 3.78 (m, 3 HꢀC(31)); 3.79 – 3.86 (m, 1 HꢀC(35)); 3.92 (s, 2 HꢀC(19)); 3.90 –
3.97 (m, 1 HꢀC(32)); 4.15 – 4.22 (m, 1 HꢀC(32)); others 1.20 – 1.60, 1.75 – 1.97.
(5aR,7aR,7bR,9aR,13R,13aR,13bR,15aR,15bR)-Eicosahydro-5,5,7a,7b,12,12,15b-heptamethyl-
2,4,17-trioxo-13,9a-(epoxymethano)-9aH-chryseno[1,2-d]azepine-3(4H)-propanoic Acid Methyl Ester
1
(16): M.p. 261.48. IR: 1774 (lactone), 1740 (COOMe), 1718, 1671 (CONRCO). H-NMR (500 MHz,
CDCl3): 0.86 (s, Me(27)); 0.90 (s, Me(26)); 0.92 (s, Me(30)); 0.97 (s, Me(25)); 0.99 (s, Me(29)); 1.11
(dddd, 2J ¼ J(12a,11a) ¼ J(12a,13) ¼ 12.8, J(12a,11e) ¼ 4.0, HaꢀC(12)); 1.13 – 1.18 (dm, 2J ¼ 13.0,
HeꢀC(15)); 1.21 (s, Me(24)); 1.23 (s, Me(23)); 1.58 (dd, J(5,6a) ¼ 11.5, J(5,6e) ¼ 2.1, HꢀC(5)); 1.65 –
1.70 (dm, 2J ¼ 12.8, HeꢀC(12)); 1.72 – 1.77 (dm, 2J ¼ 12.5, HeꢀC(11)); 1.78 (d, J(18,13) ¼ 11.0,
HꢀC(18)); 1.78 (br. d, J(9a,11a) ¼ 12.5, HaꢀC(9)); 1.84 (ddd, 2J ¼ 13.5, J(16e,15a) ¼ 3.5, J(16e,15e) ¼
2
3.0, HeꢀC(16)); 2.06 (d, J ¼ 13.3, HꢀC(1)); 2.53 (dd, J(32,31) ¼ 7.5, J(32,31’) ¼ 7.0, HꢀC(32)); 2.80 (d,
2
2J ¼ 13.3, H’ꢀC(1)); 3.63 (s, MeO); 3.75 (dt, J ¼ 13.5, J(31,32) ¼ 7.5, HꢀC(31)); 3.91 (s, HꢀC(19)); 3.98
(dt, 2J ¼ 13.5, J(31’,32) ¼ 7.0, H’ꢀC(31)); others 1.18 – 1.58. Anal. calc. for C34H51NO6 (569.77): C 71.67, H
9.02, N 2.46; found: C 71.45, 71.31, H 8.57, 8.55, N 2.58, 2.59.
(5aR,7aR,7bR,9aR,13R,13aR,13bR,15aR,15bR)-Octadecahydro-5,5,7a,7b,12,12,15b-octamethyl-
13,9a-(epoxymethano)-9aH-chryseno[1,2-d]azepine-2,4,17(1H,3H)-trione (17): M.p. 256.48. IR: 1775
(lactone), 1716, 1669 (CONRCO). 1H-NMR (500 MHz, CDCl3): 0.87 (s, Me(27)); 0.92 (s, Me(26)); 0.93

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(s, Me(30)); 0.98 (s, Me(25)); 1.00 (s, Me(29)); 1.09 – 1.19 (m, HaꢀC(12), HeꢀC(15)); 1.23 (s, Me(24));
2
1.24 (s, Me(23)); 1.58 (dd, J(5,6a) ¼ 11.5, J(5,6e) ¼ 2.0, HꢀC(5)); 1.66 – 1.72 (dm, J ¼ 13.0, HeꢀC(12));
1.73 – 1.79 (dm, 2J ¼ 12.7, HeꢀC(11)); 1.80 (d, J(18,13) ¼ 11.2, HꢀC(18)); 1.80 (br. d, J(9a,11a) ¼ 12.0,
HaꢀC(9)); 1.85 (ddd, 2J ¼ 13.5, J(16e,15a) ¼ 3.5, J(16e,15e) ¼ 2.8, HeꢀC(16)); 2.08 (d, 2J ¼ 13.3, HꢀC(1));
2.81 (d, 2J ¼ 13.3, H’ꢀC(1)); 3.06 (s, Me(31)); 3.92 (s, HꢀC(19)); others 1.23 – 1.58. Anal. calc. for
C31H47NO4 (497.71): C 74.81, H 9.52, N 2.81; found: C 75.09, 75.21, H 9.27, 8.97, N 2.72, 2.78.
(1S,3aR,5aR,5bR,7aR,11R,11aR,11bR,13aS,13bR)-Octadecahydro-3,3,5a,5b,10,10,13b-heptameth-
yl-1’-(2-phenylethyl)spiro[11,7a-(epoxymethano)-7aH-cyclopenta[a]chrysene-1(2H),3’-pyrrolidine]-
2,2’,4’,5’,15-pentone (22): M.p. 271.58. IR: 1775 (lactone), 1740, 1718 (CO). 1H-NMR (500 MHz, CDCl3):
0.53 – 0.59 (dm, 2J ¼ 13.2, HeꢀC(11)); 0.79 (dddd, 2J ¼ J(12a,11a) ¼ J(12a,13) ¼ 13.0, J(12a,11e) ¼ 4.3,
HaꢀC(12)); 0.84 (s, Me(27)); 0.90 (s, Me(30)); 0.92 (s, Me(26)); 0.98 (s, Me(29)); 1.11 (s, Me(24)); 1.14 (s,
Me(23)); 1.29 (s, Me(25)); 1.70 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.82 – 1.87 (dm, 2J ¼ 13.0, HeꢀC(16)); 2.04
(dd, J(9,11a) ¼ 13.1, J(9,11e) ¼ 3.0, HꢀC(9)); 2.70 (dd, J(5,6a) ¼ 10.5, J(5,6e) ¼ 4.4, HꢀC(5)); 2.96 (t,
J(7’,6’) ¼ 7.6, 2 HꢀC(7’)); 3.80 (s, HꢀC(19)); 3.92 – 4.06 (m, 2 HꢀC(6’)); 7.21 (tt, J(11’,10’) ¼ 7.0, J(11’,9’) ¼
1.7, HꢀC(11’)); 7.24 (br. d, J(9’,10’) ¼ 7.0, HꢀC(9’)); 7.28 (br. t, J(10’,9’(11’)) ¼ 7.0, HꢀC(10’)); others 1.12 –
1.62. Anal. calc. for C40H51NO6 (641.84): C 74.85, H 8.01, N 2.18; found: C 74.46, 74.56, H 8.18, 8.19, N
2.20, 2.21.
(1S,3aR,5aR,5bR,7aR,11R,11aR,11bR,13aS,13bR)-Octadecahydro-1’-[(4-methoxyphenyl)methyl]-
3,3,5a,5b,10,10,13b-heptamethylspiro[11,7a-(epoxymethano)-7aH-cyclopenta[a]chrysene-1(2H),3’-pyrro-
lidine]-2,2’,4’,5’,15-pentone (23): Anal. data in [16].
(1S,3aR,5aR,5bR,7aR,11R,11aR,11bR,13aS,13bR)-Octadecahydro-1’-(4-methoxyphenyl)-3,3,5a,5b,
10,10,13b-heptamethylspiro[11,7a-(epoxymethano)-7aH-cyclopenta[a]chrysene-1(2H),3’-pyrrolidine]-
2,2’,4’,5’,15-pentone (24): 1H-NMR (400 MHz, CDCl3): 0.88 (s, Me(27)); 0.90 (s, Me(30)); 0.95 (s,
Me(26)); 0.98 (s, Me(29)); 1.13 (s, Me(24)); 1.19 (s, Me(23)); 1.32 (s, Me(25)); 1.74 (d, J(18,13) ¼ 11.1,
HꢀC(18)); 1.82 – 1.88 (m, HeꢀC(16)); 2.14 (dd, J(9,11a) ¼ 12.8, J(9,11e) ¼ 2.4, HꢀC(9)); 2.76 (dd,
J(5,6a) ¼ 8.2, J(5,6e) ¼ 6.8, HꢀC(5)); 3.82 (s, MeO); 3.83 (s, HꢀC(19)); 7.31 (d, J(7’,8’) ¼ 8.9, HꢀC(7’),
HꢀC(11’)); 7.24 (d, J(8’,7’) ¼ 8.9, HꢀC(8’), HꢀC(10’)); others 0.81 – 1.71.
(1S,3aR,5aR,5bR,7aR,11R,11aR,11bR,13aS,13bR)-Octahydro-3,3,5a,5b,10,10,13b-heptamethyl-1’-
phenylspiro[11,7a-(epoxymethano)-7aH-cyclopenta[a]chrysene-1(2H),3’-pyrrolidine]-2,2’,4’,5’,15-pen-
tone (25): 1H-NMR (400 MHz, CDCl3): 0.87 (s, Me(27)); 0.89 (s, Me(30)); 0.94 (s, Me(26)); 0.97 (s,
Me(29)); 1.13 (s, Me(24)); 1.19 (s, Me(23)); 1.32 (s, Me(25)); 1.73 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.82 –
1.88 (m, HeꢀC(16)); 2.15 (dd, J(9,11a) ¼ 13.0, J(9,11e) ¼ 2.6, HꢀC(9)); 2.76 (dd, J(5,6a) ¼ 8.6,
J(5,6e) ¼ 6.4, HꢀC(5)); 3.83 (s, HꢀC(19)); 7.32 (br. d, J(7’,8’) ¼ 7.2, HꢀC(7’), HꢀC(11’)); 7.44 (br. t,
J(9’,8’) ¼ 7.2, HꢀC(9’)); 7.50 (br. tt, J(8’,9’) ¼ J(8’,7’) ¼ 7.2, HꢀC(8’), HꢀC(10’)); others 0.80 – 1.70.
2.4. Reaction of Amic Acids 19 and 21 with Oxalyl Chloride in an NMR Tube. To the soln. of the
corresponding amic acid (30 – 31 mg) in CDCl3 (0.55 ml) was added (COCl)2 (0.1 ml) and mixed with a
thin glass rod. Spectra were recorded after the termination of gas evolution (30 – 60 min). Additional
exper. data are available from http://limor1.nioch.nsc.ru/quant/conformers/shern/spiro/.
2.5. Model Compounds from Adipic Acid (¼ Hexanedioic Acid). A mixture of adipic acid (5 g),
MeOH (1.2 ml), H2SO4 (3 drops), and CHCl3 (30 ml) was refluxed for 6 h. The mixture was filtered and
the filtrate washed with an aq. Na2CO3 soln., dried (MgSO4), and concentrated to give 2.8 g of a liquid
mixture of methyl and dimethyl adipates (ratio 85 :15 by 1H-NMR). Oxalyl chloride (0.85 ml) was added
to a soln. of this ester mixture (1.1 g) in CH2Cl2 (10 ml). Two drops of dimethylformamide were added to
the mixture as catalyst. After standing for 5 h, solvent and unreacted oxalyl chloride were evaporated,
and the residue was dissolved in CH2Cl2 (12 ml) and added dropwise to a mixture of (4-methoxybenzyl)-
amine (0.95 g) and Et3N (0.8 ml) in CH2Cl2 (8 ml). After standing for 24 h, the mixture was washed with
H2O and dried (MgSO4), the solvent evaporated, and the residue subjected to CC (SiO2, CHCl3/Et2O,
CHCl3/MeOH): methyl 6-[(4-methoxybenzyl)amino]-6-oxohexanoate (27; 1.2 g, 70% with respect to the
1
methyl adipate). Low-melting solid. IR: 1734 (COOMe), 1632, 1552 (CONHR). H-NMR (400 MHz,
CDCl3): 1.55 – 1.68 (m, CH2(3), CH2(4)); 2.16 (t, J(5,4) ¼ 7.0, CH2(5)); 2.28 (t, J(2,3) ¼ 6.9, CH2(2)); 3.61
(s, COOMe); 3.75 (s, MeO); 4.30 (d, J(CH2,NH) ¼ 5.6, CH2ꢀCipso); 5.97 (br. t, J(NH,CH2) ¼ 5.6, NH);
6.81 (d, J(m,o) ¼ 8.6, 2 Hm; 7.15 (d, J(o,m) ¼ 8.6, 2 Ho). 13C-NMR (100 MHz, CDCl3): 173.7 (C(1)); 172.1

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Helvetica Chimica Acta – Vol. 96 (2013)
(C(6)); 158.8 (Cp); 130.3 (Cipso); 129.0 (2 Co); 113.9 (2 Cm); 55.1 (MeOꢀCp); 51.4 (COOMe); 42.8
(CH2ꢀCipso); 36.0 (C(5)); 33.5 (C(2)); 24.9, 24.3 (C(4), C(3)).
Hydrolysis of 27 (0.290 g, 1.04 mmol) was carried out in THF/H2O (30 ml/14 ml) with NaOH
(0.146 g, 3.65 mmol) for 5 h. After neutralization the mixture was extracted with CHCl3 and the extract
dried (MgSO4) and evaporated: 6-[(4-methoxybenzyl)amino]-6-oxohexanoic acid (0.267g, 96%). Low-
melting solid. IR: 3295 (COOH), 1690 (COOH), 1645, 1550 (CO-NHR). 1H-NMR (400 MHz,
(D6)DMSO): 1.42 – 1.56 (m, CH2(3), CH2(4)); 2.11 (t, J(5,4) ¼ 6.9, CH2(5)); 2.20 (t, J(2,3) ¼ 6.9,
CH2(2)); 3.72 (s, MeO); 4.17 (d, J(CH2,NH) ¼ 5.8, CH2ꢀCipso); 6.84 (d, J(m,o) ¼ 8.6, 2 Hm); 7.15 (d,
J(o,m) ¼ 8.6, 2 Ho); 8.24 (br. t, J(NH,CH2) ¼ 5.8, NH); 12.01 (br. s, COOH). 13C-NMR (100 MHz,
(D6)DMSO): 174.4 (C(1)); 171.8 (C(6)); 158.2 (Cp); 131.6 (Cipso); 128.5 (2 Co); 113.7 (2 Cm); 55.0
(MeOꢀCp); 41.4 (CH2ꢀCipso); 35.1 (C(5)); 33.4 (C(2)); 24.9, 24.2 (C(4), C(3)).
2.6. Reaction of Model Compound 27 with Oxalyl Chloride. 1. Oxalyl chloride (0.1 ml, 1.14 mmol)
was added to a soln. of 27 (0.100 g, 0.36 mmol) in CHCl3 (3 ml). After standing for 72 h, the mixture was
concentrated and the residue subjected to CC (SiO2, CHCl3/Et2O): 28 (0.045 g, 38%). 2. Oxalyl chloride
(0.15 ml, 1.71 mmol) was added to 27 (0.150 g, 0.54 mmol) and Et3N (0.2 ml) in CHCl3 (5 ml) (violent
reaction!). After standing for 72 h, the mixture was concentrated and worked up as described above: 29
(0.020 g, 11%).
Data of Methyl (5Z)-5-[3-(4-Methoxybenzyl)-4,5-dioxooxazolidin-2-ylidene)pentanoate (28):
1H-NMR (300 MHz, CDCl3): 1.67 (tt, J(3,2) ¼ J(3,4) ¼ 7.4, CH2(3)); 2.21 (dt, J(4,5) ¼ 7.9, J(4,3) ¼ 7.4,
CH2(4)); 2.22 (t, J(2,3) ¼ 7.4, CH2(2)); 3.62 (s, COOMe); 3.76 (s, MeO); 4.47 (t, J(5,4) ¼ 7.9, HꢀC(5));
4.75 (s, ArCH2); 6.84 (d, J(m,o) ¼ 8.6, 2 Hm); 7.17 (d, J(o,m) ¼ 8.6, 2 Ho). 13C-NMR (100 MHz, CDCl3):
173.3 (C(1)); 159.6 (Cp); 154.5 (C(5) (ox.)); 150.4 (C(4) (ox.)); 140.7 (C(2) (ox.)); 129.0 (2 Co); 125.3
(Cipso); 114.3 (2 Cm); 90.8 (C(5)); 55.5 (MeO); 51.5 (COOMe); 44.3 (ArCH2); 32.9 (C(2)); 24.8, 23.1
(C(4), C(3)).
Methyl 2,5-Dihydro-4-hydroxy-1-(4-methoxybenzyl)-2,5-dioxo-1H-pyrrole-3-butanoate (29):
1H-NMR (400 MHz, CDCl3): 1.76 (tt, J(3,2) ¼ J(3,4) ¼ 7.5, CH2(3)); 2.25 (t, J(4,3) ¼ 7.5, CH2(4)); 2.27
(t, J(2,3) ¼ 7.5, CH2(2)); 3.62 (s, COOMe); 3.77 (s, MeO); 4.73 (s, ArCH2); 6.84 (d, J(m,o) ¼ 8.7, 2 Hm);
7.22 (d, J(o,m) ¼ 8.7, 2 Ho). 13C-NMR (100 MHz, CDCl3): 180.9 (C(4) (pyr.)); 173.2 (C(1)); 161.4 (C(2)
(pyr.)); 159.4 (Cp); 156.5 (C(5) (pyr.)); 129.3 (2 Co); 127.3 (Cipso); 114.1 (2 Cm); 111.5 (C(3) (pyr.)); 55.2
(MeO); 51.5 (COOMe); 43.9 (ArCH2); 33.1 (C(2)); 22.9 (C(3)); 21.2 (C(4)).
2.7. Reaction of 30 with Oxalyl Chloride: (4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-7-{(Z)-[4,5-
Dioxo-3-(phenylmethyl)oxazolidin-2-ylidene]methyl}-hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-
13-oxo-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid Methyl Ester (31). Oxalyl chloride (0.073 g,
0.56 mmol) was added to a soln. of 30 (0.140 g, 0.23 mmol) in THF (3 ml). After standing for 24 h, the
mixture was subjected to CC (SiO2, CH2Cl2/Et2O): 31 (0.133 g, 87%). M.p. 2058. IR: 1824, 1766
(lactone), 1747, 1711. Major form in spectrum (content 79.4%, only characteristic signals): 1H-NMR
(600 MHz, ꢀ 28.28, CDCl3): 0.63 (s, Me(27)); 0.78 (s, Me(26)); 0.93 (s, Me(30)); 0.95 (s, Me(23)); 0.98 (s,
Me(29)); 1.19 (s, Me(25)); 1.12 (s, Me(24)); 0.23 (dddd, 2J ¼ J(12a,13) ¼ J(12a,11a) ¼ 12.8, J(12a,11e) ¼
3.6, HaꢀC(12)); 0.59 – 0.63 (m, HeꢀC(11)); 0.91 (dm, J(9,11a) ¼ 13.0, HꢀC(9)); 1.50 – 1.54 (m, HꢀC(5));
2
1.67 (d, J(18,13) ¼ 11.2, HꢀC(18)); 1.78 (dm, J ¼ 14.0, HeꢀC(16)); 3.46 (s, COOMe); 4.04 (s, HꢀC(1));
4.49, 5.30 (AB, J ¼ 15.3, CH2(6’)); 7.21 – 7.35 (5 arom. H). 13C-NMR (150 MHz, ꢀ 28.28, CDCl3): 180.1 (s,
C(28)); 179.2 (s, C(3)); 155.2 (s, C(3’)); 149.0 (s, C(4’)); 138.4 (s, C(1’)); 133.7 (s, C(7’)); 128.8 (d, C(9’),
C(11’)); 128.2 (d, C(10’)); 127.2 (d, C(8’), C(12’)); 106.7 (d, C(1)); 85.6 (d, C(19)); 55.6 (d, C(5)); 51.7 (q,
COOMe); 47.9 (d, C(9)); 46.2 (s, C(4)); 46.1 (d, C(18)); 45.8 (s, C(17)); 45.4 (s, C(10)); 44.2 (t, C(6’)); 39.8
(s, C(8)); 39.7 (s, C(14)); 35.5 (d, C(13)); 33.2 (s, C(20)); 32.1 (t, C(7)); 31.7 (t, C(21)); 31.4 (t, C(22)); 28.4
(q, C(29)); 27.3 (t, C(15)); 26.8 (br. q, C(24)); 25.7 (t, C(12)); 25.1 (t, C(16)); 23.6 (q, C(30)); 22.3 (br. q,
C(23)); 22.2 (t, C(11)); 19.0 (t, C(6)); 15.4 (br. q, C(25)); 15.1 (q, C(26)); 13.0 (q, C(27)). MS: 659.3832
(Mþ, C40H53NO7þ ; calc. 659.3817). Additional experimental data are available from http://limor1.-
nioch.nsc.ru/quant/conformers/shern/spiro/.
2.8. Reaction of 4 with Phosgene in THF: (4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahy-
dro-a8,a8,3,3,7,10a,10b-heptamethyl-13-oxo-7-[2-oxo-2-(piperidin-1-yl)ethyl]-1H-4,12a-(epoxymethano)-
chrysene-8-acetic Acid 4-Chlorobutyl Ester (32). To a soln. of 4 (0.138 g, 0.24 mmol) in THF (7 ml) was
added 20% phosgene soln. in toluene (1 ml) and refluxed. More 20% phosgene soln. in toluene (0.5 ml)

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was added every 4 h (total amount: 2.5 ml (4.80 mmol)). The solvent was evaporated and the residue
subjected to CC (SiO2, CH2Cl2/Et2O): 32. M.p. 145.08. IR: 1774 (lactone), 1719 (COOR), 1643
1
(CONR1R2). H-NMR (500 MHz, CDCl3): 0.86 (s, Me(26)); 0.87 (s, Me(25)); 0.89 (s, Me(27)); 0.90 (s,
Me(30)); 0.89 – 0.99 (m, HaꢀC(12)); 0.98 (s, Me(29)); 1.16 (s, Me(24)); 1.18 (s, Me(23)); 1.69 – 1.76 (m,
CH2(37)); 1.78 (d, J(18,13) ¼ 11.0, HꢀC(18)); 1.76 – 1.85 (m, HeꢀC(16), CH2(38)); 2.18; 2.31 (AB, J ¼
18.2, CH2(1)); 2.74 – 2.79 (m, HꢀC(5)); 2.94 (dd, J(9a,11a) ¼ 12.5, J(9a,11e) ¼ 2.0, HaꢀC(9)); 3.20 –
3.42, 3.61 – 3.70 (2m, CH2(31), CH2(35)); 3.53 (t, J(39,38) ¼ 6.5, CH2(39)); 3.81 (dt, 2J ¼ 11.0,
J(36,37) ¼ 6.0, HꢀC(36)); 3.88 (s, HꢀC(19)); 4.08 (dt, 2J ¼ 11.0, J(36’,37) ¼ 6.3, H’ꢀC(36)); others
1.10 – 1.65. Anal. calc. for C39H62ClNO5 (660.37): C 70.93, H 9.46, N 2.12, Cl 5.37; found: C 71.51, 71.63, H
9.50, 9.27, N 2.26, 2.03, Cl 4.70, 4.46.
2.9. Secondary Amides from Primary Amines and 2: General Procedure. The primary amine (1.05 –
1.10 mmol) was added to a soln. 2 (1.0 mmol) in the corresponding solvent (Scheme 10; 7 – 10 ml). After
standing 24 – 72 h, the solvent was evaporated and residue subjected to CC (SiO2, CHCl3/MeOH, CHCl3/
AcOEt). If necessary, fractions were resubjected to CC again.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-13-
oxo-7-{2-oxo-2-[(phenylmethyl)amino]ethyl}-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid (33):
M.p. 170 8. IR: 3398 (COOH), 1774 (lactone), 1726 (COOH), 1639, 1547 (CONHR). 1H-NMR
(500 MHz, CDCl3): 0.68 (s, Me(27)); 0.86 (s, Me(26)); 0.90 (s, Me(30)); 0.94 (s, Me(25)); 0.98 (s,
Me(29)); 1.18 (s, Me(23)); 1.19 (s, Me(24)); 0.83 – 0.92 (m, HaꢀC(12)); 1.50 – 1.56 (dm, 2J ¼ 13.0,
HeꢀC(12)); 1.71 – 1.75 (m, HeꢀC(11)); 1.75 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.76 – 1.79 (m, HꢀC(9)); 1.78 –
2
2
1.83 (dm, J ¼ 13.8, HeꢀC(16)); 2.03 (dd, J(5a,6a) ¼ 9.0, J(5a,6e) ¼ 6.5, HaꢀC(5)); 2.24, 2.35 (AB, J ¼
14.8, CH2(1)); 3.88 (s, HꢀC(19)); 4.34, 4.44 (2dd, 2J ¼ 14.8, J(2’,NH) ¼ 5.6, CH2(2’)); 7.20 (tt, J ¼ 7.1,
J ¼ 1.6, HꢀC(6’)); 7.26 (br. t, J ¼ 7.1, HꢀC(5’), HꢀC(7’)); 7.29 (br. d, J ¼ 7.1, HꢀC(4’), HꢀC(8’)); 7.32 (t,
J(NH,2’) ¼ 5.6, NH); others 1.07 – 1.52. Anal. calc. for C37H53NO5 (591.82): C 75.09, H 9.03, N 2.37;
found: C 75.49, 75.13, H 9.14, 8.87, N 1.88, 1.94.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-8-{1,1-Dimethyl-2-oxo-2-[(phenylmethyl)amino]ethyl}-
hexadecahydro-3,3,7,10a,10b-pentamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-7-acetic Acid (34):
IR: 3401 (COOH), 1774 (lactone), 1715 (COOH), 1581, 1546 (CONHR). 1H-NMR (500 MHz, CDCl3):
0.80 (s, Me(27)); 0.84 (s, Me(25)); 0.86 (s, Me(26)); 0.90 (s, Me(30)); 0.99 (s, Me(29)); 1.22 (s, Me(24));
1.27 (s, Me(23)); 1.02 – 1.14 (m, HaꢀC(11), HaꢀC(12)); 1.54 – 1.62 (m, HeꢀC(6), HeꢀC(12)); 1.73 (dd,
J(9a,11a) ¼ 12.0, J(9a,11e) ¼ 2.2, HaꢀC(9)); 1.80 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.78 – 1.85 (m, HeꢀC(11),
HeꢀC(16)); 1.99, 2.23 (AB, J ¼ 14.0, HꢀC(1)); 2.00 (dd, J(5a,6a) ¼ 11.8, J(5a,6e) ¼ 3.0, HaꢀC(5)); 3.90 (s,
HꢀC(19)); 4.44 (d, J(2’,NH) ¼ 5.5, CH2(2’)); 6.80 (t, J(NH,2’) ¼ 5.5, NH); 7.23 – 7.34 (5 arom. H); others
1.16 – 1.54. Anal calc. for C37H53NO5 (591.82): C 75.09, H 9.03, N 2.37; found: C 74.87, 75.03, H 9.69, 9.72,
N 2.74, 2.63.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-7-{2-{[(4-methoxyphenyl)methyl]ami-
no}-2-oxoethyl}-a8,a8,3,3,7,10a,10b-heptamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid
(35): 1H-NMR (400 MHz, CDCl3): 0.65 (s, Me(27)); 0.86 (s, Me(26)); 0.92 (s, Me(30), Me(25)); 0.99 (s,
Me(29)); 1.20 (s, Me(23)); 1.21 (s, Me(24)); 1.74 (d, J(18,13) ¼ 11.1, HꢀC(18)); 2.12 (dd, J(5a,6a) ¼ 8.5,
J(5a,6e) ¼ 6.6, HaꢀC(5)); 2.18, 2.32 (AB, J ¼ 15.1, CH2(1)); 3.75 (s, Me(9’)); 3.87 (s, HꢀC(19)); 4.27, 4.35
2
(2dd, J ¼ 14.4, J(2’,NH) ¼ 5.6, CH2(2’)); 6.80 (d, J(5’,4’) ¼ 8.6, HꢀC(5’), HꢀC(7’)); 6.98 (t, J(NH,2’) ¼
5.6, NH); 7.21 (d, J(4’,5’) ¼ 8.6, HꢀC(4’), HꢀC(8’)); others 0.78 – 1.85.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-8-{2-{[(4-methoxyphenyl)methyl]ami-
no}-1,1-dimethyl-2-oxoethyl}-3,3,7,10a,10b-pentamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-7-
acetic Acid (19): 1H-NMR (400 MHz, CDCl3): 0.78 (s, Me(27)); 0.82 (s, Me(25)); 0.84 (s, Me(26)); 0.88 (s,
Me(30)); 0.97 (s, Me(29)); 1.19 (s, Me(24)); 1.24 (s, Me(23)); 1.70 (dd, J(9a,11a) ¼ 11.3, J(9a,11e) ¼ 2.1,
HaꢀC(9)); 1.78 (d, J(18,13) ¼ 11.2, HꢀC(18)); 1.76 – 1.85 (m, HeꢀC(11), HeꢀC(16)); 1.96, 2.20 (AB, J ¼
14.0, CH2(1)); 1.97 (dd, J(5a,6a) ¼ 11.7, J(5a,6e) ¼ 2.8, HaꢀC(5)); 3.75 (s, MeO); 3.90 (s, HꢀC(19)); 4.33,
4.38 (dd, 2J ¼ 14.5, J(2’,NH) ¼ 5.7, CH2(2’)); 6.82 (d, J(5’,4’) ¼ 8.7, HꢀC(5’), HꢀC(7’)); 6.84 (t, J(NH,2’) ¼
5.7, NH); 7.18 (d, J(4’,5’) ¼ 8.7, HꢀC(4’), HꢀC(8’)); 11.90 (br. s, COOH); others 1.16 – 1.54.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-13-
oxo-7-{2-oxo-2-[(2-phenylethyl)amino]ethyl}-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid (18): IR:
1774 (lactone), 1728 (COOH), 1626, 1546 (CONH). 1H-NMR (500 MHz, CDCl3): 0.76 (s, Me(27)); 0.87

1778
Helvetica Chimica Acta – Vol. 96 (2013)
(s, Me(26)); 0.92 (s, Me(30)); 0.93 (s, Me(25)); 0.89 – 1.00 (m, HaꢀC(12)); 1.00 (s, Me(29)); 1.15 (s,
Me(23)); 1.19 (s, Me(24)); 1.58 (dddd, 2J ¼ 12.8, J(12e,11a) ¼ 3.4, J(12e,11e) ¼ J(12e,13) ¼ 3.2,
HeꢀC(12)); 1.66 – 1.74 (m, HaꢀC(9), HeꢀC(11)); 1.79 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.82 (ddd, 2J ¼
13.5, J(16e,15a) ¼ 3.8, J(16e,15e) ¼ 3.2, HeꢀC(16)); 1.97 – 2.01 (m, HꢀC(5)); 2.16, 2.28 (AB, J ¼ 15.2,
2
CH2(1)); 2.77 – 2.87 (m, CH2(32)); 3.40 (dtd, J ¼ 13.4, J(31,32) ¼ 7.0, J(31,NH) ¼ 5.0, 1 H of CH2(31));
3.65 (dtd, 2J ¼ 13.4, J(31’,32) ¼ 7.0, J(31’,NH) ¼ 6.2, H’ꢀC(31)); 3.90 (s, HꢀC(19)); 6.73 (dd, J(NH,31’) ¼
6.2, J(NH,31) ¼ 5.0, NH); 7.17 – 7.22 (m, HꢀC(34), HꢀC(36), HꢀC(38)); 7.27 (br. t, J(35,34(36)) ¼ 7.5,
HꢀC(35), HꢀC(37)); others 1.10 – 1.55. Anal. calc. for C38H55NO5 (605.85): C 75.33, H 9.15, N 2.31;
found: C 75.15, 75.03, H 9.27, 8.97, N 2.21, 1.93.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-8-{1,1-Dimethyl-2-oxo-2-[(2-phenylethyl)amino]ethyl}-
hexadecahydro-3,3,7,10a,10b-pentamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-7-acetic Acid (10):
M.p. 263.88. IR: 1772 (lactone), 1714 (COOH), 1576, 1551 (CONH). 1H-NMR (500 MHz, CDCl3): 0.75
(s, Me(25)); 0.80 (s, Me(27)); 0.84 (s, Me(26)); 0.89 (s, Me(30)); 0.98 (s, Me(29)); 1.08 (s, Me(24)); 1.03 –
1.13 (m, HaꢀC(11), HaꢀC(12)); 1.19 (s, Me(23)); 1.70 (dd, J(9a,11a) ¼ 11.5, J(9a,11e) ¼ 2.2, HaꢀC(9));
1.81 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.77 – 1.86 (m, HeꢀC(11), HeꢀC(16)); 1.94 (dd, J(5,6a) ¼ 12.0,
J(5,6e) ¼ 3.0, HꢀC(5)); 2.00, 2.27 (AB, J ¼ 13.9, CH2(1)); 2.80 – 2.87 (m, CH2(32)); 3.50 – 3.63 (m,
CH2(31)); 3.91 (s, HꢀC(19)); 6.38 (br. t, J(NH,31) ¼ 5.6, NH); 7.16 (br. d, J(34,35) ¼ 7.5, HꢀC(34),
HꢀC(38)); 7.22 (tt, J(36,35) ¼ 7.5, J(36,34) ¼ 1.8, HꢀC(36)); 7.29 (br. t, J(35,34(36)) ¼ 7.5, HꢀC(35),
HꢀC(39)); 12.08 (br. s, COOH); others 1.14 – 1.64. Anal. calc. for C38H55NO5 (605.85): C 75.33, H 9.15, N
2.31; found: C 75.94, 76.17, H 9.20, 9.33, N 2.29, 2.26.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-13-
oxo-7-{2-oxo-2-{[(tetrahydrofuran-2-yl)methyl]amino}ethyl}-1H-4,12a-(epoxymethano)chrysene-8-acetic
Acid (36): Diastereoisomer mixture 1.0 :0.4. Major in the mixture: 1H-NMR (500 MHz, CDCl3): 0.87 (s,
Me(26)); 0.88 (s, Me(25)); 0.89 (s, Me(30)); 0.91 (s, Me(27)); 0.98 (s, Me(29)); 1.13 (s, Me(24)); 1.18 (s,
Me(23)); 1.81 (d, J(18,13) ¼ 11.0, HꢀC(18)); 1.80 – 1.85 (m, HeꢀC(16)); 1.87 – 1.95 (m, CH2(34)); 1.95 –
2.03 (m, HꢀC(33)); 2.13 – 2.17 (m, HꢀC(5)); 2.19, 2.33 (AB, J ¼ 17.1, CH2(1)); 2.66 (ddd, 2J ¼ 14.0,
J(31,32) ¼ 9.3, J(31,NH) ¼ 4.5, HꢀC(31)); 2.81 (dd, J(9a,11a) ¼ 12.0, J(9a,11e) ¼ 2.0, HaꢀC(9)); 3.72
2
2
(ddd, J ¼ 14.0, J(31’,NH) ¼ 7.5, J(31’,32) ¼ 3.0, H’ꢀC(31)); 3.79 (dt, J ¼ 8.0, J(35,34) ¼ 6.5, HꢀC(35));
3.90 (s, HꢀC(19)); 3.89 – 3.95 (m, H’ꢀC(35)); 4.16 – 4.23 (m, HꢀC(32)); 6.09 (dd, J(NH,31’) ¼ 7.5,
J(NH,31) ¼ 4.5, NH). Minor in the mixture: 1H-NMR (500 MHz, CDCl3): 0.86 (s, Me(27)); 0.88 (s,
Me(26), Me(30)); 0.90 (s, Me(25)); 0.98 (s, Me(29)); 1.16 (s, Me(24)); 1.21 (s, Me(23)); 1.80 (d,
J(18,13) ¼ 11.0, HꢀC(18)); 1.80 – 1.85 (m, HeꢀC(16)); 1.86 – 1.94 (m, CH2(34)); 1.95 – 2.03 (m, HꢀC(31));
2.15 – 2.19 (m, HꢀC(5)); 2.26, 2.32 (AB, J ¼ 16.7, CH2(1)); 2.51 (dd, J(9a,11a) ¼ 12.0, J(9a,11e) ¼ 2.0,
HaꢀC(9)); 3.20 (ddd, 2J ¼ 14.0, J(31,NH) ¼ 3.8, J(31,32) ¼ 2.8, HꢀC(31)); 3.47 (ddd, 2J ¼ 14.0,
2
J(31’,32) ¼ 9.0, J(31’,NH) ¼ 7.0, H’ꢀC(31)); 3.77 (dt, J ¼ 8.0, J(35,34) ¼ 6.5, HꢀC(35)); 3.86 – 3.91 (m,
H’ꢀC(35)); 3.90 (s, HꢀC(19)); 3.97 – 4.04 (m, HꢀC(32)); 6.06 (dd, J(NH,31’) ¼ 7.0, J(NH,31) ¼ 3.8, NH).
Others for both isomers 1.05 – 1.65.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-8-{1,1-Dimethyl-2-oxo-2-{[(tetrahydrofuran-2-yl)me-
thyl]amino}ethyl}hexadecahydro-3,3,7,10a,10b-pentamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-
7-acetic Acid (11): Diastereoisomer mixture 1:1. M.p. 2338. IR: 1774 (lactone), 1716 (COOH), 1584,
1
1545 (CONH). H-NMR (500 MHz, CDCl3): 0.80 (s, 2 Me(27)); 0.87 (s, 2 Me(26)); 0.89 (s, 2 Me(30),
Me(25)); 0.90 (s, Me(25)); 0.97 (s, 2 Me(29)); 1.02 – 1.16 (m, 2 HaꢀC(11), 2 HaꢀC(12)); 1.21 (s, Me(24));
1.22 (s, Me(24)); 1.23 (s, Me(23)); 1.24 (s, Me(23)); 1.80 (d, J(18,13) ¼ 11.1, 2 HꢀC(18)); 1.74 – 1.86 (m,
2 HaꢀC(9), 2 HeꢀC(11), 2 HeꢀC(16)); 1.84 – 1.92 (m, 2 CH2(34)); 1.94 – 2.00 (m, 2 HꢀC(33)); 2.01 (dd,
J(5,6a) ¼ 12.2, J(5,6e) ¼ 3.0, HꢀC(5)); 2.02 (dd, J(5,6a) ¼ 12.2, J(5,6e) ¼ 3.0, HꢀC(5)); 2.15, 2.18, 2.37,
2.38 (2AB, J ¼ 14.2, 2 CH2(1)); 3.07 – 3.15 (m, 2 HꢀC(31)); 3.54 – 3.65 (m, 2 H’ꢀC(31)); 3.68 – 3.75, 3.79 –
3.85 (m, 2 CH2(35)); 3.90 (s, 2 HꢀC(19)); 3.89 – 3.98 (m, 2 HꢀC(32)); 6.72 (dd, J(NH,31’) ¼ 6.2,
J(NH,31) ¼ 4.6, NH); 6.75 (dd, J(NH,31’) ¼ 6.2, J(NH,31) ¼ 4.6, NH); 11.94 (br. s, 2 COOH), others
1.15 – 1.63. Anal. calc. for C35H55NO6 (585.81): C 71.76, H 9.46, N 2.39; found: C 71.47, 71.60, H 9.32, 9.38,
N 2.52, 2.53.
N-{2-[(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-8-(1-Carbonyl-1-methylethyl)hexadecahydro-
3,3,7,10a,10b-pentamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysen-7-yl]acetyl}-b-alanine Methyl Ester
1
(37): IR: 1773 (lactone), 1739 (COOMe), 1702 (COOH), 1630, 1542 (CONH). H-NMR (500 MHz,

Helvetica Chimica Acta – Vol. 96 (2013)
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CDCl3): 0.81 (s, Me(27)); 0.88 (s, Me(26)); 0.90 (s, Me(30)); 0.92 (s, Me(25)); 0.98 (s, Me(29)); 1.00
(dddd, 2J ¼ J(12a,11a) ¼ J(12a,13) ¼ 12.7, J(12a,11e) ¼ 3.4, HaꢀC(12)); 1.20 (s, Me(24)); 1.25 (s, Me(23));
1.61 (dddd, 2J ¼ 12.7, J(12e,11a) ¼ 3.4, J(12e,11e) ¼ J(12e,13) ¼ 3.2, HeꢀC(12)); 1.63 – 1.69 (dm, 2J ¼ 12.7,
HeꢀC(11)); 1.80 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.82 (ddd, 2J ¼ 13.5, J(16e,15a) ¼ 3.8, J(16e,15e) ¼ 3.2,
HeꢀC(16)); 2.09 – 2.15 (m, HꢀC(5)); 2.22, 2.29 (AB, J ¼ 15.5, CH2(1)); 2.50 (ddd, 2J ¼ 16.8, J(32,31’) ¼ 6.7,
J(32,31) ¼ 4.7, HꢀC(32)); 2.59 (ddd, 2J ¼ 16.8, J(32’,31) ¼ 8.2, J(32’,31’) ¼ 4.7, H’ꢀC(32)); 3.36 (dddd,
2
2J ¼ 13.7, J(31,32’) ¼ 8.2, J(31,NH) ¼ 5.5, J(31,32) ¼ 4.7, HꢀC(31)); 3.62 (dddd, J ¼ 13.7, J(31’,32) ¼ 6.7,
J(31’,NH) ¼ 6.3, J(31’,32’) ¼ 4.7, H’ꢀC(31)); 3.67 (s, MeO); 3.90 (s, HꢀC(19)); 6.81 (dd, J(NH,31’) ¼ 6.3,
J(NH,31) ¼ 5.5, NH); others 1.09 – 1.55.
N-{2-[(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-7-(Carboxymethyl)hexadecahydro-3,3,7,10a,10b-
pentamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysen-8-yl]-2-methyl-1-oxopropyl}-b-alanine Methyl
Ester (12): M.p. 254.68. IR: 1768 (lactone), 1745 (COOMe), 1707 (COOH), 1574, 1553 (CONH).
1H-NMR (500 MHz, CDCl3): 0.81 (s, Me(27)); 0.87 (s, Me(25), Me(26)); 0.90 (s, Me(30)); 0.98 (s,
Me(29)); 1.03 – 1.15 (m, HaꢀC(11), HaꢀC(12)); 1.20 (s, Me(24)); 1.22 (s, Me(23)); 1.76 (dd, J(9a,11a) ¼
11.5, J(9a,11e) ¼ 2.1, HaꢀC(9)); 1.81 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.78 – 1.86 (m, HeꢀC(11), HeꢀC(16));
1.99 (dd, J(5,6a) ¼ 12.0, J(5,6e) ¼ 3.0, HꢀC(5)); 2.10, 2.38 (AB, J ¼ 13.9, CH2(1)); 2.55 (dd, J(32,31) ¼ 7.0,
J(32,31’) ¼ 5.3, CH2(32)); 3.51 – 3.58 (m, CH2(31)); 3.68 (s, MeO); 3.90 (s, HꢀC(19)); 7.12 (br. t,
J(NH,31) ¼ 5.6, NH); 11.78 (br. s, COOH); others 1.16 – 1.64. Anal. calc. for C34H53NO7 (587.79): C 69.47,
H 9.09, N 2.38; found: C 69.34, 69.62, H 8.70, 8.76, N 2.52, 2.60.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-8-[1,1-Dimethyl-2-(methylamino)-2-oxoethyl]hexade-
cahydro-3,3,7,10a,10b-pentamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-7-acetic Acid (13): M.p.
277.28. IR: 1770 (lactone), 1713 (COOH). 1578 (CONH). 1H-NMR (500 MHz, CDCl3): 0.83 (s, Me(27));
0.89 (s, Me(26)); 0.90 (s, Me(25)); 0.91 (s, Me(30)); 0.99 (s, Me(29)); 1.05 – 1.17 (m, HaꢀC(11),
HaꢀC(12)); 1.22 (s, Me(24)); 1.25 (s, Me(23)); 1.76 (dd, J(9a,11a) ¼ 11.5, J(9a,11e) ¼ 2.1, HaꢀC(9)); 1.83
(d, J(18,13) ¼ 11.1, HꢀC(18)); 1.80 – 1.90 (m, HeꢀC(11), HeꢀC(16)); 2.00 (dd, J(5,6a) ¼ 12.0, J(5,6e) ¼
3.0, HꢀC(5)); 2.07, 2.39 (AB, J ¼ 13.8, CH2(1)); 2.86 (d, J(31,NH) ¼ 4.6, Me(31)); 3.92 (s, HꢀC(19));
6.44 (br. q, J(NH,31) ¼ 4.6, NH); 12.0 (br. s, COOH); others 1.18 – 1.65. Anal. calc. for C31H49NO5
(515.72): C 72.20, H 9.58, N 2.72; found: C 72.75, 72.87, H 9.57, 9.65, N 2.31, 2.63.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-13-
oxo-7-[2-oxo-2-(phenylamino)ethyl]-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid (21): 1H-NMR
(400 MHz, CDCl3): 0.74 (s, Me(27)); 0.87 (s, Me(26)); 0.91 (s, Me(30)); 0.93 (s, Me(25)); 0.89 (s,
Me(29)); 1.20 (s, Me(24)); 1.27 (s, Me(23)); 1.80 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.93 (br. d, J(9a,11a) ¼
11.3, HaꢀC(9)); 2.10 (dd, J(5,6a) ¼ 10.2, J(5,6e) ¼ 4.6, HꢀC(5)); 2.29, 2.37 (AB, J ¼ 15.1, CH2(1)); 3.92
(s, HꢀC(19)); 7.06 (br. t, J(5’,4’(6’)) ¼ 7.4, HꢀC(5’)); 7.27 (br. dd, J(4’,3’) ¼ 7.8, J(4’,5’) ¼ 7.4, HꢀC(4’),
HꢀC(6’)); 7.52 (br. d, J(3’,4’) ¼ 7.8, HꢀC(3’), HꢀC(7’)); 8.81 (s, NH); others 1.02 – 1.84. 13C-NMR
(100 MHz, CDCl3): 185.3 (C(3)); 180.2 (C(28)); 170.3 (C(2)); 138.1 (C(2’)); 128.8 (C(6’), C(4’)); 123.9
(C(5’)); 119.9 (C(3’), C(7’)); 85.9 (C(19)); 50.1 (C(5)); 46.3 (C(18)); 46.1 (C(17)); 45.8 (C(1)); 45.5
(C(4)); 43.6 (C(10)); 43.6 (C(9)); 40.1, 40.1 (C(8), C(14)); 36.2 (C(3)); 33.4 (C(20)); 32.3 (C(7)); 32.1
(C(21)); 31.7 (C(22)); 30.1 (C(23)); 28.6 (C(29)); 27.6 (C(15)); 25.9 (C(12)); 25.3 (C(16)); 23.8 (C(30));
22.4 (C(11)); 21.6 (C(24)); 20.1 (C(6)); 19.6 (C(25)); 15.7 (C(26)); 13.3 (C(27)).
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-7-{2-[(4-methoxyphenyl)amino]-2-oxo-
ethyl}-a8,a8,3,3,7,10a,10b-heptamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid (20):
1H-NMR (500 MHz, CDCl3): 0.75 (s, Me(27)); 0.88 (s, Me(26)); 0.91 (s, Me(30)); 0.94 (s, Me(25));
0.99 (s, Me(29)); 1.22 (s, Me(24)); 1.28 (s, Me(23)); 1.76 – 1.84 (m, HeꢀC(16), HeꢀC(11)); 1.80 (d,
J(18,13) ¼ 11.1, HꢀC(18)); 1.93 (dd, J(9a,11a) ¼ 11.9, J(9a,11e) ¼ 2.0, HaꢀC(9)); 2.14 (dd, J(5,6a) ¼ 10.4,
J(5,6e) ¼ 4.8, HꢀC(5)); 2.30, 2.38 (AB, J ¼ 15.1, CH2(1)); 3.75 (s, MeO)); 3.91 (s, HꢀC(19)); 6.80 (d,
J(4’,3’) ¼ 8.9, HꢀC(4’), HꢀC(6’)); 7.40 (d, J(3’,4’) ¼ 8.9, HꢀC(3’), HꢀC(7’)); 8.53 (s, NH); others 1.02 –
1.64. 13C-NMR (125 MHz, CDCl3): 185.0 (C(3)); 180.0 (C(28)); 170.2 (C(2)); 156.2 (C(5’)); 131.2
(C(2’)); 121.7 (C(4’), C(6’)); 114.0 (C(3’), C(7’)); 85.9 (C(19)); 55.4 (C(8’)); 50.0 (C(5)); 46.4 (C(18));
46.1 (C(4)); 45.6 (C(1)); 43.7 (C(9)); 43.6 (C(10)); 40.2, 40.2 (C(8), C(14)); 36.2 (C(13)); 33.4 (C(20));
32.4 (C(7)); 32.2 (C(21)); 31.7 (C(22)); 29.9 (C(23)); 28.6 (C(29)); 27.6 (C(15)); 26.0 (C(12)); 25.4
(C(16)); 23.9 (C(30)); 22.4 (C(11)); 21.8 (C(24)); 20.2 (C(6)); 19.6 (C(25)); 15.7 (C(26)); 13.4 (C(27)).

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Helvetica Chimica Acta – Vol. 96 (2013)
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-13-
oxo-1H-4,12a-(epoxymethano)chrysene-7,8-diacetic Acid 7-[2-(Pyridin-4-ylcarbonyl)hydrazide (38): IR:
1
1773 (lactone), 1724 (COOH), 1657, 1573 (CO-NHR). H-NMR (500 MHz, CDCl3/(D6)DMSO): 0.81
(s, Me(27)); 0.84 (s, Me(26)); 0.85 (s, Me(30)); 0.92 (s, Me(25)); 0.93 (s, Me(29)); 0.99 (dddd, 2J ¼ 12.8,
J(11a,12a) ¼ 12.8, J(11a,9a) ¼ 12.2, J(11a,12e) ¼ 3.7, HaꢀC(11)); 1.13 (s, Me(24)); 1.20 (s, Me(23)); 1.62
(dm, 2J ¼ 12.8, HeꢀC(11)); 1.72 (ddd, 2J ¼ 13.5, J(16e,15a) ¼ 4.0, J(16e,15e) ¼ 3.1, HeꢀC(16)); 1.74 (d,
J(18,13) ¼ 11.1, HꢀC(18)); 2.31 (dd, J(5,6a) ¼ 12.0, J(5,6e) ¼ 3.1, HꢀC(5)); 2.34, 2.39 (AB, J ¼ 16.8,
CH2(1)); 3.84 (s, HꢀC(19)); 7.71 (d, J ¼ 6.1, HꢀC(35)); 8.62 (d, J ¼ 6.1, HꢀC(36)); 9.48 (d, J(31,32) ¼ 2.1,
HꢀN(31)); 8.48 (d, J(32,31) ¼ 2.1, HꢀN(32)). 13C-NMR (125 MHz, CDCl3/(D6)DMSO): 182.42 (C(3));
179.24 (C(28)); 170.03 (C(2)); 164.18 (C(33)); 149.65 (C(36), C(38)); 138.87 (C(34)); 121.09 (C(35),
C(39)); 85.25 (C(19)); 49.18 (C(5)); 45.93 (C(18)); 45.47 (C(17)); 44.87 (C(4)); 42.64 (C(10)); 42.05
(C(9)); 40.80 (C(1)); 39.85 (C(8)); 39.74 (C(14)); 35.68 (C(13)); 32.93 (C(20)); 32.09 (C(7)); 31.76
(C(21)); 31.25 (C(22)); 28.93 (C(23)); 28.18 (C(29)); 27.27 (C(15)); 25.66 (C(12)); 24.95 (C(16)); 23.31
(C(30)); 21.49 (C(11)); 21.42 (C(24)); 19.76 (C(25)); 19.43 (C(6)); 15.13 (C(26)); 13.10 (C(27)). Anal.
calc. for C36H51N3O6 (621.81): C 69.54, H 8.27, N 6.76; found: C 69.76, 69.86, H 8.10, 8.30, N 6.37, 6.43.
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-13-
oxo-7-[2-oxo-2-(tricyclo[3.3.1.13,7]dec-1-ylamino)ethyl]-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid
(39): 1H-NMR (500 MHz, CDCl3): 0.80 (s, Me(27)); 0.87 (s, Me(26)); 0.91 (s, Me(30), Me(25)); 0.97 (s,
Me(29)); 1.19 (s, Me(24)); 1.25 (s, Me(23)); 1.64 (br. s, CH2(5’), CH2(7’), CH2(11’)); 1.80 (d, J(18,13) ¼
11.1, HꢀC(18)); 1.99 (br. s, CH2(3’), CH2(10’), CH2(9’)); 2.03 (br. s, HꢀC(4’), HꢀC(6’), HꢀC(8’)); 2.06,
2.21 (AB, J ¼ 14.9, CH2(1)); 3.89 (s, HꢀC(19)); 6.48 (s, NH); others 1.00 – 2.12. 13C-NMR (125 MHz,
CDCl3): 184.1 (C(3)); 179.8 (C(28)); 171.4 (C(2)); 85.8 (C(19)); 51.9 (C(2’)); 49.5 (C(5)); 46.3 (C(18));
46.0 (C(17)); 45.8 (C(1)); 45.7 (C(4)); 43.5 (C(9)); 43.2 (C(10)); 41.4 (C(3’), C(10’), C(9’)); 40.2 (C(8));
40.1 (C(14)); 36.2 (C(5’), C(7’), C(11’)); 36.12 (C(13)); 33.4 (C(20)); 32.5 (C(7)); 32.2 (C(21)); 31.7
(C(22)); 29.7 (C(23)); 29.2 (C(4’), C(6’), C(8’)); 28.6 (C(29)); 27.6 (C(15)); 25.9 (C(12)); 25.3 (C(16));
23.8 (C(30)); 22.4 (C(11)); 22.0 (C(24)); 20.3 (C(6)); 19.5 (C(25)); 15.7 (C(26)); 13.2 (C(27)).
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-8-[1,1-Dimethyl-2-oxo-2-(tricyclo[3.3.1.13,7]dec-1-yl-
amino)ethyl]hexadecahydro-3,3,7,10a,10b-pentamethyl-13-oxo-1H-4,12a-(epoxymethano)chrysene-7-
acetic Acid (40): M.p. 281.48. IR: 1776 (lactone), 1721 (COOH), 1586, 1536 (CO-NHR). 1H-NMR
(500 MHz, CDCl3/(D6)DMSO): 0.58 (s, Me(27)); 0.64 (s, Me(26)); 0.68 (s, Me(25)); 0.69 (s, Me(30));
0.75 (s, Me(29)); 0.90, 1.02 (2s, Me(23), Me(24)); 0.80 (dddd, 2J ¼ 12.7, J(12a,11a) ¼ J(12a,13) ¼ 12.7,
J(12a,11e) ¼ 3.3, HaꢀC(12)); 1.36 – 1.42 (dm, 2J ¼ 12.7, HeꢀC(12)); 1.41 (br. s, CH2(5’), CH2(7’),
CH2(11’)); 1.52 – 1.58 (m, HeꢀC(11), HeꢀC(16)); 1.57 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.73 (d, J ¼ 2.7,
CH2(3’), CH2(9’), CH2(10’)); 1.78 – 1.82 (m, HꢀC(4’), HꢀC(6’), HꢀC(8’)); 1.90 (dd, J(5a,6a) ¼ 11.5,
J(5a,6e) ¼ 3.4, HꢀC(5)); 2.17, 2.30 (AB, J ¼ 14.5, CH2(1)); 3.66 (s, HꢀC(19)); 5.85 (s, NH); others 0.88 –
1.34. MS: 635.4533 (Mþ, C40H61NO5þ ; calc. 635.4544).
(4R,4aR,4bR,6aR,7R,8R,10aR,10bR,12aR)-Hexadecahydro-a8,a8,3,3,7,10a,10b-heptamethyl-13-
oxo-7-{2-oxo-2-[(phenylmethyl)amino)ethyl}-1H-4,12a-(epoxymethano)chrysene-8-acetic Acid Methyl
Ester (30): To a soln. of 33 0.279 g (0.47 mmol) in CHCl3 (10 ml) was added freshly prepared CH2N2
soln. in Et2O (6.5 ml; obtained from N-nitrosomethylurea (0.6 g), KOH (1.7 g), H2O (3 ml), and Et2O
(10 ml). When the excess CH2N2 was decomposed of the solvent was evaporated: 30 0.286 g (100%).
Colorless powder. M.p. 175 – 1768. IR: 1775 (lactone), 1723 (COOMe), 1663, 1531 (CONHR2). 1H-NMR
(500 MHz, CDCl3): 0.74 (s, Me(27)); 0.87 (s, Me(26)); 0.90 (s, Me(30)); 0.91 (s, Me(25)); 0.99 (s,
Me(29)); 1.15 (s, Me(23)); 1.17 (s, Me(24)); 1.04 (dddd, 2J ¼ 12.8, J(12a,11a) ¼ J(12a,13) ¼ J(12a,11e) ¼
12.8, HaꢀC(12)); 1.57 (dm, 2J ¼ 12.8, HeꢀC(12)); 1.80 (d, J(18,13) ¼ 11.1, HꢀC(18)); 1.81 (m, HeꢀC(11));
1.90 (dd, J(9a,11a) ¼ 12.0, J(9a,11e) ¼ 2.2, HaꢀC(9)); 1.91, 2.23 (AB, J ¼ 14.8, CH2(1)); 1.97 (m,
HaꢀC(5)); 3.90 (s, MeO); 3.90 (s, HꢀC(19)); 4.28 (dd, 2J ¼ 14.6, J(2’,NH) ¼ 5.1, HꢀC(2’)); 4.56 (dd, 2J ¼
14.6, J(2’,NH) ¼ 6.2, HꢀC(2’)); 7.06 (dd, J ¼ 6.2, J ¼ 5.1, NH); 7.22 (tt, J(6’,5’) ¼ 7.1, J(6’,4’) ¼ 1.5,
HꢀC(6’)); 7.29 (tt, J ¼ 7.1, J ¼ 1.5, HꢀC(5’), HꢀC(7’)); 7.32 (br. d, J ¼ 7.1, HꢀC(4’), HꢀC(8’)); others
1.08 – 1.54. MS: 605.4068 (Mþ, C38H55NO5þ ; calc. 605.4075).

Helvetica Chimica Acta – Vol. 96 (2013)
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Received August 22, 2012