Synthesis of cytostatic tetradecacyclic pyrazines and a novel reduction-oxidation sequence for spiroketal opening in sapogenins

Article abstract of DOI:10.1002/1522-2675(20000809)83:8<1854::AID-HLCA1854>3.0.CO;2-4

Aiming towards spiroketal-modified artificial cephalostatin molecules, two orthogonal approaches were investigated. First, the introduction of 17-O-functionality into hecogenin derivatives with a closed spiroketal moiety was accomplished by different remote-oxidation procedures. These allowed the synthesis of tetradecacyclic artificial cephalostatin molecules with improved tumor-inhibiting properties. Second, a novel reduction-oxidation pathway for spiroketal opening in sapogenins was discovered, which should provide the basis for a broad access towards spiroketal-modified building blocks for cephalostatins.

Full text of DOI:10.1002/1522-2675(20000809)83:8<1854::AID-HLCA1854>3.0.CO;2-4

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Helvetica Chimica Acta ± Vol. 83 (2000)
Synthesis of Cytostatic Tetradecacyclic Pyrazines and a Novel Reduction-
Oxidation Sequence for Spiroketal Opening in Sapogenins
by Siegfried Bäslera), Annette Brunckb), Rolf Jautelatc), and Ekkehard Winterfeldtb)*
a) Institut für Physikochemie, Schering AG, D-13342 Berlin
b) Institut für Organische Chemie der Universität, Schneiderberg 1b, D-30167 Hannover
c) Medicinal Chemistry, Schering AG, D-13342 Berlin
Dedicated to Prof. Albert Eschenmoser on the occasion of his 75th birthday
Aiming towards spiroketal-modified artificial cephalostatin molecules, two orthogonal approaches were
investigated. First, the introduction of 17-O-functionality into hecogenin derivatives with a closed spiroketal
moiety was accomplished by different remote-oxidation procedures. These allowed the synthesis of
tetradecacyclic artificial cephalostatin molecules with improved tumor-inhibiting properties. Second, a novel
reduction-oxidation pathway for spiroketal opening in sapogenins was discovered, which should provide the
basis for a broad access towards spiroketal-modified building blocks for cephalostatins.
Introduction. ± The cephalostatins [1] and ritterazines [2], e.g., cephalostatin 1 (1)
and cephalostatin 7 (2), constitute a class of marine natural products consisting of 45
tridecacyclic pyrazines that exhibit extraordinarily high cytostatic activity [1 ± 3].
Moreover, these tridecacyclic pyrazines operate via a novel mechanism that has not
been elucidated so far [1c]. Despite their promising biological activity, the scarce
availability from natural sources [1], which is typical for marine natural products [4],
has limited investigations on the cephalostatins to date.
The scarcity and potency of cephalostatins, in combination with the new and
interesting molecular architecture, has stimulated synthetic activities in various
laboratories [5 ± 7]. Among those, the Fuchs group has targeted and recently achieved
the total synthesis of several members of the cephalostatin family, but due to the
complex nature of the target structures, this was an enormous synthetic endeavor [7].
Differently, our approach aims at gaining fast access to cephalostatin analogs as tools to
determine the pharmacologically active structural elements, and, if reaching significant
activity, to eventually participate in in vivo studies [8].
In previous work, a short synthetic approach to the cytostatically active
cephalostatin analog hydroxy ketone 3 (and to diketone 4) starting from commercially
available hecogenin acetate was established [8][9]. Hydroxy ketone 3 showed, in the
NCIꢀs in vitro panel [10], an overall good tumor-inhibiting activity in the range of
common anticancer drugs (Table 1, Entries 3 and 7 ± 9)1). Furthermore, it exhibited the
same activity pattern as the cephalostatins [1b], indicating that it deploys its activity in
the general novel ꢁcephalostatin-likeꢀ mode [11].
1
)
Detailed informations about the cytostatic activity of adriamycin (NSC-123127), cisplatin (NSC-119875),
and 5-fluorouracil (NSC-19893) are available from the National Cancer Institute (NCI) via the internet [3].

Helvetica Chimica Acta ± Vol. 83 (2000)
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The task was now to transform the spiroketal areas into a more cephalostatin-like
appearance. Therefore, two orthogonal approaches were investigated. The first one
consisted of selectively introducing additional functionality into the still closed
spiroketal area ± namely the introduction of 17-O-functionality (vide infra). The other
approach called for a selective spiroketal opening to prepare the system for a wide
variety of transformations without loss of any C-atoms or configurational information.
For a selective modification of the still closed spiroketal moiety, the introduction of
a 17-O-functionality seemed worthwhile to investigate, because structure-activity
relationships (SARs) available from the growing family of cephalostatins and
ritterazines pointed to the importance of a 17-OH group for strong biological activity.
Two pairs of ritterazine, for instance (ritterazine A/ritterazine T and ritterazine B/
ritterazine Y; structures not shown) missing this particular functional group show a 25-
to 330-fold drop of tumor-inhibiting activity [2][7b].
Results and Discussion. ± To transform the unactivated HÀC(17) into the
corresponding tertiary alcohol, remote-oxidation approaches were investigated [12].
Aiming at the direct introduction of O-functionality to the 17-position, the Pb(OAc)4
reaction [13] and an O-variation of the venerable Barton reaction [14] (Oxygen-Barton
reaction) seemed suitable. Both processes require a six-membered chair-like transition
state with an optimum distance between the O-radical and the C-atom of ca. 250 ±
270 pm [13]. From the inspection of molecular models, we assumed that these

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Helvetica Chimica Acta ± Vol. 83 (2000)
conditions could be fulfilled by temporarily adding an a-orientated CH2OH group at
the 12-position as a handle to functionalize the HÀC(17) as depicted in Fig. 1.
Fig. 1. Stereochemical rationalization of a possible remote oxidation at C(17)
Parallel to these considerations, an orientating experiment was conducted to probe
the straightforward access to the HÀC(17) via the readily available 12a-OH group in
homoallylic alcohol 5 [15][9b], since both these functions appeared to be in close
proximity due to the concave shape of the steroidal region of rings C and D. Interestingly,
when homoallylic alcohol 5 was directly subjected to the conditions of a photolytic
Pb(OAc)4 reaction, the regioisomeric allyl acetates 6 and 7 were formed by a b-frag-
mentation followed by recombination of the allyl radical with an acetate radical
(Scheme 1) [16]. The observed diastereoselectivity ± the acetate radical attacks only from
the a-side ± is caused by the concave shape of the rings D and E region and is in line
with several other processes observed on hecogenin derived C-secosteroids [9b][15].
To attach the ꢁ12-handleꢀ, homoallylic alcohol 5 was first transformed into methoxy
ketone 10 via 8 and 9 by a sequence of oxidation [17] and exchange of protecting groups
[18] (Scheme 2). The sterically hindered C(12)ˆOgroup of 10 was then smoothly
transformed by a Wittig reaction to the corresponding alkene 11, which provided, after
Scheme 1. C-Ring Cleavage in Homoallylic Alcohol 5 via Radical-Induced b-Fragmentation

Helvetica Chimica Acta ± Vol. 83 (2000)
Scheme 2. Successful Oxygen-Barton Reaction
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a chemoselective hydroboration-oxidation [19] and chromatographic separation, the
two epimeric alcohols 12 and 13 ready for remote oxidation experiments (Scheme 2).
For the evaluation of the Oxygen-Barton reaction, the corresponding nitrites 14 and
17 (Scheme 2; nitrite 17 resulting from 13, not shown) were prepared from alcohols 12
and 13. On irradiation with UV light in an O2-saturated benzene solution, a-nitrite 14
gave rise to the projected nitrate 15, albeit in very low yield (10%; see Scheme 2). These
conditions also afforded 10% of the aldehyde 16 and 18% of the free alcohol 12 [20].
The b-nitrite 17 behaved ± to our surprise (vide infra) ± similarly under identical
reaction conditions, providing the corresponding nitrate 18 (9%), aldehyde 19 (19%),
and alcohol 13 (22%; compounds not shown). The very low yield of the nitrates led to
the termination of these particular investigations at this point. Nevertheless, the
synthesis of nitrates 15 and 18 presents, to our knowledge, the first successful
application of the Oxygen-Barton reaction on a tertiary center.
Fortunately, subjecting the a-alcohol 12 to the conditions of the photolytic
Pb(OAc)4 reaction delivered the projected a-ether 20 in good yield (Scheme 3) [21].
Interestingly, the b-alcohol 13 gave, under the same conditions, mainly rise to the 12,17-
ether 21 and provided the expected 12,18-ether 22 only as a by-product (Scheme 3),

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Scheme 3. LeadTetraacetate Reaction of Alcohols 12 and 13
though from the inspection of molecular models, b-alcohol 13 appeared to be an
excellent candidate to furnish the 12,18-ether 22.
Although the generation of 20 proved the feasibility of our plans, further
transformations of this product, including the removal of the added CH2 group, did
not look very promising2). Therefore, an attempt was started to accomplish the 17-
functionalization in a system that should permit the removal of this extra handle
necessary for the remote oxidation. The synthesis of benzoate 26 was targeted
(Scheme 4), which should then be transformed into the 12-keto-17-hydroxy compound
via regioselective base-induced elimination followed by a chemoselective oxidative
enol-ether cleavage (for examples, see [23]).
Addition of in situ generated [(4-methoxyphenoxy)methyl]lithium [24] to the
hindered 12-keto function of methoxy ketone 10 proceeded smoothly with excellent
yield and moderate diastereoselectivity (a/b 3.5 :1) from the a-side to afford the 12a (4-
methoxyphenoxy)methyl-substituted alcohol 23 (73%; absolute configuration 12b;
Scheme 4) and its 12-epimer 23a (23%; compound not shown). The protection of the
sterically shielded tertiary alcohol function in 23 under vigorous conditions (deproto-
nation with BuLi followed by benzoyl-chloride treatment) furnished benzoate 24 and
subsequent oxidative removal of the methoxyphenoxy group (Ce(NH4)2(NO3)6 in
MeCN) provided the corresponding free primary alcohol 25 (Scheme 4)3). In contrast
to alcohol 12, benzoate 25, when subjected to the Pb(OAc)4 reaction, led only to slow
decomposition of the starting material, and no 26 was formed.
Since the benzoyloxy group of 25 seemed to have a pivotal impact on the remote-
oxidation procedure ± possibly changing significantly the favorable orientation of the
CH2OH group and thereby ꢁhinderingꢀ the optimal conformation necessary for a
successful remote reaction [13] ± the synthesis of the free glycol 30 (Scheme 4) was
targeted. A straightforward attempt to remove the methoxyphenoxy protecting group
of alcohol 23 under standard oxidative conditions provided the unexpected quinone
monoketal 27 (Scheme 4). Although this product represents a dead end in our efforts,
2
)
Few attempts to open the newly generated tetrahydrofuran system under Lewis acid catalyzed conditions
[22a] or to oxidize it to the corresponding lactone [22b] were unsuccessful due to insufficient stability of the
allyl-ether region and the spiroketal moiety under the required conditions.
The tertiary benzoate 25 showed modest stability to intramolecular transbenzoylation (on prolonged
standing in polar solvents, e.g., CHCl3, the benzoyl shift proceeded slowly), and the existence of the tertiary
benzoate in 25 was established by the coupling pattern of the CH2OH protons (see Exper. Part).
3
)

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1859
Scheme 4. Attempts towards Heptacycle 26. CAN ˆ Ce(NH4)2(NO3)6, MO Mˆ MeOCH2
its easy formation merits a few comments. Several synthetic pathways to quinone
monoketals ± as important precursors for various types of natural products ± exist, but
none of them utilizes the versatile reagent Ce(NH4)2(NO3)6 [25 ± 27]. Furthermore, the
direct transformation of alkoxyanisoles into quinone monoketals had only so far been
accomplished by electrochemical reactions [28]. Therefore ± to our knowledge ± the
transformation 23 ! 27 represents the first Ce(NH4)2(NO3)6-facilitated generation of a
quinone monoketal.
Additionally, this quinone derivative 27 showed strong cytostatic activity (Table 1,
Entry 6), but since all other monomeric steroids proved to be biologically inactive in
our hands and also in the investigations from other groups [7], this unusual activity is
most likely due to the strong Michael-acceptor system of the quinone monoketal
moiety, therefore implying general toxic properties of this compound [29]. The attempt
to hydrolyze the quinone monoketal 27 under acidic conditions (aq. HCl solution in
THF) furnished the corresponding chlorohydroquinone 27 in a dienone-phenol-type
rearrangement (Scheme 4) [30].

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Table 1. SelectedBiological Data of Cephalostatins andCephalostatin Analogs: Decadic Logarithms of Tumor-
Inhibiting in vitro Concentrations against NCIꢀs Standard Screening Panel and Other Cell Lines (n.t. ˆ not
tested)
Entry
MG-MIDa)
Ov-Mz-10b)
Ov-Mz-17ab)
Ov-Mz-1bb)
Natural products:
1
2
Cephalostatin 1 (1)
Cephalostatin 7 (2)
À 8.9
À 7.9
n.t.
n.t.
n.t.
n.t.
n.t.
n.t.
Artificial molecules:
3
4
5
6
Hydroxy ketone 3
a-Ether 36
b-Ether 37
Quinone monoketal 27
À 5.3
n.t.
n.t.
À 5.2
À 5.5
À 6.3
À 6.1
>À 5.0
>À 5.0
>À 5.0
À 6.0
>À 5.0
>À 5.0
>À 5.0
À 6.1
n.t.
Anticancer drugs:
7
8
9
Adriamycin [3]
Cisplatin [3]
5-Fluorouracil [3]
À 6.9
À 5.7
À 4.7
À 7.2
À 5.1
n.t.
À 7.2
>À 5.0
n.t.
À 7.0
À 5.1
n.t.
a) NCIꢀs standard in vitro screening panel (average value). b) Cell lines at university of Ulm.
A simple change in protecting-group strategy then allowed the synthesis of glycol 30
from methoxy ketone 10 and generated [(methoxymethoxy)methyl]lithium [31]
( ! 29) in situ, followed by deprotection (aq. HCl solution in THF) and separation
of the 12-epimers (Scheme 4). Since the Pb(OAc)4-triggered cleavage of glycols is
reported to proceed with extremely varying reactions rates ± depending on the nature
of the substrate [32] ± we dared to subject glycol 30 to the Pb(OAc)4 oxidation, but
glycol splitting delivered methoxy ketone 10 as the only product4).
The results regarding 17-O-functionalization were applied to hydroxy ketone 3. It
was TBS-protected ( ! 31) and then subjected to the Wittig reaction to deliver alkene
32, which was consecutively hydroborated and oxidized to provide a mixture (a/b 2 :1)
of the epimeric primary alcohols 33 (Scheme 5). These alcohols were subjected to the
conditions of a photolytic Pb(OAc)4 reaction to furnish ± after chromatographic
separation ± TBS ethers 34 and 35 as isolated products. Finally, deprotection afforded
12a-ether 36 and 12b-ether 37 in 10 and 19% overall yield, respectively, from hydroxy
ketone 3.
A first screen of these 17-O-functionalized artificial cephalostatin molecules against
an in vitro cancer-cell-line assay provided evidence for an increased tumor-inhibiting
activity (2 Â and 13 Â ) of these analogs compared to hydroxy ketone 3 (Table 1,
Entries 4 and 5)5). Thus, the introduction of the 17-O-function did, indeed, improve
tumor-inhibiting properties of these cephalostatin analogs and, therefore, justified our
assumption from the SAR of the natural products (vide supra).
The second part of our investigations was directed towards a selective spiroketal
opening (vide supra) as an ultimate requisite for a broad access to a multitude of
4
)
)
An alternative attempt to promote oxidation at C(17) via the Baldwin protocol [33] by reacting the 12-
oxime (not shown; derived from methoxy ketone 10) and PdH2Cl2 was also unsuccessful.
One must mention that two of the three cell lines used in this first assay system were insensitive towards the
artificial cephalostatin molecules. That is not an unexpected effect since cephalostatins showed strongly
pronounced selectivity against certain cell lines in the NCIꢀs in vitro panel ± varying by a factor of 10000.
Nevertheless, further biological evaluations would be useful to verify these results.
5

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1861
Scheme 5. Synthesis of Tetradecacyclic Ethers 36 and 37. TBS ˆ tBuMe2Si.
spiroketal modifications as outlined in Scheme 6. This was a difficult task since
spiroketal opening in steroids in the desired way (A ! B in Scheme 6) are described to
occur only in low yield and demand harsh acidic conditions [34]6), and these were
expected to be detrimental to the D-ring allyl ether system. Since from our own
experiments [35], which were later confirmed by other results [7], it was evident that
the establishment of the important C(14)ˆC(15) bond at a later stage of the synthesis
would be problematic, directed spiroketal opening in the presence of this group was
mandatory.
Indeed, first attempts to open the spiroketal moiety under acid-catalyzed conditions
failed but provided a substantial variety of rearranged products, of which spiroketal
dienes 39 and 40 (Scheme 7) are worth mentioning. Treatment of either the homoallylic
6
)
Orthogonal to these results, the versatile Marker degradation of the spiroketal moiety proceeds in high
yield but via synthetic intermediates which were not suitable for our purposes.

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Scheme 6. Potential Approach to a Flexible Spiroketal Functionalization
alcohol 5 or its 12-epimer 38 [17b] with p-toluenesulfonic acid (TsOH) in pentane
afforded the rearranged dienes 39 and 40 in modest yields. The structure of diene 40
was unambiguously established by X-ray analysis (Fig. 2), while ± besides NMR, MS
and IR studies ± an important evidence for the structure of cyclopentadiene 39 was its
readiness to form with maleimide the corresponding Diels-Alder adduct 41 ± a reaction
and a type of structure this laboratory is quite experienced with [36] (Scheme 7). A
potential mechanism for these rearrangements is outlined in Scheme 8. The inversion of
the configuration at C(12) (5 ! 39 and 38 ! 40) can be accounted for by an acid-
catalyzed intramolecular nucleophilic substitution [37]. These results are consistent
with related acid-catalyzed rearrangements of hecogenin derivatives reported recently
by the Fuchs group [38].
Further studies directed at alternative spiroketal opening procedures revealed that
the reductive opening employing mild conditions (NaCNBH3 in AcOH) [39] provided
the tetrahydrofurans 44 (94% from 5) and 45 (95% from 42; Scheme 9). This
comparatively mild ring-opening procedure7) proved to be of general nature in the
sapogenin series since it was also applicable to the corresponding natural products
Scheme 7. Acid-Catalyzed Rearrangements of Homoallylic Alcohols 5 and 38
7
)
Known vigorous reductive conditions for spiroketal opening in sapogenins are PtO2/H2 [40a] and LiAlH4/
AlCl3 [40b].

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Scheme 8. Potential Mechanistic Pathways for the Formation of Dienes 39 and 40
Fig. 2. X-Ray structure of dienyl acetate 40
diosgenin 43 ( ! 97% of 46), tigogenin 47 ( ! 55% of 49), and smilagenin 48 ( ! 76%
of 50) and also to the cephalostatin analog 4 ( ! 96% of 51) (Scheme 9). The structure
of the furostane-type products was unambiguously established by X-ray analysis of the
tigogenin derivative 49 (Fig. 3).

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Scheme 9. Novel Reductive Opening of Sapogenin Spiroketals
Fig. 3. X-Ray structure of furostane-3,26-diol 49

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Conversion of the primary alcohol function of 45 into the corresponding alkene 54
was then achieved smoothly according to standard protocols (Scheme 10) [41]. The
following oxidative opening of the furan moiety of 54 required extensive optimization
along known protocols [42], but finally, treatment of furostane 54 with potassium
dichromate in AcOH at 708 for 3 h provided the desired dienedione 55 in acceptable
yield. This diketone 55 offers numerous opportunities for introduction of functionality
at all relevant C-atoms and for all possible types of cyclizations, thus giving access to the
complete structural diversity in this field8).
Scheme 10. Synthesis of Dienedione 55
Conclusion. ± The synthesis of 17-O-functionalized tetradecacyclic cephalostatins
with increased tumor-inhibiting potency is an additional piece of evidence for the
importance of 17-O-functionality for biological activity ± and a free 17-OH group is not
a sine qua non. A novel way to access the important general intermediate dienedione 55
via a reduction-oxidation sequence was discovered, and this sequence should give
general access to a variety of spiroketal-modified building blocks, which should pave
the road for more exploratory research into the SAR of cephalostatins and related
molecules.
This work was supported by the Fonds der Chemischen Industrie and the DFG. We thank Dr. Wray and Mr.
R. Christ, Gesellschaft für Biotechnologische Forschung m.b.H., Brunswick (Germany), for providing high-
resolution FAB mass spectroscopic analysis. We thank especially Prof. U. Eder and Dr. H. Laurent, Schering AG,
Berlin (Germany), for valuable support. A.B. thanks the Studienstiftung des Deutschen Volkes for a scholarship
and R.J. the Fonds der Chemischen Industrie.
Experimental Part
General. Reactions were performed under dry conditions (dry solvents) under Ar, unless otherwise stated.
Reagents were purchased from commercial sources (Acros, Aldrich, and Fluka) at highest quality available and
were used as received unless otherwise stated.
8
)
Since one of us (E.W.) will have to retire this fall, the activities at the Hannover laboratory will not
continue. Colleagues interested in these results and in the further exploitation of this area are cordially
invited to join the fun.

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Irradiation experiments were performed in a quartz flask by a mercury high-pressure lamp (Phillips-HPK
125 W) with a Pyrex filter, the quartz flask being partly dipped into a 58-cold water bath to maintain low temp.
despite strong irradiation; the Pb(OAc)4 was dried in a vacuum desiccator over P2O5 and KOH (contained in
separate bowls!) and pulverized prior to use. TLC (reaction monitoring): silica gel 60F254 alu foils (Merck),
detection by UV light at 254 nm and staining with cerium(IV) sulfate/phosphomolybdic acid and heat. Flash
column chromatography (FC): Baker silica gel, particle size 0.03 ± 0.06 mm, unless otherwise stated. M.p.:
Gallenkamp-MPD-350 apparatus; not corrected. UV Spectra: Beckman spectrometer, model 3600, lmax in nm,
s ˆ strong, w ˆ weak, and sh ˆ shoulder). IR Spectra: Perkin-Elmer-580 and FT-1710 spectrometers; in cmÀ1
.
NMR Spectra: Bruker-AM-400 instrument with Me4Si or CDCl3 as internal standards; d in ppm, J in Hz; only
Me protons and all protons downfield of 2.0 ppm are cited, other steroidal-proton signals between 0.7 ± 2.0 ppm
lacking analytical values; DEPT spectra are quoted as q (ꢀCH3), t (ꢀCH2), d (ꢀCH), and s (ꢀC), standard
steroid numbering is used [43]. MS: MAT-312 (Finnigan), ionization potential 70 eV; fast-atom-bombardment
ionization (FAB) with a VG Autospec spectrometer in a 3-nitrobenzyl alcohol (NBA) matrix; high-resolution
(HR) MS by the peak-matching method with a VG-Autospec spectrometer; HR-FAB-MS with a MAT 95
(Finnigan) at the Gesellschaft für Biotechnologische Forschung m.b.H., Brunswick. Elemental analysis were
performed on a CHN-Rapid (Heraeus) and a varioEL (elementar Analysensysteme GmbH).
(1S,2R,4aS,6S,8aS)-6-Acetoxy-2-{(2R,3S,3aR,4R,5'R,6aS)-6-acetoxy-3,3',3a,4',5',6',6,6',6a-octahydro-3,4,5'-tri-
methylspiro[2H-cyclopenta[b]furan-2,2'-[2H]pyran]-5-yl}-octahydro-8a-methylnaphthalene-1-acetaldehyde (6)
and(1 S,2R,4aS,6S,8aS)-6-Acetoxy-2-{(2R,3S,3aS,4R,5'R,6aS)-4-acetoxy-3,3',3a,4,4',5',6',6a-octahydro-3,4,5'-tri-
methyl
spiro[2H-cyclopenta[b]furan-2,2'-[2H]pyran]-5-yl}-octahydro-8a-methylnaphthalene-1-acetaldehyde
(7). A 108-cold suspension of homoallyl alcohol 5 (200 mg, 0.423 mg, 1 equiv.), Pb(OAc)4 (640 mg, 1.44 mmol,
3.3 equiv., dried prior to use, see General), and dry pyridine (0.15 ml, 1.89 mmol, 4.4 equiv.) in benzene (8 ml)
was irradiated (see General) under vigorous stirring for 80 min. Then the solid material was removed by column
filtration (silica gel, Et2O), the combined org. layer washed with 5% H2SO4 soln., sat. NaHCO3 soln., and brine,
dried (MgSO4), and evaporated. FC (petroleum ether/Et2O1:1) gave 6 (25 mg, 11%), 6/7 1 :1 (91 mg, 41%),
and finally 7 (18 mg, 8%), all as white foams. Mixture 6/7. Anal. calc. for C31H46O7 (530.70): C 70.16, H 8.74;
found: C 70.02, H 8.78.
Data of 6: IR (KBr): 2928s, 2868m, 2720w, 1736s, 1452m, 1368m, 1240s. 1H-NMR (400 MHz, CDCl3; steroid
numbering): 0.79 (d, J ˆ 6, Me(27)); 0.84 (s, Me(19)); 1.06 (d, J ˆ 7, Me(21)); 1.71 (s, Me(18)); 2.02 (s, AcO);
2.08 (s, AcO); 2.22 (br. d, J ˆ 17.5, HÀC(11)); 2.32 (br. dd, J ˆ 17.5, 5.5, HÀC(11)); 2.50 (br. td, J ˆ 11.5, 3.5,
HÀC(8)); 2.84 (dd, J ˆ 7, 6.5, HÀC(17)); 3.38 ± 3.49 (m, CH2(26)); 4.16 (br. d, J ˆ 7, H ÀC(16)); 4.69 (tt, J ˆ 11,
5, HÀC(3)); 5.77 (br. s, HÀC(15)); 9.61 (br. s, HÀC(12)). 13C-NMR (100 MHz, CDCl3; steroid numbering):
11.7, 13.3, 14.1, 17.1 (4q, C(18), C(19), C(21), C(27)); 21.4, 21.6 (2q, 2 MeCO); 27.2 (t); 28.2 (t), 28.5 (t); 30.3 (d);
30.7 (t); 31.0 (t); 33.9 (t); 36.77 (d); 36.82 (s, C(10)); 37.9 (t); 43.4 (t, C(11)); 44.1 (d); 46.9 (d); 47.8 (d); 58.7
(s, C(17)); 67.0 (t, C(26)); 73.0 (d, C(3)); 83.8, 84.7 (2d, C(15), C(16)); 107.1 (s, C(22)); 132.3, 145.4 (2s, C(13),
‡
C(14)); 170.3, 170.6 (2s, 2 MeCO); 202.9 (d, C(12)). MS (1708): 530 (1, M ), 470 (8), 452 (8), 373 (19), 356 (33),
‡
126 (100). HR-MS: 530.3250 (C31H46O7 ; calc. 530.3244).
Data of 7. IR (KBr): 2928s, 2868m, 2720w, 1736s, 1452m, 1368m, 1244s. 1H-NMR (400 MHz, CDCl3; steroid
numbering): 0.79 (d, J ˆ 6, Me(27)); 0.84 (s, Me(19)); 1.15 (d, J ˆ 7, Me(21)); 1.60 (s, Me(18)); 1.98 (s, AcO);
2.03 (s, AcO); 2.18 (m, HÀC(8)); 2.23 ± 2.38 (m, CH2(11)); 2.92 (dd, J ˆ 9.5, 7.5, HÀC(17)); 3.38 (t, J ˆ 11,
1 HÀC(26)); 3.47 (br. d, J ˆ 11, 1 HÀC(26)); 4.72 (tt, J ˆ 11, 5, HÀC(3)); 4.89 (br. d, J ˆ 7.5, HÀC(16)); 5.79
(br. s, HÀC(15)); 9.61 (br. s, HÀC(12)). 13C-NMR (100 MHz, CDCl3; steroid numbering): 12.0, 13.3, 17.1, 19.3
(4q, C(18), C(19), C(21), C(27)); 21.4, 22.2 (2q, 2 MeCO); 27.1 (t); 28.5 (t); 28.6 (t); 30.3 (d); 31.1 (t); 33.85 (t);
33.89 (t); 36.86 (d); 36.91 (t); 36.93 (s, C(10)); 43.7 (t, C(11)); 43.9 (d); 45.2 (d); 47.2 (d); 56.1 (s, C(17)); 67.1
(t, C(26)); 73.1 (d, C(3)); 83.4 (d, C(16)); 93.9 (s, C(13)); 107.6 (s, C(22)); 130.8 (d, C(15)); 152.0 (s, C(14));
‡
170.1, 170.6 (2s, 2 MeCO); 202.1 (d, C(12)). MS (1608): 530 (1, M ), 470 (10), 374 (16), 356 (34), 126 (100). HR-
‡
MS: 530.3246 (C31H46O7 ; calc. 530.3244).
(3b,5a,25R)-3-Hydroxyspirost-14-en-12-one (9). A soln. of acetoxy ketone 8 (4.749 g, 10.08 mmol, 1equiv.)
and KOH (1.12 g, 20 mmol, 2 equiv.) in CH2Cl2/MeOH 1:1 (16 ml) was stirred at 508 for 2 h. The reaction was
quenched by addition of H2O(25 ml), the aq. layer extracted with CH 2Cl2, the combined org. layer washed with
sat. aq. NH4Cl soln., dried (Na2SO4), and evaporated, and the residue recrystallized from CH2Cl2/MeOH: 9
(4.143 g, 96%). Colorless crystalline solid. M.p. 2208 (from CH2Cl2/MeOH). IR (KBr): 3456m (br.), 2928s,
2860s, 1708s, 1644w, 1460m, 1376m, 1240m. 1H-NMR (400 MHz, CDCl3): 0.80 (d, J ˆ 6.5, Me(27)); 0.93 (s,
Me(19)); 1.04 (d, J ˆ 7, Me(21)); 1.29 (s, Me(18)); 2.35 (dd, J ˆ 14.5, 5, 1 HÀC(11)); 2.43 ± 2.48 (m, HÀC(8));
2.56 (dd, J ˆ 14.5, 13.5, 1 HÀC(11)); 3.33 (t, J ˆ 8.5, HÀC(17)); 3.41 (t, J ˆ 11, 1 HÀC(26)); 3.51 (br. d, J ˆ 11,
1 HÀC(26)); 3.59 (tt, J ˆ 11, 4.5, HÀC(3)); 4.76 (dd, J ˆ 8.5, 2, HÀC(16)); 5.43 (br. s, HÀC(15)). 13C-NMR

Helvetica Chimica Acta ± Vol. 83 (2000)
1867
(100 MHz, CDCl3): 11.8, 13.8, 17.1, 20.9 (4q, C(18), C(19), C(21), C(27)); 28.0 (t); 28.7 (t); 29.5 (t); 30.3 (d);
31.17 (t); 31.22 (t); 34.2 (d); 36.3 (s, C(10)); 36.5 (t); 37.4 (t); 37.8 (t); 44.1 (d); 44.2 (d); 49.7 (d); 53.7 (d); 62.3
(s, C(13)); 67.1 (t, C(26)); 70.8 (d, C(3)); 84.0 (d, C(16)); 107.1 (s, C(22)); 120.9 (d, C(15)); 154.9 (s, C(14));
‡
211.5 (s, C(12)). MS (1408): 428 (51, M ), 411 (19), 356 (24), 313 (100), 299 (85), 148 (56), 126 (96). HR-MS:
‡
428.2931 (C27H40O4 ; calc. 428.2927). Anal. calc. for C27H40O4 (428.61): C 75.66, H 9.41; found: C 75.62, H 9.39.
(3b,5a,25R)-3-Methoxyspirost-14-en-12-one (10). To a soln. of 9 (2.011 g, 4.70 mmol, 1 equiv.) and 2,6-
di(tert-butyl)pyridine (1.28 ml, 6.11 mmol, 1.3 equiv.) in CH2Cl2 (10 ml), methyl triflate (0.67 ml, 6.11 mmol,
1.3 equiv.) was added dropwise. After 4 h, the reaction was quenched by addition of sat. NaOAc soln. (4 ml), the
aq. layer extracted with CH2Cl2, the combined org. layer washed with H2O, dried (Na2SO4), and evaporated and
the residue submitted to FC (petroleum ether/Et2O7:1): 10 (1.881 g, 91%). White crystalline solid. M.p. 1898
(from MeOH). IR (KBr): 2928s, 2860s, 1708s, 1644w, 1456m, 1372m, 1240m. 1H-NMR (400 MHz, CDCl3): 0.80
(d, J ˆ 6, Me(27)); 0.92 (s, Me(19)); 1.04 (d, J ˆ 7, Me(21)); 1.29 (s, Me(18)); 2.35 (dd, J ˆ 14.5, 4.5, 1 HÀC(11));
2.45 (m, HÀC(8)); 2.56 (t, J ˆ 14.5, 1 HÀC(11)); 3.12 (tt, J ˆ 11, 5, HÀC(3)); 3.33 (t, J ˆ 8.5, HÀC(17)); 3.34
(s, MeO); 3.41 (t, J ˆ 11, 1 HÀC(26)); 3.52 (br. d, J ˆ 11, 1 HÀC(26)); 4.76 (br. d, J ˆ 8.5, HÀC(16)); 5.43 (br. s,
HÀC(15)). 13C-NMR (100 MHz, CDCl3): 11.8, 13.8, 17.1, 20.9 (4q, C(18), C(19), C(21), C(27)); 27.6 (t); 28.2 (t);
28.8 (t); 29.5 (t); 30.3 (d); 31.2 (t); 34.19 (t); 34.24 (d); 36.4 (s, C(10)); 37.4 (t); 44.2 (br., 2 d); 49.8 (d); 53.8 (d);
55.7 (q, MeO); 62.3 (s, C(13)); 67.1 (t, C(26)); 79.3 (d, C(3)); 84.0 (d, C(16)); 107.0 (s, C(22)); 120.8 (d, C(15));
‡
154.9 (s, C(14)); 211.5 (s, C(12)). MS (1408): 442 (73, M ), 372 (33), 328 (100), 126 (93). HR-MS: 442.3078
‡
(C28H42O4 ; calc. 442.3083). Anal. calc. for C28H42O4 (442.64): C 75.98, H 9.56; found: C 75.90, H 9.45.
(3b,5a,25R)-3-Methoxy-12-methylenespirost-14-ene (11). To a suspension of triphenyl(methyl)phospho-
nium bromide (6.432 g, 18.0 mmol, 7.1 equiv.) in THF (70 ml), 1.8m PhLi in cyclohexane/Et2O7:3 (8.8 ml,
15.84 mmol, 6.3 equiv.) was added under vigorous stirring. After 6 h, 10 (1.122 mg, 2.53 mmol, 1 equiv.) was
added, and after further 2.5 h, the reaction was quenched by addition of Et2O(50 ml) and brine (40 ml). The aq.
layer was extracted with Et2O, the combined org. layer washed with brine, dried (Na2SO4), and evaporated, and
the residue subjected to FC (petroleum ether/AcOEt 15 :1): 11 (1.076 g, 96%). White foam. M.p. 1288 (after
recrystallization from petroleum ether/Et2O). IR (KBr): 2928s, 2860m, 1650w, 1632m, 1456m, 1372m, 1240m.
1H-NMR (400 MHz, CDCl3): 0.81 (d, J ˆ 6.5, Me(27)); 0.88 (s, Me(19)); 1.08 (d, J ˆ 7, Me(21)); 1.18 (s, Me(18));
2.21 ± 2.34 (m, HÀC(8), CH2(11)); 2.93 (t, J ˆ 8, HÀC(17)); 3.12 (tt, J ˆ 11, 5, HÀC(3)); 3.35 (s, MeO); 3.45
(t, J ˆ 11, 1 HÀC(26)); 3.52 (br. d, J ˆ 11, 1 HÀC(26)); 4.67 (br. s, 1 H, CH2ˆC(12)); 4.75 (br. s, 1 H,
CH2ˆC(12)); 4.82 (dd, J ˆ 8, 2 HÀC(16)); 5.30 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3): 11.9, 14.0,
17.2, 14.0 (4q, C(18), C(19), C(21), C(27)); 27.7 (t); 28.3 (t); 28.8 (t); 29.9 (t); 30.4 (d); 31.5 (t); 32.3 (t); 34.2 (t);
34.9 (t); 36.3 (s, C(10)); 36.7 (t); 44.1 (d); 44.3 (d); 53.4 (s, C(13)); 54.1 (d); 55.4 (d); 55.6 (q, MeO); 67.1
(t, C(26)); 79.6 (d, C(3)); 84.3 (d, C(16)); 105.8 (t, CH2ˆC); 107.5 (s, C(22)); 117.5 (d, C(15)); 155.9, 159.5 (2s,
‡
C(12), C(14)). MS (1108): 440 (98, M ), 425 (18), 353 (41), 326 (100), 297 (41), 169 (60), 127 (98). HR-MS:
‡
440.3292 (C29H44O3 ; calc. 440.3290). Anal. calc. for C29H44O3 (440.66): C 79.04, H 10.06; found: C 78.96, H 9.97.
(3b,5a,12a,25R)- and(3 b,5a,12b,25S)-3-Methoxyspirost-14-ene-12-methanol (12 and 13, resp.). To a 08-
cold soln. of 11 (410 mg, 0.930 mmol, 1 equiv.) in THF (4 ml), 10m BH3 ´ SMe2 (0.28 ml, 2.8 mmol, 3 equiv.) was
added dropwise. After 1.5 h, 6n aq. NaOH (1 ml) was slowly added, followed by EtOH (0.1 ml) and Et2O
(0.4 ml). After further 30 min, the mixture was warmed to r.t., 35% aq. H2O2 soln. (0.5 ml) was added and the
mixture stirred for 2 h at 508. Then the mixture was neutralized by addition of solid NH4Cl, and the aq. layer was
extracted with Et2O. The combined org. layer was dried (Na2SO4) and evaporated and the residue recrystallized
from Et2O: 13 (289 mg, 0.630 mmol) as colorless crystals. The mother liquor was evaporated and provided, after
FC (petroleum ether/AcOEt 2 :1), 13 (15 mg, altogether 71%) and 12 (67 mg, 16%, 0.146 mmol), both as white,
crystalline solids.
Data of 12: M.p. 1758 (from Et2O). IR (KBr): 3452m, 2928s, 2860s, 1644w, 1456m, 1372m, 1240m. 1H-NMR
(400 MHz, CDCl3): 0.80 (d, J ˆ 6.5, Me(27)); 0.87 (s, Me(19)); 1.01 (d, J ˆ 7, Me(21)); 1.21 (s, Me(18)); 2.14
(m, HÀC(8)); 2.60 (dd, J ˆ 9.5, 8, HÀC(17)); 3.10 (tt, J ˆ 11, 5, HÀC(3)); 3.29 (br. d, J ˆ 10, Ha of CH2OH);
3.34 (s, MeO); 3.42 (t, J ˆ 11, 1 HÀC(26)); 3.49 (m, 1 HÀC(26)); 3.68 (dd, J ˆ 10, 4.5, Hb of CH2OH); 4.78
(dd, J ˆ 8, 1, HÀC(16)); 5.32 (br. s, HÀC(15)). NOE (CDCl3): irr. at 3.68 (Hb of CH2OH)! 4.78 (3.3%,
HÀC(16)); 3.29 (10.6%, Ha of CH2OH); 2.60 (12.9%, HÀC(17)); irr. at 2.60 (HÀC(17)) ! 4.78 (8.8%,
HÀC(16)); 3.68 (9.6%, Hb of CH2OH); irr. at 1.21 (Me(18)) ! 2.14 (4.8%, HÀC(8)); 1.79 (7.4%, HÀC(20) !
dq, J(22,17) ˆ 9.5, J(20,21) ˆ 7), 1.66 (4.6%, HÀC(11) ! br. d, J(11b,9) ˆ 14.5), 1.01 (2.0%, Me(21)); 0.87
(2.7%, Me(19)). NMR Data connectivity was established by C,H-COSY. 13C-NMR (100 MHz, CDCl3): 11.9
(q, Me(19)); 14.2 (q, Me(21)); 17.2 (q, Me(27)); 20.8 (q, Me(18)); 22.7 (t); 27.8 (t); 28.5 (t); 28.7 (t); 29.8 (t); 30.4
(d); 31.2 (t); 34.3 (t); 34.6 (d); 36.3 (s, C(10)); 36.8 (t); 44.8 (d); 45.0 (d); 48.9 (d); 49.3 (s, C(13)); 50.5 (d); 54.0
(d, C(17)); 55.6 (q, MeO); 61.9 (t, CH2OH); 67.2 (t, C(26)); 79.7 (d, C(3)); 85.0 (d, C(16)); 106.5 (C, C(22));

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‡
‡
118.7 (d, C(15)); 155.6 (s, C(14)). FAB-MS: 481 (16, [M ‡ Na] ), 459 (43, [M ‡ H] ), 315 (34), 154 (100). HR-
‡
MS: 458.3401 (C29H46O4 ; calc. 458.3396). Anal. calc. for C29H46O4 (458.68): C 75.94, H 10.11; found: C 75.58,
H 10.04.
Data of 13: M.p. 1978 (from Et2O). IR (KBr): 3464m, 2928s, 2872s, 1652w, 1456m, 1372m, 1240m. 1H-NMR
(400 MHz, CDCl3): 0.81 (d, J ˆ 6, Me(27)); 0.86 (s, Me(19)); 0.87 (s, Me(18)); 1.03 (d, J ˆ 7, Me(21)); 2.04 ± 2.09
(m, HÀC(8)); 2.45 (t, J ˆ 8.5, HÀC(17)); 3.12 (tt, J ˆ 11, HÀC(3)); 3.43 ± 3.38 (m, MeO, Ha of CH2OH); 3.43
(t, J ˆ 11, 1 HÀC(26)); 3.51 (br. d, J ˆ 11, 1 HÀC(26)); 3.75 (dd, J ˆ 10.5, Ha of CH2OH); 4.87 (dd, J ˆ 8.5, 2,
HÀC(16)); 5.33 (br. s, HÀC(15)). NOE (CDCl3): irr. at 3.75 (Hb of CH2OH)! 3.35 (23.6%, Ha of CH2OH),
2.45 (5.9%, HÀC(17)); irr. at 2.45 (HÀC(17)) ! 4.87 (11.2%, HÀC(16)); 3.75 (4.8%, Hb of CH2OH); 1.24
(6.6%, HÀC(12) ! br. d, J(12, Ha) ˆ 10), 1.03 (3.6%, Me(21)); irr. at 0.86 (Me(18)) ! 2.06 (4.6%, HÀC(8));
1.76 (5.0%, HÀC(20) ! dq, J(20,17) ˆ 8.5, J(20,21) ˆ 7), 1.35 ± 1.28 and 1.25 ± 1.19 (6.1%, two different protons,
m). NMR Data connectivity was established by C,H-COSY. 13C-NMR (100 MHz, CDCl3): 12.2 (q, Me(19));
14.1 (q, Me(21)); 15.6 (q, Me(18)); 17.1 (q, Me(27)); 24.9 (t); 27.7 (t); 28.4 (t); 28.7 (t); 29.9 (t); 30.4 (d); 31.1 (t);
34.3 (t); 34.9 (d); 36.4 (s, C(10)); 36.8 (t); 44.2 (d); 44.6 (d); 48.6 (s, C(13)); 52.2 (d); 54.8 (d); 55.6 (q, MeO);
56.8 (d, C(17)); 65.0 (t, CH2OH); 67.1 (t, C(26)); 79.7 (d, C(3)); 84.7 (d, C(16)); 106.9 (s, C(22)); 116.8
‡
‡
(d, C(15)); 160.8 (s, C(14)). MS (1808): 458 (76, M ), 440 (43, [M À H2O] ), 428 (75), 369 (77), 344 (83), 330
‡
(77), 313 (100), 285 (73), 126 (87). HR-MS: 458.3400 (C29H46O4 ; calc. 458.3396). Anal. calc. for C29H46O4
(458.68): C 75.94, H 0.11; found: C 75.67, H 10.09.
[(3b,5a,12a,25R)-3-Methoxyspirost-14-en-12-yl]methyl Nitrite (14). A soln. of 12 (112 mg, 0.245 mmol,
1 equiv.) and tert-butyl nitrite (0.29 ml, 2.4 mmol, 10equiv.) in CHCl3 (1.6 ml; 0.15m) was stirred for 4 h. After
addition of pyridine (3 ml), the solvent was rapidly evaporated. Basic-gradient FC (petroleum ether/Et2O
5 :1 ‡ 2% Et3N ( ! 14), then petroleum ether/AcOEt 2 :1 ( ! 12)) gave 14 (103 mg, 86%) as a colorless foam
and recovered 12 (9 mg, 0.020 mmol). 14: UV (MeCN): 213. IR (KBr): 2948s, 1652m (ONO), 1616s (ONO),
1456m, 1360m, 1240m. 1H-NMR (400 MHz, (D5)pyridine): 0.73 ± 0.75 (m, Me(19), Me(27)); 1.18 (d, J ˆ 6.5,
Me(21)); 1.28 (s, Me(18)); 1.98 (dq, J ˆ 9.5, 6.5, HÀC(20)); 2.09 (m, 1 H); 2.17 (br. t, J ˆ 11, HÀC(8)); 2.81
(dd, J ˆ 9.5, 7.5, HÀC(17)); 3.09 (tt, J ˆ 11, 5, HÀC(3)); 3.32 (s, MeO); 3.62 ± 3.66 (m, 2 HÀC(26)); 4.58 (br. m,
Ha of CH2ONO); 4.79 (br. m, Hb of CH2ONO); 5.14 (br. d, J ˆ 7.5, HÀC(16)); 5.59 (br. s, HÀC(15)). 13C-NMR
(100 MHz, (D5)pyridine): 8.0, 11.8, 14.5, 17.3 (4q, C(18), C(19), C(21), C(27)); 22.9 (t); 28.2 (t); 28.6 (t);
29.2 (t); 30.0 (t); 30.7 (d); 31.6 (t); 34.6 (t); 34.7 (d); 36.4 (s, C(10)); 36.7 (t); 44.6 (d); 45.6 (d); 46.0 (br. d,
C(12)); 49.5 (s, C(13)); 50.4 (d); 54.9 (d); 55.3 (q, MeO); 67.3 (t, C(26)); 68.4 (br. t, CH2ONO); 79.6
‡
(d, C(3)); 85.3 (d, C(16)); 106.6. (s, C(22)); 120.5 (d, C(15)); 154.1 (s, C(14)). FAB-MS: 488 (22, [M ‡ H] ), 457
‡
‡
(26, [M À NO] ), 307 (27, NBA matrix), 154 (100, NBA matrix). HR-MS: 487.3294 (C29H45O5N ; calc.
487.3298).
(3b,5a,12a,25R)-3-Methoxy-17-(nitrooxy)spirost-14-ene-12-methanol (15) and(3 b,5a,12a,25S)-3-Methoxy-
spirost-14-ene-12-carbaldehyde (16). Through a vigorously stirred 48-cold soln. of 14 (68 mg, 0.139 mmol) in
benzene (10 ml) in a quartz flask, O2 was bubbled for 20 min. Then the soln. was irradiated (see General) for
100 min under continuous O2 bubbling and mild cooling (T ca. 108). Then the soln. was evaporated and the
residue subjected to gradient FC (petroleum ether/Et2O 3 :1 ( ! 16), then petroleum ether/Et2O1:1 ( ! 15),
and finally petroleum ether/Et2O1:2 ( ! 12)): 16 (6.2 mg, 10%), 15 (7.3 mg, 10%), and 12 (11.7 mg, 18%), all as
colorless, amorphous solids.
Data of 15: IR (CHCl3): 3618w (OH), 3392w (br., OH), 2932s, 2860m, 1636s (ONO2), 1456m, 1384m, 1284s
(ONO2), 1244m. 1H-NMR (400 MHz, CDCl3): 0.79 (d, J ˆ 6, Me(27)); 0.88 (s, Me(19)); 1.14 (d, J ˆ 7, Me(21));
1.45 (s, Me(18)); 2.02 (m, HÀC(12)); 2.16 ± 2.22 (m, HÀC(8), HÀC(20)); 3.11 (tt, J ˆ 11, 5, HÀC(3)); 3.34 ±
3.37 (m, MeO, Ha of CH2OH); 3.39 (t, J ˆ 11, 1 HÀC(26)); 3.48 (br. d, J ˆ 11, 1 HÀC(26)); 3.84 (dd, J ˆ 10, 3,
Hb of CH2OH); 5.26 (br. s, HÀC(16)); 5.33 (br. s, HÀC(15)). 13C-NMR (150 MHz, CDCl3): 9.6, 11.9, 17.1, 19.9
(4q, C(18), C(19), C(21), C(27)); 22.2 (t); 27.9 (t); 28.5 (t); 28.7 (t); 29.4 (t); 30.0 (d); 32.6 (t); 34.3 (d); 34.5 (t);
36.4 (s, C(10)); 36.6 (t); 45.0 (d); 46.5 (d); 50.9 (d); 51.1 (d); 55.7 (q, MeO); 55.8 (s, C(13)); 61.5 (t, CH2OH),
67.1 (t, C(26)); 79.7 (d, C(3)); 88.4 (d, C(16)); 106.2 (s, C(22)); 108.5 (s, C(17)); 118.9 (d, C(15)); 151.7
‡
‡
(s, C(14)). FAB-MS: 520 (27, [M ‡ H] ), 473 (40, [M À NO2] ), 154 (100, NBA matrix). HR-MS: 473.3264
‡
([C29H45O7N À NO2] ; calc. 473.3267).
Data of 16: IR (CHCl3): 2932s, 2860m, 2717w (aldehyde CH), 1712s (CˆO), 1456m, 1376m, 1240m.
1H-NMR (400 MHz, CDCl3): 0.80 (d, J ˆ 6, Me(27)); 0.86 (s, Me(19)); 1.01 (d, J ˆ 7, Me(21)); 1.21 (s, Me(18));
2.25 (m, HÀC(8)); 2.38 (br. s, HÀC(12)); 2.52 (dd, J ˆ 9, 8, HÀC(17)); 3.11 (tt, J ˆ 11, 5, HÀC(3)); 3.34
(s, MeO); 3.40 (t, J ˆ 11, 1 HÀC(26)); 3.49 (br. d, J ˆ 11, 1 HÀC(26)); 4.85 (br. d, J ˆ 8, HÀC(16)); 5.48 (br. s,
HÀC(15)); 9.63 (d, J ˆ 3, CHO). 13C-NMR (100 MHz, CDCl3): 11.5, 14.2, 17.1, 20.2 (4q, C(18), C(19), C(21),
C(27)); 24.2 (t); 27.7 (t); 28.3 (t); 28.7 (t); 29.7 (t); 30.4 (d); 31.0 (t); 34.2 (t); 34.6 (d); 36.5 (s, C(10)); 36.6 (t);

Helvetica Chimica Acta ± Vol. 83 (2000)
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44.6 (d); 44.8 (d); 49.4 (s, C(13)); 51.6 (d); 55.6 (q, MeO); 55.8 (d); 58.2 (d, C(12)); 67.1 (t, C(26)); 79.5
(d, C(3)); 84.8 (d, C(16)); 106.6 (s, C(22)); 120.0 (d, C(15)); 156.1 (s, C(14)); 207.1 (d, CHO). MS (1508): 456
‡
‡
(32, M ), 425 (7), 384 (6), 342 (13), 302 (18), 126 (100). HR-MS: 456.3240 (C29H44O4 ; calc. 456.3240).
12b-Isomer 17 of Nitrite 14. As described for 14, from 13 (322 mg, 0.702 mmol, 1 equiv.): 17 (261 mg, 76%)
and recovered 13 (58 mg, 0.126 mmol). 17: UV (MeCN): 212. IR (CHCl3): 2932s, 2860m, 1648m (ONO), 1608m
(ONO), 1456m, 1376m, 1240m. 1H-NMR (400 MHz, (D5)pyridine): 0.74 ± 0.76 (m, Me(19), Me(27)); 1.02
(s, Me(18)); 1.16 (d, J ˆ 6.5, Me(21)); 2.07 (m, HÀC(8)); 2.67 (t, J ˆ 8.5, HÀC(17)); 3.09 (tt, J ˆ 11, 5, HÀC(3));
3.31 (s, MeO); 3.55 ± 3.67 (m, CH2(26)); 4.58 (br. m, Ha of CH2ONO); 4.88 (br. m, Hb of CH2ONO); 5.12
(dd, J ˆ 8.5, 1.5, HÀC(16)); 5.52 (br. s, HÀC(15). 13C-NMR (100 MHz, (D5)pyridine): 12.0, 14.5, 15.8, 17.3 (4q,
C(18), C(19), C(21), C(27)); 25.4 (t); 28.3 (t); 28.6 (t); 29.1 (t); 30.2 (t); 30.7 (d); 31.6 (t); 34.6 (t); 34.8 (d); 36.5
(s, C(10)); 36.8 (t); 44.4 (d); 44.8 (d); 48.9 (s, C(13)); 49.0 (br. d, C(12)); 54.7 (d); 55.3 (q, MeO); 57.3 (d); 67.2
(t, C(26)); 71.1 (br. t, CH2ONO); 79.6 (d, C(3)); 85.0 (d, C(16)); 107.0 (s, C(22)); 118.4 (d, C(15)); 159.4
‡
‡
(s, C(14)). MS (1608): 487 (15, M ), 457 (15, [M À NO] ), 428 (29), 343 (68), 313 (81), 126 (100). HR-MS:
‡
487.3310 (C29H45O5N ; calc. 487.3298).
12b-Isomer 18 and12 b-Isomer 19 of Nitrooxy Derivative 15 andAldehyde 16, resp. As described for 15 and
16, from 17 (100 mg, 0.205 mmol); 19 (18 mg, 19%), 18 (10 mg, 9%), and 13 (21 mg, 22%), all as colorless,
amorphous solids.
Nitrooxy Derivative 18: IR (CHCl3): 3620w (OH), 3400w (br., OH), 2932s, 2864m, 1628s (ONO2), 1452m,
1380m, 1284s (ONO2), 1244m. 1H-NMR (400 MHz, CDCl3): 0.81 (d, J ˆ 6, Me(27)); 0.84 (s, Me(19)); 1.03
(s, Me(18)); 1.08 (d, J ˆ 7.5, Me(21)); 2.05 (m, HÀC(8), HÀC(12)); 2.32 (q, J ˆ 7, H ÀC(20)); 3.13 (tt, J ˆ 11, 5,
HÀC(3)); 3.35 ± 3.40 (m, MeO, Ha of CH2OH); 3.46 ± 3.55 (m, CH2(26)); 3.82 (dd, J ˆ 10.5, 3, Hb of CH2OH);
5.43 (br. s, HÀC(16)); 5.45 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3): 7.9, 12.1, 17.1, 20.3 (4q, C(18),
C(19), C(21), C(27)); 25.9 (t); 27.7 (t); 28.25 (t); 28.31 (t); 29.6 (t); 29.9 (d); 31.1 (t); 34.3 (t); 35.4 (d); 36.2
(s, C(10)); 36.8 (t); 43.6 (d); 44.1 (d); 49.5 (d); 52.4 (d); 54.2 (s, C(13)); 55.6 (q, MeO); 65.7 (t); CH2OH); 67.1 (t,
C(26)); 79.7 (d, C(3)); 86.9 (d, C(16)); 106.8 (s, C(17)); 107.2 (s, C(22)); 115.6 (d, C(15)); 160.0 (s, C(14)). FAB-
‡
‡
MS: 520 (15, [M ‡ H] ), 457 (10), 154 (100, NBA matrix). HR-MS: 473.3251 ([C29H45O7N À NO2] ; calc.
473.3267).
Aldehyde 19: IR (CHCl3): 2932s, 2860m, 2728w (aldehyde CH), 1716s (CˆO), 1628w, 1456m, 1376m,
1
1240m. H-NMR (400 MHz, CDCl3): 0.81 (d, J ˆ 6, Me(27)); 0.88 (s, Me(19)); 1.02 (s, Me(18)); 1.05 (d, J ˆ 7,
Me(21)); 2.07 (m, HÀC(8)); 2.10 (br. dd, J ˆ 12, 3, HÀC(12)); 2.78 (t, J ˆ 8.5, HÀC(17)); 3.12 (tt, J ˆ 11, 5,
HÀC(3)); 3.34 (s, MeO); 3.41 ± 3.54 (m, CH2(26)); 4.95 (br. d, J ˆ 8.5, HÀC(16)); 5.42 (br. s, HÀC(16)); 9.78
(br. s, CHO). 13C-NMR (100 MHz, CDCl3): 12.1, 14.0, 16.7, 17.1 (4q, C(18), C(19), C(21), C(27)); 21.2 (t); 27.7
(t); 28.3 (t); 28.7 (t); 29.8 (t); 30.3 (d); 31.1 (t); 34.2 (d); 34.6 (t); 36.5 (s, C(10)); 36.7 (t); 44.4 (d); 44.6 (d); 48.3
(s, C(13)); 54.2 (d); 55.6 (q, MeO); 56.9 (d); 61.3 (s, C(12)); 67.2 (t, C(26)); 79.6 (d, C(3)); 84.6 (d, C(16)); 107.0
‡
(s, C(22)); 118.2 (d, C(15)); 159.1 (s, C(14)); 204.3 (d, CHO). MS (1708): 456 (10, M ), 427 (4), 384 (11), 342
‡
(24), 314 (21), 126 (100). HR-MS: 456.3230 (C29H44O4 ; calc. 456.3240).
(3b,5a,12a,25R)-17,12-(Epoxymethano)-3-methoxyspirost-14-ene (20). A vigorously stirred 108-cold sus-
pension of 12 (100 mg, 0.218 mmol, 1 equiv.), Pb(OAc)4 (293 mg, 0.66 mmol, 3 equiv.; dried prior to use, see
General), and pyridine (0.07 ml, 0.88 mmol, 4 equiv.) in benzene (4 ml) was irradiated (see General) for 2 h in a
quartz flask. Then the solid particles were filtered off and washed with warm Et2O. The combined org. layer was
washed with 5% H2SO4 soln., 0.5m NaHCO3 and brine, dried (MgSO4), and evaporated. FC (petroleum ether/
Et2O2 :1) of the crude product afforded 20 (73 mg, 73%). White crystalline solid. M.p. 1678 (from Et2O). IR
(CHCl3): 2932s, 2864m, 1640w, 1452m, 1372m, 1244m. 1H-NMR (400 MHz, CDCl3): 0.80 (d, J ˆ 6, Me(27)); 0.85
(s, Me(19)); 0.91 (d, J ˆ 7.5, Me(21)); 1.12 (s, Me(18)); 2.08 (m, HÀC(8)); 3.10 (tt, J ˆ 11, 5, HÀC(3)); 3.34 ±
3.38 (m, MeO, Ha of CH2OÀC(17)); 3.43 (t, J ˆ 11, 1 HÀC(26)); 3.61 (br. dd, J ˆ 11, 2.5, 1 HÀC(26)); 3.78
(t, J ˆ 7.5, Hb of CH2OÀC(17)); 4.45 (d, J ˆ 2, HÀC(16)); 5.52 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3):
8.4 (q); 12.1 (q); 17.2 (q); 20.7 (t); 21.8 (q); 27.8 (t); 28.1 (t); 28.4 (t); 29.2 (t); 30.0 (d); 31.8 (t); 34.3 (t); 35.7 (d);
36.3 (s, C(10)); 36.8 (t); 44.6 (d); 45.7 (d); 45.9 (d); 51.2 (d); 55.55 (s, C(13)); 55.59 (q, MeO); 67.1 (t, C(26));
68.9 (t, CH2OÀC(17)); 79.6 (d, C(3)); 90.8 (d, C(16)); 98.5 (s, C(17)); 107.9 (s, C(22)); 117.8 (d, C(15)); 158.1
‡
(s, C(14)). MS (1708): 456 (15, M ), 358 (13), 342 (100), 330 (34), 315 (58), 148 (40), 133 (44). HR-MS:
‡
456.3245 (C29H44O4 ; calc. 456.3240). Anal. calc. for C29H44O4 (456.66): C 76.27, H 9.71; found: C 76.54, H 9.72.
(3b,5a,12b,25R)-17,12-(Epoxymethano)-3-methoxyspirost-4-ene (21) and(3 b,5a,12b,25R)-18,12-(Epoxy-
methano)-3-methoxyspirost-4-ene (22). As described for 20, from 13 (100 mg, 0.218 mmol, 1 equiv.): 22 (14 mg,
14%) as a white foam and 21 (35 mg, 35%) as a white crystalline solid.
Data of 21: M.p. 1738 (from Et2O). IR (KBr): 2928s, 2856m, 1632w, 1448m, 1372m, 1240m. 1H-NMR
(400 MHz, CDCl3): 0.80 (d, J ˆ 6, Me(27)); 0.93 (s, Me(18), Me(19)); 1.01 (d, J ˆ 7, Me(21)); 2.38 (m, HÀC(8));

1870
Helvetica Chimica Acta ± Vol. 83 (2000)
3.14 (tt, J ˆ 11, 5, HÀC(3)); 3.35 (s, MeO); 3.44 (t, J ˆ 11, 1 HÀC(26)); 3.50 (dd, J ˆ 12, 7.5, Ha of
CH2OÀC(17)); 3.63 (m, 1 HÀC(26)); 3.92 (dd, J ˆ 7.5, 5.5, Hb of CH2OÀC(17)); 4.74 (d, J ˆ 1.5, HÀC(16));
5.08 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3): 7.8 (q); 11.0 (q); 12.3 (q); 17.2 (q); 21.2 (t); 27.9 (t); 28.5 (t);
28.8 (t); 29.4 (t); 30.1 (d); 31.5 (t); 34.2 (t); 36.1 (d); 36.95 (t); 37.00 (s, C(10)); 45.2 (d); 47.3 (d); 55.6 (q, MeO);
56.9 (s, C(13)); 57.2 (d); 59.6 (d); 67.3 (t, C(26)); 71.2 (t, CH2O); 79.6 (d, C(3)); 93.3 (d, C(16)); 99.3 (s, C(17));
‡
106.6 (s, C(22)); 112.8 (d, C(15)); 159.3 (s, C(14)). MS (1608): 456 (28, M ), 441 (15), 342 (77), 331 (100), 314
‡
(27), 274 (12), 126 (32). HR-MS: 456.3246 (C29H44O4 ; calc. 456.3240). Anal. calc. for C29H44O4 (456.66):
C 76.27, H 9.71; found: C 76.15, H 9.58.
1
Data of 22: IR (CHCl3): 2932s, 2868m, 1640w, 1456m, 1372m, 1240m. H-NMR (400 MHz, CDCl3): 0.81
(d, J ˆ 6, Me(27)); 0.83 (s, Me(19)); 1.05 (d, J ˆ 6.5, Me(21)); 2.09 (m, HÀC(8)); 2.23 (t, J ˆ 8.5, HÀC(17)); 3.12
(tt, J ˆ 11, 5, HÀC(3)); 3.34 (s, MeO); 3.44 (t, J ˆ 11, 1 HÀC(26)); 3.52 (m, 1 HÀC(26)); 3.65 (d, J ˆ 8,
1 HÀC(18)); 3.73 (br. d, J ˆ 9.5, Ha of CH2OÀC(18)); 3.82 ± 3.87 (m, 1 HÀC(18), Hb of CH2OÀC(18)); 4.89
(dd, J ˆ 8.5, 2, HÀC(16)); 5.54 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3): 12.2 (q); 13.1 (q); 17.2 (q); 27.7
(t); 28.0 (t); 28.3 (t); 28.7 (t); 29.9 (t); 30.3 (d); 31.3 (t); 34.2 (d); 35.7 (t); 36.4 (s, C(10)); 36.9 (t); 44.5 (d); 45.4
(d); 51.4 (d); 55.0 (d); 55.6 (q, MeO); 57.9 (d); 58.1 (s, C(13)); 67.2 (t, C(26)); 68.7 (t, CH2OÀC(18)); 73.5
(t, C(18)); 79.6 (d, C(3)); 84.0 (d, C(16)); 107.3 (s, C(22)); 121.0 (d, C(15)); 153.9 (s, C(14)). MS (1608): 456 (19,
‡
‡
M ), 342 (40), 311 (26), 126 (100). HR-MS: 456.3237 (C29H44O4 ; calc. 456.3240).
(3b,5a,12b,25R)- and (3b,5a,12a,25R)-3-Methoxy-12-[(4-methoxyphenoxy)methyl]spirost-14-en-12-ol (23
and 23a resp.). To a À788-cold soln. of [(4-methoxyphenoxy)methyl]stannane [24] (1.44 g, 3.39 mmol, 5 equiv.)
in THF (2.5 ml), 1.6m BuLi in hexane (1.9 ml, 3.05 mmol, 4 equiv.) was added slowly. After 30 min, 10 (300 mg,
0.677 mmol, 1 equiv.) was added (as a solid!), and the mixture was stirred for further 2 h. The reaction was
quenched by addition of sat. NH4Cl soln. (6 ml), the mixture warmed to r.t., the aq. layer extracted with Et2O,
the combined org. layer washed with brine, dried (MgSO4), and evaporated, and the residue subjected to FC
(petroleum ether/Et2O 3 :2): 23 (287 mg, 73%) and 23a (89 mg, 23%), both as white foams.
Data of 23: M.p. 114 ± 1158 (from petroleum ether/Et2O). UV (MeOH): 225 (s), 288 (w). IR (KBr): 3456m
(br.), 3056w, 2928s, 2856m, 1648w (CˆC), 1508s (arom. CˆC), 1464m (arom. CˆC), 1372m, 1228s. 1H-NMR
(400 MHz, CDCl3): 0.81 (d, J ˆ 6, Me(27)); 0.88 (s, Me(19)); 1.05 (d, J ˆ 6.5, Me(21)); 1.23 (s, Me(18)); 2.08
(dd, J ˆ 13.5, 3.5, 1 HÀC(11)); 2.16 (m, HÀC(8)); 2.41 (s, exchange with D2O, OH); 2.82 (t, J ˆ 9, HÀC(17));
3.06 (tt, J ˆ 11, 5, HÀC(3)); 3.32 (s, MeO); 3.43 (t, J ˆ 11, 1 HÀC(26)); 3.52 (br. d, J ˆ 11, 1 HÀC(26)); 3.73
(d, J ˆ 9, Ha of OCH2ÀC(12)); 3.77 (s, MeOC6H4); 3.90 (d, J ˆ 9, Hb of OCH2ÀC(12)); 4.82 (br. d, J ˆ 9,
1
HÀC(16)); 5.34 (br. s, HÀC(15)); 6.84 (br. s, 4 arom. H). H-NMR (400 MHz, C6D6): 0.66 ± 0.68 (m, Me(19),
Me(27)); 1.37 (d, J ˆ 6.5, Me(21)); 1.40 (s, Me(18)); 2.01 (dq, J ˆ 9.5, 6.5, Me(20)); 2.09 (m, HÀC(8)); 2.12
(dd, J ˆ 13.5, 4, 1 HÀC(11)); 2.29 (s, OH); 2.87 (tt, J ˆ 11, 5, HÀC(3)); 3.18 (s, MeO); 3.23 (dd, J ˆ 9.5, 8,
HÀC(17)); 3.31 (s, MeOC6H4); 3.66 (br. J ˆ 11, 1 HÀC(26)); 3.64 (t, J ˆ 11, 1 HÀC(26)); 3.84 (d, J ˆ 9, Ha of
OCH2ÀC(12)); 4.01 (d, J ˆ 9, Hb of OCH2ÀC(12)); 5.23 (br. d, J ˆ 8, HÀC(16)); 5.51 (br. s, HÀC(15)); 6.68 ±
6.74 (m, 4 arom. H). NOE (CDCl3): irr. at 4.82 (HÀC(16)) ! 5.34 (5.6%, HÀC(15)); 3.90 (2.0%, Hb of
OCH2ÀC(12)); 2.82 (5.4%, HÀC(17)); irr. at 3.90 (Hb of OCH2ÀC(12)) ! 4.82 (5.8%, HÀC(16)); 3.73 (9.6%,
Ha of OCH2ÀC(12)); 2.82 (14.0%, HÀC(17)); irr. at 3.73 (Ha of OCH2ÀC(12)) ! 3.90 (12.5%, Hb of
OCH2ÀC(12)); irr. at 2.82 (HÀC(17)) ! 4.82 (8.6%, HÀC(16)); 3.90 (8.8%, Hb of OCH2ÀC(12)); 2.41 (1.6%,
OHÀC(12)); 1.05 (6.9%, Me(21)); irr. at 1.23 (Me(18)) ! 2.41 (0.8%, OH), 2.16 (2.0%, HÀC(8)); 1.80 (5.0%,
HÀC(20)); 1.66 (3.5%, 1 HÀC(11)); 1.05 (1.8%, Me(21)). 13C-NMR (100 MHz, CDCl3): 11.8 (q); 13.9 (q); 16.5
(q); 17.2 (q); 27.7 (t); 28.4 (t); 28.7 (t); 29.6 (t); 30.4 (d); 30.7 (t); 31.2 (t); 33.7 (d); 34.1 (t); 36.3 (s, C(10)); 36.5
(t); 44.5 (d); 44.9 (d); 51.2 (d); 51.6 (d); 54.4 (s, C(13)); 55.6 (q, MeO); 55.7 (q, MeO); 67.2 (t, C(26)); 70.7
(t, OCH2ÀC(12)); 77.2 (s, C(12)); 79.6 (d, C(3)); 85.1 (d, C(16)); 106.6 (s, C(22)); 114.6 (d, 2 arom. C); 116.1
(d, 2 arom. C); 119.7 (d, C(15)); 152.9 (s, arom. C); 154.2 (s, arom. C); 155.8 (s, C(14)). MS (2008): 580 (14,
‡
‡
‡
M ), 562 (6, [M À H2O] ), 443 (100), 329 (55), 316 (47), 138 (90), 124 (85). HR-MS: 580.3750 (C36H52O6 ; calc.
580.3764).
Data of 23a: UV (MeOH): 227 (s), 290 (w). IR (KBr): 3452m (br.), 3056w, 2928s, 2860m, 1652w (CˆC),
1508s (arom. CˆC), 1460m (arom. CˆC), 1372m, 1228s. 1H-NMR (400 MHz, CDCl3): 0.80 (d, J ˆ 6, Me(27));
0.86 (s, Me(19)); 1.02 (d, J ˆ 7, Me(21)); 1.11 (s, Me(18)); 2.14 (m, HÀC(8)); 2.26 (s, exchange with D2O , O H);
2.98 (t, J ˆ 9, HÀC(17)); 3.13 (tt, J ˆ 11, 5, HÀC(3)); 3.35 (s, MeO); 3.44 (t, J ˆ 10.5, 1 HÀC(26)); 3.51
(br. d, J ˆ 10.5, 1 HÀC(26)); 3.77 (s, MeOC6H4); 3.79 (d, J ˆ 9, Ha of OCH2ÀC(12)); 3.88 (d, J ˆ 9, Hb of
OCH2ÀC(12)); 4.91 (br. d, J ˆ 9, HÀC(16)); 5.51 (br. s, HÀC(15)); 6.85 (m, 4 arom. H). NOE (CDCl3): irr. at
4.91 (HÀC(16)) ! 5.51 (6.0%, HÀC(15)); 2.98 (7.2%, HÀC(17)); irr. at 3.88 (Hb of OCH2ÀC(12)) ! 2.98
(10.3%, HÀC(17)); 3.79 (Ha of OCH2ÀC(12)) and 1.11 (Me(18)) give no clear result; irr. at 3.79 (Ha of
OCH2ÀC(12)) ! 6.85 (8.0%, arom. H), 3.88 (8.8%, Hb of OCH2ÀC(12)); irr. at 2.98 (HÀC(17)) ! 4.91

Helvetica Chimica Acta ± Vol. 83 (2000)
1871
(12.2%, HÀC(16), 3.88 (1.5%, Hb of OCH2ÀC(12)); 2.26 (4.0%, OH), 1.02 (5.3%, Me(21)); irr. at 1.11
(Me(18)) ! 3.88 (1.4%, Hb of OCH2ÀC(12)); 2.98 (1.0%, HÀC(17)); 2.14 (3.9%, HÀC(8)); 1.74 (5.2%,
HÀC(20)); 1.62 (1.7%, 1 HÀC(11)). 13C-NMR (100 MHz, CDCl3): 12.1 (q); 14.3 (q); 17.1 (q); 18.4 (q); 27.7 (t);
28.4 (t); 28.7 (t); 29.6 (t); 30.4 (d); 30.9 (t); 31.1 (t); 34.2 (t); 34.3 (d); 36.1 (s, C(10)); 36.6 (t); 44.3 (d); 44.5 (d);
49.7 (d); 51.4 (d); 53.3 (s, C(13)); 55.6 (q, MeO); 55.7 (q, MeO); 67.1 (t, C(26)); 73.3 (t, OCH2ÀC(12)); 76.2
(s, C(12)); 79.6 (d, C(3)); 85.4 (d, C(16)); 106.7 (s, C(22)); 114.6 (d, 2 arom. C); 115.8 (d, 2 arom. C); 119.9
‡
(d, C(15)); 152.8 (s, arom. C); 154.2 (s, arom. C); 156.0 (s, C(14)). MS (2008): 580 (21, M ), 457 (21), 443 (58),
‡
329 (45), 138 (87), 124 (100). HR-MS: 580.3761 (C36H52O6 ; calc. 580.3764).
(3b,5a,12b,25R)-3-Methoxy-12-[(4-methoxyphenoxy)methyl]spirost-4-en-12-yl Benzoate (24). To a À788-
cold soln. of 23 (50 mg, 0.086 mmol, 1 equiv.) in THF (0.5 ml), 1.6m BuLi in hexane (0.065 ml, 0.103 mmol,
1.2 equiv.) was added dropwise. After 30 min, benzoyl chloride (0.014 ml, 0.129 mmol, 1.5 equiv.) was added and
after additional 45 min, the mixture was slowly warmed to r.t. within 3 h. The reaction was quenched by addition
of 0.5m NaHCO3 (0.5 ml) and Et2O(15 ml), the org. layer washed with brine, dried (MgSO 4), and evaporated,
and the residue submitted to gradient FC (petroleum ether/Et2O 5 :2 ( ! 24) and 3 :2 ( ! 23)): 24 (35 mg, 59%,
82% based on recovered 23) and recovered 23 (14 mg, 0.024 mmol), both as white foams. 24: UV (MeOH): 229
(s), 280 (br. m). IR (KBr): 3060w (arom. CH), 2928s, 2860m, 1720s (CˆO), 1648w (CˆC), 1508s
1
(arom. CˆC), 1464m, 1450m, 1372m, 1276s, 1228s. H-NMR (400 MHz, CDCl3): 0.79 (d, J ˆ 6, Me(27)); 0.88
(s, Me(19)); 1.13 (d, J ˆ 7, Me(21)); 1.37 (s, Me(18)); 2.22 (m, HÀC(8)); 2.94 (dd, J ˆ 13, 3.5, 1 HÀC(11)); 3.12
(tt, J ˆ 11, 5, HÀC(3)); 3.34 (s, MeO); 3.36 (t, J ˆ 11, 1 HÀC(26)); 3.48 (br. d, J ˆ 11, 1 HÀC(26)); 3.53 (dd, J ˆ
9, 8, HÀC(17)); 3.73 (s, arom. MeO); 4.27 (d, J ˆ 10, Ha of OCH2ÀC(12)); 4.32 (d, J ˆ 10, Hb of OCH2ÀC(12));
4.76 (br. d, J ˆ 8, HÀC(16)); 5.48 (br. s, HÀC(15)); 6.76 (br. s, 4 arom. H); 7.42 (t, J ˆ 7.5, 2 arom. H); 7.54
‡
(t, J ˆ 7.5, 1 arom. H); 8.02 (d, J ˆ 7.5, 2 arom. H). MS (2008): 684 (9, M ), 562 (22), 547 (32), 439 (40), 105
‡
‡
(100). FAB-MS: 685 (17, [M ‡ H] ), 563 (30), 446 (75), 154 (100, NBA matrix). HR-MS: 684.4023 (C43H56O7
;
calc. 684.4026).
(3b,5a,12b,25R)-12-(Benzoyloxy)-3-methoxyspirost-14-ene-12-methanol (25). A 08-cold mixture of 24
(28 mg, 0.041 mmol, 1equiv.) and cerium ammonium nitrate (32 mg, 0.095 mmol, 2.3 equiv.) in MeCN/H2O 4 :1
(1 ml) was stirred vigorously for 30 min. Then the reaction was quenched by addition of sat. NaHCO3 soln., the
aq. layer extracted with CH2Cl2, the combined org. layer washed with brine, dried (Na2SO4), and evaporated,
and the residue submitted to FC (petroleum ether/AcOEt 5 :1): 25 (17 mg, 72%). White foam. UV (MeOH):
232 (s), 274 (m). IR (CHCl3): 3468m (br.), 3000w (arom. CH), 2932s, 2860m, 1692s (CˆO), 1648w (CˆC),
1600m (arom. CˆC), 1452m, 1372m, 1292s, 1240m. 1H-NMR (400 MHz, C6D6): 0.56 (s, Me(19)); 0.68
(d, J(27,25) ˆ 6.5, Me(27)); 1.29 (d, J(21,20) ˆ 6.5, Me(21)); 1.40 (s, Me(18)); 2.00 (dq, J(20,17) ˆ 9, J(20,21) ˆ
6.5, HÀC(20)); 2.04 (br. t, J(8,7a and 9) ˆ 10, HÀC(8)); 2.80 (dd, J(17,20) ˆ 9, J(17,16) ˆ 8, HÀC(17)); 2.89 ±
2.97 (m, HÀC(3), 1 HÀC(11)); 3.20 (s, MeO); 3.59 (br. d, Jgem ˆ 10.5, 1 HÀC(26)); 3.64 (t, Jgem ˆ J(26,25) ˆ
10.5, 1 HÀC(26)); 3.68 (dd, Jgem ˆ 13.5, J(Ha,OH) ˆ 12, Ha of CH2OH); 3.87 (br. d, Jgem ˆ 13.5, Hb of CH2OH);
4.64 (dd, J(OH, Ha of CH2OH)ˆ 12, J(OH, Hb of CH2OH)ˆ 2, CH2OH); 5.01 (br. d, J(16,17) ˆ 8, HÀC(16));
‡
5.49 (br. s, HÀC(15)); 7.07 (m, 3 arom. H); 8.18 (d, J ˆ 6.5, 2 arom. H). MS (1808): 578 (2, M ), 560 (11, [M À
‡
‡
H2O] ) 445 (25), 425 (22), 323 (43), 126 (92), 105 (100). HR-MS: 578.3608 (C36H50O6 ; calc. 578.3607).
(3''b,5''a,12''b,25''R)-3''-Methoxydispiro[cyclohexa-2,5-diene-1,2'-[1,3]dioxolane-4',12''-spirost[14]en]-4-
one (27). As described for 25, at À88 for 10 min, with 23 (118 mg, 0.203 mmol, 1 equiv.), cerium ammonium
nitrate (263 mg, 0.480 mmol, 2.4 equiv.), and MeCN/H2O4 :1 (2.5 ml). FC (petroleum ether/Et 2O3 :2) gave 27
(85 mg, 74%). White crystalline solid. M.p. 2218 (from petroleum ether/Et2O). UV (MeOH): 219 (s). IR (KBr):
2928s, 2860s, 1676s (conj. CˆO), 1636s (conj. CˆC), 1456m, 1384m, 1240m, 1176s, 1112s. 1H-NMR (400 MHz,
CDCl3; steroid numbering): 0.82 (d, J ˆ 6, Me(27)); 0.89 (s, Me(19)); 1.08 (d, J ˆ 7, Me(21)); 1.19 (s, Me(18));
2.08 ± 2.17 (m, HÀC(8), 1HÀC(11)); 2.76 (t, J ˆ 8.5, HÀC(17)); 3.13 (tt, J ˆ 11, 5, HÀC(3)); 3.35 (s, MeO);
3.41 (t, J ˆ 11, 1 HÀC(26)); 3.53 (br. d, J ˆ 11, 1 HÀC(26)); 3.77 (br. s, CH2O); 4.89 (br. d, J ˆ 8.5, HÀC(16));
5.42 (br. s, HÀC(15)); 6.12 (m, CO CHˆCH); 6.21 (m, CO CHˆCH); 6.73 ± 6.75 (m, 2 COHˆCH). 13C-NMR
(100 MHz, CDCl3; steroid numbering): 12.0, 14.3, 16.8, 17.2 (4q, C(18), C(19), C(21), C(27)); 27.7 (t); 28.2 (t);
28.7 (t); 29.5 (t); 30.4 (d); 31.0 (t); 33.6 (d); 34.0 (t); 35.1 (t); 36.2 (s, C(10)); 36.9 (t); 44.5 (d); 45.0 (d); 51.5 (d);
52.4 (d); 54.7 (s, C(13)); 55.6 (q, MeO); 67.2 (t, C(26)); 72.8 (t, CH2O); 79.4 (d, C(3)); 84.9 (d, C(16)); 89.8
(s, C(12)); 99.2 (s, C(OR)2); 106.4 (s, C(22)); 120.4 (d, C(15)); 127.6 (d, COCHˆCH); 130.0 (d, COCHˆCH);
‡
143.3, 144.3 (2d, 2 CO CHˆCH); 156.7 (s, C(14)); 185.1 (s, COCHˆCH). FAB-MS: 587 (15, [M ‡ Na] ), 565
‡
‡
(100, [M ‡ H] ), 307 (35) 154 (82, NBA matrix). HR-MS: 564.3454 (C35H48O6 ; calc. 564.3451).
(3b,5a,12b,25R)-12-[(2-Chloro-4-hydroxyphenoxy)methyl]-3-methoxyspirost-4-en-12-ol (28). A soln. of
27 (47 mg, 0.083 mmol) and conc. HCl soln. (0.1 ml) in THF (0.8 ml) and H2O(0.2 ml) was stirred at 30 8 for 4
days. The reaction was quenched by addition of sat. K2CO3 soln. (2 ml), the aq. layer extracted with CH2Cl2, the

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Helvetica Chimica Acta ± Vol. 83 (2000)
combined org. layer washed with brine, dried (Na2SO4), and evaporated, and the residue submitted to FC
(petroleum ether/Et2O1 :1): 28 (25 mg, 48%). White crystalline solid. M.p. 2388 (dec.; from Et2O). UV
(MeOH): 223 (s), 293 (w). IR (CHCl3): 3548m (OH); 3400w (br., OH); 3000m, 2932s, 2860m, 1496s (arom.
CˆC), 1464m (arom. CˆC), 1372m, 1240m. 1H-NMR (400 MHz, CDCl3): 0.81 (d, J ˆ 6, Me(27)); 0.88
(s, Me(19)); 1.05 (d, J ˆ 6.5, Me(21)); 1.23 (s, Me(18)); 2.04 (dd, J ˆ 13.5, 3.5, 1 HÀC(11)); 2.16 (m,HÀC(8));
2.27 (s, exchange with D2O , O ÀHC(12)); 2.80 (dd, J ˆ 9, 8, HÀC(17)); 3.08 (tt, J ˆ 11, 5, HÀC(3)); 3.33
(s, MeO); 3.44 (t, J ˆ 11, 1 HÀC(26)); 3.53 (br. d, J ˆ 11, 1 HÀC(26)); 3.72 (d, J ˆ 9, Ha of OCH2ÀC(12)); 3.87
(d, J ˆ 9, Hb of OCH2ÀC(12)); 4.83 (br. d, J ˆ 8, HÀC(16)); 5.27 (s, exchange with D2O , O HÀC6H3); 5.36 (br. s,
HÀC(15)); 6.75 (dd, J ˆ 9, 3, Hm); 6.88 (d, J ˆ 3, Hm); 6.94 (d, J ˆ 9, Ho); the position of the OH signals varied
with the experiments. NOE (CDCl3): irr. at 6.94 (Ho) ! 6.75 (5.1%, Hm); irr. at 6.88 (Hm) ! no effect; irr. at 6.75
(Hm) ! 6.94 (14.1%, Ho); irr. at 2.30 (OHÀC(12) ! 6.94 (3.1%, Ho), 5.44 (À 91.9%, OHÀC6H3), 2.80 (1.5%,
HÀC(17)). 13C-NMR (100 MHz, CDCl3): 11.8, 13.9, 16.5, 17.2 (4q, C(18), C(19), C(21), C(27)); 27.7 (t); 28.4 (t);
28.7 (t); 29.6 (t); 30.4 (d); 30.7 (t); 31.2 (t); 33.7 (d); 34.1 (t); 36.3 (s, C(10)); 36.5 (t); 44.6 (d); 44.9 (d); 51.2 (d);
51.6 (d); 54.5 (s, C(13)); 55.6 (q, MeO); 67.3 (t, C(26)); 70.9 (t, CH2O); 77.2 (s, C(12)); 79.6 (d, C(3)); 85.1
(d, C(16)); 106.7 (s, C(22)); 115.5, 115.6, 116.6 (3d, arom. C); 119.9 (br.; 1 d of C(15), 1 s of arom. C); 146.1,
‡
‡
152.7 (2s, arom. C); 155.7 (s, C(14)). MS (2208): 600 (2, [M(35Cl)] ), 582 (2, [M À H2O] ), 542 (3), 486 (5), 443
‡
(100), 329 (55), 126 (22). HR-MS: 600.3192 (C35H49O6Cl ; calc. 600.3218).
(3b,5a,12b,25R)- and(3 b,5a,12a,25R)-3-Methoxy-12-[(methoxymethoxy)methyl]spirost-14-en-12-ol (29
and 29a, resp.). As described for 23 and 23a, with [(methoxymethoxy)methyl]stannane [31] (985 mg,
2.70 mmol, 4 equiv.), THF (2.5 ml), 1.6m BuLi in hexane (1.47 ml, 2.36 mmol, 3.5 equiv.), and 10 (300 mg,
Ã
0.677 mmol, 1equiv.). Workup with sat. NH4Cl soln. (4 ml) and Et2O(40 ml). FC (petroleum ether/AcOEt
2 :3): 29 (39 mg, 11%) and 29/29a 3 :2 (250 mg, 72%), both as white foams.
Data of 29: IR (CHCl3): 3560w, 3428w (br.), 3050w, 2932s, 2860s, 1648w, 1464m, 1372m, 1240m. 1H-NMR
(400 MHz, CDCl3): 0.80 (d, J ˆ 6, Me(27)); 0.87 (s, Me(19)); 1.03 (d, J ˆ 7, Me(21)); 1.18 (s, Me(18)); 2.14
(m, HÀC(8)); 2.73 (s, OH), 2.76 (dd, J ˆ 9.5, 8, HÀC(17)); 3.10 (tt, J ˆ 11, 5, HÀC(3)); 3.34 (s, MeO); 3.39
(s, MeO); 3.35 ± 3.55 (m, 2 CH2O); 4.63 (d, J ˆ 6.5, Ha of OCH2O); 4.67 (d, J ˆ 6.5, Hb of OCH2O); 4.79
(br. d, J ˆ 8, HÀC(16)); 5.32 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3): 11.8, 13.9, 16.5, 17.2, (4q, C(18),
(C19), C(21), C(27)); 27.8 (t); 28.5 (t); 28.7 (t); 29.7 (t); 30.4 (d); 31.1 (br., 2t); 33.6 (d); 34.2 (t); 36.3 (s, C(10));
36.7 (t); 44.7 (d); 44.8 (d); 51.1 (d); 51.4 (d); 54.3 (s, C(13)); 55.6, 55.7 (2q, MeO); 67.2 (t, C(26)); 70.6 (t, CH2O);
76.7 (s, C(12)); 79.6 (d, C(3)); 85.2 (d, C(16)); 97.4 (t, O CHO); 106.5 (s, C(22)); 119.6 (d, C(15)); 155.7
2
‡
‡
(s, C(14)). MS (1808): 518 (1, M ), 500 (8, [M À H2O] ), 487 (3), 443 (100), 426 (19), 387 (10), 329 (35), 317
‡
(18), 126 (36). HR-MS: 518.3616 (C31H50O6 ; calc. 518.3607).
Data of 29a: Data from epimer mixture. 1H-NMR (400 MHz, CDCl3): 0.80 (d, J ˆ 6, Me(27)); 0.85
(s, Me(19)); 1.01 (d, J ˆ 6.5, Me(21)); 1.04 (s, Me(18)); 2.11 (m, HÀC(8)); 2.33 (s, OH); 2.88 (dd, J ˆ 9, 8,
HÀC(17)); 3.11 (tt, J ˆ 11, 5, HÀC(3)); 3.34 (s, MeO); 3.38 (s, MeO); 3.39 ± 3.53 (m, 2 CH2O); 4.67 (br. s,
OCH2O); 4.89 (br. d, J ˆ 8, HÀC(16)); 5.48 (br. s, HÀC(15)).
(3b,5a,12b,25R)- and(3 b,5a,12a,25R)-12-Hydroxy-3-methoxyspirost-14-ene-12-methanol (30 and 30a,
resp.). A soln. of 29/29a 1.6 :1 (190 mg, 0.366 mmol) and 12n aq. HCl in THF (2 ml; not dry, no Ar) and H2O
(1 ml) was stirred for 5 h. Then the soln. was cooled to 08 and CH2Cl2 (25 ml) and sat. aq. K2CO3 soln. (2.5 ml)
were added slowly. The org. layer was washed with brine, dried (Na2SO4) and evaporated and the residue
submitted to FC (CH2Cl2/MeOH 30 :1): 30a (59 mg, 34%) as a crystalline solid and 30 (103 mg, 59%) as a white
foam.
Data of 30: IR (KBr): 3440m (br.), 2928s, 2860m, 1652w, 1456m, 1372m, 1240m. 1H-NMR (400 MHz,
CDCl3): 0.80 (d, J ˆ 6, Me(27)); 0.87 (s, Me(19)); 1.02 (d, J ˆ 7, Me(21)); 1.18 (s, Me(18)); 2.13 (m, HÀC(8));
2.73 (t, J ˆ 8.5, HÀC(17)); 3.11 (tt, J ˆ 11, 5, HÀC(3)); 3.34 (s, MeO); 3.35 ± 3.44 (m, 1 HÀC(26), Ha of
CH2OH); 3.50 (br. d, J ˆ 11, 1 HÀC(26)); 3.58 (br. d, J ˆ 11.5, Hb of CH2OH); 4.79 (br. d, J ˆ 8.5, HÀC(16));
1
5.32 (br. s, HÀC(15)). H-NMR (400 MHz, C6D6): 0.66 (s, Me(19)); 0.69 (d, J ˆ 6, Me(27)); 1.25 (s, Me(18));
1.30 (d, J ˆ 7, Me(21)); 2.01 (m, HÀC(8)); 2.96 (tt, J ˆ 11, 5, HÀC(3)); 2.99 (dd, J ˆ 10, 8, HÀC(17)); 3.20
(d, J ˆ 10.5, Ha of CH2OH); 3.21 (s, MeO); 3.28 (d, J ˆ 10.5, Hb of CH2OH); 3.65 (br. d, J ˆ 11, 1 HÀC(26));
3.72 (t, J ˆ 11, 1 HÀC(26)); 5.02 (br. d, J ˆ 8, HÀC(16)); 5.41 (br. s, HÀC(15)). NOE (CDCl3): irr. at 4.79
(HÀC(16)) ! 5.32 (4.2%, HÀC(15)); 3.58 (1.8%, Hb of CH2OH); 2.73 (4.8%, HÀC(17)); irr. at 3.58 (Hb of
CH2OH)! 4.79 (5.3%, HÀC(16)); 3.36 (6.3%, Ha of CH2OH); 2.73 (10.7%, HÀC(17)); irr. at 2.73
(HÀC(17)) ! 4.79 (8.2%, HÀC(16)); 3.58 (10.6%, Hb of CH2OH); 1.02 (5.1%, Me(21)). 13C-NMR (100 MHz,
CDCl3): 11.8, 13.9, 16.4, 17.1 (4q, C(18), C(19), C(21), C(27)); 27.7 (t); 28.5 (t); 28.7 (t); 29.7 (t); 30.2 (t); 30.4
(d); 31.1 (t); 33.6 (d); 34.2 (t); 36.3 (s, C(10)); 36.6 (t); 44.7 (d); 44.8 (d); 51.0 (d); 51.3 (d); 54.4 (s, C(13)); 55.6
(q, MeO); 63.4 (t, CH2OH); 67.2 (t, C(26)); 77.6 (s, C(12)); 79.6 (d, C(3)); 85.2 (d, C(16)); 106.6 (s, C(22)); 119.6

Helvetica Chimica Acta ± Vol. 83 (2000)
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‡
‡
(d, C(15)); 155.6 (s, C(14)). MS (1808): 474 (1, M ), 456 (5, [M À H2O] ), 443 (53), 342 (49), 329 (43), 126
‡
(100). HR-MS: 474.3352 (C29H46O5 ; calc. 474.3345). Anal. calc. for C29H46O5 (474.68): C 73.38, H 9.77; found:
C 72.92, H 9.73.
Data of 30a: M.p. 2058 (from MeOH). IR (KBr): 3440m (br.), 2928s, 2872m, 1652w, 1456m, 1372m, 1420m.
1H-NMR (400 MHz, CDCl3): 0.81 (d, J ˆ 6, Me(27)); 0.86 (s, Me(19)); 1.01 (d, J ˆ 7, Me(21)); 1.03 (s, Me(18));
2.13 (m, HÀC(8)); 2.83 (t, J ˆ 9, HÀC(17)); 3.11 (tt, J ˆ 11, 5, HÀC(3)); 3.34 (s, MeO); 3.40 ± 3.52
(m, CH2(26), Haof CH2OH); 3.62 (br. d, J ˆ 11, Hb of CH2OH); 4.85 (br. d, J ˆ 9, HÀC(16)); 5.51 (br. s,
HÀC(15)). NOE (CDCl3): irr. at 4.85 (HÀC(16)) ! 5.51 (4.0%, HÀC(15)); 2.83 (6.1%, HÀC(17)); irr. at 3.62
(Hb of CH2OH)! 3.45 (9.5%, Ha of CH2OH), 2.83 (8.2%, HÀC(17)); irr. at 2.83 (HÀC(17)) ! 4.85 (10.0%,
HÀC(16)); 3.62 (4.7%, Hb of CH2OH); 1.01 (2.9%, Me(21)). 13C-NMR (100 MHz, CDCl3): 12.2, 14.1, 17.1, 17.8
(4q, C(18), C(19), C(21), C(27)); 27.7 (t); 28.4 (t); 28.7 (t); 29.6 (t); 29.9 (t); 30.4 (d); 31.1 (t); 34.2 (t); 34.3 (d);
36.2 (s, C(10)); 36.7 (t); 44.3 (d); 44.6 (d); 50.3 (d); 51.2 (d); 53.5 (s, C(13)); 55.6 (q, MeO); 66.7 (t, CH2OH);
67.1 (t, C(26)); 76.9 (s, C(12)); 79.6 (d, C(3)); 85.2 (d, C(16)); 106.8 (s, C(22)); 120.2 (d, C(15)); 156.2 (s, C(14)).
‡
‡
‡
MS (1708): 474 (3, M ), 456 (5, [M À H2O] ), 442 (25), 342 (37), 328 (38), 126 (100). HR-MS: 474.3345
‡
(C29H46O5 ; calc. 474.3345). Anal. calc. for C29H46O5 (474.68): C 73.38, H 9.77; found: C 73.41, H 9.70.
(5a,5'a,12'b,25R,25'R)-12'-{[(tert-Butyl)dimethylsilyl]oxy}bisspirosta-2,14-dieno[2,3-b:2',3'-e]pyrazin-12-
one (31) and(5 a,5'a,12'b,25R,25'R)-12'-{[(tert-Butyl)dimethylsilyl]oxy}-12-methylenebisspirosta-2,14-di-
eno[2,3-b:2',3'-e]pyrazine (32). To a À208-cold soln. of 3 (600 mg, 0.708 mmol, 1 equiv.) and 2,6-dimethylpyr-
idine (0.25 ml, 2.13 mmol, 3equiv.) in CH2Cl2 (3 ml), (tert-butyl)dimethylsilyl triflat (0.38 ml, 1.633 mmol,
2.3 equiv.) was added drowpise. After 90 min, 0.5m NaHCO3 (5 ml) and CH2Cl2 (10 ml) were added, and after
warming to r.t., the aq. layer was extracted with CH2Cl2. The combined org. layer was washed with 0.3m HCl and
brine, dried (Na2SO4), and evaporated: crude 31 (749 mg, 110%). Yellow foam. UV (MeOH): 208 (s), 288 (s),
304 (sh). IR (KBr): 3052w (alkene H), 2928s, 2876s, 1716m (CˆO), 1648w (CˆC), 1460m, 1396s (pyrazine),
1370m, 1252m. 1H-NMR (400 MHz, CDCl3): 0.08 (s, 1 MeSi); 0.09 (s, 1 MeSi); 0.81 (br. d, J ˆ 6, Me(27),
Me(27')); 0.86 (s, Me(19')); 0.91 (s, tBuSi); 0.92 (s, Me(19)); 1.01 (s, Me(18')); 1.02 (d, J ˆ 7, Me(21')); 1.05
(d, J ˆ 7, Me(21)); 1.33 (s, Me(18)); 2.02 ± 2.10 (m, 2 H); 2.44 ± 2.90 (m, CH2(1), CH2(1'), CH2(4), CH2(4'),
CH2(11), HÀC(17')); 3.22 (dd, J ˆ 10.5, 5, HÀC(12')); 3.37 (dd, J ˆ 9, 8, HÀC(17)); 3.39 ± 3.45 (m, 1 HÀC(26),
1 HÀC(26')); 3.50 ± 3.55 (m, 1 HÀC(26), 1 HÀC(26')); 4.78 (dd, J ˆ 8, 2, HÀC(16)); 4.85 (dd, J ˆ 8, 2,
HÀC(16')); 5.43, 5.48 (2 br. s, HÀC(15), HÀC(15')). FAB-MS (monoisotopic mass 960.64116): 962 (71,
‡
t
‡
[M ‡ H] ), 847 (34, [M ‡ H À BuMe2Si] ), 207 (32), 147 (100).
To a 08-cold suspension of triphenyl(methyl)phosphonium bromide (2.0 g, 5.6 mmol) in THF (12 ml), 1.8m
(PhLi in cyclohexane/Et2O7:3) (2.83 ml, 5.1 mmol) was added slowly. After 1 h, the vigorous stirring was
stopped, and part of the soln. (6 ml) was decanted into a soln. of crude 31 (700 mg, max. 0.662 mmol) in THF
(1 ml). After 5 h, the reaction was quenched by addition of half-sat. brine (5 ml) and CH2Cl2 (20 ml), the aq.
layer extracted with CH2Cl2, the combined org. layer dried (Na2SO4) and evaporated, and the residue submitted
to FC (petroleum ether/AcOEt 7:1): 32 (538 mg, 85% from 3). White solid. M.p. 2368 (from CHCl3). UV
(MeOH): 209 (s), 288 (s), 305 (sh). IR (CHCl3): 2928s, 2876s, 1632w, 1460m, 1400s (pyrazine), 1376m, 1240s.
1H-NMR (400 MHz, CDCl3): 0.08 (s, 1 MeSi); 0.09 (s, 1 MeSi); 0.80 (d, J ˆ 6, Me(27')); 0.81 (d, J ˆ 6, Me(27));
0.86 (s, Me(19')); 0.88 (s, Me(19)); 0.91 (s, tBuSi); 1.01 (s, Me(18')); 1.02 (d, J ˆ 7, Me(21')); 1.09 (d, J ˆ 7,
Me(21)); 1.22 (s, Me(18)); 2.05 (m, HÀC(8')); 2.28 (m, HÀC(8)); 2.37 ± 2.67 (m, 4 H of CH2(1,1') and
CH2(4,4'), CH2(11), HÀC(17')); 2.79 ± 2.99 (m, 4 H of CH2(1,1') and CH2(4,4'), HÀC(17)); 3.22 (dd, J ˆ 10.5,
4.5, HÀC(12')); 3.40 ± 3.54 (m, CH2(26), CH2(26')); 4.70 (br. s, 1 H, CH2ˆC); 4.80 (m, 1 H, CH2ˆC); 4.83 ± 4.86
(m, HÀC(16), HÀC(16')); 5.35 (br. s, HÀC(15)); 5.43 (br. s, HÀC(15')). 13C-NMR (100 MHz, CDCl3): À4.2,
À3.6 (2q, Me2Si); 11.6, 11.8, 13.6, 14.0, 14.1, 17.2 (br.) (6q, C(18'), C(19), C(19'), C(21), C(21'), C(27), C(27'));
18.0 (s, Me3CSi); 23.7 (q, Me(18)); 26.0 (q, Me3CSi); 27.9 (t); 28.2 (t); 28.79 (t); 28.82 (t); 29.2 (t); 29.4 (t); 30.38
(d); 30.45 (d); 30.7 (t); 31.2 (t); 31.5 (t); 32.3 (t); 33.8 (d); 34.6 (d); 35.3 (t); 35.4 (t); 36.0, 36.1 (2s, C(10), C(10'));
41.3 (d); 41.5 (d); 44.2 (d); 44.8 (d); 45.55 (t); 45.61 (t); 52.0 (d); 53.3, 53.4 (2s, C(13), C(13')); 54.0 (d); 54.8 (d);
55.5 (d); 67.09, 67.14 (2t, C(26), C(26')); 79.7 (d, C(12')); 84.3 (d, C(16)); 84.5 (d, C(16')); 106.1 (t, CH2ˆC);
106.5, 107.4 (2s, C(22), C(22')); 117.8, 119.7 (2d, C(15), C(15')); 148.3, 148.55, 148.64, 148.69 (4s, C(pyrazine));
‡
155.2, 157.2, (2s, C(14), C(14')); 158.8 (s, C(12)). FAB-MS (monoisotopic mass 958.66189): 960 (100, [M ‡ H] ),
t
‡
845 (32, [M ‡ H À BuMe2Si] ), 126 (40). Anal. calc. for C61H90N2O5Si (959.48): C 76.36, H 9.45, N 2.92; found:
C 76.10, H 9.48, N 2.83.
(5a,5'a,12a and12 b,12'b,25R,25'R)-12'-{[(tert-Butyl)dimethylsilyl]oxy}bisspirosta-2,14-dieno[2,3-b :2',3'-
e]pyrazin-12-methanol (33). To a 08-cold soln. of 32 (200 mg, 0.209 mmol, 1 equiv.) in THF (2 ml), 1m borane in
THF (1.2 ml, 1.2 mmol, 5.8 equiv.) was added dropwise. After 6 h, 6n aq. NaOH (1.5 ml) was slowly added
followed by EtOH (0.2 ml), H2O(1 ml), and Et 2O(1 ml). After further 30 min, the mixture was warmed to r.t.

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Helvetica Chimica Acta ± Vol. 83 (2000)
followed by addition of 35% aq. H2O2 soln. (0.4 ml). Then the mixture was stirred for 1 h. After neutralization
by addition of solid NH4Cl, the aq. layer was extracted with CH2Cl2, the combined org. layer dried (Na2SO4) and
evaporated, and the residue submitted to FC (CH2Cl2/MeOH 30 :1): inseparable mixture 33 (184 mg, 90%).
White foam. UV (MeOH): 206 (s), 288 (s), 304 (sh). IR (CHCl3): 3040w, 2956s, 2928s, 2876s, 2860s, 1648w
(CˆC), 1460m, 1400s (pyrazine), 1376m, 1240m. 1H-NMR (400 MHz, CDCl3): 0.08 (s, 3 H, MeSi); 0.09 (s, 3 H,
MeSi); 0.81 (br. d, J ˆ 6, Me(27), Me(27')); 0.86 (s, Me(19')); 0.87 (s, 2 H, Me(19) (12b)); 0.88 (s, 1 H, Me(19)
(12a)); 0.91 (s, tBuSi); 1.00 (s, Me(18')); 1.02 (d, J ˆ 7, 4 H, Me(21'), Me(21) (12a)); 1.04 (d, J ˆ 7, 2 H, Me(21)
(12b)); 1.25 (s, 1 H, Me(18) (12a)); 2.02 ± 2.16 (m, HÀC(8), HÀC(8')); 2.45 ± 2.66 (m, 6 H, 4 H of CH2(1,1') and
CH2(4,4'), HÀC(17), HÀC(17')); 2.78 ± 3.00 (m, 4 H of CH2(1,1') and CH2(4,4')); 3.22 (dd, J ˆ 10.5, 4.5, 1 H,
HÀC(12')); 3.35 ± 3.47 (m, 3 H, 1 HÀC(26), 1 HÀC(26'), Ha of CH2OH); 3.47 ± 3.54 (m, 2 H, HÀC(26),
HÀC(26')); 3.71 ± 3.74 (m, 0.3 H, Hb of CH2OH (12a)); 3.77 (dd, J ˆ 10, 0.7 H, Hb of CH2OH (12b)); 4.79
(dd, J ˆ 8, 1.5, 0.3 H, HÀC(16) (12a)); 4.85 (dd, J ˆ 8, 2, 1 H, HÀC(16')); 4.87 (dd, J ˆ 8, 1.5, 0.7 H, HÀC(16)
(12b)); 5.38, 5.43 (2 br. s, 2 H, HÀC(15), HÀC(15')). FAB-MS (monoisotopic mass 976.67245): 978 (100,
‡
[M ‡ H] ), 136 (29).
(5a,5'a,12a,12'b,25R,25'R)- and(5 a,5'a,12b,12'b,25R,25'R)-12'-{[(tert-Butyl)dimethylsilyl]oxy}-17,12-(ep-
oxymethano)bisspirosta-2,14-dieno[2,3-b:2',3'-e]pyrazine (34 and 35, resp.). A vigorously stirred 108-cold
suspension of mixture 33 (150 mg, 0.154 mmol, 1equiv.), Pb(OAc)4 (200 mg, 0.45 mmol, 3 equiv.; dried prior to
use (see General)) and pyridine (0.05 ml, 0.60 mmol, 4 equiv.) in benzene (3 ml) was irradiated (see General) in
a quartz flask for 2 h. Then the solid particles were removed by column filtration (silica gel, CH2Cl2/MeOH 5 :1).
The org. layer was evaporated and the residue submitted to ꢁgradientꢀ FC (petroleum ether/AcOEt ( ! 34), 2 :1
then CH2Cl2/MeOH 30 :1) ( ! 35): 34 (20 mg, 14%) and 35 (50 mg, 34%), both as colorless, glass-like solids.
Data of 34: UV (MeOH): 205 (s), 287 (s), 303 (sh). IR (CHCl3): 3040w, 2956s, 2928s, 2872s, 2860s, 1644w
1
(CˆC), 1460m, 1400s (pyrazine), 1376m, 1244m. H-NMR (400 MHz, CDCl3): 0.08 (s, MeSi); 0.09 (s, MeSi);
0.80 (br. d, J ˆ 6, Me(27), Me(27')); 0.85, 0.86 (s, Me(19), Me(19')); 0.91 (s, tBuSi); 0.93 (d, J ˆ 7.5, Me(21)); 1.00
(s, Me(18')); 1.02 (d, J ˆ 7, Me(21')); 1.15 (s, Me(18)); 2.00 ± 2.14 (m); 2.41 ± 2.67 (m, 4 H of CH2(1,1') and
CH2(4,4')), HÀC(17')); 2.77 ± 2.90 (m, 4 H of CH2(1,1') and CH2(4,4')); 3.22 (dd, J ˆ 10.5, J ˆ 5, HÀC(12'));
3.38 ± 3.46 (m, 1 HÀC(26), 1 HÀC(26'), Ha of CH2OÀC(17)); 3.51 (br. d, J ˆ 11, 1 HÀC(26')); 3.62 (br. d, J ˆ
11, 1 HÀC(26)); 3.81 (dd, J ˆ 8, 7, Hb of CH2OÀC(17)); 4.47 (d, J ˆ 2.5, HÀC(16)); 4.85 (dd, J ˆ 8, 2,
HÀC(16')); 5.43 (br. s, HÀC(15')); 5.57 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3): À4.2, À3.6 (2q, MeSi);
8.4, 11.6, 11.8, 13.6, 14.1, 17.2 (br.) (6q, C(18'), C(19), C(19'), C(21), C(21'), C(27), C(27')); 18.0 (s, Me3CSi);
20.7 (t); 21.7 (q, Me(18)); 26.0 (q, Me3CSi); 27.7 (t); 28.2 (t); 28.4 (t); 28.77 (t); 28.83 (t); 29.2 (t); 30.0 (d); 30.5
(d); 30.7 (t); 31.2 (t); 31.8 (t); 33.8 (d); 35.3 (t); 35.38 (t); 35.41 (d); 36.05, 36.09 (2s, C(10), C(10')); 41.5 (d); 41.6
(d); 44.8 (d); 45.53 (t); 45.55 (d); 45.7 (t); 45.9 (d); 50.4 (d); 52.0 (d); 53.3 (C, C(13')); 55.5 (br., d, 1s, C(13));
67.1, 67.2 (2t, C(26), C(26')); 68.8 (t, CH2O); 79.8 (d, C(12')); 84.5 (d, C(16')); 90.7 (d, C(16)); 98.4 (s, C(17));
106.5, 107.9 (2s, C(22), C(22')); 118.5, 119.7 (2d, C(15), C(15')); 148.2, 148.5, 148.6, 148.7 (4s, C(pyrazine));
‡
157.2, 157.5 (s, C(14), C(14')). FAB-MS (monoisotopic mass 974.6568): 976 (100, [M ‡ H] ), 861 (22,
‡
t
[M ‡ H À BuMe2Si]), 136 (94).
Data of 35: UV (MeOH): 207 (s), 288 (s), 304 (sh). IR (CHCl3): 2956s, 2928s, 2876s, 2860s, 1645w (CˆC),
1620w (CˆC), 1460m, 1400s (pyrazine), 1384m, 1240m. 1H-NMR (400 MHz, CDCl3): 0.08 (s, MeSi); 0.09
(s, MeSi); 0.81 (d, J ˆ 6, Me(27), Me(27')); 0.86 (s, Me(19')); 0.91 (s, tBuSi); 0.93 (s, Me(19)); 0.97, 1.01
(s, Me(18), Me(18')); 1.018, 1.022 (2d, J ˆ 7, Me(21), Me(21')); 2.05 (m, HÀC(8')); 2.40 (m, HÀC(8)); 2.48 ±
2.65 (m, 4 H of CH2(1,1') and CH2(4,4'), HÀC(17')); 2.79 ± 2.91 (m, 4 H of CH2(1,1') and CH2(4,4')); 3.22
(dd, J ˆ 10.5, 4.5, HÀC(12')); 3.43 (t, J ˆ 11, 1 HÀC(26')); 3.45 (t, J ˆ 11, HÀC(26)); 3.51 (br. d, J ˆ 11,
1 HÀC(26')); 3.55 (dd, J ˆ 12, 7.5, 1 H of CH2OÀC(17)); 3.64 (br. d, J ˆ 11, 1 HÀC(26)); 3.96 (dd, J ˆ 7.5, 5.5,
1 H of CH2OÀC(17)); 4.76 (d, J ˆ 2, HÀC(16)); 4.85 (dd, J ˆ 8, 2, HÀC(16')); 5.13 (br. s, HÀC(15)); 5.43 (br. s,
HÀC(15')). 13C-NMR (100 MHz, CDCl3): À4.2, À3.6 (2q, MeSi); 7.8, 11.0, 11.8, 12.2, 13.6, 14.1, 17.17, 17.19 (8q,
C(18), C(18'), C(19), C(19'), C(21), C(21'), C(27), C(27')); 18.0 (s, Me3CSi); 21.2 (t); 26.0 (q, Me3CSi); 28.1 (t);
28.46 (t); 28.52 (t); 28.8 (t); 29.0 (t); 29.2 (t); 30.1 (d); 30.4 (d); 30.7 (t); 31.2 (t); 31.6 (t); 33.8 (d); 35.4 (t); 36.0
(d); 36.1, 36.7 (2s, C(10), C(10')); 41.5 (d); 42.2 (d); 44.8 (d); 45.6 (t); 45.9 (t); 47.3 (d); 52.0 (d); 53.3 (s, C(13'));
55.5 (d); 56.8 (s, C(13)); 57.0 (d); 67.2, 67.4 (2t, C(26), C(26')); 71.2 (t, CH2O); 79.7 (d, C(12')); 84.5 (d, C(16'));
93.2 (d, C(16)); 99.3 (s, C(17)); 106.5, 106.7 (2s, C(22), C(22')); 113.3 (d, C(15)); 119.7 (d, C(15')); 148.3, 148.5,
148.6, 148.8 (4s, C(pyrazine)); 157.2, 158.7 (2s, C(14), C(14')). FAB-MS (monoisotopic mass 974.6568): 976 (94,
‡
[M ‡ H] ), 103 (100).
(5a,5'a,12a,12'b,25R,25'R)-17,12-(Epoxymethano)bisspirosta-2,14-dieno[2,3-b :2',3'-e]pyrazin-12'-ol (36).
A soln. of 34 (11.5 mg, 0.012 mmol) and Bu4NF (20 mg) in THF (1 ml) was stirred for 13 days in the dark. The
reaction was quenched by addition of CH2Cl2 and H2O, the aq. layer extracted with CH2Cl2, the combined org.

Helvetica Chimica Acta ± Vol. 83 (2000)
1875
layer dried (Na2SO4) and evaporated, and the residue submitted to FC (CH2Cl2/MeOH 30 :1): 36 (9.1 mg, 90%).
White, crystalline solid. UV (MeCN): 289 (s), 306 (sh). IR (CHCl3): 3605w (OÀH), 3065w (alkene H), 2956s,
1
2928s, 2872s, 1456m, 1400s (pyrazine), 1376m, 1240m. H-NMR (400 MHz, CDCl3/CD3OD 5 :1): 0.818, 0.825
(d, J ˆ 6, Me(27), Me(27')); 0.876, 0.883 (s, Me(19), Me(19')); 0.93 (d, J ˆ 7, Me(21)); 1.03 (s, Me(18')); 1.05
(d, J ˆ 7, Me(21')); 1.17 (s, Me(18)); 2.00 ± 2.17 (m); 2.42 ± 2.67 (m, 4 H of CH2(1,1') and CH2(4,4'), HÀC(17'));
2.79 ± 2.92 (m, 4 H of CH2(1,1') and CH2(4,4')); 3.21 (dd, J ˆ 11, 4.5, HÀC(12')); 3.41 (dd, J ˆ 11.5, 8.5, Ha of
CH2OÀC(17)); 3.43 (t, J ˆ 11, 1 HÀC(26')); 3.45 (t, J ˆ 11, 1 HÀC(26)); 3.52 (br. d, J ˆ 11, HÀC(26')); 3.59
(br. d, J ˆ 11, 1 HÀC(26)); 3.83 (dd, J ˆ 8.5, 7, Hb of CH2OÀC(17)); 4.46 (d, J ˆ 2.5, HÀC(16)); 4.88 (dd, J ˆ 8,
1.5, HÀC(16')); 5.42 (br. s, HÀC(15')); 5.57 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3/CD3OD 5 :1): 8.4,
11.8, 12.0, 13.4, 13.6, 17.18, 17.19 (7q, C(18'), C(19), C(19'), C(21), C(21'), C(27), C(27')); 20.8 (t); 21.8
(q, C(18)); 27.8 (t); 28.2 (t); 28.5 (t); 28.8 (t); 29.0 (t); 29.4 (t); 29.9 (t); 30.2 (d); 30.5 (d); 31.3 (t); 31.8 (t); 33.9
(d); 35.0 (t); 35.1 (t); 35.6 (d); 36.1, 36.2 (2s, C(10), C(10')); 41.5 (d); 41.6 (d); 44.7 (d); 45.3 (t); 45.4 (t); 45.7 (d);
46.0 (d); 50.5 (d); 52.4 (d); 53.0 (s, C(13')); 55.69 (d); 55.72 (s, C(13)); 67.2, 67.4 (2t, C(26), C(26')); 69.0 (t,
CH2O); 78.7 (d, C(12')); 85.0 (d, C(16')); 90.9 (d, C(16)); 98.8 (s, C(17)); 107.2, 108.3 (2s, C(22)); 118.5, 119.6
(2d, C(15), C(15')); 148.6, 148.91, 148.92, 149.1 (4s, C(pyrazine)); 157.8, 157.9 (2s, C(14), C(14')). FAB
‡
‡
‡
(monoisotopic mass 860.57033): 862 (100, [M H] ). HR-FAB-MS: 861.5811 ([C55H76N2O6 ‡ H] ; calc. 861.5782).
(5a,5'a,12b,12'b,25R,25'R)-17,12-(Epoxymethano)bisspirosta-2,14-dieno[2,3-b :2',3'-e]pyrazin-12'-ol (37).
To a soln. of 35 (20.4 mg, 0.021 mmol) in CH2Cl2 (0.5 ml) kept in a Nalgene vessel, MeCN (1.5 ml) and 48% aq.
HF soln. (0.2 ml) were added. After 16 h stirring, the mixture was poured onto sat. NaHCO3 soln. the aq. layer
extracted with CH2Cl2, the combined org. layer washed with sat. NaHCO3 soln., dried (Na2SO4), and
evaporated, and the residue submitted to FC (CH2Cl2/MeOH 30 :1): 37 (13.0 mg, 72%). White crystalline solid.
UV (MeCN): 290 (s), 308 (sh). IR (CHCl3): 3610w (OÀH), 2956s, 2932s, 2872s, 1448m, 1400s (pyrazine),
1384m, 1224s. 1H-NMR (400 MHz, CDCl3/CD3OD 5 :1): 0.81, 0.82 (2d, J ˆ 6, Me(27), Me(27')); 0.88 (s, Me(19),
Me(19')); 0.99 (s, Me(18)); 1.02 (d, J ˆ 6.5, Me(21)); 1.03 (s, Me(18')); 1.05 (d, J ˆ 7, Me(21')); 2.08
(m, HÀC(8')); 2.40 (br. t, J ˆ 10, HÀC(8)); 2.49 ± 2.66 (m, 4 H of CH2(1,1') and CH2(4,4'), HÀC(17')); 2.80 ±
2.93 (m, 4 H of CH2(1,1') and CH2(4,4')); 3.21 (dd, J ˆ 11, 4.5, HÀC(12')); 3.43, 3.45 (2t, J ˆ 11, 1 HÀC(26),
1 HÀC(26')); 3.52 (br. d, J ˆ 11, 1 HÀC(26')); 3.58 (dd, J ˆ 12, 7.5, Ha of CH2OÀC(17)); 3.61 (br. d, J ˆ 11,
1 HÀC(26)); 3.96 (dd, J ˆ 7.5, 5.5, Hb of CH2OÀC(17)); 4.75 (d, J ˆ 2, HÀC(16)); 4.88 (dd, J ˆ 8, 1.5,
HÀC(16')); 5.12 (br. s, HÀC(15)); 5.42 (br. s, HÀC(15')). 13C-NMR (100 MHz, CDCl3/CD3OD 5 :1): 7.8, 11.1,
12.0, 12.4, 13.4, 13.6, 17.19, 17.22 (8q, C(18), C(18'), C(19), C(19'), C(21), C(21'), C(27), C(27')); 21.4 (t); 28.2
(t); 28.54 (t); 28.57 (t); 28.8 (t); 29.2 (t); 29.4 (t); 29.9 (t); 30.2 (d); 30.5 (d); 31.3 (t); 31.5 (t); 33.9 (d); 35.0 (t);
36.1 (br., 1d and 1s, C(10')); 36.9 (s, C(10)); 41.6 (d); 42.3 (d); 44.7 (d); 45.4 (t); 45.6 (t); 47.4 (d); 52.4 (d); 53.0
(s, C(13')); 55.7 (d); 57.0 (s, C(13)); 57.2 (d); 58.7 (d); 67.4 br. (2t, C(26), C(26')); 71.3 (t, CH2O); 78.7 (d, C(12'));
85.0 (d, C(16')); 93.4 (d, C(16)); 99.8 (s, C(17)); 107.0, 107.2 (2s, C(22), C(22')); 113.5 (d, C(15)); 119.6
(d, C(15')); 148.8, 148.90, 148.95, 149.1 (4s, C(pyrazine)); 157.7, 158.9 (2s, C(14), C(14')). FAB-MS
‡
‡
(monoisotopic mass 860.57033): 862 (100, [M ‡ H] . HR-FAB-MS: 861.5838 [C55H76N2O6 ‡ H] ; calc. 861.5782).
(3b,5a,12b,20x,25x})-3-(Acetyloxy)-12,26-dihydroxycholesta-14,16-dien-22-one Inner Spirobicyclic Acetal
(39). To a 08-cold soln. of 5 (300 mg, 0.64 mmol, 1 equiv.) and Ph3P (505 mg, 1.92 mmol, 3 equiv.) in CH2Cl2
(4 ml), a soln. of tetrabromomethane (637 mg, 1.92 mmol, 3 equiv.) in CH2Cl2 (4 ml) was added. The mixture
was warmed to r.t. and turned greenish while a precipitate formed. After 20 h, the reaction was quenched by
addition of Et2Oand brine. A yellow precipitate was removed by filtration, and the aq. layer was extracted with
Et2O. The combined org. layer was dried (MgSO4) and evaporated and the residue submitted to FC (petroleum
ether/AcOEt): 39 (115 mg, 40%). Yellow foam. UV (MeCN): 206, 255. IR (KBr): 3548m, 3476s, 3416s, 2932s,
2868m, 1732s, 1616m, 1244s, 1028m, 980m. 1H-NMR (400 MHz, C6D6): 0.70 (s, 3 H); 1.01 (s, 3 H); 1.02 (d, J ˆ 6,
Me(27)); 1.39 (d, J ˆ 7, Me(21)); 1.75 (s, AcO); 2.24 ± 2.34 (m, 2 H); 2.54 (m, 1 H); 2.60 (dd, J ˆ 11.5, 4.5,
HÀC(12)); 3.17 (d, J ˆ 10.5, 1 HÀC(26)); 3.78 (dd, J ˆ 11, 3, 1HÀC(26)); 4.76 (m, HÀC(3)); 6.04
(m, HÀC(15)); 6.14 (m, HÀC(16)). 13C-NMR (100 MHz, C6D6): 12.0, 12.3, 12.8, 16.3 (4q, C(18), C(19),
C(21), C(27)); 21.0 (q, MeCO); 25.5 (t); 26.3 (t); 27.2 (t); 27.4 (t); 27.8 (t); 28.6 (t); 29.4 (t); 34.3 (t); 35.1 (d); 36.2
(s, C(10)); 37.3 (t); 41.2 (d); 44.5 (d); 54.8 (s, C(13)); 56.6 (d); 65.0 (t, C(26)); 73.2 (d, C(3)); 78.3 (d, C(12));
101.8 (s, C(22)); 121.0 (d, C(16)); 121.0 (d, C(15)); 155.6 (s, C(14)); 157.1 (s, C(17)); 169.6 (s, MeCO). FAB-MS:
‡
‡
‡
455 (45, [M H] ), 340 (100). HR-MS: 454.3087 (C29H42O4 ; calc. 454.3083).
(3b,5a,12a,17a,20S,25R)-3-(Acetyloxy)-12,26-dihydroxycholesta-8(14),15-dien-22-one Inner Spirobicyclic
Acetal (40). A soln. of 38 (50 mg, 0.106 mmol, 1 equiv.) and TsOH ´ H2O(25 mg, 0.13 mmol, 1.2 equiv.) in
pentane (3 ml) was refluxed for 2 h. Then the soln. was separated from the solid residue by filtration and
evaporated and the residue submitted to FC (petroleum ether/AcOEt): 39 (11 mg, 23%) and 40 (9 mg, 18%).
White foam. UV (MeCN): 257 (s). IR (KBr): 3552m, 3476s, 3416s, 2932s, 2864m, 1732s, 1616m, 1244m, 1052m,

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Helvetica Chimica Acta ± Vol. 83 (2000)
1
1028m. H-NMR (400 MHz, C6D6): 0.77 (s, 3 H), 0.81 (d, J ˆ 7, 3 H); 1.19 (d, J ˆ 6.5, 3 H); 1.54 (s, 3 H); 1.90
(s, AcO); 2.18 (dd, J ˆ 11, 8, 1 H); 2.40 (dd, J ˆ 10, 3, HÀC(17)); 2.69 (m, 1 H); 3.42 (t, J ˆ 11, HÀC(26)); 3.71
(m, HÀC(26)); 4.07 (br. s, HÀC(12)); 4.91 (m, HÀC(3)); 6.25 (dd, J ˆ 5.8, 2.7, HÀC(16)); 6.53 (d, J ˆ 6,
HÀC(15)). 13C-NMR (100 MHz, C6D6): 12.9, 14.5, 17.4, 21.0 (4q, C(18), C(19), C(21), C(27)); 25.4 (t); 27.1 (t);
27.2 (q, Me3CO); 28.0 (t); 28.9 (t); 29.8 (t); 30.5 (d); 31.7 (t); 34.5 (t); 36.4 (s, C(10)); 37.0 (t); 42.0 (s, C(13)); 44.0
(d); 45.1 (d); 45.5 (d); 54.2 (d); 67.4 (t, C(26)); 68.3 (d, C(12)); 73.3 (d, C(3)); 96.6 (s, C(22)); 128.9 (s, C(8));
‡
‡
129.3 (d, C(15)); 138.2 (d, C(16)); 139.9 (s, C(14)); 169.6 (s, MeCO). FAB: 455 (45, [M H] ), 328 (100). HR-
‡
MS: 454.3084 (C29H42O4 ; calc. 454.3083). Subjecting 5 to a similar procedure afforded 39 (7%) and 40 (19%)
after 25 h.
(3b,5a,12b,15b,16b,20x,25x)-3-(Acetyloxy)-15,16-dihydro-12,26-dihydroxy-14,17-etheno-1'H-cholest-15-eno-
[15,16-c]pyrrole-2',5',22-trione Inner Spirocyclic Acetal (41). A soln. of 39 (76 mg, 0.17 mmol, 1 equiv.) and
maleic imide (20 mg, 0.2 mmol, 1.2 equiv.) in CH2Cl2 (2 ml) was kept for 3 days under a pressure of 14 kbar.
Evaporation and FC (petroleum ether/AcOEt) gave 41 (50 mg, 64%). White foam. IR (CHCl3): 2936m, 1768m,
1720s, 1360m, 1344m, 1252s, 1176m, 1028m, 992m, 964m. 1H-NMR (400 MHz, C6D6): 0.49 (s, 3 H); 0.61 (s, 3 H);
1.00 (d, J ˆ 7, 3 H); 1.63 (d, J ˆ 4.5, 3 H); 1.76 (s, AcO); 1.93 (m, 1 H); 2.20 (m, 1 H); 2.52 (d, J ˆ 6.5, 1 H); 2.65
(m, 1 H); 2.68 (d, J ˆ 6.5, 1 H); 3.19 (d, J ˆ 11, 1 HÀC(26)); 3.80 (dd, J ˆ 10.5, 2.5, 1 HÀC(26)); 4.10 (dd, J ˆ
12.5, 4.5, HÀC(12)); 4.77 (m, HÀC(3)); 5.84 (d, J ˆ 6, C(14)CHˆCHC(17)); 6.29 (d, J ˆ 6,
C(14)CHˆCHC(17)); 7.93 (s, NH). 13C-NMR (100 MHz, C6D6): 11.1, 12.0, 12.6, 16.3 (4q, C(18), C(19),
C(21), C(27)); 21.0 (q, MeCO); 25.0 (t); 25.6 (t); 26.5 (t); 27.3 (d); 27.8 (t); 28.6 (t); 29.8 (t); 34.3 (t); 35.9 (d);
36.3 (s, C(10)); 37.1 (t); 40.9 (d); 44.3 (d); 51.9 (d); 53.8 (d); 55.5 (d); 60.5 (d); 61.6 (s); 62.9 (d); 64.7 (t, C(26));
66.6 (d); 73.2 (d, C(3)); 100.7 (s, C(22)); 128.3 (d); 130.2 (d); 169.8 (s, MeCO); 176.7 (s, CˆO); 176.8 (s, CˆO).
‡
‡
‡
FAB: 552 (80, [M H] ), 307 (100). HR-MS: 551.3236 (C33H45NO6 ; calc. 551.3247).
(3b,5a,12a,22b,25R)-Furost-14-ene-3,12,26-triol 3-Acetate (44). NaCNBH3 (excess) was added to a soln. of
5 (150 mg, 0.31 mmol) in AcOH (1 ml). After 90 min, the reaction was quenched by addition of CH2Cl2 and sat.
Na2CO3 soln., the aq. layer extracted with Et2O, the combined org. layer dried (MgSO4) and evaporated, and the
residue submitted to FC (AcOEt): 44 (140 mg, 94%). White foam. IR (CHCl3): 2936m, 2872w, 1724m, 1456w,
1380w, 1264s, 1100w, 1028m, 960w. 1H-NMR (400 MHz, CDCl3): 0.87 (s, Me(19)); 0.89 (d, J ˆ 6.5, Me(27)); 0.98
(d, J ˆ 6.5, Me(21)); 1.12 (s, Me(18)); 2.01 (s, AcO); 2.12 (m, HÀC(8)); 2.52 (d, J ˆ 9, 1 HÀC(17)); 3.30 (d, J ˆ
8.5, Me(22)); 3.43 (dd, J ˆ 10.5, 6, 1 HÀC(26)); 3.49 (dd, J ˆ 10.5, 6, 1 HÀC(26)); 3.67 (br. s, HÀC(12)); 4.66
(m, HÀC(3)); 4.79 (dd, J ˆ 8, 1.5, HÀC(16)); 5.51 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3): 11.9, 16.6,
16.8, 18.9 (4q, C(18), C(19), C(21), C(27)); 21.4 (q, MeCO); 27.3 (t); 28.1 (t); 28.6 (t); 29.5 (t); 30.0 (t); 30.1 (t);
33.8 (t); 34.4 (d, C(25)); 35.8 (s, C(10)); 35.8 (d); 36.4 (t); 41.7 (d); 44.6 (d); 49.7 (d); 52.7 (s, C(13)); 55.8
(d, C(17)); 68.1 (t, C(26)); 73.3 (d, C(3)); 76.1 (d, C(12)); 86.1 (d, C(16)); 86.5 (d, C(22)); 121.5 (d, C(15));
‡
154.0 (s, C(14)); 170.6 (s, MeCO). FAB-MS: 475 (77, [M ‡ H] ), 359 (35), 154 (100, NBA matrix). HR-MS:
‡
474.3347 (C29H46O5 ; calc. 474.3345).
(3b,5a,12a,22b,25R)-Furost-14-ene-3,12,26-triol 3,12-Diacetate (45). NaCNBH3 (917 mg, 14.6 mmol,
1.2 equiv.) was added to a soln. of 42 (6.26 g, 12.2 mmol, 1equiv.) in AcOH (2 ml). After 150 min, CH2Cl2 was
added and then sat. Na2CO3 soln. The aq. phase was extracted with CH2Cl2 and the combined org. layer dried
(MgSO4) and evaporated: 6.02 g (11.6 mmol, 95%) of 45. IR (CHCl3): 3452w, 3428w, 2940m, 2936m, 2872w,
1724s, 1648w, 1456w, 1376m, 1252s, 1176w, 1104w, 1028s, 960w, 960w. 1H-NMR (400 MHz, CDCl3): 0.85 (s, Me(19));
0.88 (d, J ˆ 6.6, Me(27)); 0.94 (d, J ˆ 6.5, Me(21)); 1.13 (s, Me(18)); 2.00 (s, AcO); 2.02 (s, AcO); 2.09 (t, J ˆ 8.5,
HÀC(17)); 2.12 (m, HÀC(8)); 3.29 (m, HÀC(22)); 3.42 (dd, J ˆ 10.5, 6.0, 1 HÀC(26)); 3.48 (dd, J ˆ 10.5, 6.0,
1 HÀC(26)); 4.65 (m, HÀC(3)); 4.75 (dd, J ˆ 8.5, 2, HÀC(16)); 4.91 (br. s, HÀC(12)); 5.42 (br. s, HÀC(15)).
13C-NMR (100 MHz, CDCl3): 11.8, 16.6, 16.8, 19.0 (4q, C(18), C(19), C(21), C(27)); 21.4 (q, MeCO); 21.4
(q, MeCO); 26.1 (t); 27.2 (t); 28.0 (t); 29.4 (t); 30.0 (t); 30.2 (t); 33.8 (t); 34.3 (d, C(25)); 35.6 (s, C(10)); 35.7 (d);
36.5 (t); 41.2 (d); 44.4 (d); 49.8 (d); 50.3 (s, C(13)); 55.6 (d, C(17)); 68.0 (t, C(26)); 73.3 (d, C(3)); 78.1
(d, C(12)); 86.3 (d, C(16)); 86.8 (d, C(22)); 120.8 (d, C(15)); 153.5 (s, C(14)); 170.6 (s, MeCO); 170.7
‡
‡
(s, MeCO). MS (1708): 516 ([M ‡ H] , 7), 456 (26), 340 (100). HR-MS: 516.3450 (C31H48O6 ; calc. 516.3450).
(3b,22b,25R)-Furost-5-ene-3,26-diol (46). As described for 45, with diosgenin (43; 200 mg, 0.48 mmol): 46
(195 mg, 97%), after recrystallization of the crude product from MeOH/petroleum ether. IR (CHCl3): 3612w,
3420w, 3000m, 2932s, 2904s, 2868m, 1452w, 1376w, 1240s, 1132w, 1096m, 1044s, 1016m, 964w. 1H-NMR
(400 MHz, CDCl3): 0.80 (s, 3 H); 0.90 (d, J ˆ 6.5, 3 H); 0.98 (d, J ˆ 7, Me(21)); 1.01 (s, 3 H); 1.94 ± 2.04 (m, 2 H);
2.17 ± 2.32 (m, 2 H); 3.32 (td, J ˆ 8, 3, HÀC(22)); 3.41 ± 3.54 (m, CH2(26), HÀC(3)); 4.29 (m, HÀC(17)); 5.33
(m, HÀC(6)). 13C-NMR (100MHz, CDCl3): 16.4, 16.6, 18.9, 19.4 (4q, C(18), C(19), C(21), C(27)); 20.7 (t); 30.1
(t); 30.4 (t); 31.6 (d); 31.6 (t); 32.0 (t); 32.2 (t); 35.7 (t); 36.6 (s, C(10)); 37.2 (t); 37.9 (d); 39.4 (t); 40.7 (s, C(13));

Helvetica Chimica Acta ± Vol. 83 (2000)
1877
42.3 (d); 50.1 (d); 57.0 (d); 65.1 (d); 68.0 (t); 71.7 (d); 83.2 (d); 90.3 (d); 121.4 (d); 140.8 (s). MS (1208): 417 (3,
‡
‡
‡
[M H] ), 272 (100), 105 (73). HR-MS: 416.3291 (C27H44O7 ; calc. 416.3290).
(3b,5a,22b,25R)-Furostane-3,26-diol (49). As described for 45, with tigogenin (47, 300 mg, 0.72 mmol): 49
(165 mg, 55%). White foam after FC (petroleum ether/AcOEt). IR (CHCl3): 3612w, 2996m, 2932s, 2848s,
1452m, 1380w, 1240w, 1096w, 1072w, 1032s, 960w. 1H-NMR (400 MHz, CDCl3): 0.77 (s, 3 H); 0.81 (s, 3 H); 0.90
(d, J ˆ 7, 3 H); 0.98 (d, J ˆ 7, 3 H); 1.99 (m, 1 H); 3.31 (m, HÀC(22)); 3.45 (m, CH2(26)); 3.57 (m, HÀC(3));
4.27 (m, HÀC(16)). 13C-NMR (100 MHz, CDCl3): 16.3, 16.6, 16.6, 18.9 (4q, C(18), C(19), C(21), C(27)); 20.9
(t); 28.6 (t); 30.0 (t); 30.3 (t); 31.5 (t); 32.1 (t); 32.2 (t); 35.3 (d); 36.5 (s, C(10)); 35.7 (d); 37.0 (t); 37.9 (d); 38.2 (t);
39.7 (t); 41.0 (s, C(13)); 44.8 (d); 54.4 (d); 56.7 (d); 65.2 (d); 68.0 (t); 71.2 (d); 83.2 (d); 90.3 (d). MS (1608): 418
‡
‡
(5, M ), 331 (32), 274 (100). HR-MS: 418.3445 (C27H46O3 ; calc. 418.3447).
(3b,5b,22b,25R)-Furostane-3,26-diol (50). As described for 45, with smilagenin (48, 300 mg, 0.72 mmol): 50
(230 mg, 76%). White foam after FC (petroleum ether/AcOEt). IR (CHCl3): 3404m, 2932s, 2864m, 1448w,
1376w, 1096w, 1032m, 1004w, 988w. 1H-NMR (400 MHz, CDCl3): 0.77 (s, 3 H); 0.90 (d, J ˆ 6.5, 3 H); 0.97
(s, 3 H); 0.98 (d, J ˆ 7, 3 H); 1.96 (m, 1 H); 3.31 (td, J ˆ 8, 4, HÀC(22)); 3.46 (m, CH2(26)); 4.01 (m, HÀC(3));
4.28 (dt, J ˆ 7.5, 5, HÀC(16)). 13C-NMR (100 MHz, CDCl3): 16.6, 16.6, 18.9, 23.9 (4q, C(18), C(19), C(21),
C(27)); 20.7 (t); 26.4 (t); 26.5 (t); 27.8 (t); 29.9 (t); 30.1 (t); 30.3 (t); 32.2 (t); 33.5 (t); 35.2 (s, C(10)); 35.4 (d); 35.7
(d); 36.5 (d); 37.9 (d); 39.8 (d); 39.9 (t); 41.4 (s, C(13)); 56.9 (d); 65.3 (d); 67.0 (d); 68.0 (t); 83.3 (d); 90.3 (d).
‡
‡
FAB-MS: 419 (97, [M ‡ H] ), 154 (100, NBA matrix). HR-MS: 418.3449 (C27H46O3 ; calc. 418.3447).
(5a,5'a,12b,12'b,22b,22'b,25R,25'R)-Difurosta-2,14-dieno[2,3-b :2',3'-e]pyrazine-12,12',26,26'-tetrol (51).
NaCNBH3 (71 mg, 1.1 mmol, 5.5 equiv.) was added to a suspension of 4 (170 mg, 0.2 mmol, 1 equiv.) in
AcOH (2 ml). After 60 min, the reaction was quenched by addition of CH2Cl2 and sat. Na2CO3 soln., the aq.
phase extracted with CH2Cl2 and the combined org. layer dried (MgSO4) and evaporated: 51 (164 mg, 96%).
White foam. IR (CHCl3): 3616w (OH), 2956s, 2932s, 2872s, 1648w, 1600w, 1460m, 1400s (pyrazine), 1328w,
1232m, 1252w, 1100m, 1032m, 964m. 1H-NMR (400MHz, CDCl3): 0.85 (s, Me(19), Me(19')); 0.89 (d, J ˆ 7,
Me(27), Me(27')); 1.03 (s, Me(18), Me(18')); 1.04 (d, J ˆ 6.5, Me(21), Me(21')); 2.31 (t, J ˆ 8, HÀC(17),
HÀC(17')); 2.44 ± 2.64 (m, 4 H of CH2(1,1') and CH2(4,4')); 2.76 ± 2.93 (m, 4 H of CH2(1,1') and CH2(4,4')); 3.23
(dd, J ˆ 10.5, 4.5, HÀC(12), HÀC(12')); 3.31 (td, J ˆ 8.5, 6, HÀC(22), HÀC(22')); 3.42 (dd, J ˆ 10.5, 6,
CH2(26)); 3.48 (dd, J ˆ 10.5, 6, HÀC(26), HÀC(26')); 4.76 (dd, J ˆ 8.5, 2, HÀC(16), HÀC(16')); 5.43 (br. s,
HÀC(15), HÀC(15')). 13C-NMR (100 MHz, CDCl3): 11.8, 13.9, 16.6, 16.8 (4q, C(18), C(18'), C(19), C(19'),
C(21), C(21'), C(27), C(27')); 28.0 (t); 29.2 (t); 30.1 (t); 30.1 (t); 30.3 (t); 33.8 (d); 35.2 (t); 35.8 (d); 35.9
(s, C(10), C(10')); 41.2 (d); 41.4 (d); 45.6 (d); 51.9 (d); 52.9 (s, C(13), C(13')); 59.2 (d); 68.0 (t, C(26), C(26'));
79.2 (d); 86.0 (d); 87.1 (d); 119.8 (d, C(15), C(15')); 148.4, 148.5 (2s, C(pyrazine)); 157.6 (s, C(14), C(14')). FAB:
‡
853 (42, M ), 154 (92, NBA matrix), 136 (100).
(3b,5a,12a,22b,25R)-Furost-14-ene-3,12,26-triol 3,12-Diacetate 26-(4-Methylbenzenesulfonate) (52).
A
soln. of 45 (21.8 g, 42.2 mmol, 1 equiv.), pyridine (7.2 ml, 84.3 mmol), TsCl (9.63 g, 50.6 mmol, 1.2 equiv.),
and 4-(dimethylamino)pyridine (catalytic amount) in CH2Cl2 (300 ml) was stirred for 20 h. The reaction was
quenched by addition of CH2Cl2 and 2m HCl, the org. layer washed with 2m HCl, sat. NaHCO3 soln., and brine,
dried (MgSO4), and evaporated, and the residue submitted to FC (petroleum ether/AcOEt); 52 (27.2 g, 96%).
White foam. IR (CHCl3): 2932m, 2860w, 1724s (CˆO), 1364w, 1252s, 1176s, 1096w, 1028m, 964m. 1H-NMR
(400 MHz, CDCl3): 0.85 (s, Me(19)); 0.87 (d, J ˆ 7, Me(27)); 0.92 (d, J ˆ 6.5, Me(21)); 1.12 (s, Me(18)); 2.01
(s, AcO); 2.03 (s, AcO); 2.08 (t, J ˆ 8.5, HÀC(17)); 2.14 (m, HÀC(8)); 2.44 (s, MeC6H4); 3.21 (m, HÀC(22));
3.80 (dd, J ˆ 9.5, 6.5, 1 HÀC(26)); 3.87 (dd, J ˆ 9.5, 5.5, 1 HÀC(26)); 4.65 (m, HÀC(3)); 4.72 (dd, J ˆ 8.5,
1 HÀC(16)); 4.91 (br. s, HÀC(12)); 5.41 (br. s, HÀC(15)); 7.32 (d, J ˆ 8.0, 2 arom. H); 7.76 (d, J ˆ 8,
2 arom. H). 13C-NMR (100 MHz, CDCl3): 11.9, 16.4, 16.7, 19.1 (4q, C(18), C(19), C(21), C(27)); 21.4 (q);
21.4 (q); 21.6 (q); 26.1 (t); 27.2 (t); 28.1 (t); 29.4 (t); 29.7 (t); 30.3 (t); 33.0 (d); 33.8 (t); 34.3 (d); 35.5 (s, C(10));
36.5 (t); 41.2 (d); 44.4 (d); 49.8 (d); 50.3 (s, C(13)); 55.9 (d, C(17)); 73.3 (d, C(3)); 75.0 (t, C(26)); 78.0
(d, C(12)); 86.3 (d, C(16)); 86.4 (d, C(22)); 120.8 (d, C(15)); 127.9 (d, arom. C); 129.8 (d, arom. C); 133.1 (s);
‡
144.5 (s); 153.6 (s, C(14)); 170.6 (s, MeCO); 170.7 (s, MeCO). FAB-MS: 670 (45, M ), 281 (60). HR-MS:
‡
670.3536 (C38H54O8S ; calc. 670.3539).
(3b,5a,12a,22b,25R)-26-Iodofurost-14-ene-3,12-diol Diacetate (53).
A 408-warm soln. of 52 (5.2 g,
77.6 mmol, 1 equiv.) and NaI (11.68 g, 0.78 mol, 10 equiv.) in MeCN (35 ml) was stirred for 14 h. Then AcOEt
was added, the org. layer washed with H2O, sat. NaHCO3 soln., and brine, dried (MgSO4), and evaporated and
the residue submitted to FC (petroleum ether/AcOEt): 53 (4.08 g, 84%). White foam. IR (CHCl3): 2928m,
1
2860w, 1724s (CˆO), 1456w, 1376m, 1264s, 1028m. H-NMR (400 MHz, CDCl3): 0.85 (s, Me(19)); 0.95 ± 0.97
(m, Me(27), Me(21)); 1.14 (s, Me(18)); 2.01 (s, AcO); 2.03 (s, AcO); 2.10 (t, J ˆ 8.5, HÀC(17)); 2.12
(m, HÀC(8)); 3.14 (dd, J ˆ 9.5, 5.5, 1 HÀC(26)); 3.24 (dd, J ˆ 9.5, 4, 1 HÀC(26)); 3.28 (m, HÀC(22)); 4.65

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Helvetica Chimica Acta ± Vol. 83 (2000)
(m, HÀC(3)); 4.75 (dd, J ˆ 8.0, 2, HÀC(16)); 4.91 (br. s, HÀC(12)); 5.43 (br. s, HÀC(15)). 13C-NMR
(100 MHz, CDCl3): 11.9 (q); 16.9 (q); 17.7 (t, C(26)); 19.2 (q); 20.5 (q); 21.4 (q, MeCO); 21.4 (q, MeCO); 26.1
(t); 27.3 (t); 28.1 (t); 29.4 (t); 30.7 (t); 33.5 (t); 33.8 (t); 34.3 (d, C(25)); 34.9 (d); 35.6 (s, C(10)); 36.5 (t); 4.3 (d);
44.4 (d); 49.8 (d); 50.3 (s, C(13)); 56.0 (d, C(17)); 73.3 (d, C(3)); 78.0 (d, C(12)); 86.3 (d, C(16)); 86.6 (d, C(22));
‡
120.8 (d, C(15)); 153.6 (s, C(14)); 170.6 (s, MeCO); 170.7 (s, MeCO). MS (1708): 627 (12, [M ‡ H] ), 340 (100).
‡
HR-MS: 626.2469 (C31H47IO5 ; calc. 626.2468).
(3b,5b,12a,22b)-Furosta-14,25-diene-3,12-diyl Diacetate (54). A soln. of 53 (4.07 g, 6.5 mmol, 1 equiv.) and
DBU (1.9 ml, 12.8 mmol, 1.9 equiv.; freshly distilled) in MeCN (40 ml) was refluxed for 15 min. Then AcOEt
was added, the org. layer washed with 2m HCl, sat. NaHCO3 soln., and brine, dried (MgSO4), and evaporated,
and the residue submitted to FC (petroleum ether/AcOEt): 54 (2.68 g, 83%). White foam. IR (CHCl3): 2936m,
2860w, 1724s (CˆO), 1376m, 1252s, 1104w, 1024m. 1H-NMR (400 MHz, CDCl3): 0.87 (s, Me(19)); 0.96 (d, J ˆ
6.5, Me(21)); 1.14 (s, Me(18)); 1.71 (d, Me(27)); 2.01 (s, AcO); 2.03 (s, AcO); 2.10 (t, J ˆ 8.5, HÀC(17)); 2.14
(m, 1 H); 2.25 (m, 1 H); 3.31 (td, J ˆ 9, 2.5, HÀC(22)); 4.65 (m,HÀC(3)); 4.68 (br. d, CH2(26)); 4.76 (dd, J ˆ
8.5, 2, HÀC(16)); 4.91 (br. s, HÀC(12)); 5.44 (br. s, HÀC(15)). 13C-NMR (100 MHz, CDCl3): 11.8, 16.8, 19.2,
(3q, C(18), C(19), C(21)); 21.41 (q, MeCO); 21.44 (q, MeCO), 22.6 (q, C(27)); 26.1 (t); 27.3 (t); 28.1 (t); 29.4 (t);
31.2 (t); 33.8 (t); 34.3 (d); 34.6 (t); 35.6 (s, C(10)); 36.5 (t); 41.3 (d); 44.4 (d); 49.8 (d); 50.4 (s, C(13)); 56.1
(d, C(17)); 73.3 (d, C(3)); 78.1 (d, C(12)); 86.3 (d, C(16)); 86.3 (d, C(22)); 109.5 (t, C(26)); 120.9 (d, C(15));
‡
145.7 (s, C(25)); 153.5 (s, C(14)); 170.6 (s, MeCO); 170.7 (s, MeCO). MS (1608): 498 (44, M ), 382 (100). HR-
‡
MS: 498.3348 (C31H46O5 ; calc. 498.3345).
(3b,5a,12a)-3,12-Bis(acetyloxy)cholesta-14,25-diene-16,22-dione (55). A 708-warm soln. of 54 (996 mg,
2 mmol, 1 equiv.) and potassium dichromate (2.47 g, 5 mmol, 2.5 equiv.) in glacial AcOH (25 ml) was stirred for
3 h. Then EtOH and H2Owere added. The aq. layer was extracted with CH 2Cl2, the combined org. layer washed
with sat. Na2CO3 soln., dried (MgSO4), and evaporated, and the residue submitted to FC (Alox-N; petroleum
ether/AcOEt): 55 (410 mg, 40%; 47% based on recovered 54) and recovered 54 (160 mg, 0.23 mmol), both as
white foams. 55: IR (CHCl3): 3688w, 2984w, 2932w, 1720m (CˆO), 1700m (CˆO), 1600w, 1372w, 1264s, 1028w.
1H-NMR (400 MHz, CDCl3): (s, Me(19)); 1.04 (d, J ˆ 7, Me(21)); 1.22 (Me(18)); 1.75 (s, Me(27)); 2.01 (s, AcO);
2.09 (s, AcO); 2.31 ± 2.37 (m, 2 H); 2.45 (m, 1 H); 2.63 ± 2.73 (m, 2 H); 2.83 ± 2.91 (m, 1 H), 3.20 (d, J ˆ 10.5,
HÀC(17)); 4.68 (m, HÀC(3)); 4.71 (br. d, J ˆ 9.5, CH2(26)); 5.10 (br. s, HÀC(12)); 5.76 (d, J ˆ 2, HÀC(15)).
13C-NMR (100 MHz, CDCl3): 11.6, 15.9, 21.1 (3q, C(18), C(19), C(21)); 21.3 (q, MeCO); 21.5 (q, MeCO); 22.7
(q, C(27)); 25.5 (t); 26.9 (t); 27.2 (t); 27.6 (t); 29.1 (t); 33.7 (t); 35.5 (s, C(10)); 35.9 (t); 36.4 (d); 40.9 (t); 42.6 (d);
43.8 (d); 46.2 (d); 48.7 (s, C(13)); 55.9 (d); 73.0 (d); 74.5 (d); 109.7 (t, C(26)); 124.5 (d, C(15)); 145.0 (s, C(25));
‡
170.0 (s, MeCO); 170.5 (s, MeCO); 185.0 (s, C(14)); 206.7 (s, C(16)); 212.5 (s, C(22)). MS (1608): 512 (30, M ),
‡
‡
‡
356 (100). FAB-MS: 513 (100, [M H] ), 136 (95). HR-MS: 512.3143 (C31H44O6 ; calc. 512.3138).
X-Ray Structure Determinations for 40 and 49. Preparation andCrystal Growing . Crystals were obtained by
slow evaporation of a soln. of 40 in MeOH with some CH2Cl2 and a soln. of 49 in CHCl3, resp., at r.t. A crystal of
0.6 Â 0.1 Â 0.1 mm in the case of 40 and of 0.7 Â 0.3 Â 0.1 mm in the case of 49 was selected and mounted on a
glass fiber for data collection.
Data Collection. Data for both structures was collected on a Bruker-AXS-P4 four-circle diffractometer with
graphite-monochromated MoKa(l 0.71073 Š) at r.t. Intensities were obtained from w scans with a maximum
scan time of 1.58/min for 40 and 2.58/min for 49; 4966 reflections (3961 unique) were measured to 2qmax of 508
for 40, and 6931 reflections (3522 unique) to 2qmax of 46.58 for 49. In both cases, Friedel opposites were not
merged. Further details of data collection parameters are given in Table 2.
Structure Solution andRefinement . Compound 40 crystallizes in the orthorhombic space group P212121 and
49 in the monoclinic space group P21, each with one molecule in the asymmetric unit. Both structures were
solved by direct methods with the program SHELXS-86 [44]. Both structures were refined on F2 (all data) with
the program SHELXL-97 [45]. All H-atoms were added in idealized positions and refined with a ꢁridingꢀ model.
For 40, the refinement converged to R1 ˆ 0.0549 for the 2346 Fo > 4a(Fo) and 0.1359 for all 3961 data. For 49,
restraints concerning the anisotropic displacement parameters were used for the whole molecule [46 ± 48]. The
refinement converged to R1 ˆ 0.0913 for the 2976 Fo > 4s(Fo) and 0.2700 for all 3522 data. The very bad quality
of the crystal in the case of 49 explains the relatively high values of R1 as well as wR2 and thus the relatively bad
model. Nevertheless, the relative configuration could be determined for both structures. Further details of
refinement parameters are listed in Table 2.
Crystallographic data (excluding structure factors) have been deposited in the Cambridge Crystallographic
Data Centre as supplementary publication No. CCDC-141277 for 40 and No. CCDC-141276 for 49. Copies of
the data can be obtained free of charge, on application to the director, CCDC, 12 Union Road, Cambridge
CB21EZ, UK (fax: ‡44 (0)1223 (336033; e-mail: teched@chemcrys.cam.ac.uk).

Helvetica Chimica Acta ± Vol. 83 (2000)
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Table 2. Crystal Data andStructure Refinement for 40 and 49
40
49
Empirical formula
Mr
C29H42O4
454.63
C27H46O3
418.64
Temperature [K]
Wavelength [Š]
Crystal system
Space group
293
0.71073
orthorhombic
P212121
293
0.71073
monoclinic
P21
Unit-cell dimensions [Š]
a ˆ 8.664(2)
b ˆ 10.507(2)
c ˆ 28.384(5)
a ˆ 10.357(3)
b ˆ 7.274(2)
c ˆ 16.545(4)
b ˆ 91.75(1)
1245.9(6)
2
V [Š3]
Z
2583.8(9)
4
1.169
Density (calc.) [Mg/m3]
1.116
0.070
Absorption coefficient [mm3] 0.076
F(000)
992
464
Crystal size [mm]
2q Range for data collection 4.14 to 50.00
0.6 Â 0.1 Â 0.1
0.7 Â 0.3 Â 0.1
3.94 to 46.52
Limiting indices
À 9 ꢁ h ꢂ 9, À11 ꢁ k ꢂ 1, À1 ꢁ 1 ꢂ 31 À 11 ꢁ h ꢂ 11, À8 ꢁ k ꢂ 8, À18 ꢁ 1 ꢂ 18
Reflections collected
Independent reflections
Refinement method
Data/restraints/parameter
Goodness-of-fit Sa)
4966
6931
3961 (Rint ˆ 0.0380)
full-matrix least-squares on F2
3960/0/299
3522 (Rint ˆ 0.0436)
full-matrix least-squares on F2
3522/293/274
1.076
1.028
Final R indices (F > 4s(F)b)) R1 ˆ 0.0549, wR2 ˆ 0.1114
R1 ˆ 0.0913, wR2 ˆ 0.2538
R1 ˆ 0.1064, wR2 ˆ 0.2700
À 2(4)
R indices (all data)c)
R1 ˆ 0.1132, wR2 ˆ 0.1359
Absolute structure parameter 2.96(204)
Max. difference density [aŠ3] 0.145
Min. difference density [aŠ3] À 0.174
0.348
À 0.221
a
b
)
S ˆ [S[w(F 2o À F 2c )2]/(n À p)]1/2
.
)
wR2 ˆ {S[w(F 2o À F 2c )2]S[w(F2o)2]}1/2
;
wÀ 1 ˆ s2 (F2o) ‡ (g1P)2 ‡ g2P,
where P ˆ (F 2o ‡ 2 F c2 )/3. c) R1 ˆ S jk Fo j À j Fc k /S j Fo j
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ReceivedMarch 8, 2000