Some observations on solasodine reactivity

Article abstract of DOI:10.1016/j.steroids.2017.08.015

This article presents new transformations of solasodine – a representative steroid alkaloid sapogenin from the Solanum family. Oxidation of N,O-diacetylated solasodine with either NaNO₂/BF_3·Et₂O or t-BuONO/BF_3·Et₂O resulted in partial degradation of the side chain to (20S)-3β-acetoxypregn-5-ene-20,16β-carbolactone (vespertilin acetate). The same starting compound when treated with TMSOTf afforded the corresponding pseudosapogenin after aqueous work-up. However, when the crude reaction mixture was directly subjected to purification on a silica gel column, efficient autoxidation to pregna-5,16-dien-3β-ol-20-one acetate was observed. One-step synthesis of this important drug intermediate from spirosolan alkaloids may be potentially exploited for large-scale production of steroid hormones.

Full text of DOI:10.1016/j.steroids.2017.08.015

Accepted Manuscript
Some observations on solasodine reactivity
Izabella Jastrzebska, Jacek W. Morzycki
PII:
S0039-128X(17)30157-5
http://dx.doi.org/10.1016/j.steroids.2017.08.015
STE 8149
DOI:
Reference:
Steroids
To appear in:
Received Date:
Revised Date:
Accepted Date:
28 June 2017
21 August 2017
30 August 2017
Please cite this article as: Jastrzebska, I., Morzycki, J.W., Some observations on solasodine reactivity, Steroids
(2017), doi: http://dx.doi.org/10.1016/j.steroids.2017.08.015
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Some observations on solasodine reactivity
Izabella Jastrzebska*, Jacek W. Morzycki
Institute of Chemistry, University of Białystok, Ciołkowskiego 1K, 15-245 Białystok, Poland
* Corresponding author:
Tel.: +48 85 7388043, Fax: +48 85 7388103, e-mail: gierdas@uwb.edu.pl

Highlights
 The oxidation of N,O-diacetylsolasodine with NaNO2/BF3·Et2O or t-BuONO/BF3·Et2O
results in partial degradation of the side chain affording (20S)-3β-acetoxypregn-5-ene-
20,16β-carbolactone (vespertilin acetate).
 The reaction of N,O-diacetylsolasodine with TMSOTf leads to the corresponding
pseudosapogenin.
 If no aqueous work-up is applied, crude pseudosapogenin readily undergoes
autoxidation with concomitant elimination of a five-carbon atom fragment to pregna-
5,16-dien-3β-ol-20-one acetate, which is an important intermediate in the synthesis of
steroid hormones.

Abstract – This article presents new transformations of solasodine – a representative steroid
alkaloid sapogenin from the Solanum family. Oxidation of N,O-diacetylated solasodine with
either NaNO2/BF3·Et2O or t-BuONO/BF3·Et2O resulted in partial degradation of the side chain
to (20S)-3β-acetoxypregn-5-ene-20,16β-carbolactone (vespertilin acetate). The same starting
compound when treated with TMSOTf afforded the corresponding pseudosapogenin after
aqueous work-up. However, when the crude reaction mixture was directly subjected to
purification on a silica gel column, efficient autoxidation to pregna-5,16-dien-3β-ol-20-one
acetate was observed. One-step synthesis of this important drug intermediate from spirosolan
alkaloids may be potentially exploited for large-scale production of steroid hormones.
Keywords: alkaloids, autoxidation, sapogenins, solasodine, steroids

1. Introduction
Steroidal alkaloid glycosides (SAGs) are natural products showing diverse biological
activity [1,2]. The largest source of SAGs is the Solanaceae family, which includes
economically important genera such as the potato, tomato, eggplant, and capsicum. Upon
hydrolysis, steroidal alkaloid glycosides yield sugars and steroidal alkaloid sapogenins
(SASs). Solanum alkaloids are in fact the nitrogen-analogs of steroidal sapogenins (Figure 1).
Figure 1 insert here
SASs containing oxa-aza spiro (spirosolan) structures may have either an R or S
configuration at the spiro carbon atom (C-22), which is very rare for their oxygen
counterparts. The C27 methyl group in spirosolans is always in equatorial position, whereas
spirostanes show various orientation of this methyl group. The 21-methyl group is -oriented
(20S) in both spirostanes and spirosolans.
The chemistry of steroidal sapogenins has been extensively explored since the 1950s
[3,4]. In contrast, knowledge regarding the chemistry of SASs is rather limited [5,6]. In this
paper we present the results of a study on selected reactions of the representative steroid
alkaloid sapogenin – solasodine.
2. Methods and materials
2.1. Chemistry
2.1.1. General methods
Reagent-grade chemicals were purchased and used as received. Methylene chloride
was freshly distilled. Flash column chromatography and dry flash chromatography were
performed with silica gel, pore size 40A (70-230 mesh), unless otherwise stated. All reactions
were monitored by TLC on silica gel plates 60 F254. 1H (400 MHz) and 13C NMR (100 MHz)
spectra for all compounds were recorded at ambient temperature and were referenced to TMS

(0.0 ppm) and CDCl3 (77.0 ppm), respectively, unless otherwise noted. NMR resonance
multiplicities were reported using the following abbreviations: b = broad, s = singlet, d =
doublet, t = triplet, q = quartet, and m = multiplet; coupling constants J were reported in Hz.
IR spectra were obtained in a CHCl3 solution with an FT-IR spectrometer, and data are
reported in cm-1. Melting points were determined by a Kofler bench (Boetius type) apparatus
and are uncorrected.
Acetylation of solasodine acetate: Solasodine acetate (750 mg; 1.6 mmol) was
dissolved in pyridine (25 ml) and acetic anhydride (5 ml) was added. The reaction mixture
was stirred in room temperature overnight. The reaction mixture was poured into aqueous
HCl and extracted with dichloromethane. The combined organic extracts were washed with
brine, dried over Na2SO4 and evaporated in vacuo. Silica gel column chromatography with
ethyl acetate/hexane 18:82 elution afforded N,O-diacetylosolasodine in 80% yield (1, 655
mg). Compound 1 proved identical in all respects with the same compound described in the
literature [7]. M.p. (DCM/hexane) 161-163C (lit. [7] 162-164C); 1H NMR:  5.31 (m, 1H),
4.54 (m, 1H), 4. 13 (q, J = 7.1 Hz, 1H), 3.95 (bd, J = 11.5 Hz, 1H), 3.05 (m, 1H), 2.80 (dd, J
= 13.0, 6.6 Hz, 1H), 2.14 (s, 3H), 1.98 (s, 3H), 1.03 (d, J = 6.8 Hz, 3H), 0.98 (s, 3H), 0.88 (d,
J = 6.5 Hz, 3H), 0.86 (s, 3H); 13C NMR:  170.7 (C), 170.3 (C), 139.6 (C), 122.1 (CH), 101.0
(C), 78.6 (CH), 73.6 (CH), 61.9 (CH), 55.6 (CH), 49.9 (CH), 48.9 (CH2), 40.8 (C), 39.9
(CH2), 38.0 (CH), 37.9 (CH2), 36.8 (CH2), 36.6 (C), 31.9 (CH2 x 2), 30.9 (CH), 27.8 (CH),
27.6 (CH2), 25.1 (CH3), 24.1 (CH2), 23.8 (CH2), 21.2 (CH3), 20.7 (CH2), 19.1 (CH3), 18.4
(CH3), 16.2 (CH3), 16.0 (CH3).
Oxidation of 1 with NaNO2/BF3Et2O: N,O-Diacetylsolasodine 1 (75 mg; 0.14 mmol)
was dissolved in glacial AcOH (10 ml). Then BF3·Et2O (0.005 ml; 6 equiv) was added.
Sodium nitrite (30 mg; 3 equiv) was added portion-wise for 30 min. The reaction mixture was
stirred at room temperature for 1 hour. The reaction mixture was poured into water and pH

was adjusted to 8-9 by adding NaHCO3. The product was extracted with dichloromethane.
The combined organic layers were washed with saturated aqueous NaCl solution, dried over
Na2SO4 and evaporated in vacuo. Silica gel column chromatography with ethyl
acetate/hexane 15:85 elution afforded (20S)-3β-acetoxypregn-5-ene-20,16β-carbolactone in
80% yield (2, 46 mg). Compound 2 proved identical in all respects with the same compound
described in the literature [8]. M.p. (DCM/hexane) 216-220C (lit. [8] 210-212C; [9] 216-
220C); 1H NMR:  5.38 (m, 1H), 4.96 (m, 1H), 4.61 (m, 1H), 2.60 (q, J = 7.6 Hz, 1H), 2.04
(s, 3H), 1.33 (d, J = 7.6 Hz, 3H), 1.05 (s, 3H), 0.78 (s, 3H); 13C NMR:  181.3 (C), 170.5 (C),
139.8 (C), 121.9 (CH), 82.7 (CH), 73.7 (CH), 58.9 (CH), 54.7 (CH), 49.9 (CH), 41.4 (C), 38.1
(CH2), 38.0 (CH2), 36.9 (CH2), 36.6 (C), 36.0 (CH), 33.1 (CH2), 31.8 (CH2), 31.2 (CH), 27.7
(CH2), 21.4 (CH3), 20.3 (CH2), 19.3 (CH3), 18.0 (CH3), 13.7 (CH3).
Oxidation of 1 with t-BuONO/BF3Et2O: N,O-Diacetylsolasodine 1 (250 mg; 0.5
mmol) was dissolved in glacial AcOH (10 ml). Then BF3·Et2O (0.03 ml; 0.5 equiv) was added
followed by tert-butyl nitrite (0.3 ml; 5 equiv). The reaction mixture was stirred at room
temperature for 3 h. The reaction mixture was poured into water and pH was adjusted to 8-9
by adding NaHCO3. The product was extracted with dichloromethane. The combined organic
extracts were washed with saturated aqueous NaCl solution, dried over Na2SO4 and
evaporated in vacuo. Silica gel column chromatography with ethyl acetate/hexane 15:85
elution afforded (20S)-3β-acetoxypregn-5-ene-20,16β-carbolactone in 90% yield (2, 175 mg).
Compound 2 proved identical in all respects with the same compound described in the
literature.
Reaction of 1 with TMSOTf without aqueous work-up: N,O-Diacetylsolasodine 1
(50 mg, 0.1 mmol) was dissolved in dry dichloromethane (15 ml). TMSOTf (1 equiv, 0.018
ml) was then added to the solution. The solution was placed on a silica gel column after a
period of 10 min. The reaction mixture remained on the column for 72 h. Then pregna-5,16-

dien-3β-ol-20-one acetate (21 mg, 60%) was eluted with an ethyl acetate/hexane 35:65
mixture. Compound 3 proved identical in all respects with the same compound described in
the literature [10]. M.p. (DCM/hexane) 169-172C (lit. [10] 172-174C); 1H NMR:  6.72 (m,
1H), 5.35 (d, J = 5.0 Hz, 1H), 4.62 (m, 1H), 2.27 (s, 3H), 2.04 (s, 3H), 1.07 (s, 3H), 0.93 (s,
13
3H); C NMR:  196.8 (C), 170.5 (C), 155.4 (C), 144.4 (CH), 140.3 (C), 121.9 (CH), 73.8
(CH), 56.3 (CH), 50.4 (CH), 46.1 (C), 38.1 (CH2), 36.8 (CH2), 36.7 (C), 34.6 (CH2), 32.2
(CH2), 31.5 (CH2), 30.1 (CH), 27.7 (CH2), 27.1 (CH3), 21.4 (CH3), 20.6 (CH2), 19.2 (CH3),
15.7 (CH3).
Reaction of 1 with TMSOTf followed by aqueous work-up: N,O-
Diacetylsolasodine 1 (40 mg, 0.1 mmol) was dissolved in dry dichloromethane (15 ml).
TMSOTf (0.044 ml, 2 equiv) was then added to the solution. After 24 h the reaction mixture
was poured into water and extracted with dichloromethane. The combined organic extracts
were washed with saturated aqueous NaCl solution, dried over Na2SO4 and evaporated in
vacuo. Silica gel chromatography with ethyl acetate/hexane 7:3 elution afforded N-
acetylopseudosolasodine acetate (23 mg, 60%). Compound 4 proved identical in all respects
with the same compound described in the literature [7]. M.p. (DCM/hexane) 134-137C (lit.
1
[11] 134-136C); H NMR:  5.58 (bs, 1H), 5.38 (d, J = 4.6 Hz, 1H), 4.75 (m, 1H), 4.62 (m,
1H), 3.714 (m, 1H), 2.27 (s, 3H), 2.04 (s, 3H), 1.98 (s, 3H), 1.04 (s, 3H), 0.92 (d, J = 6.6 Hz,
1H), 0.69 (s, 3H); 13C NMR:  170.5 (C), 170.0 (C), 151.3 (C), 139.7 (C), 122.3 (CH), 104.0
(C), 84.3 (CH), 73.8 (CH), 64.1 (CH), 54.9 (CH), 49.9 (CH), 45.3 (CH2), 43.2 (C), 39.4
(CH2), 38.1 (CH2), 36.9 (CH2), 36.7 (C), 34.1 (CH2), 32.7 (CH), 32.1 (CH2), 31.7 (CH2), 31.2
(CH), 27.7 (CH2), 23.4 (CH3), 23.1 (CH2), 21.4 (CH3), 20.9 (CH2), 19.3 (CH2), 17.6 (CH3),
13.9 (CH3), 11.6 (CH3).

3. Results and discussion
There are many examples of interesting reactions of 23-oxo functionalized steroidal
sapogenins in the literature [3,12]. The first aim of this project was to elaborate a convenient
route to 23-oxo-solasodine acetate in order to study processes similar to those of 23-oxo-
spirostanes. Since direct functionalization of solasodine at C23 failed, the amino group was
protected by acetylation with Ac2O/Py. Then derivative 1 was subjected to oxidation with
NaNO2/BF3·Et2O according to the procedure first described by Barton [13] and improved by
Iglesias-Arteaga [14] (Scheme 1a). The structure of the obtained product (20S)-3β-
1
acetoxypregn-5-ene-20,16β-carbolactone (2) (vespertilin acetate) was elucidated from its H
NMR, in which the characteristic F ring signals of 26-methylene protons and the 27-methyl
group disappeared. Vespertilin is a naturally occurring lactone with a proven biological
activity, including antipyretic, anticarcinogenic, and plant growth promotion [8,15]. Because
the above reaction did not give the desired result, other conditions as introduced by Fuchs et
al. were applied [16]. The method employs t-butyl nitrite instead of sodium nitrite. In this
case, lactone 2 was also the only product (Scheme 1b).
Ac
N
O
O
O
NaNO2, BF3.Et2O
glacial AcOH
a)
b)
1
2 (80%)
AcO
AcO
t-BuONO, BF3.Et2O
1
2 (90%)
glacial AcOH
Scheme 1. Oxidation of N,O-diacetylsolasodine 1.
In the case of oxidation of spirostanes at C23, the reaction proceeds via intermediate
enol-ether II [13], which is attacked by the oxidizing agent followed by F ring reclosure in the
next step (Scheme 2).

Scheme 2. Formation of enol-ether intermediates I and II in the presence of acid.
Oxidation of N-acetylated solasodine 1 probably follows the same reaction
mechanism. In this case, the nitrosonium ion is an electrophile that attacks the
pseudosapogenin formed from solasodine diacetate 1. The initial 23-nitroso product
equilibrates to the more stable 23-hydroxyimino tautomer. It has already been proven that the
23-oxime readily undergoes Beckmann fragmentation under the reaction conditions
(BF3·Et2O, AcOH) [17]. The reaction leads to 20,16β-carbolactone 2 via the loss of a five-
carbon atom nitrile fragment. The presumable mechanism of oxidation with NaNO2/BF3·Et2O
is presented in Scheme 3.

Ac
O
N
Ac
O
Ac
O
BF3
BF3
N
N
BF3.Et2O
NaNO2
1
AcO
NO
Ac
BF3
Ac
O
Ac
N
N
N
NO
O
N
N
O
- BF3
O
OH
Ac
O
Ac
N
N
Ac
HN
O
BF3
H2O
N
N
+
O
O
OH
BF3
- B(OH)F3
N
2
Scheme 3. Tentative mechanism of oxidation of solasodine N,O-diacetate 1.
Previous studies on steroidal spirostanes have shown that strongly acidic reagents, e.g.
trimethylsilyl trifluoromethanesulfonate (TMSOTf), cause isomerization of sapogenins at C25
[18]. N,O-Diacetylsolasodine 1 was subjected to TMSOTf in dichloromethane in order to
check if such isomerization also takes place in spirosolans. However, the reaction took a
rather unexpected course, i.e. when the crude reaction product was subjected to silica gel
purification without prior extraction, 16-dehydroprogesterone acetate 3 was obtained in 60%
yield (Scheme 4). In contrast, when the reaction mixture was poured into water, extracted, and
then further purified on a silica gel column, the isolated product was pseudosolasodine 4
(60%).

O
Ac
O
AcO
3; 60%
N
no
extraction
TMSOTf
CH2Cl2
aqueous
work-up
SiO2
H
1
AcO
Ac N
O
4; 60%
AcO
Scheme 4. Reaction of N,O-diacetylsolasodine with TMSOTf.
The process of degradation of sapogenins is well known as the Marker degradation
and is used for sex hormone production [19]. In this classical methodology, Ac2O in the
presence of AlCl3 is used to obtain pseudosapogenin, followed by oxidation with CrO3 and
elimination [20]. In our experiment, a similar degradation of rings E and F was observed
without using a strong oxidizing agent under mild conditions. It is worth noticing that an
important drug intermediate, 16-dehydroprogesterone acetate 3, was obtained in an efficient
autoxidation process from a common spirosolan alkaloid in a single step. The likely
mechanism of this process, similar to the Marker degradation, is depicted in Scheme 5. Such
an autoxidation process is unique and was not previously observed for other
pseudosapogenins. The mechanism assumes an electrophilic attack of dioxygen to the
intermediate enol-ether at C20, followed by further transformations of 20-hydroperoxide
leading to cleavage of the C20-C22 bond. However, an alternative mechanism of the reaction
may be considered involving [2+2] cycloaddition of dioxygen to the double bond C20-C22 of
the enol-ether. The dioxetane intermediate may also evolve to 20-ketone by cleavage of the
C20-C22 and O-O bonds. This pathway is, however, less likely since the cycloaddition
requires singlet oxygen [21].

Ac
O
N
TMS Ac
N
TMS Ac
N
TMSOTf
O
O
1
AcO
TMS Ac
N
TMS Ac
N
TMS Ac
N
OH
O
O2, H2O
SiO2
O
O
O
aqueous
work-up
TMS Ac
Ac
N
TMS Ac
O
OH
N
H
O
N
O
O
O
- H+
elimination
O
O
3
4
Scheme 5. Plausible mechanism of degradation of N,O-diacetylsolasodine 1.
Interestingly, the formation of degradation products was not observed in the reaction
of free solasodine with TMSOTf in dichloromethane. The only product isolated after
evaporation of the solvent was the salt solasodinium triflate. The protonation caused
significant changes in the 1H NMR spectrum. Signals of 26-H,H are more separated from one
another than in solasodine, in which the signals appear as a triplet at 2.61 ppm (axial H pro-R,
J = 10.6 Hz) and a doublet of doublets at 2.67 ppm (equatorial H pro-S, J = 11.1, 4.2 Hz),
while for protonated solasodine these two signals showed up at 2.83 ppm (equatorial H pro-S,
triplet, J = 12.2 Hz) and 3.12 ppm (axial H pro-R, doublet of doublets, J = 11.5, 2.6 Hz, 1H)
[Figure 2]. Also, the 21-methyl group protons were shifted downfield upon protonation from
0.85 ppm (d, J = 6.3 Hz) in solasodine to 1.20 ppm (d, J = 7.3 Hz) in its salt.

Figure 2. insert here
4. Conclusion
This study presents new reactions of a spirosolan derivative. The oxidation of N,O-
diacetylsolasodine 1 with NaNO2/BF3·Et2O afforded (20S)-3β-acetoxypregn-5-ene-20,16β-
carbolactone (2, vespertilin acetate). The same compound 1 when treated with TMSOTf/DCM
afforded the corresponding pseudosapogenin 4 or 16-dehydroprogesterone acetate 3
depending on the work-up conditions. The latter compound, which is an important
intermediate for the steroid hormone industry, was presumably formed by unprecedented
autoxidation of the reaction mixture.
Acknowledgements
The authors gratefully acknowledge financial support from the Polish National
Science Centre (grant no. 2015/17/B/ST5/02892). The authors would like to thank Prof. Rosa
Santillan from Departamento de Química, Centro de Investigación y de Estudios Avanzados
del IPN in México for the gift sample of solasodine.
References
[1] K. Hostettmann, A. Marston, Saponins, Cambridge University Press, Cambridgeꢀ; New
York, 1995.
[2] M. Friedman, Chemistry and anticarcinogenic mechanisms of glycoalkaloids produced by
eggplants, potatoes, and tomatoes, J. Agric. Food Chem. 63 (2015) 3323–3337.
doi:10.1021/acs.jafc.5b00818.
[3] I. Jastrzebska, Chemistry of steroidal sapogenins - New advances in a classical field, Curr.
Org. Chem. 16 (2012) 353–372. doi:10.2174/138527212799499895.
[4] I.Y. Torgov, Chemistry of spirostanols (in Russian), Nauka, Moscow, 1986.
[5] Y. Sato, H.G. Latham, N. Ikekawa, Chemistry of the spiroaminoketal side chain of
solasodine and tomatidine. IV. Chemistry of the tomatidine side chain, J. Org. Chem. 25
(1960) 1962–1965. doi:10.1021/jo01081a035.
[6] Y. Sato, N. Ikekawa, Chemistry of the spiroaminoketal side chain of solasodine and
tomatidine. V. The synthesis of the isomeric solanidanones, J. Org. Chem. 26 (1961)
1945–1947. doi:10.1021/jo01065a062.

[7] A.V. Patel, G. Blunden, T.A. Crabb, NMR spectra and stereochemistry of N-acetyl and N-
benzoyl derivatives of solasodine, Magn. Reson. Chem. 29 (1991) 794–800.
doi:10.1002/mrc.1260290809.
[8] A. Rosado-Abón, G. de Dios-Bravo, R. Rodríguez-Sotres, M.A. Iglesias-Arteaga,
Synthesis and plant growth promoting activity of dinorcholanic lactones bearing the 5α-
hydroxy-6-oxo moiety, J. Steroid Biochem. Mol. Biol. 134 (2013) 45–50.
doi:10.1016/j.jsbmb.2012.10.007.
[9] Z.R. Valiullina, L.S. Khasanova, N.K. Selezneva, F.A. Gimalova, K.K. Pivnitsky, M.S.
Miftakhov, Unexpected fragmentation of 16β-acetoxy-22-oxocholestanes on the action of
methylenetriphenylphosphorane, Mendeleev Commun. 24 (2014) 272-273. doi:
10.1016/j.mencom.2014.09.008.[10] H. Li, H.-M. Liu, W. Ge, L. Huang, L. Shan,
Synthesis of 7α-hydroxy-dehydroepiandrosterone and 7β-hydroxy-
dehydroepiandrosterone, Steroids 70 (2005) 970–973. doi:10.1016/j.steroids.2005.07.006.
[11] R.C. Cambie, G.J. Potter, R.W. Read, P.S. Rutledge, P.D. Woodgate, Solanum alkaloids.
XVIII. Utilization of solasodine for the preparation of nitrogen analogues of ecdysones,
Australian J. Chem. 34 (1981), 599 - 622. doi: 10.1071/CH9810599. [12] I. Jastrzębska,
M. Morawiak, J.E. Rode, B. Seroka, L. Siergiejczyk, J.W. Morzycki, Oxidation of olefins
with benzeneseleninic anhydride in the presence of TMSOTf, J. Org. Chem. 80 (2015)
6052–6061. doi:10.1021/acs.joc.5b00410.
[13] D.H.R. Barton, P.G. Sammes, M.V. Taylor, E. Werstiuk, Transformation of the steroidal
sapogenin side chain. Part I. Reactions of 9(11)-dehydrohecogenin acetate with nitrous
acid and with paraformaldehyde, J. Chem. Soc. C Org. (1970) 1977–1981.
doi:10.1039/j39700001977.
[14] M.A. Iglesias-Arteaga, R. Pérez-Gil, V. Leliebre-Lara, F. Coll-Manchado, C.S. Pérez-
Martínez, Synthesis of (25R)-2α,3α-epoxy-5α-spirostan-6,23-dione, Synth. Commun. 28
(1998) 4387–4392. doi:10.1080/00397919808004473.
[15] A.G. Gonzalez, R. Freire, M.G. Garcia-Estrada, J.A. Salazar, E. Suarez, New sources of
steroid sapogenins-XIV. 25S-Ruscogenin and sasevierigenin, two new spirostan
sapogenins from Sansevieria trifasciata, Tetrahedron 28 (1972) 1289–1997.
[16] S. Lee, P.L. Fuchs, In situ nitrosonium ion generation — α-Oximinylation of enol ethers
from steroidal spiroketals: Introduction of C23 ( R )-OH in cephalostatin intermediates,
Can. J. Chem. 84 (2006) 1442–1447. doi:10.1139/v06-113.
[17] M.A. Iglesias-Arteaga, A.A. Alvarado-Nuňo, BF3·Et2O-induced Beckmann
rearrangement of 23-hydroxyiminosapogenins. A shortcut to bisnorcholanic lactones,
Tetrahedron Lett. 47 (2006) 5351–5353. doi:10.1016/j.tetlet.2006.05.118
[18] I. Jastrzębska, J.W. Morzycki, Erroneous epimerization at C-22 in sapogenins, Steroids.
100 (2015) 17–20. doi:10.1016/j.steroids.2015.04.001.
[19] R.E. Marker, Sterols. CV. The preparation of testosterone and related compounds from
sarsasapogenin and diosgenin, J. Am. Chem. Soc. 62 (1940) 2543–2547.
doi:10.1021/ja01866a077.
[20] A. Goswami, R. Kotoky, R.C. Rastogi, A.C. Ghosh, A one-pot efficient process for 16-
dehydropregnenolone acetate, Org. Process Res. Dev. 7 (2003) 306–308.
doi:10.1021/op0200625.
[21] D. Bartusik, M. Minnis, G. Ghosh, A. Greer, Autocatalytic-assisted photorelease of a
sensitizer drug bound to a silica support, J. Org. Chem. 78 (2013) 8537–8544. doi:
10.1021/jo401266r.

Figure legends:
Figure 1. Structures of steroid alkaloid sapogenins and spirostanes.
Figure 2. Comparison of spectra of a) solasodine and b) protonated solasodine.
Figure 1
H
N
25
21
26
23
27
20
16
18
N
H
12
17
22
24
11
9
19
13
14
8
O
O
1
4
2
3
15
10
7
tomatidine
solasodine
5
HO
HO
6
H
O
O
O
O
sarsasapogenin
diosgenin
HO
HO
H
Figure 2

Highlights
 The oxidation of N,O-diacetylsolasodine with NaNO2/BF3·Et2O or t-BuONO/BF3·Et2O
results in partial degradation of the side chain affording (20S)-3β-acetoxypregn-5-ene-
20,16β-carbolactone (vespertilin acetate).
 The reaction of N,O-diacetylsolasodine with TMSOTf leads to the corresponding
pseudosapogenin.
 If no aqueous work-up is applied, crude pseudosapogenin readily undergoes
autoxidation with concomitant elimination of a five-carbon atom fragment to pregna-
5,16-dien-3β-ol-20-one acetate, which is an important intermediate in the synthesis of
steroid hormones.