Synthesis and characterization of some new 1,2,3-thiadiazole and 1,2,3-selenadiazole triterpene derivatives from allobetulone and 2-oxoallobetulin

Article abstract of DOI:10.1080/00397911.2020.1750655

The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives from triterpenoid ketones has been investigated via the corresponding semicarbazones. The intermediates 5, 8 have also been isolated, separated and their structures identified. The Hurd–Mori reaction and Lalezari method have been applied to synthesize a series of new substances 6 and 7. The regioselectivity of the functionalization mostly was centered at the C-3 position for the products 9 and 10. The structures of these compounds were confirmed by 2D-NMR spectroscopy.

Full text of DOI:10.1080/00397911.2020.1750655

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: https://www.tandfonline.com/loi/lsyc20
Synthesis and characterization of some new 1,2,3-
thiadiazole and 1,2,3-selenadiazole triterpene
derivatives from allobetulone and 2-oxoallobetulin
Thuc Dinh Ngoc
To cite this article: Thuc Dinh Ngoc (2020): Synthesis and characterization of some new 1,2,3-
thiadiazole and 1,2,3-selenadiazole triterpene derivatives from allobetulone and 2-oxoallobetulin,
Synthetic Communications, DOI: 10.1080/00397911.2020.1750655
To link to this article: https://doi.org/10.1080/00397911.2020.1750655
View supplementary material
Published online: 22 Apr 2020.
Submit your article to this journal
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=lsyc20

R
SYNTHETIC COMMUNICATIONSV
https://doi.org/10.1080/00397911.2020.1750655
Synthesis and characterization of some new
1,2,3-thiadiazole and 1,2,3-selenadiazole triterpene
derivatives from allobetulone and 2-oxoallobetulin
Thuc Dinh Ngoc
Department of Science and Technology Management, Hong Duc University, Thanh Hoa City, Vietnam
ABSTRACT
ARTICLE HISTORY
Received 20 February 2020
The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole
derivatives from triterpenoid ketones has been investigated via
the corresponding semicarbazones. The intermediates 5, 8 have also
been isolated, separated and their structures identified. The
Hurd–Mori reaction and Lalezari method have been applied to
synthesize a series of new substances 6 and 7. The regioselectivity
of the functionalization mostly was centered at the C-3 position for
the products 9 and 10. The structures of these compounds were
confirmed by 2D-NMR spectroscopy.
KEYWORDS
Triterpenoid ketone;
semicarbazone; Hurd–Mori
reaction; Lalezari method
GRAPHICAL ABSTRACT
Introduction
Compounds containing 1,2,3-thiadiazole and 1,2,3-selenadiazole fragments in molecule are
now being interested by scientists because they have interesting activities.[1,2] For example,
derivatives of 1,3,4-thiadiazoles are known to exhibit antimicrobial activity,[3,4] antifungal
activity,[5] anti-inflammatory,[6] antiviral,[7] analgesic,[8] while 1,2,3-selenadiazoles have
been studied because of their potential activities as antibacterial, antimicrobial activity,[9,10]
analgesic, and anti-inflammatory drugs,[11] anti HIV activity against HIV-I in MT-4
cells,[12] antitumor.[13] Although there are many routes to synthesize heterocyclic substan-
ces containing S and Se, there are only a few possible methods to synthesize these type
substances. The Hurd–Mori reaction is the most widely used method in the research on
1,2,3-thiadiazoles,[14] and 1,2,3-selenadiazole derivatives are being followed by the Lalezari
method.[15] Currently, few reports have appeared about the synthesis of 1,2,3-thiadiazoles
CONTACT Thuc Dinh Ngoc
dinhngocthuc@hdu.edu.vn
Department of Science and Technology Management,
Hong Duc University, No 565, Quang Trung Street, Dong Ve Ward, Thanh Hoa City 440000, Vietnam.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2020 Taylor & Francis Group, LLC

2
T. D. NGOC
Scheme 1. Synthesis of allobetulone and 2-oxoallobetulin.
and 1,2,3-selenadiazoles triterpene derivatives on the basis of naturally occurring
compounds. Only limited data were reported about using the Hurd–Mori reaction for the
synthesis of 1,2,3-thiadiazolo terpenoids starting from cyclopentanonopimaric and
betulonic acid,[16] and using the Lalezari method for the synthesis of 1,2,3-selenadiazole
derivatives of friedelin.[17]
Betulin 1 which is a triterpenoid based on the lupane skeleton, is found in high amounts
in birch bark, and is now commercially available. Allobetulin 2 ((18a)-19b, 28-epoxyo-
leanan-3b-ol) is an isomer of betulin, obtained from betulin by a Wagner–Meerwein
rearrangement in the presence of different acid catalysts.[18,19] Various derivatives were
obtained from allobetulin and these possess many interesting biological properties[20] includ-
ing antiviral,[21,22] antifeedant,[23] immunotropic,[24,25] antibacterial,[26] anti-inflammatory
and anti-ulcer activities,[27] cytotoxicity,[28,29] and inhibition of glycogen phosphorylase.[30]
Allobetulin 2 can be transformed into valuable allobetulone 3 by reaction with vari-
ous oxidative reagents.[31,32] Allobetulone was rearranged to 2-oxoallobetulin 4 by using
Willgerodt–Kindler conditions in the presence of sulfur in morpholine.[33] In this study,
a series of new triterpene derivatives have been synthesized from allobetulone 3 and
2-oxoallobetulin 4 by condensation of ketones group with semicarbazide and continuing
to the thiadiazoles and selenadiazoles by the Hurd–Mori reaction and Lalezari method,
respectively.
Results and discussions
Synthesis of starting substances was realized following the procedure of a previous
study,[34] wherein betulin 1 can be transformed to allobetulin 2 (93%), and then allobe-
tulone 3 (90%) and 2-oxoallobetulin 4 (67%) in high yields (Scheme 1).
The reaction of allobetulone 3 with semicarbazide hydrochloride in the presence of
potassium acetate in ethanol afforded allobetulone semicarbazone 5 in very high yields
(86%). The reaction of 5 with thionyl chloride following the standard literature condi-
tions of the Hurd–Mori synthesis gave 1,2,3-thiadiazole allobetulin 6 in a moderate
yield (66%). Synthesis of 1,2,3-selenadiazole 7 by the reaction of 5 with selenium
dioxide in acetic acid at 70 ꢀC following the Lalezari method fused selenadiazole 7 with
reasonable yield (45%) (Scheme 2).
Reaction of 2-oxoallobetulin 4 with semicarbazide hydrochloride in the presence of
potassium acetate in ethanol leads to 2-oxoallobetulin semicarbazone 8 in very high
yields (74%). The reaction of 8 with thionyl chloride following the Hurd–Mori synthesis
afforded 1,2,3-thiadiazole derivative 9 in moderate yield (61%) (Scheme 3). However,
only one product was obtained, this means that the semicarbazone derivative 8 could

R
SYNTHETIC COMMUNICATIONSV
3
Scheme 2. Synthesis of triterpene derivatives from allobetulone.
Scheme 3. Synthesis of triterpene derivatives from 2-oxoallobetulin.
exist in the E form. The structure of compound 9 was confirmed by 2D-NMR spectros-
copy. Some correlations in 2 D-NMR of the obtained compounds are similar to those in
the previous study because of the same skeleton in the lupane triterpene type.[34] In the
HMBC spectra, the signals of the protons on the C-1 at 3.49 ppm and 2.46 ppm correl-
ate with only one signal of C-25 at 16.5 ppm. According to the NOESY spectra, the sig-
nal of the proton on the C-1 at 3.49 ppm correlates with the signal of the proton on the
C-25 at 0.84 ppm.
Synthesis of 1,2,3-selenadiazole 10 is carried out by reaction of 8 with selenium
dioxide in acetic acid at 70 ꢀC following the Lalezari method to give a product with
reasonable yield (43%). Again, only one compound was obtained, and the structure
of compound 10 was confirmed by 2D-NMR spectroscopy (Scheme 3).
In the HMBC spectra, the signals of the protons on the C-1 at 3.58 ppm and
2.58 ppm correlate with only one signal of C-25 at 16.4 ppm. According to COSY spec-
tra, the signal of the proton on the C-1 at 2.58 ppm correlates with the signal of the

4
T. D. NGOC
proton on C-25 at 0.88 ppm. In the NOESY spectra, the signal of the proton on the C-1
at 3.58 ppm correlates with the signal of the proton on the C-25 at 0.88 ppm.
Conclusions
Two semicarbazone triterpenoid substances 5, 8 were prepared by condensation reac-
tions. A series of new 1,2,3-thiadiazole derivatives 6, 9 and 1,2,3-selenadiazole deriva-
tives 7, 10 have been successfully obtained by the Hurd–Mori reaction and Lalezari
method, respectively. This research direction will be continued and the synthesized
substances could be investigated for further applications.
Experimental
General
Melting points were determined with a Reichert Thermovar with a microscope, and are
uncorrected. Infrared spectra were measured and processed on a Bruker Alpha-T FT-IR
1
spectrometer with a universal sampling module coupled to OPUS software. The H-
NMR and 13C-NMR spectra were recorded on a Bruker 300 (operating respectively at
300 MHz and 75 MHz), Bruker 400 Avance (operating respectively at 400 MHz and
100 MHz) (Bruker, Billerica, MA). Mass spectra were recorded on a Hewlett-Packard
5989 A mass spectrometer (EI or CI mode), coupled with an HP Apollo 900 series
(Hewlett-Packard, Palo Alto, CA). High-resolution mass data were recorded on a Kratos
MS50TC (Kratos, Manchester, UK), with an electron impact ionizer energy of 70 eV, at
a temperature of 250 ꢀC. Reagents and solvents were purchased from Sigma Aldrich,
ABCR and Acros. Solvents were mostly dried and in some cases were used as received.
Betulin was purchased from Kaden Chemicals GmbH and used as received. All reac-
tions were carried out in flame-dried glassware, but no special precautions were taken
to exclude moisture.
General procedures for the synthesis of allobetulin-3-semicarbazone (5) and allobe-
tulin-2-semicarbazone (8)
A solution of allobetulone (2-oxoallobetulin) (100 mg, 0.227 mmol) in ethanol (3 ml)
was stirred at 40 ꢀC. Semicarbazide hydrochloride (304 mg, 2.72 mmol) and potassium
acetate (89 mg, 0.908 mmol) in 3 ml water were added and the mixture was continuously
stirred with TLC or mass spectral monitoring. After the reaction had finished, the mix-
ture was poured into water (30 ml). The precipitate was filtered, washed with water, and
dried over sodium sulfate. The crude product was purified by column chromatography
on silica with eluent CHCl3.
Allobetulin-3-semicarbazone (5): Yield: 97 mg (86%); mp 252–254 ꢀC. 1H-NMR
(CDCl3, 300 MHz, ppm): 3.77 (d, 1H, J ¼ 7.71 Hz, H-28), 3.53 (s, 1H, H-19), 3.45
(d, 1H, J ¼ 7.80 Hz, H-28), 2.33–2.22 (m, 2H, H-2), 1.81–1.28 (m, 25H-complex CH,
CH2), 1.25 (s, 3H, CH3-23), 1.15 (s, 3H, CH3-26), 1.04 (s, 3H, CH3-24), 1.00 (s, 3H,
CH3-30), 0.93, (s, 3H, CH3-27), 0.90 (s, 3H, CH3-25), 0.79 (s, 3H, CH3-29). 13C-NMR
(CDCl3, 75 MHz, ppm): 205.43 (C ¼ O), 159.12 (C-3), 87.91 (C-19), 71.26 (C-28), 55.26,

R
SYNTHETIC COMMUNICATIONSV
5
50.35, 46.76, 41.47, 41.26, 40.76, 40.59, 38.47, 37.04, 36.72, 36.27, 34.21, 33.36, 32.69,
29.70, 28.80, 28.43, 26.39, 26.23, 24.55, 23.51, 21.36, 19.55, 19.44, 15.87, 15.63, 13.41.
HRMS: C31H51N3O2, calculated: 497.39813, found: 497.39803. IR (ATR, neat, cmꢁ1):
3471, 2926, 2859, 1692, 1581, 1468, 1452.
General procedures for the synthesis of 1,2,3-thiadiazolo[3,2-b] allobetulin (6) and
1,2,3-thiadiazolo[2,3-b] allobetulin (9)
A solution of allobetulin-3-semicarbazone (allobetulin-2-semicarbazone) (50 mg, 0.100 mmol)
in dry DCM (3 ml) was stirred at room temperature under an argon atmosphere. Thionyl
chloride (0.147 ml, 2.01 mmol) was added and the mixture was continuously stirred with
TLC or mass spectral monitoring. After the reaction had finished, 3 ml water was added,
the mixture was washed by Na2CO3 (3ꢂ 3 ml) and water (3 ꢂ 3 ml), and dried over magne-
sium sulfate. The solvent was evaporated and the residue mixture was purified by column
chromatography with heptane/EtOAc 9:1 to obtain the product.
General procedures for the synthesis of 1,2,3-selenadiazolo[3,2-b]allobetulin (7) and
1,2,3-selenadiazolo[2,3-b]allobetulin (10)
A solution of allobetulin-3-semicarbazone (allobetulin-2-semicarbazone) (50 mg, 0.100 mmol)
and selenium dioxide (16.72 mg, 0.151 mmol) in AcOH (3 ml) was stirred at 70 ꢀC under an
argon atmosphere under mass or TLC monitoring. After the reaction had finished, the mix-
ture was cooled to room temperature and filtered from the precipitated selenium. Water
(6 ml) was added and the precipitate was isolated. The crude mixture was purified by col-
umn chromatography with heptane/EtOAc 9:1 to obtain the product.
1
Full experimental detail, H-NMR and 13C-NMR spectra of all the new compounds
can be found via the “Supplementary Content” section.
Acknowledgments
The author would like to thank Prof. Wim Dehaen for his valuable discussions and guidance, the
Technical Assistants at University of Leuven, Belgium for valuable advice and help.
Disclosure statement
No potential conflict of interest was reported by the authors.
ORCID
Thuc Dinh Ngoc
http://orcid.org/0000-0001-6307-5139
Referencess
[1] Shafran, Y.; Glukhareva, T.; Dehaen, W. Recent Developments in the Chemistry of 1,2,3-
Thiadiazoles. In Advances in Heterocyclic Chemistry; Scriven, E. F. V., Ramsden, C. A.,
Eds.; Academic Press Inc.: Waltham, MA, 2018; pp 109–172.
[2] Yalpani, M.; Lalezari, I.; Shafiee, A. 1,2,3-Selenadiazole and Its Derivatives. J. Org. Chem.
1971, 36, 2836–2838. DOI: 10.1021/jo00818a023.

6
T. D. NGOC
€
€
ꢀ
[3] Onkol, T.; Dogruer, D. S.; Uzun, L.; Adak, S.; Ozkan, S.; Fethi S¸ahin, M. Synthesis and
Antimicrobial Activity of New 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives. J. Enz.
Inhib. Med. Chem. 2008, 23, 277–284. DOI: 10.1080/14756360701408697.
[4] Popiołek, L.; Kosikowska, U.; Mazur, L.; Dobosz, M.; Malm, A. Synthesis and
Antimicrobial Evaluation of Some Novel 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives.
Med. Chem. Res. 2013, 22, 3134–3147. DOI: 10.1007/s00044-012-0302-9.
[5] Matysiak, J.; Malinski, Z. 2-(2,4-dihydroxyphenyl)-1,3,4-Thiadiazole Analogues: Antifungal
Activity in Vitro against Candida Species. Russ. J. Bioorg. Chem. 2007, 33, 594–601. DOI:
10.1134/S1068162007060106.
[6] Kadi, A. A.; Al-Abdullah, E. S.; Shehata, I. A.; Habib, E. A.; Ibrahim, T. M.; El-Emam,
A. A. Synthesis, Antimicrobial and anti-Inflammatory Activities of Novel 5-(1-
Adamantyl)-1,3,4-Thiadiazole Derivatives. Euro. J. Med. Chem. 2010, 45, 5006–5011. DOI:
10.1016/j.ejmech.2010.08.007.
[7] Chen, Z.; Xu, W.; Liu, K.; Yang, S.; Fan, H.; Bhadury, P. S.; Hu, D.; Zhang, Y. Synthesis
and Antiviral Activity of 5-(4-Chlorophenyl)-1,3,4-Thiadiazole Sulfonamides. Molecules
2010, 15, 9046–9056. DOI: 10.3390/molecules15129046.
[8] Schenone, S.; Brullo, C.; Bruno, O.; Bondavalli, F.; Ranise, A.; Filippelli, W.; Rinaldi, B.;
Capuano, A.; Falcone, G. New 1,3,4-Thiadiazole Derivatives Endowed with Analgesic and
anti-Inflammatory Activities. Bioorg. Med. Chem. 2006, 14, 1698–1705. DOI: 10.1016/j.
bmc.2005.10.064.
[9] Al-Smadi, M.; Al-Momani, F. Synthesis, Characterization and Antimicrobial Activity
of New 1,2,3-Selenadiazoles. Molecules 2008, 13, 2740–2749. DOI: 10.3390/molecu
les13112740.
[10] Jadhav, A. A.; Dhanwe, V. P.; Joshi, P. G.; Khanna, P. K. Solventless Synthesis of New
4,5-Disubstituted 1,2,3-Selenadiazole Derivatives and Their Antimicrobial Studies. Cogent
Chem. 2016, 2, 1144670. DOI: 10.1080/23312009.2016.1144670.
[11] Mhaidat, N. M.; Al-Smadi, M.; Al-Momani, F.; Alzoubi, K. H.; Mansi, I.; Al-Balas, Q.
Synthesis, Antimicrobial and in Vitro Antitumor Activities of a Series of 1,2,3-Thiadiazole
and 1,2,3-Selenadiazole Derivatives. Drug. Des. Devel. Ther. 2015, 9, 3645–3652. DOI: 10.
2147/DDDT.S86054.
[12] Zhan, P.; Liu, X.; Fang, Z.; Pannecouque, C.; Clercq, E. Bioorganic Medicinal Chemistry.
Bioorg. Med. Chem. 2009, 17, 6374–6379. DOI: 10.1016/j.bmc.2009.07.027.
[13] El-Desoky, S. I.; Badria, F. A.; Abozeid, M. A.; Kandeel, E. A.; Abdel-Rahman, A. H.
Synthesis and Antitumor Studies of Novel Benzopyrano-1,2,3-Selenadiazole and
Spiro[Benzopyrano]-1,3,4-Thiadiazoline Derivatives. Med. Chem. Res. 2013, 22,
2105–2114. DOI: 10.1007/s00044-012-0201-0.
[14] Hurd, C. D.; Mori, R. I. On Acylhydrazones and 1,2,3-Thiadiazoles. J. Am. Chem. Soc. 1955,
77, 5359–5364. DOI: 10.1021/ja01625a047.
[15] Lalezari, I.; Shafiee, A.; Yalpani, M. A Novel Synthesis of Selenium Heterocycles:
Substituted 1,2,3-Selenadiazoles. Tetrahedron Lett. 1969, 10, 5105–5106. DOI: 10.1016/
S0040-4039(01)88895-X.
[16] Flekhter, O. B.; Tret’yakova, E. V.; Medvedeva, N. I.; Baltinax, L. A.; Galin, F. Z.;
Tolstikov, G. A.; Bakulev, V. A. Synthesis of 1,2,3-Thiadiazolo Terpenoids on the Basis of
Cyclopentanonopimaric and Betulonic Acids. Russ. J. Org. Chem. 2004, 40, 90–92. DOI:
10.1023/B:RUJO.0000034915.91472.fb.
[17] Parveen, M.; Mehdi, S. H.; Ghalib, R. M.; Alam, M.; Hashim, R.; Sulaiman, O. Synthesis,
Characterization and Antimicrobial Activity of Friedelin [2,3-d] Selenadiazole. Indones. J.
Chem. 2009, 9, 285–288. DOI: 10.22146/ijc.21554.
[18] Green, B.; Bentley, M. D.; Chung, B. Y.; Lynch, N. G.; Jensen, B. L. Isolation of Betulin
and Rearrangement to Allobetulin. A Biomimetic Natural Product Synthesis. J. Chem.
Educ. 2007, 84, 1985. DOI: 10.1021/ed084p1985.
[19] Li, T. S.; Wang, J. X.; Zheng, X. J. Simple Synthesis of Allobetulin, 28-Oxyallobetulin and
Related Biomarkers from Betulin and Betulinic Acid Catalysed by Solid Acids. J. Chem.
Soc, Perkin Trans. 1 1998, 23, 3957–3966. DOI: 10.1039/a806735j.

R
SYNTHETIC COMMUNICATIONSV
7
[20] Dehaen, W.; Mashentseva, A. A.; Seitembetov, T. S. Allobetulin and Its Derivatives:
Synthesis and Biological Activity. Molecules 2011, 16, 2443–2466. DOI: 10.3390/
molecules16032443.
[21] Flekhter, O. B.; Nigmatullina, L. R.; Baltina, L. A.; Karachurina, L. T.; Galin, F. Z.;
Zarudii, F. S.; Tolstikov, G. A.; Boreko, E. I.; Pavlova, N. I.; Nikolaeva, S. N.; et al.
Synthesis of Betulinic Acid from Betulin Extract and Study of the Antiviral and Antiulcer
Activity of Some Related Terpenoids. Pharma. Chem. J. 2002, 36, 484–487. DOI: 10.1023/
A:1021844705853.
[22] Kazakova, O. B.; Giniyatullina, G. V.; Yamansarov, E. Y.; Tolstikov, G. A. Betulin and
Ursolic Acid Synthetic Derivatives as Inhibitors of Papilloma Virus. Bioorg. Med. Chem.
Lett. 2010, 20, 4088–4090. DOI: 10.1016/j.bmcl.2010.05.083.
[23] Lugemwa, F. N.; Huang, F.-Y.; Bentley, M. D.; Mendel, M. J.; Alford, A. R. A Heliothis
Zea Antifeedant from the Abundant Birchbark Triterpene, Betulin. J. Agric. Food Chem.
1990, 38, 493–496. DOI: 10.1021/jf00092a035.
[24] Tolmacheva, I. A.; Anikina, L. V.; Vikharev, Y. B.; Shelepen’kina, L. N.; Grishko, V. V.;
Tolstikov, G. A. Synthesis and Immunotropic Activity of 2-Alkylaminomethylene-19b,28-
Epoxyolean-3-Ones. Russ. J. Bioorg. Chem. 2008, 34, 125–129. DOI: 10.1134/
S1068162008010172.
[25] Anikina, L. V.; Tolmacheva, I. A.; Vikharev, Y. B.; Grishko, V. V. Effects of Lupane and
Oleanane b-Enaminoketones on the Number and Morphology of White Blood Cells.
Pharm. Chem. J. 2009, 43, 378–380. DOI: 10.1007/s11094-009-0318-8.
[26] Salin, O.; Alakurtti, S.; Pohjala, L.; Siiskonen, A.; Maass, V.; Maass, M.; Yli-Kauhaluoma,
J.; Vuorela, P. Inhibitory Effect of the Natural Product Betulin and Its Derivatives against
the Intracellular Bacterium Chlamydia Pneumoniae. Biochem. Pharmacol. 2010, 80,
1141–1151. DOI: 10.1016/j.bcp.2010.06.051.
[27] Flekhter, O. B.; Medvedeva, N. I.; Karachurina, L. T.; Baltina, L. A.; Galin, F. Z.; Zarudii,
F. S.; Tolstikov, G. A. Synthesis and Pharmacological Activity of Betulin, Betulinic Acid, and
Allobetulin Esters. Pharm. Chem. J. 2005, 39, 401–404. DOI: 10.1007/s11094-005-0167-z.
€
[28] Csuk, R.; Barthel, A.; Kluge, R.; Strohl, D.; Kommera, H.; Paschke, R. Synthesis and
Biological Evaluation of Antitumour-Active Betulin Derivatives. Bioorg. Med. Chem. 2010,
18, 1344–1355. DOI: 10.1016/j.bmc.2009.12.024.
[29] Gauthier, C.; Legault, J.; Piochon, M.; Lavoie, S.; Tremblay, S.; Pichette, A. Synthesis,
Cytotoxicity, and Haemolytic Activity of Chacotrioside Lupane-Type Neosaponins and
Their Germanicane-Type Rearrangement Products. Bioorg. Med. Chem. Lett. 2009, 19,
2310–2314. DOI: 10.1016/j.bmcl.2009.02.076.
[30] Zhang, P.; Hao, J.; Liu, J.; Zhang, L.; Sun, H. Efficient Synthesis of Morolic Acid and
Related Triterpenes Starting from Betulin. Tetrahedron 2009, 65, 4304–4309. DOI: 10.
1016/j.tet.2009.03.100.
[31] Flekhter, O. B.; Ashavina, O. Y.; Smirnova, I. E.; Baltina, L. A.; Galin, F. Z.; Kabal’nova,
N. N.; Tolstikov, G. A. Selective Oxidation of Triterpene Alcohols by Sodium
Hypochlorite. Chem. Nat. Comp. 2004, 40, 141–143. DOI: 10.1023/B:CONC.0000033930.
76751.b7.
[32] Kim, D. S. H. L.; Chen, Z.; Nguyen, v. T.; Pezzuto, J. M.; Qiu, S.; Lu, Z.-Z. A Concise
Semi-Synthetic Approach to Betulinic Acid from Betulin. Z. Z. Synth. Commun. 1997, 27,
1607–1612. DOI: 10.1080/00397919708006099.
ꢁ
[33] Sejbal, J.; Klinot, J.; Protiva, J.; Vystrcil, A. Reactions of Triterpenoid Ketones with Sulfur
and Morpholine under the Conditions of Willgerodt-Kindler Reaction. Collect. Czech.
Chem. Commun. 1986, 51, 118–127. DOI: 10.1135/cccc19860118.
[34] Dinh Ngoc, T.; Dehaen, W. Selective Functionalization of 2-Oxoallobetulin Derivatives.
Tetrahedron 2014, 70, 1836–1840. DOI: 10.1016/j.tet.2013.12.075.