Different pathways for the deoxygenation of the A-ring of natural triterpene compounds

Article abstract of DOI:10.1080/14786410903172098

Some deoxygenation pathways were tested to remove the hydroxyl groups of the natural triterpenes oleanolic acid and maslinic acid to obtain a practical starting material for the semisynthesis of other interesting organic synthons. Different deoxygenation processes were carried out starting from these triterpenic acids or from several derivatives such as methyl esters and epoxy derivatives. The hydroxyl groups were transformed into some intermediate compounds including xanthyl, thiocarbonyl or tosyl derivatives. The opening of the oxirane ring between C-2 and C-3 was also achieved through different methods using deoxygenating reagents such as Me₃SiCl/NaI, WCl ₄/n-BuLi and Cp2TiCl.

Full text of DOI:10.1080/14786410903172098

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Different pathways for the
deoxygenation of the A-ring of natural
triterpene compounds
Andres Parra a , Pilar E. Lopez a & Andres Garcia-Granados a
a Departamento de Quimica Organica, Facultad de Ciencias ,
Universidad de Granada , E-18071 Granada, Spain
Published online: 13 Jan 2010.
To cite this article: Andres Parra , Pilar E. Lopez & Andres Garcia-Granados (2010) Different
pathways for the deoxygenation of the A-ring of natural triterpene compounds, Natural Product
Research: Formerly Natural Product Letters, 24:2, 177-196, DOI: 10.1080/14786410903172098
To link to this article: http://dx.doi.org/10.1080/14786410903172098
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Natural Product Research
Vol. 24, No. 2, 20 January 2010, 177–196
Different pathways for the deoxygenation of the A-ring of natural
triterpene compounds
*
Andres Parra , Pilar E. Lopez and Andres Garcia-Granados
Departamento de Quimica Organica, Facultad de Ciencias, Universidad de Granada, E-18071
Granada, Spain
(Received 2 April 2009; final version received 6 July 2009)
Some deoxygenation pathways were tested to remove the hydroxyl groups of the
natural triterpenes oleanolic acid and maslinic acid to obtain a practical starting
material for the semisynthesis of other interesting organic synthons. Different
deoxygenation processes were carried out starting from these triterpenic acids or
from several derivatives such as methyl esters and epoxy derivatives. The
hydroxyl groups were transformed into some intermediate compounds including
xanthyl, thiocarbonyl or tosyl derivatives. The opening of the oxirane ring
between C-2 and C-3 was also achieved through different methods using
deoxygenating reagents such as Me3SiCl/NaI, WCl4/n-BuLi and Cp2TiCl.
Keywords: oleanolic acid; maslinic acid; triterpene; deoxygenation
1. Introduction
In several areas of natural product chemistry, it is frequently necessary to replace a
secondary hydroxyl with a hydrogen atom without the possibility of rearrangement.
Deoxygenation of alcohols and epoxides is a useful and important process in organic
synthesis which is often conducted efficiently using free radical chemistry. Thus, one of the
most well-known methods with which to deoxygenate hydroxyl compounds was described
by Barton and co-workers forming the corresponding thiocarbonates and xanthates which
were treated with Bu3SnH as a reducing agent (Barton & McCombie, 1975). Afterwards,
considerable efforts have been made to improve this procedure and to avoid the use of the
tin hydride because of its toxic properties (Barton, Dorchak, & Jaszberenyi, 1992b;
Barton, Jang, & Jaszberenyi, 1991a, 1991b, 1991c, 1992a, 1993; Lopez, Hays, & Fu, 1997).
The hydroxyl group can also be converted into the corresponding tosylate or mesylate,
which is later eliminated. However, when the SN2 process is hindered, the deoxygenation
of some secondary hydroxyl groups is very difficult and several rearrangement processes
can occur. A new procedure to deoxygenate hydroxyl groups is via their trifluoroacetate
derivatives with diphenylsilane (Jang, Kim, Cho, & Chung, 2001; Kim, Cho, & Jang,
2004). The process is quite simple and appropriate for the deoxygenation of tertiary
alcohol without side reactions and with high yields of reaction products. Another typical
*Corresponding author. Email: aparra@ugr.es
ISSN 1478–6419 print/ISSN 1029–2349 online
ß 2010 Taylor & Francis
DOI: 10.1080/14786410903172098
http://www.informaworld.com

178
A. Parra et al.
procedure to eliminate hydroxyl groups is the method of Wolff–Kishner modified by
Huang-Minlon through the corresponding hydrazone under basic medium (Abad, Agullo,
Arno, Marin, & Zaragoza, 1997; Huang-Minlon, 1946, 1949; Hutchins & Hutchins, 1991).
Moreover, epoxides are versatile intermediates in organic chemistry and relatively few
general methods exist for removing oxygen atoms from the epoxy compounds. Generally,
these procedures require expensive reagents and severe reaction conditions, which may
affect other functional groups present in the molecule. In this sense, epoxides have been
deoxygenated by several protocols using Me3SiCl/NaI, Ph3P/I2, ZrCl4/NaI, WCl4/n-BuLi,
Cp TiCl (Caputo, Mangoni, Neri, & Palumbo, 1981; Cuerva et al., 2006; Gansauer,
2
¨
Pierobon, & Bluhm, 1998; Nugent & Rajanbabu, 1988, 1989, 1994; Nugent, Rajanbabu, &
Beattie, 1990; Paryzek & Wydra, 1984).
30
29
19
R1
Name
Number
R2
H
H
CH3
CH 3
20
18
21
22
12
H
13
11
26
Oleanolic acid
Maslinic acid
Methyl oleanoate
Methyl maslinate
1
2
3
4
H
25
17
9
COOR2
14
1
OH
H
R1
28
16
2
8
10
15
5 H
3
27
OH
7
HO
4
6
H
24 23
Figure 1. Structures of compounds 1–4.
On the other hand, oleanolic acid (1) (3ꢀ-hydroxy-12-oleanen-28-oic acid) and maslinic
acid (2) (2ꢁ,3ꢀ-dihydroxy-12-oleanen-28-oic acid) (Figure 1) are natural triterpene acids
widespread in plants in the form of free acids or derivatives such as methyl esters, acetyl-,
oxo-, glycosyl- and other compounds (Bianchi, Pozzi, & Vlahov, 1994; Garcia-Granados,
Martinez, Moliz, Parra, & Rivas, 1998a, 1998b). Previously, our research group reported a
general isolation method that allowed us to obtain large quantities of both compounds
from olive-oil pressing residues (Garcia-Granados, Martinez, Parra, & Rivas, 1998c).
Deoxygenation of these compounds was initially studied via reduction of the correspond-
ing thionoformates (Garcia-Granados et al., 2000a) and, although giving the desired A-
ring deoxygenated products in good yield, these processes were very expensive due to
requiring high amounts of starting material to semisynthesise other chemically useful
compounds. On the other hand, in previous papers, we have also described the conversion
of the corresponding esters, 3 and 4 (Figure 1), into several A-ring and C-ring modified
derivatives. In this sense, our preliminary work has shown that, when these compounds
were treated with phosphorus pentachloride or mesyl chloride, several rearrangements
occurred and different A-ring contracted compounds were obtained (Garcia-Granados
et al., 2000a, 2000b). Similarly, when methyl 2ꢀ,3ꢀ-epoxy-12-oleanen-28-oate was
deoxygenated with Ph3P/I2, a minor A-ring deoxygenated product and several halohydrin
derivatives were semisynthesised (Garcia-Granados et al., 2003a). We have also reported
on the initial study of the formation of several C-ring derivatives from oleanolic and
maslinic acids, and the cleavage of the triterpene molecule (Garcia-Granados, Lopez,
Melguizo, Parra, & Simeo 2003b, 2004a, 2004b, 2006). Our research group has also
described the remote hydroxylation of the C-23 and C-24 methyl groups of these natural
triterpene compounds by a regioselective cyclopalladation process, producing other

Natural Product Research
179
natural compounds with potentially useful biological activities (Garcia-Granados, Lopez,
Melguizo, Parra, & Simeo, 2007). Recently, we have reported the preparation of several
maslinic acid derivatives containing amino acids and peptides as potent anti-HIV agents
(Parra et al., 2009).
In the light of these results, in this article, we explore the scope of some of these
deoxygenation protocols of the A-ring of these natural oleanene compounds with the aim
to optimise these procedures and to obtain A-ring deoxygenated compounds, which will be
a useful starting material for the semisynthesis of other interesting organic synthons.
2. Results and discussion
Oleanolic acid (1) and maslinic acid (2) were obtained from olive-pressing residues by
successive extractions with hexane and ethyl acetate in a Soxhlet apparatus (Garcia-
Granados et al., 1998c). The hexane extract contained mostly oleanolic acid (1) (80–85%),
whereas the EtOAc extract contained mostly maslinic acid (2) (80–85%). After flash
chromatography on a silica gel column, large amounts of these compounds were obtained
and our principal goal was its A-ring deoxygenation, starting from several derivatives.
Firstly, we used oleanolic acid (1) as the starting material, which was deoxygenated via its
3-tosyl derivative (Scheme 1). This tosyl derivative 5 was deoxygenated in an acceptable
yield (42%) by treatment with sodium acetate in DMF at 120ꢀC, giving compound 6,
which had a double bond between C-2 and C-3. The esterification of the C-28 carboxylic
group of 3,12-oleandien-28-oic acid (6) was carried with NaOH/MeI and thus the desired
final product (7), 3-deoxy D2,3 methyl oleanoate (Garcia-Granados et al., 2000a), was
formed (Scheme 1). Finally, catalytic hydrogenation of the 2,12-oleandiene compound 6
with H2/Pt gave 3-deoxyoleanolic acid (8), and its esterification with NaOH/MeI yielded
3-deoxymethyl oleanoate (9) (Garcia-Granados et al., 2000a). Therefore, the key and
limiting process for the deoxygenation procedure starting with oleanolic acid (1), given in
Scheme 1, was the tosyl elimination (42%), because the other steps are practically
quantitative.
COOH
COOH
a
HO
TsO
1
5
b
COOR
COOH
COOCH3
d
c
R=H: 8
R=CH3: 9
d
7
6
Scheme 1. Deoxygenation of oleanolic acid (1). Reagents and conditions: (a) PTSCl, py, rt, 24 h; (b)
NaAcO, DMF, 120ꢀC, 24 h; (c) H2, Pt, 12 h; (d) (i) NaOH 5N, THF, reflux, 3 h; (ii) CH3I, THF, 2 h.

180
A. Parra et al.
Subsequently, we started from the methyl oleanoate (3) which was deoxygenated at the
A-ring through several pathways (Scheme 2). Thus, when compound 3 was treated with
sec-butyllithium/CS2/MeI, the corresponding C-28 demethylated-xanthate derivative (10)
and the xanthyl methyl ester (11) were obtained. Xanthate (11) was only formed in a good
yield (80%) when the deprotonation process was carried out with NaH instead of sec-
butyllithium (Scheme 2, treatment b). The trifyl derivative (12) was also prepared by
treatment with trifluoroacetic anhydride. Finally, the 3-oxoderivative (13) (Garcia-
Granados et al., 2000a) was also formed by treatment of methyl oleanoate (3) with Jones’
reagent. 3-Xanthyl (11), 3-trifyl (12) and 3-oxo (13) derivatives were deoxygenated by
different procedures and with diverse yields (see Scheme 2 and Section 4) to give the
desired compound 9, 3-deoxymethyl oleanoate. The best route to deoxygenate methyl
oleanoate 3 was through its 3-xanthyl derivative (11), since this pathway gave a global
yield of 70%.
Deoxygenation of methyl maslinate (4) was more complex, because of the presence of
two hydroxyl groups in the A-ring of the skeleton. In Scheme 3, two deoxygenation
pathways are shown through its xanthyl or tosyl derivatives, which led us to the two
desired A-ring deoxygenated compounds, 7 and/or 9. First, methyl maslinate (4) was
treated with sec-butyllithium/CS2/MeI or NaH/MeI to give (in similar yields) the C-2
monosubstituted xanthyl derivative 14 (40% or 60%, respectively) and the cyclic
thiocarbonate 15 (50% or 30%, respectively). Compound 14 was deoxygenated at C-2
by the xanthyl group, yielding the reusable methyl oleanoate (3). Reductive treatment of
thiocarbonate (15) gave a mixture of the previously known compounds 3, 4, 7 and the
3-deoxygenated compound 16, which was also deoxygenated through its 2-xanthyl
COOCH3
HO
3
a or b
d
c
COOCH3
COOCH3
COOR
F3C
O
O
H3C
S
O
O
12
S
13
10
R=H:
R=CH3: 11
e
i
h
f or g
9
Scheme 2. Deoxygenation of methyl oleanoate (3). Reagents and conditions: (a) (i) sec-BuLi, THF,
reflux, 2 h; (ii) CS2, reflux, 30 min; (iii) CH3I, reflux 2 h; (b) (i) NaH, THF, reflux, 3 h; (ii) CS2, reflux,
30 min; (iii) CH3I, reflux, 2 h; (c) (CF3)2O, py, rt, 24 h; (d) Jones reagent, acetone, rt, 30 min; (e) (i)
NaOH 5N, THF, reflux, 3 h; (ii) CH3I, THF, reflux, 2 h; (f) H3PO2, AIBN, Et3N, dioxane, reflux,
3 h; (g) (Bu3Sn)2O, toluene, PMHS, AIBN, 80ꢀC, 3h; (h) Ph2SiH2, (tBuO)2, 130ꢀC, 24 h; (i) N2H4,
KOH, ethylene glycol, reflux, 5 h.

Natural Product Research
181
derivative 17. Methyl maslinate (4) was also deoxygenated through selective tosylation,
forming the 2-tosyl methyl maslinate 18 (Garcia-Granados et al., 2000b), but its treatment
with KI/TMSCl at reflux in DMF led us mainly to the iodohydrin 19. Deoxygenation of
methyl maslinate (4) was also attempted by epimerisation at C2 by oxidation/reduction
treatments (compounds 20 and 21) but the final triol did not form the corresponding
thiocarbonate.
COOCH3
CH2OH
HO
HO
I
7
+
l
HO
21
19
k
i
COOCH3
COOCH3
HO
O
COOCH3
TsO
HO
HO
HO
h
j
20
18
4
a or b
S
COOCH3
COOCH3
H3C
S
O
O
O
3
+
S
c or d
HO
15
14
e
3 + 4 + 7
+
S
f
COOCH3
COOCH3
H3C
S
O
HO
9
g
16
17
Scheme 3. Deoxygenation of methyl maslinate (4). Reagents and conditions: (a) (i) sec-BuLi, THF,
reflux, 2 h; (ii) CS2, reflux, 30 min; (iii) CH3I, reflux 2 h; (b) (i) NaH, THF, reflux, 3 h; (ii) CS2, reflux,
30 min; (iii) CH3I, reflux, 2 h; (c) (Bu3Sn)2O, toluene, PMHS, AIBN, 80ꢀC, 3 h; (d) H3PO2, AIBN,
Et3N, dioxane, reflux, 3 h; (e) (Bu3Sn)2O, toluene, PMHS, AIBN, 80ꢀC, 3 h; (f) (i) NaH, THF,
reflux, 3 h; (ii) CS2, reflux, 30 min; (iii) CH3I, reflux, 1 h; (g) H3PO2, AIBN, Et3N, dioxane, reflux,
3 h; (h) TsCl, py, rt, 24 h; (i) KI, TMSCl, DMF, reflux, 12 h; (j) Dess–Martin reagent, DCM, rt, 2 h;
(k) LiAlH4, THF, reflux, 3 h; (l) (a) (i) NaH, THF, reflux, 3 h; (ii) CS2, reflux, 30 min; (iii) CH3I,
reflux, 1 h.

182
A. Parra et al.
As methyl maslinate (4) had two A-ring hydroxyl groups its deoxygenation was also
tested by a sequential process protecting selectively the less hindered C-2 hydroxyl group
(Scheme 4). Thus, methyl maslinate (4) was selectively silylised at C-2 by treatment with
TBDMSCl in pyridine yielding a good yield of 2-tertbutyldimethylsilyl methyl maslinate
(22) which was transformed into the 2ꢁ-silyl 3ꢀ-xanthyl methyl maslinate (23). The typical
reduction of 23 gave 2-deprotected 3-desulphured compound 16, the corresponding 2-
tertbutyldimethylsilyl derivative (24) and the 2-deprotected 3-xanthyl derivative (25). On
the other hand, compounds 16 and 24 were usable to an efficient total deoxygenation of
the A-ring through the corresponding 2-xanthyl derivative according to the previously
detailed reaction conditions. Therefore, the deoxygenation procedure established for the
A-ring of methyl maslinate (4) in Scheme 4 was accomplished with an acceptable global
yield and can be considered as a viable method for this aim.
The last method tested for the total A-ring deoxygenation of methyl maslinate (4) was
through its 2ꢀ,3ꢀ-epoxy derivative 26 (Scheme 5) (Garcia-Granados et al., 2003a) which
was obtained from 4 by Mitsunobu reaction or via tosylation and, later, it was
deoxygenated following different pathways (Scheme 5, treatments c, d and e). Initially,
compound 26 was treated with trimethylchlorosilane/potassium iodide, giving 7, and
mainly the iodohydrins 19 and 27. An unsuccessful deoxygenation process of the epoxide
26 was also carried out with tungsten chloride/n-butyllithium because the chlorohydrin 28
was the major compound of this reaction (Scheme 5, treatment d).
COOCH3
COOCH3
TBDMSO
HO
HO
HO
a
22
4
b
COOCH3
COOCH3
16: R=OH
TBDMSO
O
R
c
H3C
S
d
23
24: R=OSMDBT
O
+
COOCH3
HO
O
H3C
S
25
S
Scheme 4. Controlled deoxygenation of methyl maslinate (4). Reagents and conditions:
(a) TBDMSCl, py, reflux, 2 h; (b) (i) NaH, THF, reflux, 3 h; (ii) CS2, reflux, 30 min; (iii) CH3I,
reflux, 2 h; (c) H3PO2, AIBN, Et3N, dioxane, reflux, 3 h; (d) BF3, DCM, rt, 3 h.

Natural Product Research
183
Lastly, the epoxy derivative (26) was treated with titanocene chloride (Cp2TiCl) formed
in situ by treatment of dicyclopentadienyl titanium dichloride, Cp2TiCl2, with Mn in THF
by a stoichiometric or catalytic procedure (see Section 4). Both methods gave a high yield
(around 80%) of the desired 3-deoxyD2,3methyl oleanoate, 7 and a small amount of the
reutilisable compound 29. The axial configuration of the hydroxyl group at C-2 of
compound 29 was corroborated by the easy dehydration that this compound underwent
when treated with phosphorus trichloride oxide in pyridine. The diaxial disposition of the
hydroxyl group at C-2 and a hydrogen atom at C-3 allowed easy water elimination and
thus the objective compound, 3-deoxymethyl oleanoate (9), was obtained in very high
yield. Consequently, a complete and valuable deoxygenation of methyl maslinate (4) was
achieved when its 2ꢀ,3ꢀ-epoxy derivative of methyl was treated with titanocene chloride in
both stoichiometric and catalytic conditions.
COOCH3
Cl
7
+
HO
28
d
COOCH3
COOCH3
a or b
HO
HO
O
26
4
c
e
COOCH3
COOCH3
HO
I
HO
27
7
29
+
+
f
7
19
+
9
Scheme 5. Deoxygenation of methyl maslinate (4) through its 2ꢀ,2ꢀ-epoxy derivative (26). Reagents
and conditions: (a) (i) PTSCl, py, rt, 24 h; (ii) Na, MeOH, reflux, 1 h; (b) DEAD, PPh3, DMF, reflux,
2 h; (c) Me3SiCl, KI, 1 h, 0ꢀC or rt or reflux; (d) WCl6, n-BuLi, rt, 20 min; (e) Cp2TiCl2, Mn, THF, rt,
3 h or Cp2TiCl2, Mn, collidine, Me3SiCl, THF, 3 h, rt; (f) POCl3, py, reflux, 30 min.

184
A. Parra et al.
3. Conclusions
Starting with several derivatives of natural triterpene acids, oleanolic acid and maslinic
acid, from the waste products of the olive industry, a deoxygenation of their A-ring was
attempted using different procedures. Direct deoxygenation of oleanolic acid (1) was
achieved with acceptable yield (around 50%) by means of the elimination of its 3-tosyl
derivative, whereas methyl oleanoate (3) was efficiently deoxygenated through its 3-
xanthyl derivative (approximately 70%).
Methyl maslinate (4) showed some complexity for the complete deoxygenation of its
A-ring because there are two equatorial hydroxyl groups at C-2 and C-3 that were difficult
to eliminate. Methyl maslinate (4) was satisfactorily deoxygenated (about 60%) through
the successive xanthyl derivatives obtained by controlled semisynthesis or using an
appropriate protecting group. However, the best procedure with which to deoxygenate
methyl maslinate (4) was through its 2ꢀ,3ꢀ-epoxy derivative (26), which was treated with
titanocene chloride in catalytic proportion to give a high yield (around 90%) of
3-deoxyD2,3methyl oleanoate (7) and 3-deoxymethyl oleanoate (9).
4. Experimental
4.1. General
Measurements of NMR spectra (300.13 MHz 1H and 75.47 MHz 13C) were made in CDCl3
(which also provided the lock signal) using BRUKER AM-300 or ARX-400 spectro-
meters. The assignments of 13C chemical shifts were made with the aid of distortionless
enhancement by polarisation transfer (DEPT) using a flip angle of 135ꢀ. Bruker’s
programs were used for COSY (45ꢀ) and C/H and C/C correlation. IR spectra were
recorded on a MATTSON SATELLITE FTIR spectrometer. High-resolution mass
spectra were made in a MICROMASS AUTOSPEC-Q spectrometer (EBE geometry).
Melting points were determined using a Kofler (Reichter) apparatus and are uncorrected.
Optical rotations were measured on a Perkin–Elmer 241 polarimeter at 25ꢀC. All reaction
solvents were dried and distilled immediately prior to use; chromatography solvents were
distilled prior to use. Commercially available reagents were used without further
purification. Silica gel Scharlau 60 (40–60 mm) was used for flash chromatography.
CH2Cl2 or CHCl3 containing increasing amounts of Me2CO were used as eluents.
Analytical plates (silica gel, Merck 60 G) were rendered visible by spraying with H2SO4-
AcOH, followed by heating to 120ꢀC.
4.2. Isolation of oleanolic acid (1) and maslinic acid (2) and obtention of their methyl
esters (3) and (4)
Oleanolic acid (1) and maslinic acid (2) were isolated from the solid wastes resulting from
olive-oil production (Garcia-Granados et al., 1998c), which were macerated and extracted
in a Soxhlet apparatus with hexane and EtOAc successively. Hexane extracts were a
mixture of oleanolic acid and maslinic acid (80 : 20), whereas this relationship was (20 : 80)
for the EtOAc extracts. Both products were purified from these mixtures by CC over silica
gel, eluting with a CHCl3-MeOH or CH2Cl2-Me2CO mixtures of increasing polarity.
Oleanolic acid (1) and maslinic acid (2) were transformed into the corresponding methyl

Natural Product Research
185
esters with ethereal CH2N2 or NaOH-MeI, and thus methyl 3ꢀ-hydroxy-12-oleanen-28-
oate (3) and methyl 2ꢁ,3ꢀ-dihydroxy-12-oleanen-28-oate (4) were obtained (Garcia-
Granados et al., 2000a).
4.3. Tosylation of oleanolic acid (1)
To a solution of oleanolic acid (1) (500 mg, 1.1 mmol) in py (20 mL), p-toluenesulfonyl
chloride (731 mg, 3.8 mmol) was added. The reaction mixture was stirred at room
temperature for 24 h, diluted with water and extracted with DCM. The organic layer was
washed with saturated KHSO4 solution and dried over anhydrous Na2SO4. The solvent
was evaporated at reduced pressure and the residue was chromatographed on a silica gel
column to give 5 (625 mg, 95%).
4.4. Tosyl oleanolic acid (5)
White solid, m.p. 110–112ꢀC; ½ꢁꢁD þ 48ꢀ (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 2930, 2862, 1745,
25
3
1
1690; H NMR (300 MHz, CDCl3): ꢃ 7.30 and 7.80 (4H each, m, OTs), 5.24 (1H, dd,
J ¼ 3.5 Hz, H-12), 4.21 (1H, dd, J1 ¼ 5.1 Hz, J2 ¼ 11.5 Hz, H-3), 2.83 (1H, dd, J1 ¼ 4.0 Hz,
J2 ¼ 13.9 Hz, H-18), 2.42 (3H, s, OTs), 1.09 (3H, s, Me), 0.90 (3H, s, Me), 0.88 (3H, s, Me),
0.87 (3H, s, Me), 0.78 (3H, s, Me), 0.78 (3H, s, Me), 0.67 (3H, s, Me); 13C NMR (75 MHz,
CDCl3): Table 1; HRLSIMS (m/z) 433.3648 [M þ Na]þ (Calcd for C37H54O5SNa,
633.3646).
4.5. Detosylation of tosyl oleanolic acid (5)
To a solution of compound 5 (600 mg, 0.80 mmol) in DMF (5 mL), sodium acetate
(300 mg, 2.2 mmol) was added and the mixture was heated at 120ꢀC for 24 h. The solvent
was removed in vacuum and the resultant residue was washed with water and extracted
three times with DCM (3 ꢃ 20 mL). The organic layer was dried on anhydrous Na2SO4,
concentrated in vacuum and chromatographed on a silica gel column, yielding 6 (205 mg,
42%).
4.6. Deoxyoleanolic acid (6)
1
Syrup; ½ꢁꢁD þ 74 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 3421, 2947, 1693, 146, 758; H NMR
(300 MHz, CDCl3): ꢃ 5.36 (3H, m, H-1, H-2, H-12), 2.82 (1H, dd, J1 ¼ 4.0 Hz, J2 ¼ 13.9 Hz,
H-18), 1.25 (3H, s, Me), 1.13 (3H, s, Me), 0.94 (3H, s, Me), 0.93 (3H, s, Me), 0.92 (3H, s,
Me), 0.89 (3H, s, Me), 0.77 (3H, s, Me); 13C NMR (75 MHz, CDCl3): Table 1; HRLSIMS
(m/z) 461.3398 [M þ Na]þ (Calcd for C30H46O2Na, 461.3395).
25
3
4.7. Esterification of 3,12-oleandien-28-oic acid (6)
To a solution of compound 6 (150 mg, 0.34 mmol) in THF (10 mL), a solution of NaOH
(1 mL, 5N) was added and the mixture was refluxed for 3 h. After this time, CH3I (2 mL)
was added and the reaction mixture was shaken for 2 h at rt. The solvent was removed in
vacuum and the residue was washed with aqueous 1 N HCl solution and extracted with

186
A. Parra et al.
Table 1. 13C chemical shifts (in Cl3CD, ꢃ in ppm) for compounds 5, 6, 8, 10–12, 14–16.
Compound no.
Carbon
5
6
8
10
11
12
14
15
16
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Me
Me
38.3
24.7
91.0
36.7
55.5
18.4
32.5
39.5
47.5
38.5
23.3
122.1
143.5
41.6
27.7
23.0
46.7
41.8
45.9
30.7
33.9
32.5
15.1
16.4
16.8
23.7
25.7
27.8
33.2
180.9
40.7
121.5
138.0
34.5
52.1
19.6
32.1
39.5
46.2
36.3
23.3
122.9
143.5
41.9
27.8
23.3
46.7
41.1
46.0
30.7
33.9
32.5
15.6
16.9
22.8
23.6
25.9
31.9
33.2
180.7
40.1
18.6
42.1
33.2
56.3
18.6
32.7
39.5
47.8
37.4
23.5
123.0
143.6
41.7
27.7
23.5
46.6
41.0
46.0
30.8
33.9
32.7
15.3
17.3
21.8
27.7
26.1
33.2
33.2
180.6
37.9
22.5
91.4
37.0
55.4
18.1
32.5
39.3
47.5
38.7
23.4
122.5
143.7
41.6
27.7
22.8
46.6
40.9
45.9
30.7
33.8
32.5
15.4
17.2
17.4
23.6
26.0
28.1
33.1
180.8
38.0
22.6
91.4
37.0
55.4
18.2
32.6
39.3
47.6
38.7
23.5
122.3
143.9
41.7
27.7
23.1
46.8
41.3
45.9
30.7
33.9
32.6
15.4
16.9
17.5
23.7
26.0
28.1
33.2
178.4
51.6
18.6
215.8
38.0
23.0
86.3
37.9
55.2
18.2
32.5
41.3
47.6
38.7
23.1
122.1
143.9
41.3
27.7
23.5
46.7
41.2
45.9
30.7
33.9
32.5
15.4
16.4
16.8
23.7
25.9
27.9
33.1
178.4
51.6
114.2
158.0
42.6
80.6
83.5
38.8
55.3
18.3
32.5
40.2
47.6
39.4
23.6
122.0
144.0
41.7
27.7
23.6
46.8
41.3
45.9
30.8
33.9
32.4
16.3
16.8
16.9
23.7
26.0
28.6
33.2
178.3
51.6
19.1
216.6
40.9
81.0
95.0
40.8
56.0
17.6
32.3
38.1
47.9
39.8
23.7
121.4
144.3
41.8
27.7
23.0
46.7
41.3
45.9
30.7
33.9
32.6
16.1
17.1
17.2
23.7
26.0
27.9
33.1
178.1
51.5
193.4
51.2
65.2
51.2
39.6
55.7
18.5
32.5
39.6
47.8
39.6
23.6
122.4
143.9
41.8
27.7
23.2
46.8
41.4
45.9
30.8
34.0
32.7
16.5
17.0
22.7
23.7
26.0
33.2
33.2
178.3
51.6
Me
Me
Me
Me
Me
28
COOMe
Groups in A-ring
21.5
127.7
129.7
134.9
134.9
18.7
215.8
DCM. The organic layer was neutralised with saturated solution of NaHCO3, dried with
anhydrous Na2SO4, filtered, concentrated in vacuum and chromatographed on a silica gel
column to give 3-deoxyD2,3methyl oleanoate (7) (135 mg, 90%) (Garcia-Granados et al.,
2000a).
4.8. Hydrogenation of 3,12-oleandien-28-oic acid (6)
Compound 6 (200 mg, 0.46 mmol) in DCM (10 mL) was hydrogenated on Pt/C at rt for
12 h at 4 atm of H2. The mixture reaction was filtered, concentrated in vacuum and
chromatographed on a silica gel column to give 8 (199 mg, 98%).

Natural Product Research
187
4.9. 12-Oleanen-28-oic acid (8)
White solid, m.p. 233–235ꢀC; ½ꢁꢁD þ 69 (c 1, CHCl3); IR ꢂmCHaxCl cmꢂ1: 2923, 2360, 1689; 1H
NMR (300 MHz, CDCl3): ꢃ 5.26 (1H, dd, J1 ¼ 3.5 Hz, J2 ¼ 3.5 Hz, H-12), 2.80 (1H, dd,
J1 ¼ 3.6 Hz, J2 ¼ 13.9 Hz, H-18), 1.12 (3H, s, Me), 0.91 (3H, s, Me), 0.90 (3H, s, Me), 0.89
(3H, s, Me), 0.84 (3H, s, Me), 0.79 (3H, s, Me), 0.79 (3H, s, Me); 13C NMR (75 MHz,
CDCl3): Table 1; HRLSIMS (m/z) 463.3557 [M þ Na]þ (Calcd for C30H48O2Na,
463.3552).
25
3
Compound 8 was esterificated under the above mentioned conditions to give 3-deoxy
methyl oleanoate (9, 93%) (Garcia-Granados et al., 2000a).
4.10. Xanthylation of methyl oleanoate (3) with sec-butyllithium
To a solution of methyl oleanoate (3) (500 mg, 1.1 mmol) in THF (25 mL), a solution of
sec-BuLi (2 mL, 1.4 M in cyclohexane) was added and the reaction was refluxed with
stirring for 2 h. After that, S2C (2 mL, 33 mmol) was added, the reaction mixture stirred for
30 min at reflux, MeI (1 mL, 16 mmol) was added and the mixture was again refluxed for
2 h. The mixture was neutralised with aqueous 1 N HCl solution and extracted with DCM.
The organic layer was dried with anhydrous Na2SO4 and concentrated in vacuum. The
residue was chromatographed on a silica gel column to provide 10 (58 mg, 10%) and 11
(357 mg, 60%).
4.11. Xanthyl-12-oleanen-28-oic acid (10)
White solid, m.p. 177–179ꢀC; ½ꢁꢁD þ 29 (c 0.6, CHCl3); IR ꢂCmHaxCl cmꢂ1: 2946, 2863, 1694,
25
3
1
1238, 1058; H NMR (300 MHz, CDCl3): ꢃ 5.25 (1H, dd, J1 ¼ 4.9 Hz, J2 ¼ 12.0 Hz, H-3),
5.20 (1H, dd, J1 ¼ 3.4 Hz, J2 ¼ 3.4 Hz, H-12), 2.81 (1H, dd, J1 ¼ 4.1 Hz, J2 ¼ 13.8 Hz, H-
18), 2.54 (3H, s, CSSCH3), 1.12 (3H, s, Me), 0.96 (3H, s, Me), 0.95 (3H, s, Me), 0.92 (3H, s,
Me), 0.92 (3H, s, Me), 0.90 (3H, s, Me), 0.74 (3H, s, Me); 13C NMR (75 MHz, CDCl3):
Table 1; HRLSIMS (m/z) 569.3099 [M þ Na]þ (Calcd for C32H50O3S2Na, 569.3099).
4.12. Xanthyl methyl oleanoate (11)
White solid, m.p. 202–204ꢀC; ½ꢁꢁD þ 48 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 2922, 1724, 1233,
25
3
1
1058; H NMR (300 MHz, CDCl3): ꢃ 5.31 (1H, dd, J1 ¼ 4.6 Hz, J2 ¼ 10.8 Hz, H-3), 5.26
(1H, dd, J1 ¼ 3.6 Hz, J2 ¼ 3.6 Hz, H-12), 3.61 (3H, s, COOMe), 2.84 (1H, dd, J1 ¼ 4.6 Hz,
J2 ¼ 13.6 Hz, H-18), 2.53 (3H, s, CSSMe), 1.11 (3H, s, Me), 0.95 (3H, s, Me), 0.95 (3H, s,
Me), 0.91 (3H, s, Me), 0.91 (3H, s, Me), 0.88 (3H, s, Me), 0.71 (3H, s, Me); 13C NMR
(75 MHz, CDCl3): Table 1; HRLSIMS (m/z) 583.3258 [M þ Na]þ (Calcd for
C33H52O3S2Na, 583.3255).
4.13. Xanthylation of methyl oleanoate (3) with sodium hydride
Methyl oleanoate (3) (450 mg, 0.96 mmol) in THF (20 mL) was treated with NaH (110 mg,
4.8 mmol) at reflux for 3 h. After that, S2C (2 mL, 33 mmol) was added, the reaction
mixture shaken for 30 min at reflux, MeI (1 mL, 16 mmol) was added and the mixture was
again refluxed for 2 h. The mixture was neutralised with aqueous 1 N HCl solution and

188
A. Parra et al.
extracted with DCM. The organic layer was dried with anhydrous Na2SO4, concentrated
in vacuum and purified on a silica gel column to obtain 11 (415 mg, 77%).
Xanthate (10) was esterificated according to the previously mentioned reaction
conditions to obtain 11 (95%).
4.14. Trifylation of methyl oleanoate (12)
Methyl oleanoate (3) (500 mg, 1.1 mmol) in py (10 mL) was treated with trifluoroacetic
anhydride (0.5 mL, 2.75 mmol) and the reaction mixture was stirred at rt for 24 h. The
mixture was washed with aqueous 1N HCl solution, neutralised with saturated solution of
NaHCO3, and extracted with DCM. The organic layer was dried on anhydrous Na2SO4
and concentrated in vacuum. The residue was purified on a silica gel column to obtain 12
(579 mg, 93%).
4.15. Trifyl methyl oleanoate (12)
White solid, m.p. 171–172ꢀC; ½ꢁꢁD þ 48 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 2950, 1777, 1724,
25
3
1
1218, 773; H NMR (300 MHz, CDCl3): ꢃ 5.24 (1H, dd, J1 ¼ J ¼ 3.4 Hz, H-12), 4.65 (1H,
dd, J1 ¼ 4.9 Hz, J2 ¼ 11.3 Hz, H-3), 3.58 (3H, s, COOMe), 2.83 (1H, dd, J1 ¼ 4.2 Hz,
J2 ¼ 13.8 Hz, H-18), 1.09 (3H, s, Me), 0.91 (3H, s, Me), 0.88 (3H, s, Me), 0.87 (3H, s, Me),
0.86 (3H, s, Me), 0.69 (3H, s, Me); 13C NMR (75 MHz, CDCl3): Table 1; HRLSIMS (m/z)
589.3483 [M þ Na]þ (Calcd for C33H49O2F3Na, 589.3481).
4.16. Oxidation of methyl oleanoate (3)
Jones reagent was added dropwise to a stirred solution of methyl oleanoate (3) (200 mg,
0.42 mmol) in acetone at 0ꢀC until an orange-brown colour persisted. Methanol was then
added and the reaction mixture was diluted with water and extracted with DCM. The
organic layer was dried over anhydrous Na2SO4, evaporated to dryness and chromato-
graphed on a silica gel column to obtain 13 (196 mg, 95%) (Garcia-Granados et al.,
2000a).
4.17. Reduction of xanthate (11) with H3PO2
Xanthate (11) (95 mg, 0.17 mmol) in dioxane (5 mL), was treated with Et3N (0.05 mL,
0.3 mmol), H3PO2 (0.1 mL, 0.9 mmol) and AIBN (15 mg in 3 mL of dioxane) with stirring
at reflux for 3 h. The reaction mixture was washed with water and extracted with diethyl
ether. The organic layer was dried with anhydrous Na2SO4, concentrated in vacuum and
purified on a silica gel column giving 3-deoxy methyl oleanoate (9) (67 mg, 87%).
4.18. Reduction of xanthate (11) with (Bu3Sn)2O/PMHS
To a solution of xanthate (11) (150 mg, 0.3 mmol) in toluene (3 mL), PMHS (0.1 mL,
1.006 g mLꢂ1), AIBN (10 mg), n-butanol (0.2 mL) and (Bu3Sn)2O (0.01 mL, 1.170 g mLꢂ1
)
were added. The mixture was stirred under argon atmosphere at 80ꢀC for 3 h, after that
AIBN (20 mg) and (Bu3Sn)2O (0.01 mL) were again added and the reaction mixture was

Natural Product Research
189
stirred at rt for 3 h. The reaction mixture was diluted with THF and an aqueous 2N NaOH
solution (2 mL) was added. The mixture was extracted with ethyl ether, the organic layer
was dried with anhydrous Na2SO4 and the solvent concentrated in vacuum. The residue
was purified on a silica gel column to give 9 (110 mg, 80%).
4.19. Reduction of triflate (12) with Ph2SiH2
A mixture of triflate (12) (200 mg, 0.37 mmol), Ph2SiH2 (211 mg, 1.11 mmol) and (tBuO)2
(0.07 mL, 0.37 mmol) was heated at 130ꢀC and stirred for 24 h. The reaction mixture was
diluted with water and extracted with DCM. The organic extract was dried with
anhydrous Na2SO4, concentrated in vacuum and purified on a silica gel column to obtain
methyl 3-deoxyoleanoate (9) (55 mg, 30%).
4.20. Huang-Minlon reduction of 3-oxomethyl oleanoate (13)
A mixture of 3-oxoderivative 13 (50 mg, 0.11 mmol), KOH (12 mg, 0.33 mmol) and N2H2
(1 mL in 15 mL of ethyleneglycol) was stirred and refluxed for 5 h. The reaction mixture
was diluted with DCM, washed with water and neutralised with a saturated solution of
KHSO3. The organic layer was dried with anhydrous Na2SO4 and concentrated in
vacuum. The residue was purified on a silica gel column to provide methyl 3-
deoxyoleanoate (9) (6 mg, 11%).
4.21. Xanthylation of methyl maslinate (4) and reduction of its derivatives
Methyl maslinate (4, 500 mg, 1.1 mmol) was xanthylated under similar conditions and after
work-up, compounds 14 (237 mg, 40%) and 15 (272 mg, 50%) were obtained. Similarly,
when the xanthylation of 4 was carried out with sodium hydride and after work-up,
products 14 (355 mg, 60%) and 15 (165 mg, 30%) were formed.
Compound 14: White solid, m.p. 164–166ꢀC; ½ꢁꢁD þ 4 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 2947,
25
3
2360, 1724, 1232, 1053; 1H NMR (300 MHz, CDCl3): ꢃ 5.83 (1H, ddd, J1 ¼ 4.5 Hz,
J2 ¼ 10.0 Hz, J3 ¼ 10.7 Hz, H-2), 5.25 (1H, dd, J1 ¼ 3.6 Hz, J2 ¼ 3.6 Hz, H-12), 3.61 (3H, s,
COOCH3), 3.44 (1H, d, J ¼ 10.0 Hz, H-3), 2.84 (1H, dd, J1 ¼ 4.2 Hz, J2 ¼ 13.8 Hz, H-18),
2.55 (1H, s, CSSCH3), 1.11 (3H, s, Me), 1.07 (3H, s, Me), 0.94 (3H, s, Me), 0.91 (3H, s,
Me), 0.88 (3H, s, Me), 0.88 (3H, s, Me), 0.71 (3H, s, Me); 13C NMR (75 MHz, CDCl3):
Table 1; HRLSIMS (m/z) 599.3206 [M þ Na]þ (Calcd for C33H52O4S2Na, 599.3204).
Compound 15: White solid, m.p. 245–247ꢀC; ½ꢁꢁD þ 85 (c 1, CHCl3); IRꢂCmHaxCl cmꢂ1: 2948,
25
3
1802, 1724, 1290; 1H NMR (300 MHz, CDCl3): ꢃ 5.25 (1H, dd, J1 ¼ 3.6 Hz, J2 ¼ 3.6 Hz, H-
12), 4.50 (1H, ddd, J1 ¼ 4.4 Hz, J2 ¼ 11.5 Hz, J3 ¼ 12.4 Hz, H-2), 3.88 (1H, d, J ¼ 12.4 Hz,
H-3), 3.59 (3H, s, COOCH3), 2.84 (1H, dd, J1 ¼ 4.4 Hz, J2 ¼ 13.9 Hz, H-18), 2.24 (1H, dd,
J1 ¼ 4.1 Hz, J2 ¼ 11.5 Hz, H-1ꢀ, 1.13 (3H, s, Me), 1.11 (3H, s, Me), 1.02 (3H, s, Me), 0.95
(3H, s, Me), 0.90 (3H, s, Me), 0.87 (3H, s, Me), 0.72 (3H, s, Me); 13C NMR (75 MHz,
CDCl3): Table 1; HRLSIMS (m/z) 551.3171 [M þ Na]þ (Calcd for C32H48O4SNa,
551.3171).
Reduction of xanthate (14) with H3PO2 and (Bu3Sn)2O gave similar yields of methyl
oleanoate (3) (80–85%). Reduction of thiocarbonate (15) with (Bu3Sn)2O yielded methyl

190
A. Parra et al.
oleanoate (3, 29%), methyl maslinate (4, 33%), 3-deoxyD2,3methyl oleanoate (7, 20%) and
(16, 9%).
Compound 16: Syrup; ½ꢁꢁD þ 23 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 3385, 2947, 2874,
25
3
1
1725, 1458; H NMR (300 MHz, CDCl3): ꢃ 5.28 (1H, dd, J1 ¼ 3.6 Hz, J2 ¼ 3.6 Hz, H-12),
3.87 (1H, dddd, J1 ¼ 4.3 Hz, J2 ¼ 4.3 Hz, J3 ¼ 11.2 Hz, J4 ¼ 11.2 Hz, H-2), 3.60
(3H, s, COOCH3), 2.85 (1H, dd, J1 ¼ 4.2 Hz, J2 ¼ 13.8 Hz, H-18), 1.12 (3H, s, Me),
0.93 (3H, s, Me), 0.92 (3H, s, Me), 0.92 (3H, s, Me), 0.89 (3H, s, Me), 0.85 (3H, s, Me), 0.71
(3H, s, Me); 13C NMR (75 MHz, CDCl3): Table 1; HRLSIMS (m/z) 493.3652 [M þ Na]þ
(Calcd for C33H50O5Na, 493.3658).
Likewise, compound 16 was xanthylated at C-2 to form derivative 17 (80%) and its
reduction with H3PO2 led to compound 9 (80%).
ꢂ1
25
Compound 17: White solid, m.p. 192–194ꢀC; ½ꢁꢁD þ11 (c 0.7, CHCl3); IR ꢂmCHaxCl cm
:
3
2946, 1728, 1460, 1230, 1053; 1H NMR (300 MHz, CDCl3): ꢃ 5.88 (1H, dddd, J1 ¼ 4.2 Hz,
J2 ¼ 8.4 Hz, J3 ¼ 11.6 Hz, J4 ¼ 15.9 Hz, H-2), 5.26 (1H, dd, J1 ¼ J2 ¼ 3.6 Hz, H-12), 3.61
(3H, s, COOCH3), 2.85 (1H, dd, J1 ¼ 4.5 Hz, J2 ¼ 14.0 Hz, H-18), 2.52 (3H, s, CH3S–), 1.12
(3H, s, Me), 1.01 (3H, s, Me), 0.96 (3H, s, Me), 0.92 (3H, s, Me), 0.89 (3H, s, Me), 0.89
(3H, s, Me), 0.71 (3H, s, Me); 13C NMR (75 MHz, CDCl3): Table 2; HRLSIMS m/z
583.3253 [M þ Na]þ (Calcd for C33H52O3 S2Na, 583.3256).
4.22. Tosylation of methyl maslinate (4) and deoxygenation of its derivative
Methyl maslinate (4, 500 mg, 1.02 mmol) was dissolved in py (10 mL) and treated with
TsCl (300 mg) at rt with stirring for 24 h. The reaction mixture was diluted with water and
extracted with DCM. The organic layer was washed with saturated KHSO4 solution and
dried over anhydrous Na2SO4. The solvent was evaporated at reduced pressure and the
residue was chromatographed on a silica gel column to give 18 (600 mg, 90%) (Garcia-
Granados et al., 2000b). Treatment of 18 with TMSCl/KI yielded 3-deoxyD2,3methyl
oleanoate (7) (70 mg, 20%) and 19 (349 mg, 75%).
–1
1
25
Compound 19: Syrup; ½ꢁꢁD þ 22 (c 0.5, CHCl3); IR ꢂCmHaxCl cm : 3424, 2946, 1722, 1162; H
NMR (300 MHz, CDCl3): ꢃ 5.26 (1H, dd, J1 ¼ 3.6 Hz, J2 ¼ 3.6 Hz, H-12), 4.57 (1H, ddd,
J1 ¼ 4.2 Hz, J2 ¼ 10.7 Hz, J3 ¼ 12.8 Hz, H-2), 3.60 (3H, s, COOCH3), 3.32 (1H, dd,
J ¼ 3.4 Hz, J2 ¼ 10.7 Hz, H-3), 2.84 (1H, dd, J1 ¼ 4.2 Hz, J2 ¼ 13.8 Hz, H-18), 2.41 (1H, dd,
J1 ¼ 4.2 Hz, J2 ¼ 12.9 Hz, H-1ꢀ), 1.11 (3H, s, Me), 1.08 (3H, s, Me), 0.94 (3H, s, Me), 0.91
(3H, s, Me), 0.86 (3H, s, Me), 0.82 (3H, s, Me), 0.69 (3H, s, Me). 13C NMR (75 MHz,
CDCl3): Table 2; HRLSIMS (m/z) 619.2628 [M þ Na]þ (Calcd for C31H49O3INa,
619.2624).
3
Methyl maslinate (4) was also oxygenated with Dess–Martin reagent to give 20 (79%)
(Garcia-Granados et al., 2000b); its reduction with LiAlH4 gave 21 (95%), which could
not be deoxygenated.
ꢂ1
25
Compound 21: White solid, m.p. 133–135ꢀC; ½ꢁꢁD þ 23 (c 0.5, CHCl3); IR ꢂmCHaxCl cm
:
3
3421, 2948, 2865, 1733, 1460, 1364; 1H NMR (300 MHz, CDCl3): ꢃ 5.18 (1H, dd,
J1 ¼ 3.5 Hz, J2 ¼ 3.5 Hz, H-12), 3.67 (1H, ddd, J1 ¼ 6.7 Hz, J2 ¼ 6.7 Hz, J3 ¼ 6.7 Hz, H-2),
3.53 (1H, d, J ¼ 11.0 Hz, H-28a), 3.19 (1H, d, J ¼ 6.7 Hz, H-3), 3.18 (1H, d, J ¼ 11.0 Hz,
H-28b), 1.23 (3H, s, Me), 1.13 (3H, s, Me), 0.99 (3H, s, Me), 0.98 (3H, s, Me), 0.93

Natural Product Research
Table 2. 13C chemical shifts (in Cl3CD, ꢃ in ppm) for compounds 17, 19, 21–24, 27–29.
Compound no.
191
Carbon
17
19
21
22
23
24
27
28
29
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Me
Me
44.5
79.9
44.5
35.3
55.9
18.4
32.5
39.5
47.8
39.6
23.1
122.2
143.9
41.8
27.7
23.6
46.8
41.4
46.0
30.8
32.5
33.6
16.3
17.0
22.5
23.7
26.0
33.2
33.4
178.3
51.6
18.8
215.2
52.8
41.8
83.6
39.5
55.5
18.4
32.4
40.7
47.4
41.5
23.1
122.0
144.0
41.8
27.7
23.5
46.8
41.3
45.9
30.8
32.5
33.9
15.6
16.2
17.0
23.7
26.0
29.3
33.2
178.3
51.7
46.5
71.1
78.5
41.9
55.2
18.2
32.6
38.2
48.1
37.0
23.1
122.5
144.3
40.0
25.5
23.7
46.8
42.4
44.3
31.0
31.1
34.2
16.5
16.8
17.4
23.7
26.0
31.8
33.32
69.7
46.0
70.8
83.2
39.5
55.3
18.2
32.4
38.5
47.6
38.8
23.1
122.1
144.1
41.4
27.7
23.6
46.8
41.4
47.2
30.7
32.6
33.9
16.6
16.9
17.0
23.7
26.0
28.8
33.2
178.3
51.6
ꢂ4.5
ꢂ3.8
18.1
25.9
45.9
67.9
93.3
40.6
55.0
18.2
32.6
38.0
48.3
39.4
23.1
122.0
144.1
41.8
27.7
23.5
46.8
41.4
47.5
30.8
32.4
33.9
16.7
16.9
18.4
23.7
26.0
28.8
33.2
178.3
51.6
ꢂ4.8
ꢂ4.3
19.0
18.9
25.7
216.8
46.0
79.6
38.5
31.0
55.4
18.6
32.8
37.0
47.8
39.4
23.2
122.5
143.9
41.7
27.7
23.5
46.8
41.4
46.0
30.8
32.5
34.0
14.1
15.4
16.2
16.9
23.7
28.6
33.2
178.3
51.5
ꢂ4.8
ꢂ3.7
18.2
26.0
47.3
69.2
64.9
38.3
51.6
21.6
32.4
37.5
48.2
39.6
23.2
122.4
143.8
41.9
27.7
23.4
46.9
41.5
45.9
30.8
32.4
34.0
16.5
16.5
20.4
23.7
24.2
26.0
33.2
178.4
51.6
48.9
64.1
82.9
40.4
55.3
18.3
32.4
39.4
47.5
39.6
23.1
122.0
144.0
41.8
27.7
23.5
46.8
41.3
45.9
30.8
32.4
33.9
16.1
16.6
17.0
23.7
26.0
29.0
33.2
178.3
51.6
45.9
67.7
47.3
32.8
53.6
19.0
32.5
39.7
48.1
37.9
23.2
122.7
143.8
41.9
27.7
23.5
46.8
41.5
46.6
30.8
32.5
34.0
16.8
18.5
23.7
24.7
26.0
33.2
33.2
178.3
51.6
Me
Me
Me
Me
Me
28
COOMe
Groups in A-ring
(3H, s, Me), 0.86 (3H, s, Me), 0.85 (3H, s, Me); 13C NMR (75 MHz, CDCl3): Table 2;
HRLSIMS (m/z) 481.3659 [M þ Na]þ (Calcd for C30H50O3Na, 481.3658).
4.23. Silylation and xanthylation of methyl maslinate (4)
Methyl maslinate (4) (1.45 g, 3 mmol) was dissolved in py (10 mL) and TBDMSCl (900 mg,
6 mmol) was added. The reaction mixture was refluxed for 2 h and extracted with DCM.
The organic layer was washed with aqueous 1 N HCl solution, neutralised with saturated
NaHCO3 solution and dried over anhydrous Na2SO4. The solvent was evaporated at

192
A. Parra et al.
reduced pressure and the residue was chromatographed on a silicagel column to give 22
(1.7 g, 95%). This compound was xanthylated in the usual manner to give 23 (70%).
Compound 22: White solid, m.p. 180–182ꢀC; ½ꢁꢁD þ17 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 3596,
25
3
1
2949, 1726, 1462, 1258, 1078, 838, 758; H NMR (300 MHz, CDCl3): ꢃ 5.27 (1H, dd,
J1 ¼ J2 ¼ 3.7 Hz, H-12), 3.67 (1H, ddd, J1 ¼ 4.5 Hz, J2 ¼ 9.2 Hz, J3 ¼ 11.1 Hz, H-2), 3.60
(3H, s, COOCH3), 2.99 (1H, d, J ¼ 9.2 Hz, H-3), 2.84 (1H, dd, J1 ¼ 4.4 Hz, J2 ¼ 13.9 Hz,
H-18), 1.11 (3H, s, 3H-27), 1.03 (3H, s, 3H-23), 0.94 (3H, s, 3H-25), 0.91 (3H, s, 3H-30),
0.87 (3H, s, 3H-29), 0.87 (9H, s, (CH3)3C–), 0.81 (3H, s, 3H-24), 0.70 (3H, s, 3H-26), 0.08
(3H, s, CH3Si–), 0.06 (3H, s, CH3Si–); 13C NMR (75 MHz, CDCl3): Table 2; HRLSIMS
m/z 623.4480 [M þ Na]þ (Calcd for C37H64SiO4Na, 623.4472).
Compound 23: White solid, m.p. 256–258ꢀC; ½ꢁꢁD þ 10 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 2948,
25
3
1728, 1462, 1236, 1054; 1H RMN (300 MHz, CDCl3): ꢃ 5.60 (1H, d, J ¼ 9.6 Hz, H-3), 5.27
(1H, dd, J1 ¼ J2 ¼ 3.7 Hz, H-12), 3.98 (1H, ddd, J1 ¼ 4.7 Hz, J2 ¼ 9.6 Hz, J3 ¼ 11.0 Hz,
H-2), 3.61 (3H, s, COOCH3), 2.85 (1H, dd, J1 ¼ 4.1 Hz, J2 ¼ 14.0 Hz, H-18), 2.54 (3H, S,
CH3S–), 1.11 (3H, s, Me), 0.99 (3H, s, Me), 0.91 (3H, s, Me), 0.91 (3H, s, Me), 0.89 (3H, s,
Me), 0.88 (3H, s, Me), 0.81 (9H, s, (CH3)3C–), 0.71 (3H, s, Me), 0.03 (3H, s, CH3Si–), 0.01
(3H, s, CH3Si–); 13C RMN (75 MHz, CDCl3): Table 2; HRLSIMS m/z 713.4069
[M þ Na]þ (Calcd for C39H66O4SiNaS2, 713.4061).
4.24. Reduction of xanthate (23) with H3PO2
The usual reduction of xanthate (23) gave 16 (85 mg, 40%), 24 (77 mg, 33%) and 25
(23 mg, 10%).
Compound 24: White solid, m.p. 268–270ꢀC; ½ꢁꢁD þ31 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 2928,
25
3
1
1732, 1463, 1254, 1162, 1099, 1073, 836; H NMR (300 MHz, CDCl3): ꢃ 5.27 (1H, dd,
J1 ¼ J2 ¼ 3.5 Hz, H-12), 3.61 (3H, s, COOCH3), 3.17 (1H, dd, J1 ¼ 4.6 Hz, J2 ¼ 11.0 Hz,
H-2), 2.85 (1H, dd, J1 ¼ 4.5 Hz, J2 ¼ 13.8 Hz, H-18), 1.11 (3H, s, Me), 0.91 (3H, s, Me),
0.89 (3H, s, Me), 0.89 (3H, s, Me), 0.89 (3H, s, (CH3)3C–), 0.87 (3H, s, Me), 0.87 (6H, s,
(CH3)3C–), 0.73 (3H, s, Me), 0.70 (3H, s, Me), 0.02 (6H, s, CH3Si–); 13C NMR (75 MHz,
CDCl3): Table 2; HRLSIMS, m/z 607.4519 [M þ Na]þ (Calcd for C37H64O3SiNa,
607.4522).
Compound 25: Syrup; ½ꢁꢁD þ58 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 3439, 2947, 1727, 1457,
25
3
1
1235, 1055, 758; H NMR (300 MHz, CDCl3): ꢃ 5.54 (1H, d, J ¼ 9.9 Hz, H-3), 5.27 (1H,
dd, J1 ¼ J2 ¼ 3.5 Hz, H-12), 4.01 (1H, ddd, H-2), 3.61 (3H, s, COOCH3), 2.85 (1H, dd,
J1 ¼ 4.3 Hz, J2 ¼ 13.9 Hz, H-18), 2.59 (3H, s, CH3S–), 1.12 (3H, s, Me), 1.00 (3H, s, Me),
0.95 (3H, s, Me), 0.92 (3H, s, Me), 0.91 (3H, s, Me), 0.89 (3H, s, Me), 0.71 (3H, s, Me); 13
C
NMR (75 MHz, CDCl3): Table 2; HRLSIMS m/z 599.3209 [M þ Na]þ (Calcd for
C33H52O4NaS2, 599.3198).
4.25. Epoxidation of methyl maslinate (4)
Epoxy derivative 26 was obtained by Mitsunobu reaction or via tosylation according to
the routes given in the literature (Garcia-Granados et al., 2003a) in a very good yield.
Deoxygenation of 26 with Me3SiCl-KI gave 3-deoxyD2,3methyl oleanoate 7, (12%), 19
(80%) and 27 (7%).

Natural Product Research
193
Compound 27: Syrup; ½ꢁꢁD þ66 (c 0.5, CHCl3); IR ꢂCmHaxCl cmꢂ1: 3402, 2943, 1723,
1124: 1 H NMR (300 MHz, CDCl3): ꢃ 5.29 (1H, dd, J1 ¼ 3.6 Hz, J2 ¼ 3.6 Hz, H-12), 4.73
(1H, d, J ¼ 4.8 Hz, H-3), 4.01 (1H, ddd, J1 ¼ 4.8 Hz, J2 ¼ 9.4 Hz, J3 ¼ 10.5 Hz, H-2), 3.61
(3H, s, COOCH3), 2.85 (1H, dd, J1 ¼ 4.5 Hz, J2 ¼ 14.4 Hz, H-18), 1.14 (3H, s, Me), 1.12
(3H, s, Me), 1.09 (3H, s, Me), 1.03 (3H, s, Me), 0.91 (3H, s, Me), 0.89 (3H, s, Me),
0.71 (3H, s, Me). 13C NMR (75 MHz, CDCl3): Table 2; HRLSIMS (m/z) 619.2623
[M þ Na]þ (Calcd for C31H49O3INa, 619.2624).
25
3
Deoxygenation of 26 with WCl6/n-BuLi yielded 3-deoxyD2,3methyl oleanoate (7)
(8 mg, 8%) and 28 (50 mg, 46%).
ꢂ1
25
Compound 28: Yellow solid, m.p. 185–187ꢀC; ½ꢁꢁD þ 50 (c 1, CHCl3); IR ꢂmCHaxCl cm
3
1
3404, 2947, 1724, 1125; H NMR (300 MHz, CDCl3): ꢃ 5.27 (1H, dd, J1 ¼ J2 ¼ 3.6 Hz,
H-12), 4.12 (1H, ddd, J1 ¼ 4.3 Hz, J2 ¼ 10.2 Hz, J3 ¼ 12.2 Hz, H-2), 3.61 (3H, s, COOCH3),
3.17 (1H, d, J ¼ 10.2 Hz, H-3), 2.85 (1H, dd, J1 ¼ 4.5 Hz, J2 ¼ 13.8 Hz, H-18), 1.12 (3H, s,
Me), 1.08 (3H, s, Me), 0.96 (3H, s, Me), 0.91 (3H, s, Me), 0.89 (3H, s, Me), 0.83 (3H, s,
Me), 0.70 (3H, s, Me); 13C NMR (75 MHz, CDCl3): Table 2; HRLSIMS m/z 527.3269
[M þ Na]þ (Calcd for C31H49O3ClNa, 527.3268).
4.26. Deoxygenation of 2b,3b-epoxy methyl maslinate (26) with Cp2TiCl
A. Stoichiometric procedure: To a solution of Cp2TiCl2 (700 mg, 3 equiv) and Mn
(1000 mg, 8 equiv) in THF (20 mL), compound 26 (468 mg, 1 mmol) in THF (10 mL) was
added. The reaction mixture was stirred for 3 h at rt, washed with aqueous 1N HCl
solution and extracted with DCM. The organic layer was dried over anhydrous Na2SO4,
concentrated in vacuum and purified on a silica gel column yielding 3-deoxyD2,3methyl
oleanoate (7) (370 mg, 82%) and 29 (28 mg, 6%).
4.27. 2-Epi 3-deoxy methyl maslinate (29)
White solid, m.p. 190–192ꢀC; ½ꢁꢁD þ22 (c 1, CHCl3); IR ꢂCmHaxCl cmꢂ1: 3423, 2947, 2865,
25
3
1
1723, 1462, 1034; H NMR (300 MHz, CDCl3): ꢃ 5.27 (1H, dd, J1 ¼ 3.8 Hz, J2 ¼ 7.4 Hz,
H-12), 4.05 (1H, dddd, J1 ¼ 5.4 Hz, J2 ¼ 5.4 Hz, J3 ¼ 5.4, J4 ¼ 5.4 Hz, H-2), 3.59 (3H, s,
COOCH3), 2.83 (1H, dd, J1 ¼ 4.0 Hz, J2 ¼ 13.8 Hz, H-18), 1.15 (3H, s, Me), 1.10
(3H, s, Me), 0.98 (3H, s, Me), 0.90 (3H, s, Me), 0.90 (3H, s, Me), 0.87 (3H, s, Me), 0.71
(3H, s, Me); 13C NMR (75 MHz, CDCl3): Table 2; HRLSIMS (m/z) (Calcd for
C31H50O3Na 493.3657 [M þ Na]+, found 493.3659).
B. Catalytic procedure: A solution of Cp2TiCl2 (22 mg, 0.0086 mmol) and Mn (186 mg,
8 equiv) in THF (5 mL) was maintained at rt for 15 min until it gave a green colour. After
that, compound 26 (200 mg, 0.42 mmol) in THF (5 mL) and a mixture of Me3SiCl (0.2 mL,
0.17 mmol) and collidine (0.4 mL, 0.29 mmol) in THF (2 mL) were added. The reaction
mixture was stirred for 3 h at rt in argon atmosphere, washed with aqueous 1N HCl
solution and extracted with DCM. The organic layer was dried over anhydrous Na2SO4,
concentrated in vacuum and purified on a silica gel column yielding 3-deoxyD2,3methyl
oleanoate (7) (146 mg, 77%) and 29 (22 mg, 11%).

194
A. Parra et al.
4.28. Dehydration of compound 29 with POCl3
Compound 29 (200 mg, 0.4 mmol) was dissolved in py (5 mL) and 1 mL de POCl3 was
added. The reaction mixture was refluxed for 30 min, washed with cold water and an
aqueous saturated solution of NaHSO4, and then extracted with DCM. The organic layer
was dried over anhydrous Na2SO4, concentrated in vacuum and purified on a silica gel
column, yielding 3-deoxyD2,3methyl oleanoate (7) (166 mg, 92%).
Acknowledgements
This work was supported by a grant from the Comision Interministerial de Ciencia y Tecnologia and
´
by a project from the Ministerio de Educacion y Cultura. We thank David Nesbitt for reviewing the
article for English language.
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