Reaction of 18β,19β-epoxylupan-21-one derivatives with acids: A way to 21,22-disubstituted lup-18-ene triterpenoids

Article abstract of DOI:10.1135/cccc19990329

Depending on the conditions and the acid employed, 18β,19β-epoxy-28-hydroxy-21-oxolupan-3β-yl acetate (2a) and 18β,19β-epoxy-21-oxolupane-3β,28-diyl diacetate (2b) on treatment with acid gave three types of products: (i) 28-nor derivatives: 21-oxo28-norlu

Full text of DOI:10.1135/cccc19990329

Triterpenes
329
REACTION OF 18β,19β-EPOXYLUPAN-21-ONE DERIVATIVES
WITH ACIDS: A WAY TO 21,22-DISUBSTITUTED LUP-18-ENE
TRITERPENOIDS+
1,
3
Eva KLINOTOVÁ *, Jitka ČERMÁKOVÁ, Martin REJZEK2,++, Václav KŘEČEK ,
4
1
Jan SEJBAL , Petr OLŠOVSKÝ and Jiří KLINOT
Department of Organic Chemistry, Faculty of Science, Charles University, 128 40 Prague 2,
1
2
Czech Republic; e-mail: klinot@prfdec.natur.cuni.cz, rejzek@uochb.cas.cz,
3
4
krecek@prfdec.natur.cuni.cz, sejbal@prfdec.natur.cuni.cz
Received July 28, 1998
Accepted Septem ber 25, 1998
Dedicated to the memory of Dr Miroslav Protiva.
Depen din g on th e con dition s an d th e acid em ployed, 18β,19β-epoxy-28-h ydroxy-
21-oxolupan -3β-yl acetate (2a) an d 18β,19β-epoxy-21-oxolupan e-3β,28-diyl diacetate (2b) on
treatm en t with acid gave th ree types of products: (i) 28-n or derivatives: 21-oxo-
28-n orlupa-16,18-dien -3β-yl acetate (6), 19β-h ydroxy-21-oxo-28-n orlup-17-en -3β-yl acetate
(7) an d 17ξ-h ydroxy-21-oxo-28-n orlup-18-en -3β-yl acetate (8), (ii) lupa-12,18-dien -21-on es
4a an d 4b , an d (iii) 22β-substituted lup-18-en -21-on e derivatives of th e type 5. Th e
formation of 22β-substituted derivatives of the type 5 probably proceeds in the enol form of epoxy
keton e 2. Open in g of th e epoxide rin g with sh ift of th e double bon d to position 19(21) an d
attack by n ucleoph ilic species at C-22 followed by elim in ation of water an d re-form ation of
th e 22-oxo group leads to derivatives of th e type 5.
Key words: Triterpen es; Triterpen oids; Lupan e; Epoxy keton es; NMR spectroscopy, 1H an d 13C.
Triterpen oid com poun ds derived from lup-18-en e an d 18,19-epoxylupan e
are suitable startin g m aterial for th e preparation of E-secolupan e an d
des-E-lupan e com poun ds wh ich represen t a tran sition to tetracyclic
triterpen oids of th e bacch aran e type an d to sesterterpen oids2–10. In our
previous paper10, we h ave sh own th at treatm en t of 18β,19β-epoxy-
21-oxolupane-3β,28-diyl diacetate (2b) with peroxyacetic acid un der cataly-
sis with stron g acids (4-toluen esulfon ic, sulfuric or trifluoroacetic acids) re-
sults in Baeyer–Villiger oxidation , open in g of th e epoxide rin g an d
+ Part CIX in th e series Triterpen es; Part CVIII: see ref.1
++Presen t address: In stitute of Organ ic Ch em istry an d Bioch em istry, Academ y of Scien ces of
th e Czech Republic, 166 10 Prague 6, Czech Republic
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

330
Klinotová et al.:
subsequen t cyclization . Th e reaction th us leads to 19,21-secolupan e com -
poun ds – spirolacton es of th e type 3, wh ich on subsequen t oxidative degra-
dation can be con verted in to tetran or an d pen tan or derivatives
(des-E-com poun ds), sim ilar to n atural skalaran e sesterterpen oids. In som e
cases, th e m en tion ed reaction of epoxy keton e 2b with peroxyacetic acid
also afforded side products wh ich in th e cited paper10 h ave n ot been iden ti-
fied. Now we h ave foun d th at th ese com poun ds are n ot th e products of oxi-
dation with th e peroxy acid an d m ust th erefore arise by action of acids on
th e epoxy keton e 2b. For th is reason , we h ave studied th e reaction of vari-
ous acids with th e epoxy keton e 2b an d with th e an alogous epoxy keton e
2a, con tain in g free h ydroxyl in position 28 (Sch em e 1).
O
O
O
O
O
HO
O
(ii)
(i)
2
OR
2
OR
1
R O
1
2
1
2
1
R
R
H
R
R
H
R
H
Ac
Ac
Ac
Ac
H
1a
1b
2a
3a
3b
Ac
Ac
H
Ac
2b
2c
(iii)
O
O
O
3
OR
2
2
OR
OR
3
1
2
R
R
R
H
1
6, R = Ac
Ac
H
H
5a
5b
5c
5d
5e
5f
1
2
R
R
Ac Ac
Ac Ac
Ac
Ac
H
4a
4b
Ac
Ac
Tos
Tos
Tos
H
H
H
Ac
Ac Ac
Ac Ac
CF CO
3
5g
(i) 3-chloroperoxybenzoic acid/CHCl ; (ii) boric acid, air/benzene, dioxane; (iii) acid
3
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
331
Th e startin g 21-oxolup-18-en e-3β,28-diyl diacetate (1b) was prepared by
oxidation of lup-18-en e-3β,28-diyl diacetate with ch rom ium trioxide11; th e
epoxy keton e 2b was obtain ed by reaction of keton e 1b with 3-ch loro-
peroxyben zoic acid accordin g to th e literature10. Mild alkalin e h ydrolysis of
diacetate 1b gave m on oacetate 1a with free h ydroxyl in position 28.
Epoxidation of th e double bon d in m on oacetate 1a with 3-ch loroperoxy-
ben zoic acid led to epoxy keton e 2a wh ich was also obtain ed by partial al-
kalin e h ydrolysis of diacetate 2b; as a side product of th e h ydrolysis, we
isolated th e kn own 10 diol 2c.
On h eatin g with 4-toluen esulfon ic acid in ben zen e, th e epoxy keton e 2b
afforded 22-tosyloxy derivative 5f as th e sole product. Reaction of epoxy
keton e 2b with acetic acid un der catalysis with sulfuric acid gave th e an alo-
gous 22-acetoxy derivative 5c (71%), togeth er with a sm all am oun t of side
products th at were n ot iden tified. In both th e reaction s we added to th e re-
action m ixture a sm all am oun t of acetic an h ydride to preven t th e un de-
sired h ydrolysis of th e acetate groups in position s 3, 28 or 22. Th e tosylate
5f an d acetate 5c were iden tical with th e side products obtain ed10 in th e
Baeyer–Villiger oxidation of epoxy keton e 2b with peroxyacetic acid wh en
4-toluen esulfon ic or sulfuric acid was used as catalyst. Reaction of epoxy
keton e 2b with trifluoroacetic acid afforded m ain ly th e 22-trifluoroacetate 5g
which was very unstable and was converted into the corresponding 22-hydroxy
derivative 5b durin g th e work-up of th e reaction m ixture an d ch rom ato-
graph ic purification . In addition to th ese two 22-substituted com poun ds
(5g, 5b), we also isolated th e dien on e 4b. Treatm en t of epoxy keton e 2b
with zin c iodide in boilin g acetic acid resulted in predom in an t elim in ation
of th e epoxide oxygen atom an d th e un saturated keton e 1b was obtain ed as
th e m ain product. A m in or am oun t of th e 22-acetoxy derivative 5c was also
isolated.
With boron trifluoride eth erate in ben zen e at room tem perature, epoxy
keton e 2b afforded a com plex m ixture of products from wh ich we were able
to isolate and identify only one compound, dienone 4b, in very low yield (10%).
Sim ilarly, reaction with sulfuric acid in boilin g aqueous peroxide-free
dioxan e in an argon atm osph ere afforded a m ixture of m an y un iden tified
products n eith er of wh ich predom in ated. However, wh en th is reaction was
perform ed in th e presen ce of air oxygen , a Baeyer–Villiger-type reaction
took place an d we isolated from th e product m ixture spirolacton e 3a in
46% yield. Also, wh en epoxy keton e 2b was reacted with boric acid in boil-
in g m ixture of ch loroform an d acetic an h ydride in th e presen ce of air, an
oxidation reaction took place, spirolacton e 3b bein g isolated as th e prin ci-
pal product (61%), alon g with th e 22-acetoxy derivative 5c (24%).
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

332
Klinotová et al.:
Baeyer–Villiger oxidation of th e epoxy keton e 2b an d subsequen t cycli-
zation to th e spirolacton es 3a an d 3b is th us extrem ely facile an d does n ot
require an y peroxy acids. Sim ilarly to its 28-acetate 2b, th e epoxy keton e 2a
with free h ydroxyl on C-28 reacted with 4-toluen esulfon ic acid un der for-
m ation of 22-tosylate 5e. Th e reaction also gave sm all am oun ts of tosylate
5d , deacetylated in position 3, an d of dien on e 4a. Com pared with th e reac-
tion s of th e keton e 2b, th e epoxy keton e 2a often un derwen t elim in ation
of form aldeh yde from C-17 with form ation of 28-n or derivatives: its reac-
tion with boron trifluoride eth erate afforded th e n ordien on e 6 as th e sole
product. Treatm en t with zin c iodide in boilin g acetic acid also gave th e
nordienone 6 (29%), together with the 28-acetates – the unsaturated ketone 1b
(23%) an d th e dien on e 4b (11%). Th e n ordien on e 6 was also isolated in a
23% yield from th e product m ixture after reaction of epoxy keton e 2a with
trifluoroacetic acid which afforded dienone 4a as the principal product (60%).
O
O
HO
(i)
(ii)
(iii)
2a
OH
6
AcO
AcO
7
8
(iv)
O
O
O
(v)
O
5b
OAc
AcO
AcO
9
10
(i) boric acid/benzene, dioxane, argon; (ii) allylic rearrangement; (iii) TosOH/CHCl ;
3
(iv) Pb(OAc) , AcOH, Ac O/benzene; (v) CrO on alumina/CHCl
3
4
2
3
SCHEME 2
Heatin g of th e epoxy keton e 2a with boric acid in a m ixture of ben zen e
an d dioxan e un der argon (Sch em e 2) afforded furth er two 28-n or deriva-
tives: 19-h ydroxy keton e 7 (66%) an d 17-h ydroxy keton e 8 (15%). Wh en
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
333
th e reaction was perform ed in th e presen ce of air, oxidation took place (as
in th e case of th e epoxy keton e 2b), th e spirolacton e 3b (65%) bein g th e
predom in an t product. Th e h ydroxy keton es 7 an d 8 are obviously in term e-
1
diates in th e form ation of dien on e 6: a TLC an d H NMR study of reaction
of h ydroxy keton e 7 with 4-toluen esulfon ic acid in ch loroform at room
tem perature revealed th at th e 19-h ydroxy keton e 7 un dergoes first an allylic
rearran gem en t to give th e isom eric 17-h ydroxy keton e 8 wh ose deh ydra-
tion leads to 16,18-dien -21-on e 6 as th e sole product.
Hydrolysis of th e acetate groups in position s 22 an d 28 of th e triacetate
5c an d of th e 28-acetate group in diacetate 5b is extraordin arily facile:
treatm en t of th e triacetate 5c an d diacetate 5b with potassium h ydroxide in
a m ixture of eth an ol an d ben zen e at room tem perature (two an d on e equiv-
alen t, respectively) gives th e 3-acetate 5a with in few m in utes. Both th e
O-acetyl groups in position s 3 an d 28 in th e tosylate 5f can be rem oved by
reaction with sulfuric acid in m eth an ol, th e 22-tosyloxy group rem ain in g
in tact, an d th e product is tosylate 5d . Th e com poun ds with out acetate
groups an d th e partially acetylated derivatives were ch em ically correlated
with th e peracetyl derivatives by acetylation with acetic an h ydride in
pyridin e; dien on e 4a gave dien on e 4b, com poun ds 5a an d 5b afforded th e
triacetate 5c an d tosylates 5d an d 5e were con verted in to th e tosylate 5f.
Th e 22-h ydroxy derivative 5b was oxidized with ch rom ium trioxide on alu-
m in a to give 21,22-diketon e 10. In th e 19-h ydroxy keton e 7 th e presen ce of
an α-ketol groupin g was con firm ed by cleavage of th e C(19)–C(21) bon d
with lead tetraacetate; h owever, th e expected 19-oxo-21-oic acid was ob-
tain ed in th e form of th e en ol lacton e, i.e. th e dien olide 9. Th e β-con figura-
tion of th e h ydroxyl in th e 19-h ydroxy keton e 7 follows from th e
β-configuration of the epoxide oxygen atom 10 in the starting epoxy ketone 2a.
Structures of th e prepared com poun ds were con firm ed by IR, UV an d
m ass spectra (see Experim en tal); h owever, m ost of th e eviden ce is based
1
m ain ly on th e H an d 13C NMR spectra. Th e proton NMR data are sum m a-
rized in Tables I–III, th e 13C NMR data in Tables IV an d V. In th e 13C NMR
spectra, th e n um ber of directly bon ded h ydrogen atom s was determ in ed
from APT or DEPT spectra an d for com poun ds 4b an d 7 also from proton
coupled spectra. Th e ch em ical sh ifts were assign ed to th e in dividual h ydro-
gen an d carbon atom s (Tables I–V) usin g th e followin g two-dim en sion al
tech n iques: COSY (com poun ds 2a, 4b, 5a–5e, 6, 7, 9 an d 10), LRCOSY (4b,
5b an d 10), NOESY (5a, 5c–5e an d 7), TOCSY (7), HMQC or HETCOR
(5a–5e, 7 an d 9) an d COLOC (5a an d 9). By com bin ation of th e m en tion ed
m eth ods we h ave foun d an d assign ed all th e h ydrogen sign als for com -
poun ds 5a, 5c–5e an d 7. If we assign ed un equivocally also th e con figura-
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

334
Klinotová et al.:
tion of th e m eth ylen e proton s, in Tables I–III th e in dividual proton s are
described by stereodescriptors α an d β, if th e con figuration is un certain ,
th ese proton s are den oted as a (h igh field sign al) an d b (lowfield sign al). In
all th e studied com poun ds, th e ch em ical sh ifts of proton s H-2α an d H-2β
differ on ly sligh tly an d appear in th e region δ 1.6–1.7 an d th eir sign als
could n ot be distin guish ed n eith er in th e h om ocorrelated n or in th e
1
h eterocorrelated 2D NMR spectra. Th e H NMR spectra of all th e m easured
com poun ds exh ibit ch aracteristic two m eth yl doublets at δ 0.9–1.3 an d a
septet at δ 2.0–3.5 (J ≈ 7 Hz), wh ich correspon d to an isolated isopropyl
group, an d furth er (except dien on e 4b) a doublet of doublets of H-13 in th e
region δ 2.6–3.2 with vicin al couplin g con stan ts J(12α,13β) = 12–13 Hz an d
J(12β,13β) = 3–4 Hz. Th e 1H as well as 13C NMR spectra of 22-substituted
com poun ds of th e type 5 are very sim ilar to th ose of th e un saturated ke-
ton es 1a (Tables I an d IV) an d 1b (ref.11), except th e H-22 sign al wh ich in
com poun ds of th e type 5 appears as a sin glet at δ 3.7–5.1, depen din g on th e
ch aracter of substituen t in position 22, an d th e sign al of C-22 (a doublet in
th e region of δ 80–86). Iden tification of th e four-spin system of proton s in
position s 15 an d 16 is based on th e COSY spectra an d on th e H-16β sign al
wh ich is sh ifted down field to δ ≈ 2 an d form s a doublet of triplets; th e
foun d couplin g con stan ts J(16α,16β) = 13.7 Hz an d J(15α,16β) ≈ J(15β,16β) ≈
3.8 Hz correspon d to an equatorial position of H-16β. In th e NOESY spectra
of com poun ds 5a an d 5c–5e, th e followin g steric con tacts h ave been foun d:
H-1α/H-3, H-3/H-5, H-3/H-23, H-12α/H-20, H-12β/H-20, H-13/H-15β,
H-13/H-26, H-13/H-28b, H-15β/H-26, H-16α/H-22, H-16α/H-27, H-23/H-24,
H-24/H-25 an d H-25/H-26. Th e absen ce of cross-peaks of H-22/H-16β,
H-22/H-28a, H-22/H-28b an d th e presen ce of an in ten se NOESY cross-peak
of H-22/H-16α sh ows th at H-22 h as th e α-con figuration . Sin ce th ese com -
poun ds were ch em ically correlated with oth er 22-substituted derivatives
(5b, 5f, 5g), it is eviden t th at in all th e com poun ds of th e type 5, th e
substituen t on C-22 h as β-con figuration .
Th e position of th e 16(17) double bon d in n ordien on e 6 follows from th e
COSY spectrum th at exh ibits a couplin g of th e olefin ic proton H-16 with
th e two n eigh bourin g proton s on C-15, an allylic couplin g of H-16 with th e
proton s on C-22 an d a h om oallylic couplin g of proton s on C-22 with th e
H-15β an d H-13 proton s. In 19-h ydroxy keton e 7, COSY an d TOCSY spectra
sh ow four isolated spin system s, th ree of wh ich are due to adjacen t proton s
on th e rin gs A (proton s in position s 1, 2, 3) an d B (5, 6, 7) an d in th e
isopropyl side ch ain (20, 29, 30). Th e fourth spin system is – th an ks to th e
lon g-ran ge couplin gs between th e proton s separated by carbon atom s of th e
17(18) double bon d – com m on to th e proton s on th e rin gs C (9, 11, 12, 13),
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
335
D (15, 16) an d E (22). In th e NOESY spectrum we foun d steric con tacts sim -
ilar to th ose already m en tion ed for com poun d of th e type 5. Th e presen ce
of a dien olide system in th e rin g E in com poun d 9 follows from th e
13C NMR spectrum an d from th e COLOC spectrum wh ich con firm ed th e fol-
lowin g 13C-1H lon g-ran ge couplin gs: C-17/H-13, C-17/H-22, C-19/H-13,
C-19/(H-29, H-30) an d C-21/H-22. Th e spin system of proton s in position s
15, 16 an d 22 was iden tified in COSY spectra.
Mass spectra of com poun ds 1a, 2a an d 4–9 exh ibited very abun dan t
peaks correspon din g to fragm en tation in th e rin g C: ion s [M – 263]+ for
3-O-acetyl derivatives an d ion [M – 221]+ for th e 3-h ydroxy derivative 5d .
Th eir form ation can be explain ed by cleavage of th e C(11)–C(12) an d
C(8)–C(14) bon ds an d subsequen t tran sfer of h ydrogen from th e n eutral
fragm en t (rin gs A an d B) to a ch arged particle in volvin g rin gs D an d E. Th e
sam e fragm en tation type h as already been observed11 in th e case of un satu-
rated keton e 1b. In som e cases, particularly of h ydroxy keton es 7 an d 8, th e
m en tion ed ch aracteristic ion s are accom pan ied by ion s [M – 281]+ th at cor-
respon d to loss of water m olecule from ion s [M – 263]+.
We can conclude that on treatment with the described acids 18β,19β-epoxy-
21-keton es 2a an d 2b afford th ree types of products:
1. 28-Nor derivatives 6, 7 an d 8 – th eir form ation was observed on ly with
th e epoxy keton e 2a wh ich h as free h ydroxy group on th e C-28 carbon
atom ;
2. dienones 4a and 4b – they are formed predominantly from the 28-h ydroxy
derivative 2a, wh ereas in th e reaction of th e 28-acetoxy derivative 2b th ey
were foun d on ly exception ally, in both cases on ly as side products;
3. 22β-substituted derivatives of th e type 5 – th ey are typical for reaction s
of th e 28-acetoxy derivative 2b; in th e reaction s of 28-h ydroxy derivative 2a,
th ey are m ore or less accom pan ied by dien on es 4a an d 6, depen din g on th e
con dition s.
A possible explan ation of th e form ation of 22β-substituted derivatives is
given in Sch em e 3. Th e reaction probably proceeds in th e en ol form by
open in g of th e epoxide rin g with sh ift of th e double bon d from position
OH
O H
HO
O
H
Nu
OR
Nu
5
2
OR
R = H, Ac
SCHEME 3
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

336
Klinotová et al.:
21(22) to position 19(21) an d with attack by a n ucleoph ilic species at C-22.
Elim in ation of water an d re-form ation of th e 22-oxo group th en leads to
derivatives of th e type 5. Th is reaction th us represen ts a sim ple procedure
for th e preparation of 21,22-disubstituted lup-18-en e derivatives wh ich m ay
be a suitable startin g m aterial for th e syn th esis of E-secolupan e com poun ds.
EXPERIMENTAL
Meltin g poin ts were determ in ed on a Kofler block an d are un corrected. Optical rotation
m easurem en ts at 23 °C were carried out in ch loroform (c 0.3–0.5) on an autom atic
polarim eter ETL-NPL (Ben dix–Ericsson ), accuracy ±2°; th ey are given in 10–1 deg cm 2 g–1. In -
frared spectra were recorded in ch loroform on a PE 684 (Perkin –Elm er) spectrom eter,
waven um bers are given in cm –1. UV spectra were m easured on a Un icam SP-700 in strum en t.
1H an d 13C NMR spectra were taken on a Varian UNITY-INOVA 400 FT spectrom eter (1H at
400 MHz, 13C at 100.58 MHz) in deuterioch loroform with tetram eth ylsilan e as in tern al stan -
dard (for th e 13C NMR data δ (CDCl3) 77.00 ppm ). Th e ch em ical sh ift values (δ-scale, ppm )
an d couplin g con stan ts (Hz) in th e 1H NMR spectra were obtain ed by first-order an alysis.
Electron im pact m ass spectra were m easured on an INCOS 50 (Fin n igan MAT) in strum en t;
ion izin g electron en ergy 70 eV.
Colum n ch rom atograph y was carried out on silica gel Silpearl (Kavalier, Votice, Czech Re-
public). Th e purity of th e sam ples was ch ecked by th in -layer ch rom atograph y (TLC) on
DC-Alufolien Kieselgel 60 F254 (Merck) plates. Spots were detected by sprayin g with 10% sul-
furic acid an d subsequen t h eatin g. Preparative TLC was perform ed on silica gel 60 G
(Merck); com poun ds were detected by UV ligh t (254 n m ) after sprayin g with 0.3% solution
of m orin in m eth an ol. Th e iden tity of sam ples prepared by differen t procedures was verified
by TLC, IR an d 1H NMR spectra. An alytical sam ples were dried over ph osph orus pen toxide
at 100 °C un der dim in ish ed pressure.
Th e usual work-up den otes dilution of th e reaction m ixture with water, extraction of th e
products with eth er, successive wash in g of th e eth ereal layer with dilute (1 : 4) h ydroch loric
acid (if n ecessary), sodium h ydrogen carbon ate solution an d with water, dryin g over sodium
sulfate an d evaporation of th e solven t. Th e h ydroxy derivatives were acetylated with a m ix-
ture of acetic an h ydride an d pyridin e (1 : 1) at room tem perature for 12–18 h an d th e reac-
tion m ixture was worked up in th e usual m an n er. After crystallization , th e acetyl derivatives
were obtain ed in 70–90% yield.
28-Hydroxy-21-oxolup-18-en -3β-yl Acetate (1a)
A solution of potassium h ydroxide (0.5 g, 8.9 m m ol) in eth an ol (40 m l) was added to a solu-
tion of diacetate 1b (4.0 g, 7.4 m m ol, ref.11) in ben zen e (40 m l), th e m ixture was set aside
for 8 h at room tem perature an d th en worked up in the usual m anner. Repeated crystallization
from chloroform –m ethanol afforded m onoacetate 1a (2.4 g, 65%), m .p. 292–294 °C, [α]D –69.
IR: 3 621, 1 719, 1 687, 1 602, 1 254. MS, m/z (%): 498 (M+, 8), 438 (5), 395 (12), 259 (5),
235 (70), 189 (24), 43 (100). For C32H50O4 (498.7) calculated: 77.06% C, 10.11% H; foun d:
76.84% C, 9.88% H.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
337
18β,19β-Epoxy-28-h ydroxy-21-oxolupan -3β-yl Acetate (2a)
Method A) By epoxidation of keton e 1a: A solution of th e keton e 1a (3.0 g, 6.02 m m ol)
an d 3-ch loroperoxyben zoic acid (70%, 3.0 g, 12.2 m m ol) in ch loroform (30 m l) was allowed
to stan d at room tem perature. After 8 days, it was diluted with ch loroform (30 m l) an d
wash ed successively with 5% solution of sodium iodide, saturated solution of sodium sulfite,
saturated solution of sodium h ydrogen carbon ate an d water, an d dried over sodium sulfate.
Crystallization from ch loroform –m eth an ol afforded th e epoxy keton e 2a (2.5 g, 81%), m .p.
253–255 °C, [α]D +36. IR: 3 620, 1 734, 1 255. MS, m/z (%): 514 (M+, 3), 496 (2), 484 (3), 483 (3),
441 (2), 383 (25), 251 (74), 203 (36), 189 (55), 43 (100). For C32H50O5 (514.7) calculated:
74.67% C, 9.79% H; foun d: 74.86% C, 10.01% H.
Method B) By h ydrolysis of diacetate 2b: A solution of potassium h ydroxide (0.2 g, 3.6 m m ol)
in eth an ol (20 m l) was added to a solution of diacetate 2b (1.7 g, 3.1 m m ol, ref.10) in ben -
zen e (20 m l) an d th e m ixture was set aside at room tem perature for 8 h . After th e usual
work-up, the mixture of products was separated on a column of silica gel (40 g). Light petroleum–-
eth er (4 : 1) eluted successively th e startin g diacetate 2b (0.2 g, 12%) an d m on oacetate 2a
(0.9 g, 57%); ligh t petroleum –eth er (1 : 1) eluted th e diol 2c (0.3 g, 21%), m .p. 182–183 °C
(ch loroform –m eth an ol) (reported10 m .p. 182–183 °C).
Reaction of 18β,19β-Epoxy-28-h ydroxy-21-oxolupan -3β-yl Acetate (2a)
Method A) With 4-toluen esulfon ic acid: A solution of epoxy keton e 2a (120 m g, 0.23 m m ol)
an d 4-toluen esulfon ic acid m on oh ydrate (50 m g, 0.26 m m ol) in ch loroform (5 m l) was
h eated at 50 °C for 6 h . After coolin g, th e reaction m ixture was worked up as usual an d sub-
jected to preparative TLC on silica gel in ben zen e–eth er (3 : 2) wh ich afforded tosylate 5e
(110 m g, 71%), dien on e 4a (10 m g, 9%) an d tosylate 5d (8 m g, 5%).
Method B) With trifluoroacetic acid: A solution of epoxy keton e 2a (200 m g, 0.39 m m ol)
in trifluoroacetic acid (4 m l, 52 m m ol) was set aside for 12 h at room tem perature, diluted
with eth er, poured in to a solution of sodium h ydrogen carbon ate an d worked up in th e
usual m an n er. Ch rom atograph y on a colum n of silica gel (25 g) in ben zen e–eth er (5 : 1) af-
forded n ordien on e 6 (42 m g, 23%) an d dien on e 4a (115 m g, 60%).
Method C) With boron trifluoride eth erate: Boron trifluoride eth erate (0.2 m l, 1.6 m m ol)
was added to a solution of epoxy keton e 2a (100 m g, 0.19 m m ol) in ben zen e (6 m l) an d th e
reaction m ixture was set aside at room tem perature for 5 h . Meth an ol (5 m l) was added an d
th e m ixture was worked up in th e usual m an n er. Crystallization from ch loroform –m eth an ol
afforded n ordien on e 6 (82 m g, 90%).
Method D) With boric acid: Boric acid (210 m g, 3.40 m m ol) was added to a solution of ep-
oxy keton e 2a (210 m g, 0.41 m m ol) in a m ixture of an h ydrous ben zen e (10 m l) an d an h y-
drous dioxan e (10 m l) an d th e reaction m ixture was refluxed un der argon for 60 h . Th e
usual work-up an d preparative TLC on silica gel in ligh t petroleum –eth er (1 : 1) afforded
h ydroxy keton e 7 (130 m g, 66%) an d h ydroxy keton e 8 (30 m g, 15%). Perform in g th e reac-
tion un der th e sam e con dition s but with out th e in ert atm osph ere afforded th e h ydroxy
keton e 7 (10%) an d th e spirolacton e 3b (65%), m .p. 336–340 °C (ch loroform –m eth an ol),
iden tical with a sam ple obtain ed accordin g to th e literature10 (reported10 m .p. 342–346 °C).
Method E) With zin c iodide: A solution of epoxy keton e 2a (100 m g, 0.19 m m ol) an d zin c
iodide (250 m g, 0.78 m m ol) in acetic acid (10 m l) was refluxed for 4 h an d th en th e m ixture
was worked up in th e usual m an n er. Preparative TLC on silica gel in ligh t petroleum –eth er
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

338
Klinotová et al.:
(1 : 1) afforded n ordien on e 6 (26 m g, 29%), dien on e 4b (11 m g, 11%) an d th e un saturated
keton e 1b (24 m g, 23%).
Reaction of 18β,19β-Epoxy-21-oxolupan e-3β,28-diyl Diacetate (2b)
Method A) With acetic acid un der catalysis with sulfuric acid: Acetic acid (15 m l), acetic
an h ydride (0.5 m l) an d sulfuric acid (0.5 m l) were added to a solution of epoxy keton e 2b
(500 m g, 0.90 m m ol, ref.10) in ch loroform (5 m l). Th e m ixtu re was allowed to stan d for
5 days at room tem perature an d th en warm ed for 2 h at 40 °C. After coolin g an d dilution
with ch loroform , th e solution was worked up in th e usual m an n er. Crystallization from
ch loroform –m eth an ol gave triacetate 5c (380 m g, 71%).
Method B) With 4-toluen esulfon ic acid: A solution of epoxy keton e 2b (200 m g, 0.36 m m ol),
4-toluen esulfon ic acid m on oh ydrate (90 m g, 0.47 m m ol) an d a sm all am oun t of acetic an -
h ydride (0.1 m l) in ben zen e (8 m l) was refluxed for 8 h . After coolin g, th e reaction m ixture
was diluted with eth er an d worked up in th e usual m an n er. Crystallization from eth yl ace-
tate–m eth an ol gave tosylate 5f (240 m g, 94%).
Method C) With trifluoroacetic acid: A solution of epoxy keton e 2b (230 m g, 0.41 m m ol)
in a m ixture of ben zen e (4 m l) an d trifluoroacetic acid (4 m l, 52 m m ol) was refluxed for 3 h
an d th en about h alf of th e volum e was distilled off. Th e reaction m ixture was cooled, di-
luted with ben zen e an d stirred with solid sodium h ydrogen carbon ate. After th e carbon diox-
ide evolution ceased, th e solution was filtered th rough a colum n of alum in a (5 g). Th e
ben zen e eluate (80 m g) was twice extracted with boilin g eth er; th e eth er-in soluble portion
was trifluoroacetate 5g (56 m g, 21%). Eth er eluted from th e colum n a m ixture of products
wh ich were com bin ed with th e eth ereal extract from th e trifluoroacetate an d separated by
preparative TLC on silica gel in ligh t petroleum –eth er (2 : 3), affordin g dien on e 4b (35 m g,
16%), 22-h ydroxy derivative 5b (94 m g, 41%) an d a m ixture of oth er com poun ds (30 m g)
wh ich were n ot iden tified.
Method D) With zin c iodide: A solution of epoxy keton e 2b (100 m g, 0.18 m m ol) an d zin c
iodide (350 m g, 1.1 m m ol) in acetic acid (10 m l) was refluxed for 20 h an d th en th e re-
action m ixture was worked up in th e usual m an n er. Preparative TLC on silica gel in ligh t
petroleum –eth er (1 : 1) afforded th e un saturated keton e 1b (60 m g, 62%) iden tical with th e
sam ple described in th e literature11. M.p. 235–238 °C (ch loroform –h eptan e) or 150–152 °C
an d after resolidification 199–201 °C (ch loroform –m eth an ol). (Reported11 m .p. 198–201 °C
with ch an ge of m odification at 150 °C (ch loroform –m eth an ol)). Th e TLC gave furth er th e
triacetate 5c (29 m g, 27%).
Method E) With boric acid: A solution of epoxy keton e 2b (100 m g, 0.18 m m ol) in a m ix-
ture of ch loroform (4 m l) an d acetic an h ydride (4 m l) was refluxed with boric acid (100 m g,
1.6 m m ol) for 6 h an d th e m ixture was worked up in th e usual m an n er. Preparative TLC on
silica gel in ligh t petroleum –eth er (1 : 1) afforded triacetate 5c (26 m g, 24%) an d spiro-
lacton e 3b (58 m g, 61%). Usin g con dition s described for th e reaction of th e epoxy keton e
2a un der m eth od D), n o reaction of epoxy keton e 2b with boric acid was observed.
Method F) With sulfuric acid in dioxan e: Sulfuric acid (0.1 m l) was added to a solution of
epoxy keton e 2b (100 m g, 0.18 m m ol) in a m ixture of dioxan e (5 m l) an d water (1 m l) an d
th e m ixture was refluxed for 4 h . After th e usual work-up, th e product m ixture was sub-
jected to preparative TLC on silica gel in ligh t petroleum –aceton e (5 : 2) to give spirolacton e
3a (40 m g, 46%), m .p. 353–358 °C (reported10 m .p. 356–361 °C) an d epoxy keton e 2c (15 m g,
18%), m .p. 184–186 °C (reported10 m .p. 182–183 °C). Wh en th e reaction was perform ed in
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
339
an argon atm osph ere an d with dioxan e fresh ly distilled from lith ium alum in ium h ydride,
but un der oth erwise th e sam e con dition s, a com plex m ixture of un iden tified products was
obtain ed.
28-Hydroxy-21-oxolupa-12,18-dien -3β-yl Acetate (4a)
Th e com poun d was obtain ed in th e reaction s of epoxy keton e 2a described un der A) an d B).
M.p. 238–239 °C (eth er–h eptan e), [α]D +331. IR: 3 620, 1 723, 1 686, 1 648, 1 605, 1 254. UV
(m eth an ol): λm ax, n m (log ε): 277 (4.15). MS, m/z (%): 496 (M+, 43), 481 (56), 436 (4), 421 (8),
233 (100), 215 (21), 189 (15), 43 (64). For C32H48O4 (496.7) calculated: 77.37% C, 9.74% H;
foun d: 77.52% C, 9.60% H.
21-Oxolupa-12,18-dien e-3β,28-diyl Diacetate (4b)
Th e com poun d was obtain ed in th e reaction s of epoxy keton e 2a, described un der E), an d of
epoxy keton e 2b, described un der C), an d also by acetylation of dien on e 4a. M.p. 191–192 °C
(ch loroform –h eptan e), [α]D +349. IR: 1 725, 1 689, 1 648, 1 606, 1 253. MS, m/z (%): 538
(M+, 4), 523 (3), 478 (1), 463 (1), 435 (1), 275 (58), 215 (18), 189 (16), 43 (100). For
C34H50O5 (538.7) calculated: 75.80% C, 9.36% H; foun d: 75.62% C, 9.45% H.
22β,28-Dih ydroxy-21-oxolup-18-en -3β-yl Acetate (5a)
Method A) By h ydrolysis of triacetate 5c: A solution of triacetate 5c (50 m g, 0.08 m m ol)
an d potassium h ydroxide (9.5 m g, 0.17 m m ol) in a m ixture of ben zen e (2 m l) an d eth an ol
(1.8 m l) was set aside for 15 m in at room tem perature an d was worked up in th e usual m an n er.
Purification by TLC on silica gel in ch loroform –eth yl acetate (1 : 1) afforded diol 5a (33 m g,
77%), m .p. 205–215 °C (decom p.)(eth er). IR: 3 536, 1 720, 1 702, 1 589, 1 255. MS, m/z (%):
514 (M+, 2), 496 (0.5), 484 (2), 466 (0.5), 406 (0.2), 264 (63), 251 (48), 189 (11), 43 (100).
For C32H50O5 (514.7) calculated: 74.67% C, 9.79% H; foun d: 74.82% C, 9.55% H.
Method B) By h ydrolysis of diacetate 5b: A solution of potassium h ydroxide (3.2 m g,
0.06 m m ol) in eth an ol (0.5 m l) was added to a solution of diacetate 5b (30 m g, 0.05 m m ol)
in ben zen e (0.5 m l). After stan din g for 5 m in at room tem perature, th e reaction m ixture was
worked up as usual an d purified as described un der A) to give diol 5a (16 m g, 58%).
22β-Hydroxy-21-oxolup-18-en e-3β,28-diyl Diacetate (5b)
Th e com poun d was obtain ed in th e reaction of epoxy keton e 2b described un der C). M.p.
213–214 °C (eth er–h eptan e), [α]D +12. IR: 3 552, 3 413, 1 728, 1 709, 1 593, 1 255. MS, m/z
(%): 556 (M+, 2), 496 (2.5), 453 (0.6), 293 (36), 189 (18), 43 (100). For C34H52O6 (556.8) cal-
culated: 73.34% C, 9.41% H; foun d: 73.36% C, 9.57% H.
21-Oxolup-18-en e-3β,22β,28-triyl Triacetate (5c)
Th e com poun d was obtain ed in th e reaction s of epoxy keton e 2b described un der A), D) an d
E), an d also by acetylation of com poun ds 5a an d 5b. M.p. 291–293 °C, [α]D +3. IR: 1 737,
1 720, 1 598, 1 254. UV (m eth an ol): λm ax, n m (log ε): 244 (4.15). MS, m/z (%): 598 (M+, 3),
538 (1), 495 (2), 335 (62), 293 (26), 189 (25), 43 (100). For C36H54O7 (598.8) calculated:
72.21% C, 9.09% H; foun d: 72.37% C, 8.87% H.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

340
Klinotová et al.:
3β,28-Dih ydroxy-21-oxolup-18-en -22β-yl 4-Toluen esulfon ate (5d )
Sulfuric acid (0.3 m l) was added to a solution of tosylate 5f (100 m g, 0.14 m m ol) in ch loro-
form (1 m l) an d m eth an ol (2 m l) an d th e m ixture was refluxed for 2 h . Th e usual work-up
followed by purification by TLC on silica gel in ch loroform –eth yl acetate (1 : 1) afforded
tosylate 5d (75 m g, 85%), m .p. 138–141 °C (eth er–h eptan e), [α]D –44. IR: 3 614, 1 716,
1 598, 1 023, 871. MS, m/z (%): 626 (M+, 2), 456 (9), 454 (7), 424 (100), 405 (27), 190 (35),
189 (28), 91 (42). For C37H54O6S (626.9) calculated: 70.89% C, 8.68% H; foun d: 70.56% C,
8.81% H.
Th e tosylate 5d was also obtain ed in th e reaction of epoxy keton e 2a described un der A).
28-Hydroxy-21-oxolup-18-en e-3β,22β-diyl 3-Acetate 22-(4-Toluen esulfon ate) (5e)
Th e com poun d was obtain ed in th e reaction of epoxy keton e 2a described un der A). M.p.
188–190 °C (ch loroform –h eptan e), [α]D –27. IR: 3 607, 1 716, 1 598, 1 255. MS, m/z (%): 668
(M+, 0.2), 498 (1), 496 (2), 466 (67), 405 (27), 235 (17), 217 (46), 203 (53), 204 (53), 190
(89), 43 (100). For C39H56O7S (668.9) calculated: 70.02% C, 8.44% H; foun d: 70.13% C,
8.61% H.
21-Oxolup-18-en e-3β,22β,28-triyl 3,28-Diacetate 22-(4-Toluen esulfon ate) (5f)
Th e com poun d was obtain ed in th e reaction of epoxy keton e 2b described un der B), an d
also by acetylation of com poun ds 5d an d 5e. M.p. 128–130 °C (eth yl acetate–m eth an ol),
204–207 °C (ch loroform –h eptan e), [α]D +8. IR: 1 728, 1 715, 1 256, 1 177, 874. MS, m/z (%):
710 (M+, 10), 650 (10), 607 (3), 538 (5), 496 (2), 484 (12), 465 (10), 447 (100), 433 (10), 405
(14), 277 (53), 189 (32). For C41H58O8S (710.9) calculated: 69.26% C, 8.22% H; foun d:
69.35% C, 8.40% H.
21-Oxolup-18-en e-3β,22β,28-triyl 3,28-Diacetate 22-Trifluoroacetate (5g)
Th e com poun d was obtain ed by reaction of epoxy keton e 2b as described un der C). M.p.
243–248 °C, [α]D –14. IR: 1 791, 1 720, 1 593, 1 254. MS, m/z (%): 652 (M+, 0.4), 592 (1), 549
(1), 478 (1), 389 (13), 375 (1), 189 (22), 43 (100). Th e trifluoroacetate 5g was con verted in to
th e 22-h ydroxy derivative 5b on stirrin g its eth ereal solution with an aqueous solution of
sodium h ydrogen carbon ate or on ch rom atograph y on silica gel or on stan din g of its ch loro-
form solution after NMR m easurem en ts.
21-Oxo-28-n orlupa-16,18-dien -3β-yl Acetate (6)
Th e com poun d was obtain ed in th e reaction s of epoxy keton e 2a described un der B), C) an d E).
M.p. 280–282 °C (ch loroform –m eth an ol), [α]D +28. IR: 1 720, 1 687, 1 561, 1 254. UV (m eth -
an ol): λm ax, n m (log ε): 218 (3.94), 290 (4.12). MS, m/z (%): 466 (M+, 9), 406 (2), 391 (4),
363 (2), 203 (82), 189 (28), 43 (100). For C31H46O3 (466.7) calculated: 79.78% C, 9.94% H;
foun d: 80.01% C, 10.06% H.
Nordien on e 6 was also obtain ed as th e sole product by reaction of h ydroxy keton es 7 an d 8
with 0.5% solution of 4-toluen esulfon ic acid in ch loroform for 4 days at room tem perature.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
341
TABLE I
Proton NMR data of com poun ds 1a, 2a, 4b, 5f an d 5g. Ch em ical sh ift values m arked with
tilde (~) were obtain ed from 2D spectra
Ch em ical sh ifts/Coupling constants
Proton
1a
2aa
4bb
5fc
5g
1α
1β
3α
1.06 td
~13;13;5
1.03 td
~13;13;5
~1.14
1.03 td
~13;13;5
1.05 td
12.5;12.5;4.9
d
d
1.76 dt
13.1;3.7;3.7
~1.72
1.73 dt
13.2;3.5;3.5
4.49 dd
4.47 dd
4.51 dd
4.48 dd
4.49 dd
11.0;5.5
11.0;5.5
11.0;5.5
10.7;5.7
10.9;5.6
d
5α
0.82 m
0.80 m
0.82 m
0.83 m
13β
2.78 dd
2.62 dd
–
2.90 dd
2.90 dd
12.5;3.4
~12;4
12.6;3.1
12.6;3.3
20
3.19 septet
2.06 septet
2.79 septet
3.19 septet
3.24 septet
6.9
6.9
7.0
6.9
6.9
22a
22b
1.92 d
18.6
1.71 d
18.6
2.02 d
18.4
4.57 s
–
5.06 s
–
2.44 d
2.61 d
2.42 d
18.6
18.6
18.4
23
24
25
26
27
28a
0.857 s
0.849 s
0.926 s
1.134 s
0.947 s
0.850 s
0.843 s
0.899 s
1.108 s
1.078 s
0.879 s
0.884 s
1.024 se
1.069 se
1.012 se
0.858 s
0.847 s
0.917 s
1.122 s
0.946 s
0.862 s
0.852 s
0.927 s
1.131 s
0.990 s
3.67 d
3.73 d
3.91 d
4.00 d
4.08 d
10.7
10.7
11.0
11.3
11.5
28b
29
3.72 d
10.7
4.03 d
10.7
4.10 d
11.0
4.62 d
11.3
4.39 d
11.5
1.214 d
1.287 d
1.200 d
1.140 d
1.192 d
6.9
6.9
7.0
6.9
7.0
30
1.194 d
1.210 d
1.159 d
1.128 d
1.192 d
6.9
6.9
7.0
6.9
7.0
3β-OAc
2.052 s
2.046 s
2.056 s
2.006 s
2.055 s
1.869 s
2.061 s
1.930 s
28-OAc
–
–
a
b
H-2α, H-2β: 1.62–1.70; H-6a: ~1.38; H-6b: ~1.54. H-2α, H-2β: 1.60–1.70; H-11α, H-11β:
c
~2.05; H-12: 5.57 bt, J = 3.9, 3.9; H-15a: ~1.22; H-16α: ~1.54; H-16β: ~2.00. OTos: 2.45 s
(CH3); 7.36 d, J = 8.2 (H-3′, H-5′); 7.90 d, J = 8.2 (H-2′, H-6′). Sign al was n ot iden tified.
d
e
Sign als m ay be m utually in terch an ged.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

342
Klinotová et al.:
TABLE II
Proton NMR data of com poun ds 5a–5e. Ch em ical sh ift values m arked with tilde (~) were ob-
tain ed from 2D spectra
Ch em ical sh ifts/Coupling constants
Proton
5a
5ba
5c
5d b
5eb
1α
1β
1.05 td
~1.04
~1.77
1.05 td
~13;13;5
~1.75
~0.96
~1.74
1.04 td
12.8;12.8;5.0
~1.73
~12.5;12.5;5.4
1.75 dt
~13.0;3.5;3.5
1.60–1.68
4.49 dd
10.7;5.8
0.82 m
~1.42
2α,2β
3α
1.60–1.68
4.49 dd
10.7;5.7
1.62–1.70
4.49 dd
11.0;5.5
0.82 m
~1.36
1.58–1.68
3.21 dd
11.3;5.2
~0.70
~1.34
~1.54
1.60–1.66
4.48 dd
10.8;5.6
0.81 m
~1.36
5α
6a
6b
7a
0.82 m
c
c
c
c
~1.52
~1.36
~1.54
~1.38
~1.54
~1.36
~1.35
7b
~1.50
~1.50
~1.49
~1.50
9α
~1.35
~1.30
~1.34
~1.28
~1.31
c
11a
11b
12α
12β
13β
~1.28
~1.62
~1.84
2.03 m
2.78 dd
12.8;3.1
~1.27
~1.85
~1.50
2.21 dt
13.7;3.8;3.8
3.22 septet
6.9
~1.32
~1.62
~1.84
2.03 m
2.87 dd
12.7;3.5
~1.28
~1.76
~1.77
~1.28
~1.54
~1.83
2.05 m
2.85 dd
12.8;3.4
~1.26
~1.76
~1.57
1.98 dt
13.7;3.8;3.8
3.22 septet
7.0
~1.30
~1.62
~1.84
2.05 m
2.85 dd
12.6;3.0
~1.26
~1.76
~1.58
1.99 dt
13.6;3.8;3.8
3.22 septet
7.0
~1.58
~1.80
1.99 m
2.92 bdd
12.8;3.5
~1.28
~1.77
~1.66
~1.92
15α
15β
16α
16β
~1.86
20
3.20 septet
6.9
3.22 septet
6.9
22α
3.69 s
3.70 bd
4.8
4.98 s
4.52 s
4.52 s
23
24
25
26
27
28a
0.859 s
0.849 s
0.918 s
1.108 s
0.957 s
3.62 d
11.0
0.861 s
0.850 s
0.925 s
1.135 s
0.953 s
3.97 d
10.7
0.859 s
0.848 s
0.922 s
1.120 s
0.974 s
4.02 d
11.3
0.971 s
0.765 s
0.882 s
1.090 s
0.955 s
3.81 d
12.0
0.857 s
0.847 s
0.915 s
1.098 s
0.955 s
3.81 d
11.8
28b
29
3.82 d
11.0
1.208 d
6.9
4.68 d
10.7
1.185 d
6.9
4.35 d
11.3
1.198 d
6.8
3.83 d
12.0
1.172 d
6.8
3.83 d
11.8
1.175 d
7.0
30
1.178 d
6.9
1.181 d
6.9
1.189 d
6.8
1.118 d
6.8
1.131 d
7.0
3β-OAc
22β-OAc
28-OAc
2.057 s
–
–
2.056 s
–
1.884 s
2.056 s
2.169 s
1.933 s
–
–
–
2.051 s
–
–
a
b
OH: 2.66 d, J = 4.8. OTos: 2.45 s (CH3); 7.36 d, J = 8.2 (H-3′, H-5′); 7.91 d, J = 8.2 (H-2′,
c
H-6′). Sign al was n ot iden tified.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
343
TABLE III
Proton NMR data of com poun ds 6–10. Ch em ical sh ift values m arked with tilde (~) were ob-
tain ed from 2D spectra
Ch em ical sh ifts/Coupling constants
Proton
6a
7b
8
9
10c
d
1α
1β
3α
1.07 td
~13;13;5
1.74 dt
13.2;3.6;3.6
4.50 dd
11.2;5.2
0.84 m
2.92 dd
12.4;4.2
1.85 dd
17.8;6.4
2.41 bd
17.8
1.03 td
~13;13;6
1.74 dt
13.1;3.6;3.6
4.50 dd
10.6;5.8
0.84 m
1.05 td
~12;12;4.6
d
1.07 td
~13.5;13.5;5.5
~1.75
d
4.49 dd
10.6;5.7
d
4.49 dd
11.2;5.3
0.83 m
4.50 dd
11.0;5.5
0.82 m
3.13 dd
5α
13β
2.59 bm
3.18 dd
12.5;3.7
d
2.78 dd
12.8;3.1
0.94 dt
14.0;8.2;8.2
2.01 dt
14.0;5.3;5.3
2.46 bdd
8.2;5.3
2.46 bdd
8.2;5.3
3.22 septet
6.8
12.4;3.6
d
15α
15β
16α
16β
20
~1.46
d
d
d
d
d
~1.62
5.69 m
6.2;2.6;1.2;1.2
–
2.20 bm
1.99 bdd
~18.2;6.0
2.22 septet
~7.0
d
3.18 septet
7.0
3.13 septet
6.9
3.37 septet
7.0
22a
22b
2.78 bs
2.54 dd
~21;3.7
2.89 bdd
~21;4
2.37 d
18.7
2.40 d
18.7
5.90 t
~1.2;1.2
–
–
2.78 bs
–
23
24
25
26
27
29
0.870 s
0.860 s
0.919 de
1.075 s
0.948 s
1.248 d
7.0
0.863 s
0.852 s
0.887 s
1.032 sf
1.004 sf
0.982 d
6.7
0.860 s
0.851 s
0.911 sf
1.163 s
0.932 sf
1.206 d
6.9
0.863 s
0.863 s
0.863 s
1.076 s
0.896 s
1.243 d
6.8
0.864 s
0.857 s
0.972 sf
1.182 s
0.946 sf
1.267 df
7.0
30
1.206 d
7.0
0.883 d
7.2
1.187 d
6.9
1.227 d
6.8
1.244 d
7.0
3β-OAc
2.050 s
2.055 s
2.056 s
2.057 s
2.059 s
a
b
H-2α, H-2β: 1.60–1.70; H-6a: ~1.42; H-6b: ~1.56; H-12α: ~1.65; H-12β: 2.46 m .
H-2α,
H-2β: 1.60–1.70; H-6a: ~1.42; H-6b: ~1.55; H-7a: ~1.40; H-7b: ~1.51; H-9: ~1.43; H-11a:
c
~1.31; H-11b: ~1.54; H-12α: ~1.32; H-12β: 2.11bm ; OH: 2.67 bs. H-2α, H-2β: 1.62–1.67;
d
H-6a: ~1.38; H-6b: ~1.55; H-28a: 4.03 d, J = 11.0; H-28b: 4.85 d, J = 11.0; 28-OAc: 1.915 s. Signal
e
f
was n ot iden tified. J = 0.8. Sign als m ay be m utually in terch an ged.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

344
Klinotová et al.:
TABLE IV
13C ch em ical sh ifts of com poun ds 1a, 2a, 4b, 6, 7, 9 an d 10
Carbon
1a
2a
4b
6
7
9
10
1
2
38.53
23.59
80.72
37.76
55.37
18.09
34.78
41.39
50.93
37.10
21.23
27.79a
42.43
45.67
27.35a
32.24
47.27
172.98
146.95
25.21
208.49
47.38
27.90
16.51
16.86
16.76
15.90
65.85
20.64
20.17
38.50
23.55
80.70
37.76
55.45
18.05
34.10
41.19
51.24
37.14
21.25
29.71
37.79
42.23
23.58a
26.47a
43.33
79.39b
72.16b
26.34
210.49
43.54
27.92
16.48
16.76c
16.68c
16.35c
64.27
18.32
17.45
38.65
23.57
80.64
37.73
55.43
18.11
34.17
38.96
47.24
36.87
23.39
127.72
136.11
44.95a
26.28
30.81
45.18a
169.57
145.58
25.32
206.98
47.24
28.09
16.12b
16.80b
20.89c
17.68c
66.56
22.93c
20.07c
38.37
23.59
80.74
37.76
55.28
18.02
34.25
40.45
49.71
36.96
20.59
25.85
40.83
43.17
32.75
121.66
134.20
164.23
147.03
26.25
206.42
38.91
27.91
16.52
16.38a
17.10a
15.79a
–
38.52
23.65
80.82
37.81
55.65
18.12
33.91
40.44a
51.00
37.14
21.20
25.03
38.67
40.63a
27.99
24.60
134.04
139.89
85.84
35.12
216.96
45.09
27.87
16.46
16.58
14.34
15.68
–
38.36
23.60
80.64
37.77
55.56
17.91
33.98
41.64a
51.06
37.02
21.60
27.37
38.36
41.80a
30.40
29.85
115.68
161.54
165.20
29.75
163.05
108.44
27.84
16.48b
16.45b
19.91
15.74
–
38.59
23.59
80.63
37.78
55.40
18.09
34.62
41.62
50.92
37.16
21.16
27.92a
43.57
45.69
27.23a
26.49a
49.58
170.17
152.36
25.87
189.41b
200.90b
27.92
16.53
16.87c
16.93c
16.03
64.17
20.30
19.65
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
3β-OAc
20.81
20.07
15.31
17.97
20.83
20.83
21.32
21.30
21.30
21.28
21.32
21.29
21.31
171.05
171.01
170.97
171.02
171.03
170.99
171.04
28-OAc
–
–
–
–
20.73
170.82
–
–
–
–
–
–
20.37
171.00
a, b, c
Sign als with iden tical sym bols m ay be in terch an ged.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
345
TABLE V
13C ch em ical sh ifts of 22β-substituted derivatives 5a–5g
Carbon
5a
5b
5c
5d a
5ea
5fb
5gc
1
2
3
4
5
6
7
8
9
38.55
23.59
80.73
37.76
55.42
18.06
34.47
41.27
50.94
37.08
21.15
27.75
43.13
45.03
27.35
29.96
51.09
170.48
144.22
25.36
208.24
82.15
27.87
16.50d
16.86
16.66
16.52d
64.62
21.39
19.70
21.30
171.07
–
38.60
23.62
80.72
37.79
55.48
18.08
34.51
41.25
51.01
37.13
21.24
27.66
43.03
44.56
27.84
30.51
49.79
166.37
144.38
25.47
207.20
81.69
27.90
16.52
16.87
16.80
16.70
63.47
21.56
19.48
21.31
171.01
–
38.56
23.60
80.69
37.77
55.43
18.04
34.53
41.26
50.92
37.10
21.20
27.79
42.99
44.78
27.66
30.72
48.66
166.76
145.38
25.53
201.43
80.08
27.89
16.52d
16.87
16.78
16.56d
62.88
21.24
19.43
21.31
171.02
20.74
170.75
20.63
170.48
38.87
27.26
78.83
38.82
55.34
18.14
34.60
41.27
50.98
37.15
21.08
27.86
43.21
44.90
27.53
30.04
50.54
169.19
145.36
25.50
199.26
85.93
27.91
15.37
16.78d
16.72d
16.68d
63.07
21.04
19.61
–
38.56
23.58
80.69
37.76
55.43
18.04
34.52
41.29
50.90
37.08
21.11
27.79
43.16
44.89
27.51
30.01
50.53
169.03
145.38
25.49
199.21
85.94
27.87
16.49
16.84
16.70d
16.62d
63.00
21.05
19.61
21.27
171.01
–
38.50
23.54
80.62
37.71
55.38
17.97
34.56
41.20
50.86
37.03
21.11
27.70
43.12
44.57
27.56
29.97
48.65
166.80
145.01
25.40
198.39
85.06
27.84
16.46
16.81
16.75d
16.62d
62.47
21.05
19.33
21.27
170.97
–
38.55
23.57
80.69
37.76
55.42
18.02
34.48
41.29
50.87
37.09
21.14
27.67
43.10
44.81
27.50
30.60
48.46
167.42
145.45
25.53
198.35
82.53
27.87
16.50
16.85
16.75d
16.61d
62.66
21.16
19.37
21.30
171.11
–
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
3β-OAc
–
–
–
–
22β-OAc
–
–
–
–
–
–
–
–
–
28-OAc
20.57
170.25
20.53
170.34
20.33
170.29
–
a
b
OTos: 21.71 (CH3), 133.10 (C-1′), 128.13 (C-2′, C-6′), 129.84 (C-3′, C-5′), 145.15 (C-4′). OTos:
21.67 (CH3), 133.31 (C-1′), 128.01 (C-2′, C-6′), 129.70 (C-3′, C-5′), 144.87 (C-4′). c OCOCF3:
157.24 J(C,F) = 46 (CO), sign al CF3 was n ot foun d. Sign als m ay be m utually in terch an ged.
d
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

346
Klinotová et al.:
19β-Hydroxy-21-oxo-28-n orlup-17-en -3β-yl Acetate (7)
Th e com poun d was obtain ed in th e reaction of epoxy keton e 2a described un der D). M.p.
217–220 °C (decom p.) (ch loroform –h eptan e), [α]D +31. IR: 3 562, 1 745, 1 718, 1 651, 1 255.
MS, m/z (%): 484 (M+, 5), 466 (8), 456 (4), 441 (95), 203 (38), 43 (100). For C31H48O4 (484.7)
calculated: 76.81% C, 9.98% H; foun d: 76.53% C, 10.11% H.
17ξ-Hydroxy-21-oxo-28-n orlup-18-en -3β-yl Acetate (8)
Th e com poun d was obtain ed in th e reaction of epoxy keton e 2a described un der D). M.p.
218–220 °C (decom p.) (m eth an ol). IR: 3 599, 1 720, 1 697, 1 610, 1 254. MS, m/z (%): 484
(M+,14), 466 (12), 424 (9), 406 (9), 391 (8), 221 (18), 203 (20), 189 (35), 43 (100).
3β-Acetoxy-19,21-seco-28-n orlupa-17(22),18-dien -21,19-olide (9)
Hydroxy keton e 7 (90 m g, 0.19 m m ol) an d lead tetraacetate (270 m g, 0.61 m m ol) were dis-
solved in a m ixture of an h ydrous ben zen e (3 m l), acetic acid (3 m l) an d acetic an h ydride
(0.5 m l) an d th e solution was refluxed for 7 h . After th e usual work-up, th e product was sub-
jected to preparative TLC in ligh t petroleum –eth er (2 : 3) wh ich afforded th e startin g
h ydroxy keton e 7 (25 m g, 28%) an d dien olide 9 (60 m g, 67%), m .p. 232–235 °C (ch loro-
form –h eptan e), [α]D –26. UV (cycloh exan e):λm ax, n m (log ε): 303 (3.75). IR: 1 732 sh , 1 705,
1 632, 1 556, 1 522, 1 248. MS, m/z (%): 482 (M+, 11), 454 (3), 439 (2), 407 (2), 379 (1), 219
(21), 203 (32), 191 (50), 43 (100). For C31H46O4 (482.7) calculated: 77.13% C, 9.61% H;
foun d: 76.96% C, 9.80% H.
21,22-Dioxolup-18-en e-3β,28-diyl Diacetate (10)
A solution of h ydroxy keton e 5b (60 m g, 0.11 m m ol) in ch loroform (2 m l) was adsorbed on
alum in a (1 g) with ch rom ium trioxide (40 m g, 0.40 m m ol). After stan din g for 24 h at room
tem perature, th e product was eluted with a ch loroform –m eth an ol m ixture. Th e solven ts were
evaporated, th e residue was dissolved in ch loroform an d th e solution was filtered through a
layer of silica gel to give diketone 10 (49 mg, 82%), m.p. 269–271 °C (chloroform–m eth an ol), [α]D
–135. IR: 1 761, 1 731, 1 710, 1 575, 1 258. UV (cycloh exan e): λm ax, n m (log ε): 199 (4.0),
288 (3.71). MS, m/z (%): 554 (M+, 5), 484 (28), 424 (3), 409 (2), 381 (3), 220 (6), 203 (7), 190 (18),
189 (14), 43 (100). For C34H50O6 (554.7) calculated: 73.61% C, 9.09% H; foun d: 73.39% C,
9.05% H.
The authors are indebted to the Grant Agency of the Charles University for the financial support
(grant No. 210/1996), to Dr S. Hilgard for measurements of IR and UV spectra and to Dr M. Štícha
for the mass spectral measurements.
REFERENCES
1. Sejbal J., Klinot J., Buděšínský M., Protiva J.: Collect. Czech. Chem. Commun. 1997, 62,
1905.
2. Suokas E., Hase T.: Acta Chem. Scand., Ser. B 1977, 31, 182.
3. Suokas E., Hase T.: Acta Chem. Scand., Ser. B 1977, 31, 231.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)

Triterpenes
347
4. Suokas E., Hase T.: Acta Chem. Scand., Ser. B 1977, 31, 633.
5. Suokas E., Hase T.: Acta Chem. Scand., Ser. B 1971, 25, 2359.
6. Denisenko M. V., Odinokova L. E., Uvarova N. I.: Khim. Prir. Soedin. 1989, 655.
7. Odinokova L. E., Denisenko M. V., Denisenko V. A., Uvarova N. I.: Khim. Prir. Soedin.
1992, 210.
8. Denisenko M. V., Odinokova L. E., Denisenko V. A., Uvarova N. I.: Zh. Org. Khim. 1991,
27, 2174.
9. Denisenko M. V., Odinokova L. E., Denisenko V. A., Uvarova N. I.: Khim. Prir. Soedin.
1991, 430.
10. Klinotová E., Rejzek M., Zůnová H., Sejbal J., Klinot J., Urban J.: Collect. Czech. Chem.
Commun. 1993, 58, 2505.
11. Sejbal J., Klinot J., Buděšínský M., Protiva J.: Collect. Czech. Chem. Commun. 1991, 56,
2936.
Collect. Czech. Chem. Commun. (Vol. 64) (1999)