Peculiar side-chain fission of steroidal glycosides

Article abstract of DOI:10.1016/S0040-4039(03)00689-0

The characteristic novel steroidal glycosides of the 23,26-oxygenated spirostanol-type and 16,22-dicarbonyl cholestanol-type obtained in our laboratory underwent the peculiar reactions of side-chain fission between C-22 and C-23 of the steroidal skeleton

Full text of DOI:10.1016/S0040-4039(03)00689-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3509–3511
Peculiar side-chain fission of steroidal glycosides
a
b
c
Alaa Mohamed Nafady, Mohamed Ahmed El-Shanawany, Mahmoud Hamed Mohamed,
b
a
a
a
Hashim Abdel-Halim Hassanean, Xing-Hua Zhu, Tsutomu Yoshihara, Masafumi Okawa,
a
a,
Tsuyoshi Ikeda and Toshihiro Nohara *
a
Faculty of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan
b
Faculty of Pharmacy, Assiut University, Assiut, Egypt
c
Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
Received 23 January 2003; revised 27 February 2003; accepted 7 March 2003
Abstract—The characteristic novel steroidal glycosides of the 23,26-oxygenated spirostanol-type and 16,22-dicarbonyl cholestanol-
type obtained in our laboratory underwent the peculiar reactions of side-chain fission between C-22 and C-23 of the steroidal
skeleton by acid or alkaline hydrolysis. These reactions would be applied to the structural determination of these sorts of
glycosides and suggest the biogenetic pathway of the occurrence of C-22 lactone-type glycosides. © 2003 Elsevier Science Ltd. All
rights reserved.
Our recent study on the constituents of the fruits of
Solanum anguivi Lam. has resulted in the isolation and
structural characterization of characteristic steroidal
glycosides such as 23,26-oxygenated spirostane-type:
J=7.3 Hz, l 1.32), H-3 (m, l 3.52) and H-6 (br s, l
1
5.31) in the H NMR spectrum (pyridine-d ). A total of
5
13
22 C NMR signals (pyridine-d ) was assigned by the
5
1
1
aid of H– H COSY, HMQC, and HMBC as follows:
signals due to l 37.3, 31.6, 71.7, 38.3, 141.0, 121.0, 31.9,
31.3, 50.2, 36.6, 20.4, 39.9, 41.5, 54.9, 33.2, 82.7, 59.0,
13.8, 19.4, 36.1, 18.0, 181.3 were assigned to C-1–22,
respectively. Consequently, the structure of 4 was char-
acterized as 3b,16b-dihydroxypregna-5-ene-20-car-
boxylic acid 22,16-lactone identical with vespertilin
e.g. 3-O-[a-
L
-rhamnopyranosyl-(1“4)]-a-
-glucopyranosyl (b-chacotriosyl)
22R,23S,25R,26R) - 3b,23,26 - trihydroxyspirost - 5 - ene
L-rhamnopy-
ranosyl-(1“2)-b-
D
(
(
1
anguivioside I, 1), 22,26-oxygenated furostane-type:
3
-O-b-chacotriosyl
23,26-epoxy-3b,22,26-trihydroxy-
2
furost-5-ene (anguivioside II, 2), and 16,22-dicarbonyl
cholestane-type: 3-O-b-chacotriosyl (23S,25R,26S)-
4
5
obtained from S. vespertilio, as shown in Chart 1.
This sapogenol was also derived from anguivioside II
(
2
3,26-epoxy-3b,26-dihydroxycholest-5-en-16,22-dione
3
(
anguivioside B, 3). On the way to their structural
2
6
2) by the same reaction. The mechanism for produc-
4
determination, we found that a peculiar side-chain
fission took place between C-22 and C-23 of their
steroidal glycosides by simple acid or alkaline treat-
ment. This paper deals with their novel reactions.
tion of this lactone sapogenol (4), was speculated as
illustrated in Chart 1. As the first step, 1 was plausibly
conceivable that 1 was transformed into 2, which subse-
quently underwent a bond–bond fission between C-22
and C-23 to afford 4. Many lactone-type sapogenols
Anguivioside I (1) was subjected to acid hydrolysis
4,7
and glycosides obtained from S. vespertilio,
S.
(
refluxed with 1N HCl–MeOH for 1 h) to provide a
8
2
9
hispidum, S. nodiflorum, S. nigrum, tomato stock
12
major sapogenol (4) in a yield of 65%. It showed a
molecular ion peak at m/z 344 corresponding to
C H O in the EI-MS and signals due to steroidal
10
11
root, Asparagus dumosus and Cestrum nocturnum
are already known; however, their biogenesis remained
unclarified. They might be biosynthetically derived
from the genuine glycosides of 23,26-oxygenated
spirostane- or furostane-type such as 1 or 2 through
Chart 1 in the plant body.
22
32
3
CH -18 (s, l 0.77), CH -19 (s, l 1.03), CH -21 (d,
3
3
3
Keywords: steroidal glycoside; 23,26-oxygenated spirostanol; 16,22-
dicarbonyl cholestanol; side-chain fission.
Anguivioside B (3) was treated with alkaline (refluxed
with 3% KOH–MeOH for 30 min) to provide a gly-
coside (5) in 73% yield. It showed a quasimolecular ion
*
Corresponding author. Tel.: +81-96-371-4380; fax: +81-96-362-7799;
e-mail: none@gpo.kumamoto-u.ac.jp
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00689-0

3
510
A. M. Nafady et al. / Tetrahedron Letters 44 (2003) 3509–3511
Chart 1. Plausible mechanism for formation of 4.
+
peak at m/z 815 [M+H] in the positive FABMS. The
for 5, as shown in Chart 2, i.e. 3-O-b-chacotriosyl
20-carboxypregna-5-ene-16-one. Production of 5 was
1
H NMR spectrum (pyridine-d ) of 5 exhibited the
signals due to CH -18 (3H, s, l 0.72), CH -19 (3H, s,
5
1
3
estimated as shown in the process of Chart 2.
3
3
l 1.02), CH -21 (3H, d, J=6.7 Hz, l 1.42), H-3 (1H,
m, l 3.83) and H-6 (1H, br d, l 5.31) together with
three anomeric protons (1H, d, J=7.3 Hz, l 5.19,
3
The reactions of both 1, 2 and 3 provided C-22
steroids by fission between C-22 and C-23 on the
spirostane, furostane and cholestane skeletons in good
yield by simple acid or alkaline treatment. These reac-
tions would occur when there is a carbonyl or acetal
at C-22, an oxygenated function (hydroxyl or epox-
ide) at C-23, and a hemiacetal at C-26. These reac-
tions themselves are not only of interest in respect to
facile CꢀC cleavage but also are applicable to the
structural determination for these sorts of steroidal
glycosides, and they strongly suggest the biogenetic
pathway for the occurrence of the lactone-type gly-
cosides of 3, the biogenesis of which has so far
remained as an unsolved problem.
1
H, s, rhamnosyl H-1, l 6.35 and 1H, s, rhamnosyl
13
H-1, l 6.35). Signals due to the C NMR signals
pyridine-d ) of 5 displayed a total of 40 carbons,
(
5
composed of seven methylenes (l 20.8, 30.0, 32.0,
3
5
7.2, 37.9, 38.9, 39.0), four methines (l 38.7, 50.1,
0.9, 65.4), two quaternary carbons (l 37.1, 41.9),
two olefinic carbons (l 121.5, 140.9), one oxygen-
bearing carbon (l 78.0), one carbonyl carbon (l
216.8) and one carboxyl carbon (l 178.3) together
with those of a b-chacotriosyl moiety. Assignments of
1
3
the C NMR signals with the aid of the HMBC
spectrum led to the characterization of the structure
Chart 2. Plausible mechanism for formation of 5.

A. M. Nafady et al. / Tetrahedron Letters 44 (2003) 3509–3511
3511
Acknowledgements
4. Gonzalez, A. G.; Francisco, C. G.; Barreira R. F.; Lopez,
E. S. Ann. Quim. 1971, 67, 433; Chem. Abstr. 1971, 75,
1
15890n.
5. The analogue having a 3-O-[a-
2)]-b- -xylopyranosyl-(1“3)-b-
(sugar A) of 1 provided the identical lactone sapogenol
with 4 in yield of 62% by the same reaction.
6. The analogous glycoside carrying the sugar A with 2 also
gave 4 in 61% yield by the same reaction.
We are grateful to Dr. Tatemi Yoshida, National
Research Institute of Vegetables, Ornamental Plants
and Tea, Ministry of Agriculture, Forestry and Fish-
eries, Ano, Mie, Japan, for supplying the seeds of the
plants.
L
-rhamnopyranosyl-(1“
D
D-glucopyranosyl moiety
7
. Gonzalez, A. G.; Freire, R.; Francisco, C. G.; Salazar, J.
A.; Sua’rez, E. Tetrahedron 1973, 29, 1731.
. Chakravarty, A. K.; Das, B.; Pakrashi, S. C. Phytochem-
istry 1982, 21, 2083–2085.
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7
7
7
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+
13
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NMR (pyridine-d ): the signals due to the sapogenol part
5
were superimposable on those of 5; sugar moiety, l 100.0,
77.8, 88.2, 77.4, 74.7, 62.4 (inner glc C-1–6), 102.4, 72.5,
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77.9, 70.7, 67.3 (terminal xyl C-1–5).
3
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3
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