The first synthetic route to furostan saponins

Article abstract of DOI:10.1016/S0040-4039(00)01889-X

26-O-β-D-Glucopyranosyl-22-methoxy-25(R)-furost-5-en-3β-ol 3-O-β-D-glucopyranoside is synthesized from diosgenin in 11 steps and 26% overall yield. The present synthetic route represents the first one to furostan saponins.

Full text of DOI:10.1016/S0040-4039(00)01889-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 77–79
The first synthetic route to furostan saponins
Biao Yu,* Jianchun Liao, Jianbo Zhang and Yongzheng Hui*
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
Received 15 August 2000; revised 9 October 2000; accepted 26 October 2000
Abstract—26-O-b-
D
-Glucopyranosyl-22-methoxy-25(R)-furost-5-en-3b-ol 3-O-b-D-glucopyranoside is synthesized from diosgenin
in 11 steps and 26% overall yield. The present synthetic route represents the first one to furostan saponins. © 2000 Elsevier
Science Ltd. All rights reserved.
Steroidal saponins comprise a diverse class of plant
glycosides that possess a broad range of interesting
biological activities.1 According to the structure of sa-
pogenins, steroidal saponins can be divided into three
classes, i.e. cholestan saponins, spirostan saponins, and
furostan saponins1 (Fig. 1). Furostan saponins have a
saponin OSW-16 and a number of spirostan saponins.7
Herein we report the synthesis of a simple furostan
saponin 1, namely 26-O-b-
D
-glucopyranosyl-22-
-glucopyra-
methoxy-25(R)-furost-5-en-3b-ol 3-O-b-
D
noside, which has been isolated from the rhizomes of
Costus spicatus.8
b-D-glucopyranose substituent at the 26-OH and an-
other sugar chain attached, usually, at the 3-OH with
few exceptions.2 The 22-O-methyl group is thought to
be introduced during extraction with methanol and can
be converted to a 22-OH in refluxing aqueous acetone.3
The 26-O-glucopyranosyl residue is readily cleaved by
enzymes present in plants, and under the acidic condi-
tions of isolation, this leads to the closure of the F ring.
Therefore, furostan saponins are regarded as precursors
of the corresponding spirostan saponins in plants.2 This
is also the reason why recognition of their existence was
much later than that of cholestan and spirostan sa-
ponins. Marker et al. postulated the existence of
furostan saponins in 1947,4 and Schreiber and Rip-
perger isolated the first furostan saponin, jurubune, 20
years later.5 We have recently synthesized cholestan
Employing a similar procedure to that developed by
Bovicelli et al.,9 the 3-O-tert-butyldiphenylsilyl ether of
diosgenin (2) was converted into the 16,22-dione 6 in
four steps and in 69% overall yield, i.e. protection of
the C5,C6 double bond with bromide gave dibromide 3
(trans diastereoisomers); selective oxyfunctionalization
of the ethereal C16 with dimethyldioxirane generated in
situ10 led to hemiketal 4; acetolytic opening of the ketal
afforded dione 5; and removal of the bromide protec-
tion using zinc and ammonium chloride in ethanol
provided 6 (Scheme 1). Compounds 3–5 have not been
purified and were directly subjected to the next reaction
after the usual workup. Cleavage of the 26-O-acetyl
group using K2CO3/THF/MeOH generated spiroketal 7
and dione 8 (total 94% yield). These two compounds
Figure 1. Typical structures of three classes of steroidal saponins.
Keywords: furostan saponin; synthesis; glycosidation.
* Corresponding authors.
0040-4039/01/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01889-X

78
B. Yu et al. / Tetrahedron Letters 42 (2001) 77–79
were found to be interconvertible during isolation and
analysis. Consequently, the mixture of 7 and 8 was
treated directly with 2,3,4,6-tetra-O-benzoyl-a-D-glu-
furostan saponin 1 in 90% yield. The 22-OH was mean-
while converted into the 22-OMe. All the isolated com-
pounds gave satisfactory analytical data,13 and those
of compound 1 were virtually identical to those re-
ported for the natural product.8
copyranosyl trichloroacetimidate (9) in the presence of
a catalytic amount of TMSOTf (0.05 equiv.) in methyl-
ene chloride, providing the 26-O-glycosylated product
10 in good yield (86%), with a trace amount of the
F-ring closure product being detected. These glycosyla-
tion conditions have been optimized for coupling with
sapogenins.11 Compound 10 was then treated with tet-
rabutylammonium fluoride to remove the 3-OTBDPS
ether to give 11 (86%), which was subjected to the
second glycosylation under similar conditions to those
employed above, giving the coupled product 12 in
excellent yield (96%). Selective reduction of the 16-ke-
tone of the cholestan-16,22-dione with NaBH4 in i-
PrOH, followed by concurrent intramolecular hemi-
ketal formation, to provide the corresponding furostan
has been well documented.12 Subjecting dione 12 to
similar conditions provided hemiketal 13 in moderate
yield (64%). Removal of the benzoyl protecting groups
using NaOMe in MeOH/CH2Cl2 afforded the target
In conclusion, the furostan saponin 1 was synthesized
from a spirostan sapogenin (diosgenin) in 11 steps and
26% overall yield. The present synthetic route repre-
sents the first one to furostan saponins. The stepwise
manner of introduction of the C26 and C3 sugar moi-
eties demonstrates the generality of the present ap-
proach to the synthesis of furostan saponins.
Acknowledgements
This work is supported by the Ministry of Science and
Technology of China (G1998051104) and the National
Natural Science Foundation of China (29925203 and
29802008).
Scheme 1. Reagents and conditions: (a) TBDPSCl, imidazole, DMF, rt, 99%; (b) Br2, CHCl3, 0°C“rt; (c) KHSO5, NaHCO3,
acetone/CH2Cl2, rt; (d) Ac2O/HOAc (v:v, 1:1), 35°C; (e) Zn, NH4Cl, EtOH, reflux, 69% (for four steps); (f) K2CO3, THF/MeOH
(1:1), rt, 94%; (g) TMSOTf (0.05 equiv.), CH2Cl2, −78°C“rt, 86%; (h) TBAF, THF, rt, 86%; (i) TMSOTf (0.1 equiv.), CH2Cl2,
rt, 96%; (j) NaBH4, i-PrOH, rt, 64%; (k) MeONa, MeOH/CH2Cl2 (1:1), rt, 90%.

B. Yu et al. / Tetrahedron Letters 42 (2001) 77–79
79
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