Efforts to total synthesis of philinopside E: Convergent synthesis of the sulfated lanostane-type tetraglycoside

Article abstract of DOI:10.1039/c5ra25845f

As an important step to total synthesis of philinopside E with important antitumor activities (Ed₅₀ 0.75-3.50 μg mL^-1), we described herein convergent synthesis of a triterpene glycoside composed of the sulfated tetrasaccharide residue identical to that of philinopside E and the aglycone of lanost-7-en-3β-ol. The stereocontrolled synthesis of the aglycone from 24,25-dihydrolanosterol was accomplished relying on the stereoselective reductions of the 2,3-unsaturated-1,4-diketone system assisted by a C3-tert-butyldimethylsilyloxy group and convenient installation of the required 7(8)-double bond via syn elimination of triflate. Sequencial convergent coupling of monoglycoside, prepared by reacting the aglycone with orthogonally protected xylosyl thioglycoside, with trisaccharide thioglycoside originated from glucose, xylose and quinovose derivatives, incorporation of sulfation and deprotection afforded the target molecule. The features of our work are that the four 1,2-trans glycosidic bonds were stereoselectively constructed and the precious aglycone was introduced in the late-stage synthesis, which would facilitate the total synthesis of philinopside E and related natural products.

Full text of DOI:10.1039/c5ra25845f

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Efforts to total synthesis of philinopside E:
convergent synthesis of the sulfated lanostane-
Cite this: RSC Adv., 2016, 6, 5442
type tetraglycoside†
Shujin Bai, Zhiyong Wu, Qingyun Huang, Li Zhang, Pengwei Chen, Cong Wang,
*
*
Xiuli Zhang, Peng Wang and Ming Li
As an important step to total synthesis of philinopside E with important antitumor activities (Ed50 0.75–3.50
mg mLꢀ1), we described herein convergent synthesis of a triterpene glycoside composed of the sulfated
tetrasaccharide residue identical to that of philinopside E and the aglycone of lanost-7-en-3b-ol. The
stereocontrolled synthesis of the aglycone from 24,25-dihydrolanosterol was accomplished relying on
the stereoselective reductions of the 2,3-unsaturated-1,4-diketone system assisted by a C3-tert-
butyldimethylsilyloxy group and convenient installation of the required 7(8)-double bond via syn
elimination of triflate. Sequencial convergent coupling of monoglycoside, prepared by reacting the
aglycone with orthogonally protected xylosyl thioglycoside, with trisaccharide thioglycoside originated
from glucose, xylose and quinovose derivatives, incorporation of sulfation and deprotection afforded the
target molecule. The features of our work are that the four 1,2-trans glycosidic bonds were
stereoselectively constructed and the precious aglycone was introduced in the late-stage synthesis,
which would facilitate the total synthesis of philinopside E and related natural products.
Received 4th December 2015
Accepted 24th December 2015
DOI: 10.1039/c5ra25845f
www.rsc.org/advances
philinopside E interacts with the extracellular portion of the
kinase insert domain-containing receptor (KDR) to block its
Introduction
interaction with vascular endothelial growth factor (VEGF) and
the resultant downstream signaling. This mechanism is distinct
from that of conventional small-molecule inhibitors which
exclusively target the cytoplasmic kinase domain of KDR.4 In
addition, philinopside E markedly suppresses anb3 integrin-
Triterpene glycosides are a large family of secondary metabo-
lites in plants and marine organisms that have been used in
traditional medicines for thousands of years.1 To date, more
than 100 sea cucumber triterpene glycosides have been isolated
and characterized.2 These saponins share a common aglycone
skeleton, 3b,20S-dihydroxy-5a-lanostano-18,20-lactone. Their
oligosaccharide moieties, being frequently sulfated, are
composed of several different monosaccharide residues,
including D-xylose, D-quinovose, D-glucose, 3-O-methyl-D-
glucose, and in rare cases, 3-O-methyl-D-xylose.2 Most sea
cucumber saponins exhibit potential therapeutic effects in the
treatment of cancer, inammation and infections.2b,c Recently,
Yi and co-workers3 isolated four new sulfated saponins, phi-
linopside A, B, E and F, from the sea cucumber Pentacta quad-
rangularis, which is widely distributed throughout the South
China Sea (Fig. 1). As a representative of sea cucumber tri-
terpene glycosides, philinopside E exhibits anti-angiogenesis
and antitumor activities with Ed50 values ranging from 0.75–
3.50 mg mLꢀ1
.
Studies on its mode of action revealed that
3b
Key Laboratory of Marine Medicine, Chinese Ministry of Education, School of Medicine
and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, Shandong
266003, China. E-mail: pengw@ouc.edu.cn; lmsnouc@ouc.edu.cn
† Electronic supplementary information (ESI) available. CCDC 1419939. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c5ra25845f
Fig. 1 Structure of philinopside A, B, E, F and target triterpene
glycoside 1.
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driven downstream signaling.4 However, further studies were synthesis of saponin 1. As outlined in Scheme 1, we envisioned
hampered by the limited availability of this natural product. that 1 could be obtained by removal of 2-naphthyl methyl (Nap)
Chemical synthesis has proved to be a powerful tool to make in 2, subsequent sulfation of the resulting hydroxyl and global
structurally complex saponins of importance in sufficient hydrolysis of all the benzoates. The intermediate 2 could be
amounts,5 however, there is no report on the total synthesis of convergently constructed by coupling lanost-7-en-3-yl xyloside 3
sea cucumber triterpene glycosides such as philinopside E.6
with the trisaccharide donor 4. Monoglycoside 3, in turn, could
Inspection of philinopside E suggested that a few key prob- be synthesized from lanost-7-en-3b-ol 5 as the aglycone and the
lems including construction of sulfated oligosaccharide residue orthogonally protected xylosyl donor 6. Trisaccharide 4 could be
and synthesis of highly multi-functionalized aglycone that have prepared by joining three monosaccharide building blocks 7, 8
to be solved before a successful total synthesis could be per- and 9. Benzoate and 2-azidomethyl benzoate are chosen as the
formed. Thus, as the rst attempt to gain knowledge about the protecting groups for the C-2 hydroxyl groups of 6–9 to ensure
synthesis of philinopside E, we undertook the synthesis of an the highly stereoselective formation of 1,2-trans glycosidic
analogue of philinopside E, the lanostane-type saponin 1 con- linkages. Since the extraction of the aglycone 5 from natural
sisting of the sulfated tetrasaccharide found in philinopside E sources such as Dracaena cinnabari9a and Azorella trifurcata9b is
and the aglycone of lanost-7-en-3b-ol (Fig. 1). We hoped that the difficult and there are few methods10 available to its synthesis,
developed protecting-group and assembly strategies for stereo- we therefore would prepare the aglycone 5 from 24,25-dihy-
controlled formation of glycosidic bonds and the extension of drolanosterol by designing a new stereoselective route.
sugar chain, coupled with the strategies for synthesis of lanost-
The synthesis of saponin 1 commenced with the synthesis of
7-en-3b-ol, would pave a practical way to the total synthesis of 5 en route to monoglycoside 3 (Scheme 2). Thus, tert-butyldi-
philinopside E.
methylsilyl (TBS) protection of the 3-OH of 24,25-dihy-
drolanosterol 10 (ref. 11) under the forcing conditions,
followed by allylic oxidation with KMnO4 in the presence of 18-
crown-6 (ref. 12) afforded the unsaturated ketone 11 in 67%
yield over two steps. Aer that, conjugate reduction of 11 with
zinc dust in reuxing acetic acid11 gave diketone 12 in an
excellent 96% yield. Simultaneous reduction of two carbonyl
groups in 12 by LiAlH4 led to diol 13 as the single product in
85% yield. Notably, bulky TBS is crucial for the highly stereo-
selective reduction of diketone 12 because the congeners of 12
with tetrahydropyranyl and acetyl groups as the protecting
Results and discussion
As shown in Fig. 1, target molecule 1 has four 1,2-trans glyco-
sidic bonds and is sulfated at the 4-OH position of the xylose
unit. Normally, the formation of 1,2-trans glycosidic linkages is
facilitated by the participation of neighboring ester protecting
groups such as acetate, benzoate, and pivalate,7 and sulfate
groups are introduced in the penultimate step of the synthesis.8
According to these guidelines, we proposed our plan for the
Scheme 1 Retrosynthetic analysis of target triterpene glycoside 1.
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Scheme 2 Preparation of the aglycone 5. Reagents and conditions: (a) (i) TBSCl, imidazole, N,N-dimethylformamide, 45 ꢁC, 5 h; (ii) KMnO4, 18-
crown-6, CH2Cl2/H2O, 18 ꢁC, 24 h, 67% for two steps; (b) zinc dust, AcOH, 120 ꢁC, 2 h, 96%; (c) LiAlH4, THF, 13 ꢁC, 3 h, 85%; (d) Ac2O, pyridine,
DMAP, 17 ꢁC, overnight, 91%; (e) MsCl, Et3N, CH2Cl2, 15 ꢁC, 89%; (f) HF$pyridine, THF, 40 ꢁC, 88%; (g) H2 (130 atm), Pd/C, AcOH, MeOH, 120 ꢁC, 72
h, 95%; (h) (i) BzCl, pyridine, DMAP, 18 ꢁC, 6 h; (ii) AcCl, CHCl3/MeOH, 40 ꢁC, 24 h, 78% for two steps; (i) MsCl, Et3N, CH2Cl2, 13 ꢁC, 5 h, 87%; (j)
NaOAc, AcOH, 120 ꢁC, 0.5 h, 87% (20/21 ¼ 1/12.5); (k) Tf2O, pyridine, CH2Cl2, ꢀ10 ꢁC, 5 h, 96% (20/21 ¼ 1/20); (l) LiAlH4, THF, 21 ꢁC, 4 h, 89%.
group of 3-OH led to a diastereomeric mixture by reducing the mesylate to remove the 11b-OH. Unexpectedly, treatment of
carbonyl groups.13 By treating 13 with acetic anhydride in alcohol 14 with mesyl chloride and triethyl amine resulted in
pyridine with N,N-dimethyl pyridine (DMAP) as a catalyst the formation of alkene 15 (Scheme 2), which is probably
acetate 14 was obtained with a 91% yield. The absolute caused by the elimination of the mesylate generated in situ. The
stereochemistry of 14 was unambiguously conrmed by X-ray ready availability of alkene 15 led to an alternative strategy for
crystallographic analysis (Scheme 2).14
removing the 11b-OH, namely, hydrogenation of the 9(11)-
On the basis of the crystal structure, the synthesis of 14 double bond in 15. Aer many attempts, we found that the
deserves some comments. The ORTEP view of the crystal illus- presence of the bulky TBS group at the C-3 position signicantly
trates that two angular methyl groups at C-10 and C-13 are both hampered the hydrogenation reaction. This issue can be simply
b-oriented, which can cause steric hindrance to 11b-OH on the solved by removing the TBS group. Aer deprotection, alcohol
same face of the rings. This explains why the acetylation of diol 16 could undergo hydrogenation under 130 atmospheric pres-
ꢁ
13 preferentially occurred to the 7b-OH. It should be also sures at 120 C to provide 17 in an excellent 95% yield.
pointed out that in 1H NMR spectrum of 14 the axial 7a-H
With alcohol 17 in hand, we turned our attention to the
resonates at 4.91 ppm as a doublet of triplets, while the equa- synthesis of 5 by a syn elimination (Scheme 2). Thus, benzoy-
torial 11a-H appears at 4.22 ppm as a broad singlet. These lation of the 3-OH followed by a facile chemoselective deacety-
splitting patterns can be predicted by Karplus equation15 on the lation using methanolic hydrogen chloride18 afforded alcohol
basis of stereochemical assignment of 14. The same trends were 18. Inspired by the synthetic work of Purdy and co-workers,19
observed for 7a-H and 11a-H in 13.
who utilized syn elimination of mesylate to form the desired
With the access to 14 secured, we initially sought to remove double bond, mesylate 19, prepared by mesylation of 18, was
the equatorial 11b-OH through a Barton–McCombie radical treated with sodium acetate in reuxing acetic acid to furnish
deoxygenation reaction16 which involves conversion of the a mixture of olens 20 and 21 in 87% yield with a ratio of 1/12.5.
1
alcohol to a xanthate, followed by reduction with tri-n-butyltin The ratio was determined by H NMR spectroscopy based on
hydride in reuxing toluene. However, subjecting the alcohol 14 comparing integration values for the H-7 of 20 (5.53 ppm) and
to the standard conditions did not afford the xanthate required 21 (5.22 ppm). It is well established that triate is a better
for the deoxygenation step. Inspired by the work of Deslong- leaving group than mesylate,20 and triates have been widely
champs et al.,17 we then tended to use the LiAlH4 reduction of used in formation of double bonds in steroids.21
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Consequencely, in order to improve the regioselectivity of the
With the synthesis of 3 fully realized, the next signicant
elimination reaction, 18 was converted into a triate using step as outlined in Scheme 1 for convergent synthesis of 1 is
triic anhydride and pyridine in CH2Cl2, which underwent the extension of the sugar chain on 3 by trisaccharide donor 4.
rapid elimination to form 21 with an exclusive selectivity (20/21 It was initially expected that thioglycoside 4 could be assem-
¼ 1/20). This result implies that an E1 mechanism might be bled by a reaction sequence involving coupling of xylosyl
responsible for the elimination of triate. Finally, reductive acceptor 7a with the trichloroacetimidate donor 8, trans-
deprotection of benzoate with LiAlH4 supplied 5 in 89% yield, formation of the resultant disaccharide into the correspond-
1H data of which are identical to the reported.22 Thus the ing imidate and subsequent glycosylation with thioglycoside 9.
transformation of 24,25-dihydrolanosterol into 5 was achieved For this purpose, 7a was synthesized by rst selective acety-
in 12 steps with an overall 24% yield.
With the aglycone 5 in hand, it is necessary to synthesize 2-OH and 4-OH, and nal removal of the acetyl group with
pyranoxylosyl donor 6 to make monoglycoside 3. Briey, Nap methanolic hydrogen Glucosyl tri-
chloride.18
lation26 of the 3-OH of thioglycoside 26,23 benzoylation of both
protection of the 4-OH in thioglycoside 22 (ref. 23) followed by chloroacetimidate 8 was then prepared from hemiacetal 28.27
removal of isopropylidene with methanol in the presence of Aer that, TMSOTf-promoted glycosylation of 7a with 8 was
camphorsulfonic acid (CSA) furnished diol 23 with a 96% yield performed. Disappointingly, the reaction did not produce any
over two steps. Dibutylstannylene-mediated regioselective ben- of the desired disaccharide and only gave glucosyl thioglyco-
zoylation24 of 23 afforded benzoate 24 in a satisfactory 60% side 29 in 56% yield (Scheme 4 eqn (1)). From this observation,
yield. Condensation of alcohol 24 with 2-azidomethyl benzoic we assumed that the vicinal electron-withdrawing benzoates
acid
(AzmbOH)
in
the
presence
of
1-ethyl-3-(3- render the 3-OH of 7a signicantly less nucleophilic than the
dimethylaminopropyl)-carbodiimide hydrochloride (EDCI) anomeric thioether of the same molecule. Thus aglycone
gave the xylosyl thioglycoside 6. The glycosylation of 5 with 6 transfer28 of thioglycoside 7a preferentially occurred in the
promoted by N-iodosuccinimide (NIS) and trimethylsilyl triate reaction.
(TMSOTf) proceeded smoothly to furnish 25 in 91% yield.
To circumvent this unexpected aglycone migration, p-
Notably, this procedure le the 7(8)-double bond on 5 intact. methoxyphenyl (PMP) group, being less nucleophilic than
The newly formed 1,2-trans glycosidic linkage on 25 is phenylthio group, was introduced as an anomeric protecting
3
0
0
conrmed by the coupling constant of JH1 –H2 ¼ 7.0 Hz. In group of xylosyl acceptor. In an analogous route to that of 7a,
addition to allowing for the selective formation of 1,2-trans xylosyl acceptor 7b was obtained from 30.29 Unfortunately, upon
glycosidic bonds through neighboring group participation, treatment of 7b with 8 in the presence of TMSOTf (0.1 equiv.),
Azmb is oen used as a temporary protecting group in carbo- orthoester 32 was obtained in 35% yield (Scheme 4 eqn (2)). By
hydrate synthesis because it can be selectively removed in the switching the activation agent from TMSOTf to tert-butyldime-
presence of other acyl groups including benzoyl group (Bz).25 As thylsilyl triate (TBSOTf) (0.3 equiv.), the reaction did produce
expected, the Azmb group on 25 was selectively cleaved in the the desired b-linked disaccharide 33b in 39% yield, but along
presence of a Bz group by rst reducing the azide with Bu3P and with a-isomer 33a in 23% yield. Although it is oen disfavored
then intramolecular aminolysis of benzoate25 to give alcohol 3 by the presence of a neighboring participatory substituent at the
in 92% yield (Scheme 3).
C-2 position of the glycosyl donor, the formation of 1,2-cis
glycosidic linkages is not unknown in similar reactions.7,30 The
formation of undesired 33a was ascribed to the decreased
reactivity of 3-OH due to intramolecular hydrogen-bond
1
between the anomeric PMP with 3-OH on 7b. H NMR data of
7b demonstrates that 7b partially adopts a 1C4 chair confor-
mation, thus offering opportunities for intramolecular
1
hydrogen-bond formation. H NMR studies31 and theoretical
calculations32 on molecules similar to 7b lend support to those
inferences.
Not satised with the relatively poor stereochemical
outcome of the reaction of 7b with 8, we sought another
approach to the desired disaccharide. Previous work by other
groups33 illustrates that benzyl a-xylosides with 3-OH free are
competent glycosyl acceptors in a wide variety of glycosylation
events. On the basis of these results, TMSOTf-promoted
coupling of benzyl a-xyloside 7c (ref. 24b) with tri-
chloroacetimidate 8 was conducted. Happily, this reaction
afforded the desirable disaccharide 34 in 80% yield (Scheme 4
eqn (3)). Conversion of benzyl glycoside 34 into disaccharide
trichloroacetimidate 35 was achieved by removing the benzyl
group of 34 with hydrogenolysis and subsequently treating
the resultant alcohol with trichloroacetonitrile in the presence
Scheme 3 Synthesis of monoglycoside 3. Reagents and conditions: (a)
(i) NapBr, NaH, N,N-dimethylformamide, 27 ꢁC, 6 h; (ii) CSA, CH2Cl2/
MeOH, 28 ꢁC, 5 h, 96% for two steps; (b) (i) Bu2SnO, toluene, 120 ꢁC, 2
h; (ii) BzCl, 0 ꢁC, 5 h, 60%; (c) AzmbOH, EDCI, DMAP, CH2Cl2, 13 ꢁC, 11
h, 91%; (d) 5, NIS, TMSOTf, CH2Cl2, 4 A˚ molecular sieves, 0 ꢁC, 2 h, 91%;
(e) Bu3P, H2O, THF, 50 ꢁC, 1 h, 92%.
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Scheme 4 Preparation of disaccharide 34. Reagents and conditions: (a) (i) Ac2O, TBAOAc, CH3CN, 40 ꢁC, 6 h; (ii) BzCl, pyridine, DMAP, 25 ꢁC, 4 h,
59% for 27, 60% for 31; (b) AcCl, CH2Cl2/MeOH, 26 ꢁC, 24 h, 95% for 7a, 93% for 7b; (c) Cl3CCN, DBU, CH2Cl2, 25 ꢁC, 8 h, 95%; (d) TMSOTf (0.1
equiv.), 4 A˚ molecular sieves, CH2Cl2, 0 ꢁC, 1 h, 56%; (e) TMSOTf (0.1 equiv.), 4 A˚ molecular sieves, CH2Cl2, 0 ꢁC, 1 h 35% for 32; (f) TBSOTf (0.3
equiv.), 4 A˚ molecular sieves, CH2Cl2, 0 ꢁC, 1 h, 39% for 33b, 23% for 33a; (g) TMSOTf, 4 A˚ molecular sieves, CH2Cl2, 0 ꢁC, 1 h, 80%.
of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (Scheme 5). Grati-
With key two building blocks 3 and 4 available, the synthesis
fyingly, coupling of 35 and quinovosyl thioglycoside acceptor 9 of our target molecule 1 was in sight. As shown in Scheme 6,
proceeded smoothly providing the expected trisaccharide thio- NIS-promoted reaction of 3 and 4 in the presence of TMSOTf
glycoside 4 in 70% yield. Thioglycoside 9, in turn, could be gave rise to the tetrasaccharide saponin 2 in a satisfactory 67%
readily prepared by selective iodination of primary hydroxyl of yield. Oxidative removal of the Nap group was then effected by
36 (ref. 34) using Ph3P/I2/imidazole and the following deiodi- 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in MeOH/
nation of the resulting 37 by hydrogenolysis.
CH2Cl2 to give alcohol 38 in 88% yield. Using pyridine$SO3 as
Scheme 5 Synthesis of trisaccharide 4. Reagents and conditions: (a)
PPh3, imidazole, I2, THF, 29 ꢁC, 1 h; (b) H2, 10% Pd–C, NaHCO3, N,N- Scheme 6 Synthesis of saponin 1. Reagents and conditions: (a) NIS,
dimethylformamide, 40 ꢁC, 24 h, 83%; (c) (i) H2, 10% Pd/C, EtOH, 50 ꢁC, TMSOTf, CH2Cl2, 4 A˚ molecular sieves, 2 h, 0 ꢁC, 67%; (b) DDQ,
24 h; (ii) Cl3CCN, DBU, CH2Cl2, 5 h, 74% for two steps; (d) TMSOTf, 4 A˚ CH2Cl2/MeOH, 20 ꢁC, 5 h, 88%; (c) pyridine$SO3, pyridine, microwave,
molecular sieves, CH2Cl2, 0 ꢁC, 1 h, 70%.
100 W, 100 ꢁC, 2 h, 94%; (d) NaOMe, MeOH, 25 ꢁC, 24 h, 86%.
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the sulfating agent, sulfated product 39 was then obtained in an M HCl, saturated aqueous NaHCO3 and brine. The collected
excellent 94% yield by microwave-assisted sulfation35 of 38 in organic phase was dried over Na2SO4, ltered, and concentrated
pyridine at 100 ꢁC. Aer treatment of 39 with MeONa in under the reduced pressure. The resultant crude product was
methanol to globally deprotect benzoyl groups and subsequent used next step. A 100 mL round bottom ask open to atmo-
dialysis against water, target molecule 1 was nally obtained. 1H sphere was charged with KMnO4 (1.16 g, 7.37 mmol) and 18-
and 13C spectroscopic data due to the tetrasaccharide moiety of crown-6 (1.95 g, 7.37 mmol), followed by the addition of 30 mL
1 match those of philinopside E.
of water. A solution of the obtained above product in 30 mL of
CH2Cl2 was then added to the resulting suspension by a quick
syringe transfer. The reaction mixture was vigorously stirred
under argon at rt for 24 h, then the solid was ltered off with
a Buche funnel and washed with CH2Cl2. The ltrate was
separated, and the aqueous layer was extracted with CH2Cl2.
The combined organic layers were dried over Na2SO4, ltered
and concentrated. The residues were puried by silica gel
column chromatography (petroleum ether/CH2Cl2 ¼ 3/1) to give
11 (478 mg, 0.84 mmol, 67% for two steps). [a]2D4 ¼ +56.4 (c 1.10,
CHCl3); 1H NMR (500 MHz, CDCl3) d 3.23 (dd, J ¼ 11.4, 4.3 Hz,
1H), 2.88–2.78 (m, 1H), 2.73 (d, J ¼ 16.0 Hz, 1H), 2.59 (d, J ¼ 16.0
Hz, 1H), 2.56–2.40 (m, 2H), 2.21–2.07 (m, 1H), 2.03–1.90 (m,
1H), 1.29 (s, 3H), 1.16 (s, 3H), 0.93 (s, 3H), 0.91–0.84 (m, 18H),
0.84 (s, 3H), 0.80 (s, 3H), 0.03 (s, 3H), 0.02 (s, 3H); 13C NMR (126
MHz, CDCl3) d 202.70, 202.65, 152.2, 150.7, 78.4, 51.9, 50.4,
49.3, 49.1, 47.5, 39.9, 39.6, 39.5, 36.9, 36.4, 36.3, 34.2, 32.4, 28.4,
28.2, 28.1, 27.5, 26.02, 26.00, 24.1, 23.0, 22.7, 18.7, 18.2, 17.8,
17.0, 16.1, ꢀ3.6, ꢀ4.8; HRMS (ESI): m/z calcd for C36H63O3Si [M
+ H]+ 571.4541, found 571.4538.
Conclusions
In conclusion, a tritepene saponin, comprised of the same tet-
rasaccharide residue as that of philinopside E and the aglycone
of lanost-7-en-3b-ol, has been accomplished by a convergent
coupling of trisaccharide thioglycoside donor with monoglyco-
side acceptor. Lanost-7-en-3b-ol was efficiently prepared from
commercially available 24,25-dihydrolanosterol in a stereo-
controlled manner involving stereoselective reduction of
unsaturated 1,4-diketone system and facile installation of 7(8)-
double bond by syn elimination of triate. The successful access
to trisaccharide thioglycoside demonstrated that a benzyl a-
xyloside was a critical glycosyl acceptor for the extension of
sugar chain at its 3-OH. Since the sugar fragment of philinop-
side E is found in more than 40 sea cucumber triterpene
glycosides,2,3 the protecting-group and assembly tactics in this
work, used to stereoselectively construct glycosidic linkages and
to extend sugar chain, sets the foundation for the synthesis,
structural modication and biological evaluation of philinop-
side E and its congeners.
3b-(tert-Butyldimethylsilyloxy)-lanost-7,11-dione (12)
To the reux solution of 11 (478 mg, 0.84 mmol) in a glacial
acetic acid (30 mL), zinc dust (2.10 g) was added portionwise
during 1 h and the stirring was continued for another 1 h. At
this stage the solid was ltered off and washed with CH2Cl2. The
ltrate was concentrated in vacuo. The residues were puried by
silica gel column chromatography (petroleum ether/CH2Cl2 ¼
3/1) to give 12 (463 mg, 0.81 mmol, 96%). [a]2D4 ¼ +33.4 (c 1.05,
CHCl3); 1H NMR (500 MHz, CDCl3) d 3.19 (dd, J ¼ 11.5, 4.3 Hz,
1H), 2.85–2.74 (m, 1H), 2.63 (d, J ¼ 13.1 Hz, 1H), 2.55 (d, J ¼ 13.6
Hz, 1H), 2.42–2.28 (m, 3H), 2.24–2.10 (m, 2H), 2.09–1.97 (m,
1H), 1.26 (s, 3H), 1.19 (s, 3H), 0.92–0.81 (m, 21H), 0.79 (s, 3H),
0.70 (s, 3H), 0.03 (s, 3H), 0.02 (s, 3H); 13C NMR (126 MHz, CDCl3)
d 209.8, 209.7, 79.0, 60.8, 53.2, 52.69, 52.65, 49.1, 48.8, 46.6,
40.1, 39.7, 39.6, 36.9, 36.4, 36.1, 36.0, 33.2, 28.8, 28.3, 28.1, 27.8,
26.0, 24.1, 23.0, 22.7, 18.6, 18.2, 17.7, 16.3, 15.5, 13.9, ꢀ3.7,
ꢀ4.8; HRMS (ESI): m/z calcd for C36H65O3Si [M + H]+ 573.4697,
found 573.4691.
Experimental
General information
All nonaqueous reactions were carried out under an atmo-
sphere of argon in ame- or oven-dried glassware with magnetic
stirring unless otherwise indicated. Dichloromethane for
glycosylation reactions was distilled from calcium hydride. All
other commercially obtained reagents were used as received,
except where specied otherwise. Flash column chromatog-
raphy was performed on Silica Gel H (300–400 mesh, Qingdao,
China). Analytical thin layer chromatography was performed on
Silicycle SiliaPlate glass-backed plates coated with silica gel (60
˚
A pore size, F-254 indicator) and visualized by exposure to
ultraviolet light and/or staining with aqueous 8% sulfuric acid
in methanol. Optical rotations were determined with a digital
polarimeter. High-resolution mass spectral (HRMS) data were
determined with a LTQ Orbitrap. 1H and 13C NMR spectra were
recorded on a 500 or 600 MHz NMR spectrometer with Me4Si as
the internal standard. Chemical shis are recorded in d values
and J values were given in Hz.
3b-(tert-Butyldimethylsilyloxy)-lanost-7b,11b-diol (13)
To a solution of 12 (700 mg, 1.22 mmol) in anhydrous THF (25
mL) at rt was added LiAlH4 (465 mg, 12.20 mmol). Aer stirring
for 3 h, the reaction mixture was cooled in an ice bath and
quenched by the addition of 5% HCl. The resulting solution was
3b-(tert-Butyldimethylsilyloxy)-lanost-8-en-7,11-dione (11)
To a solution of 10 (3.70 g, 8.63 mmol) in N,N-dimethylform- extracted with EtOAc. The combined organic phase was washed
amide (12 mL) were added TBSCl (2.60 mL, 17.26 mmol) and with brine, dried with Na2SO4, ltered and concentrated in
imidazole (2.07 g, 34.52 mmol). Aer the reaction mixture was vacuo. The residue was puried by silica gel column chroma-
warmed at 45 ꢁC, and stirred for 5 h, the volatile was evaporated tography (petroleum ether/EtOAc ¼ 25/1) to afford compound
in vacuo. The residue was taken up in CH2Cl2 and washed with 1 13 (599 mg, 1.04 mmol, 85%). [a]2D4 ¼ +47.4 (c 0.70, CHCl3); 1H
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NMR (500 MHz, CDCl3) d 4.20 (s, 1H), 3.72–3.55 (m, 1H), 3.19 Na2SO4, ltered and concentrated. The crude product was
(dd, J ¼ 11.4, 3.6 Hz, 1H), 1.19 (s, 3H), 1.01 (s, 3H), 0.92–0.83 (m, puried by silica gel column chromatography (petroleum ether/
24H), 0.81 (s, 3H), 0.04 (s, 3H), 0.03 (s, 3H); 13C NMR (126 MHz, EtOAc ¼ 5/1) to give 16 (112 mg, 0.23 mmol, 88%). [a]D24 ¼ +48.8
CDCl3) d 79.6, 72.8, 68.7, 52.4, 51.6, 50.4, 48.2, 45.3, 44.6, 42.7, (c 0.55, CHCl3); 1H NMR (500 MHz, CDCl3) d 5.34 (d, J ¼ 6.1 Hz,
39.6, 39.5, 37.44, 37.40, 36.5, 36.2, 32.1, 29.0, 28.5, 28.2, 27.9, 1H), 4.92 (td, J ¼ 11.0, 5.2 Hz, 1H), 3.31–3.14 (m, 1H), 2.43 (d, J ¼
26.1, 24.2, 23.0, 22.7, 19.0, 18.3, 18.1, 17.3, 17.1, 16.3, ꢀ3.6, 10.6 Hz, 1H), 2.04 (s, 3H), 1.08 (s, 3H), 0.99 (s, 3H), 0.90–0.83 (m,
ꢀ4.8; HRMS (ESI): m/z calcd for C36H68O3SiNa [M + Na]+ 9H), 0.81 (s, 3H), 0.77 (s, 3H), 0.67 (s, 3H); 13C NMR (126 MHz,
599.4830, found 599.4817.
CDCl3) d 170.5, 145.5, 118.3, 78.8, 77.2, 74.4, 50.4, 48.3, 46.7,
46.4, 45.0, 39.6, 39.1, 36.9, 36.6, 36.3, 36.2, 35.8, 28.6, 28.20,
28.15, 27.8, 27.7, 24.2, 23.0, 22.7, 22.1, 22.0, 18.6, 18.5, 15.7,
14.5; HRMS (ESI): m/z calcd for C32H54O3Na [M + Na]+ 509.3965,
found 509.3965.
7b-Acetoxy-3b-(tert-butyldimethylsilyloxy)-lanost-11-ol (14)
Diol 13 (264 mg, 0.458 mmol) was dissolved in pyridine (20 mL),
then DMAP (6 mg, 0.05 mmol) and Ac2O (130 mL, 1.37 mmol)
was sequentially added at 0 ꢁC. The reaction was allowed to stir
overnight under argon atmosphere. The reaction was quenched
with water and extracted with EtOAc (2 ꢂ 40 mL). The combined
organic phases were washed thrice with hydrochloric acid (1 M)
and brine. The collected organic phase was dried over Na2SO4,
ltered and concentrated under reduced pressure, which was
puried by silica gel column chromatography (petroleum ether/
EtOAc ¼ 50/1) to give 14 (258 mg, 0.42 mmol, 91%). [a]2D4 ¼ +46.4
(c 0.85, CHCl3); 1H NMR (500 MHz, CDCl3) d 4.91 (td, J ¼ 10.5,
5.8 Hz, 1H), 4.22 (s, 1H), 3.19 (dd, J ¼ 11.4, 4.1 Hz, 1H), 2.25 (dd,
J ¼ 12.4, 10.2 Hz, 1H), 2.01 (s, 3H), 1.21 (s, 3H), 1.01 (s, 3H),
0.92–0.82 (m, 21H), 0.81 (s, 3H), 0.78 (s, 3H), 0.04 (s, 3H), 0.03 (s,
3H); 13C NMR (126 MHz, CDCl3) d 170.7, 79.6, 74.3, 68.6, 52.0,
51.5, 50.6, 48.1, 45.1, 42.7, 40.9, 39.61, 39.57, 37.3, 37.2, 36.7,
36.2, 35.2, 29.0, 28.4, 28.3, 28.1, 27.7, 26.1, 24.2, 23.0, 22.7, 22.1,
19.0, 18.3, 17.8, 17.3, 17.0, 16.3, ꢀ3.7, ꢀ4.8; HRMS (ESI): m/z
calcd for C38H70O4SiNa [M + Na]+ 641.4936, found 641.4932.
7b-Acetoxy-24,25-dihydrolanosterol (17)
To a solution of olen 16 (65 mg, 0.13 mmol) in MeOH (12 mL)
was added 10% Pd/C (100 mg) and AcOH (600 mL). The reac-
tion vessel was evacuated and backlled with hydrogen (130
atm). The mixture was kept at 120 ꢁC for 72 h, then ltered
through a thin plug of Celite. The ltrate was washed with
EtOAc (2 ꢂ 50 mL) and concentrated in vacuo. The residue was
puried by silica gel column chromatography (petroleum
ether/EtOAc ¼ 5/1) to afford 17 (62 mg, 0.13 mmol, 95%).
[a]2D4 ¼ +37.7 (c 0.90, CHCl3); 1H NMR (500 MHz, CDCl3) d 4.85
(td, J ¼ 10.6, 5.3 Hz, 1H), 3.21 (dd, J ¼ 11.4, 3.2 Hz, 1H), 2.00 (s,
3H), 1.96–1.77 (m, 3H), 0.96 (s, 3H), 0.94 (s, 3H), 0.88–0.84 (m,
9H), 0.83 (s, 3H), 0.79 (s, 3H), 0.78 (s, 3H); 13C NMR (126 MHz,
CDCl3) d 170.6, 78.9, 77.2, 74.6, 51.6, 50.1, 47.3, 46.9, 45.9,
43.0, 39.6, 38.9, 37.4, 36.7, 36.2, 35.5, 31.9, 28.5, 28.24, 28.16,
28.1, 27.7, 24.2, 23.0, 22.7, 22.1, 20.3, 18.9, 16.7, 15.6, 14.5,
13.9; HRMS (ESI): m/z calcd for C32H56O3Na [M + Na]+
511.4122, found 511.4123.
7b-Acetoxy-3b-(tert-butyldimethylsilyloxy)-lanost-9-ene (15)
To a mixture of 14 (80 mg, 0.13 mmol) and Et3N (36 mL, 0.26
mmol) in CH2Cl2 (2 mL) was added methanesulfonyl chloride 3b-Benzoyloxylanost-7b-ol (18)
ꢁ
(MsCl, 20 mL, 0.26 mmol) at 0 C. Aer the reaction had been
To a solution of 17 (1.30 g, 3.03 mmol) in pyridine (20 mL) was
completed, the mixture was diluted with CH2Cl2 and washed
with saturated aqueous NH4Cl and brine. The organic phase
was dried over Na2SO4, ltered and concentrated under reduced
pressure. The residues were puried by silica gel column
chromatography (petroleum ether/EtOAc ¼ 20/1) to give 15 (80
added DMAP (37 mg, 0.30 mmol) and BzCl (528 mL, 4.55 mmol)
at 0 ꢁC. The reaction was stirred for 6 h at room temperature and
quenched with water. Aer removal of solvent, the residue was
dissolved in CH2Cl2 and washed with 0.1 M HCl, saturated
aqueous NaHCO3. The organic phase was dried over anhydrous
Na2SO4, ltered and concentrated. The resulting residue was
dissolved in 65 mL of CH3OH/CHCl3 (v/v ¼ 1.6/1) followed by
dropwise addition of acetyl chloride (4.80 mL) at 0 ꢁC. The
reaction mixture was stirred for 24 h at 40 ꢁC, and then
quenched with Et3N. The volatile was evaporated in vacuo. The
resulting residue was puried by silica gel column chromatog-
raphy (petroleum ether/EtOAc ¼ 15/1) to afford 18 (1.04 g, 1.89
mmol, 62%) with the recovery of acetate (363 mg, 0.61 mmol).
[a]2D4 ¼ +35.7 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) d 8.04
(d, J ¼ 7.7 Hz, 2H), 7.55 (t, J ¼ 7.3 Hz, 1H), 7.44 (t, J ¼ 7.6 Hz,
2H), 4.72 (dd, J ¼ 11.4, 4.3 Hz, 1H), 3.64 (td, J ¼ 10.0, 4.9 Hz, 1H),
1
mg, 0.11 mmol, 89%). [a]2D4 ¼ +34.6 (c 1.00, CHCl3); H NMR
(500 MHz, CDCl3) d 5.33 (d, J ¼ 6.2 Hz, 1H), 4.92 (td, J ¼ 11.0, 5.2
Hz, 1H), 3.18 (dd, J ¼ 10.8, 4.9 Hz, 1H), 2.43 (d, J ¼ 11.0 Hz, 1H),
2.04 (s, 3H), 1.08 (s, 3H), 0.90–0.84 (m, 21H), 0.77 (s, 3H), 0.76 (s,
3H), 0.67 (s, 3H), 0.04 (s, 3H), 0.03 (s, 3H); 13C NMR (126 MHz,
CDCl3) d 170.5, 145.8, 118.0, 79.3, 77.2, 74.5, 50.4, 48.2, 46.7,
46.4, 45.0, 39.6, 39.0, 36.9, 36.6, 36.3, 36.2, 35.8, 28.61, 28.57,
28.3, 28.2, 27.9, 26.1, 24.2, 23.0, 22.7, 22.1, 22.0, 18.6, 18.5, 18.3,
16.1, 14.5, ꢀ3.7, ꢀ4.8.
7b-Acetoxylanost-9-ene (16)
To a solution of compound 15 (157 mg, 0.26 mmol) in THF (3.0 1.05 (s, 3H), 1.00 (s, 3H), 0.94 (s, 3H), 0.91 (s, 3H), 0.79 (s, 3H);
mL) in a TEFLON tube was added a solution of 70% HF$pyr- 13C NMR (126 MHz, CDCl3) d 166.4, 132.9, 131.0, 129.6, 128.4,
idine (0.88 mL). The reaction mixture was stirred for 6 h at 40 81.5, 77.2, 73.1, 52.1, 49.8, 47.4, 46.7, 46.4, 46.1, 39.6, 38.2, 37.2,
ꢁC, and quenched with saturated NaHCO3 solution. The resul- 36.8, 36.7, 36.6, 36.2, 31.9, 31.6, 28.7, 28.3, 28.1, 24.2, 22.9, 22.7,
tant mixture was extracted with EtOAc. The combined organic 20.3, 18.9, 17.0, 16.8, 14.5, 14.1; HRMS (ESI): m/z calcd for
layers were washed with saturated aqueous NaHCO3, dried over
C
37H58O3Na [M + Na]+ 573.4278, found 573.4283.
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36.6, 35.8, 32.3, 32.2, 28.4, 28.2, 27.8, 27.6, 25.0, 24.3, 23.1, 23.0,
Lanost-7b-O-methylsulfony-3b-yl benzoate (19)
22.7, 20.2, 19.1, 16.2, 15.6, 14.3; HRMS (ESI): m/z calcd for
C
To a solution of 18 (100 mg, 0.18 mmol) in CH2Cl2 (2.0 mL) was
added MsCl (42 mL, 0.55 mmol) and Et3N (126 mL, 0.91 mmol)
dropwise at 0 ꢁC. The reaction mixture was stirred for 5 h at
room temperature, and then quenched with MeOH. The volatile
was evaporated in vacuo. The resulting residue was puried by
silica gel column chromatography (petroleum ether/EtOAc ¼ 15/
1) to afford 19 (99 mg, 0.16 mmol, 87%). [a]2D4 ¼ +33.4 (c 0.55,
CHCl3); 1H NMR (500 MHz, CDCl3) d 8.03 (d, J ¼ 7.3 Hz, 2H), 7.56
(t, J ¼ 7.4 Hz, 1H), 7.44 (t, J ¼ 7.7 Hz, 2H), 4.79 (td, J ¼ 10.6, 5.3
Hz, 1H), 4.71 (dd, J ¼ 11.6, 4.3 Hz, 1H), 3.01 (s, 3H), 2.41–2.26 (m,
1H), 1.05 (s, 3H), 1.02 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H), 0.90–0.84
(m, 9H), 0.79 (s, 3H); 13C NMR (126 MHz, CDCl3) d 166.3, 133.0,
130.9, 129.7, 128.5, 83.2, 81.2, 51.9, 50.0, 47.1, 47.0, 46.1, 44.0,
40.1, 39.6, 38.2, 37.0, 36.7, 36.5, 36.2, 35.4, 31.6, 29.6, 28.5, 28.3,
28.1, 24.2, 24.1, 23.0, 22.7, 20.4, 19.0, 17.0, 16.5, 14.5, 14.0.
30H52ONa [M + Na]+ 451.3910, found 451.3908.
p-Tolyl 4-O-(2-naphthylmethyl)-1-thio-b-D-xylopyranoside (23)
Alcohol 22 (1.69 g, 5.71 mmol) was dissolved in N,N-dime-
thylformamide (50 mL) followed by addition of NaH (457 mg,
11.42 mmol) at 0 ꢁC. Aer stirring for 20 min under argon
atmosphere, NapBr (1.55 mL, 6.85 mmol) was added to the
reaction mixture. With stirring for another 6 h, the reaction was
quenched by methanol and poured into water. The mixture was
extracted with CH2Cl2. The organic phase was collected and
washed with HCl (1 M), saturated NaHCO3, dried over Na2SO4,
ltered and concentrated in vacuo. The residue was dissolved in
50 mL of CH2Cl2/MeOH (v/v ¼ 1/1), and then CSA (1.69 g, 5.71
mmol) was added. The reaction was stirred at room temperature
for 5 h, then quenched by Et3N and concentrated. The residue
was puried by silica gel column (petroleum ether/EtOAc ¼ 2/1)
to afford 23 (2.17 g, 5.48 mmol, 96% for two steps). [a]2D4 ¼ ꢀ61.8
(c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) d 7.87–7.72 (m, 4H),
7.52–7.35 (m, 5H), 7.11 (d, J ¼ 7.8 Hz, 2H), 4.85 (d, J ¼ 11.9 Hz,
1H), 4.79 (d, J ¼ 11.9 Hz, 1H), 4.47 (d, J ¼ 9.0 Hz, 1H), 4.09 (dd, J
¼ 11.5, 4.8 Hz, 1H), 3.69 (t, J ¼ 8.4 Hz, 1H), 3.56–3.45 (m, 1H),
3b-Benzoyloxylanost-7-ene (21)
Method A. 19 (50 mg, 0.08 mmol) was dissolved in acetic acid
(2.0 mL) and then added NaOAc (46 mg, 0.56 mmol). The
reaction mixture was stirred for 0.5 h at 120 ꢁC. Aer removal of
solvent, the residue was dissolved in CH2Cl2 and washed with
brine, dried over anhydrous Na2SO4, ltered and concentrated
for ash column chromatography (petroleum ether/CH2Cl2 ¼ 3/
1) to afford a mixture of 20 and 21 (41 mg, 0.07 mmol, 87%) at
the ratio of 20/21 ¼ 1/12.5.
3.35 (t, J ¼ 8.7 Hz, 1H), 3.29 (t, J ¼ 10.7 Hz, 1H), 2.33 (s, 3H); 13
C
NMR (126 MHz, CDCl3) d 138.6, 135.5, 133.5, 133.3, 133.2, 123.0,
128.6, 128.0, 127.8, 126.9, 126.4, 126.2, 125.8, 89.0, 76.9, 76.7,
73.3, 72.0, 67.3, 21.3; HRMS (ESI): m/z calcd for C23H28O4NS [M
+ NH4]+ 414.1734, found 414.1727.
Method B. To a solution of 18 (1.50 g, 2.73 mmol) in CH2Cl2
(50 mL) was added pyridine (2.64 mL, 32.8 mmol) at ꢀ10 ꢁC
followed by Tf2O (1.15 mL, 6.81 mmol). The reaction mixture was
stirred for 5 h at ꢀ10 ꢁC, and then quenched with H2O. The
solvent was evaporated in vacuo. The resulting residue was puri-
ed by column chromatography (petroleum ether/CH2Cl2 ¼ 3/1)
to afford a mixture of 20 and 21 (1.38 g, 2.62 mmol, 96%) at the
ratio of 20/21 ¼ 1/20. [a]D24 ¼ +41.3 (c 1.00, CHCl3); 1H NMR (500
MHz, CDCl3) d 8.05 (d, J ¼ 7.3 Hz, 2H), 7.55 (t, J ¼ 7.4 Hz, 1H), 7.44
(t, J ¼ 7.7 Hz, 2H), 5.22 (d, J ¼ 5.3 Hz, 1H), 4.77 (dd, J ¼ 11.4, 4.3
Hz, 1H), 1.13 (s, 3H), 0.99 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H), 0.91–
0.85 (m, 9H), 0.66 (s, 3H); 13C NMR (126 MHz, CDCl3) d 166.3,
145.1, 132.7, 131.0, 129.5, 128.3, 116.4, 81.8, 52.0, 50.8, 50.4, 47.1,
44.3, 39.5, 37.9, 37.7, 36.5, 36.4, 35.5, 32.2, 32.1, 28.3, 28.0, 27.6,
24.8, 24.10, 24.08, 22.8, 22.8, 22.5, 20.1, 19.0, 16.9, 16.1, 14.2.
p-Tolyl 3-O-benzoyl-4-O-(2-naphthylmethyl)-1-thio-b-D-
xylopyranoside (24)
Diol 23 (1.88 g, 4.74 mmol) and dibutyltin oxide (1.30 g, 5.22
mmol) was dissolved in anhydrous toluene (45 mL). The
resulting mixture was reuxed for 2 h with a Dean–Stark trap to
remove the formed water during the reaction. At this stage the
reaction was cooled to room temperature followed by addition
of benzoyl chloride (605 mL, 5.22 mmol) dropwise. Aer the
mixture was stirred for another 5 h, the volatile was removed in
vacuo. The residue was puried by silica gel column chroma-
tography (petroleum ether/EtOAc ¼ 8/1) to afford 24 (1.42 g, 2.84
mmol, 60%). [a]2D4 ¼ ꢀ90.9 (c 0.75, CHCl3); 1H NMR (500 MHz,
CDCl3) d 8.11 (d, J ¼ 7.5 Hz, 2H), 7.84–7.76 (m, 1H), 7.76–7.67
(m, 3H), 7.58 (t, J ¼ 7.4 Hz, 1H), 7.52–7.33 (m, 7H), 7.13 (d, J ¼
8.0 Hz, 2H), 5.40 (t, J ¼ 6.2 Hz, 1H), 4.99 (d, J ¼ 5.5 Hz, 1H), 4.84
(d, J ¼ 12.1 Hz, 1H), 4.80 (d, J ¼ 12.1 Hz, 1H), 4.40 (dd, J ¼ 12.2,
3.3 Hz, 1H), 3.77 (t, J ¼ 5.8 Hz, 1H), 3.75–3.70 (m, 1H), 3.65 (dd, J
¼ 12.2, 6.2 Hz, 1H), 2.34 (s, 3H); 13C NMR (126 MHz, CDCl3)
d 166.0, 138.3, 134.7, 133.5, 133.3, 133.2, 133.0, 130.2, 130.0,
129.6, 128.59, 128.56, 128.0, 127.8, 127.0, 126.4, 126.2, 125.8,
89.5, 73.7, 72.5, 70.4, 63.5, 21.3; HRMS (ESI): m/z calcd for
Lanost-7-en-3b-ol (5)
To a solution of 21 (700 mg, 1.31 mmol) in THF (15 mL) was
added LiAlH4 (250 mg, 6.57 mmol) at 0 ꢁC. The reaction was
stirred for 4 h at room temperature and quenched with 0.1 M
HCl. The mixture was extracted with ethyl acetate. The organic
phase was washed with 0.1 M HCl, brine, dried over anhydrous
Na2SO4, ltered and concentrated. The residue was applied to
silica gel column chromatography (petroleum ether/EtOAc ¼
15/1) to afford 5 (501 mg, 1.17 mmol, 89%). [a]2D4 ¼ +3.8 (c 0.70,
C
30H28O5SNa [M + Na]+ 523.1550, found 523.1554.
1
p-Tolyl 2-O-[2-(azidomethyl)benzoyl]-3-O-benzoyl-4-O-(2-
naphthyl-methyl)-1-thio-b-D-xylopyranoside (6)
0.84 (m, 15H), 0.64 (s, 3H); 13C NMR (126 MHz, CDCl3) d 145.1, To a solution of 24 (200 mg, 0.40 mmol) in dry CH2Cl2 (5 mL)
CHCl3); H NMR (500 MHz, CDCl3) d 5.21 (d, J ¼ 4.3 Hz, 1H),
3.25 (dd, J ¼ 11.0, 4.5 Hz, 1H), 0.99 (s, 3H), 0.97 (s, 3H), 0.91–
116.8, 79.5, 52.1, 51.0, 50.4, 47.4, 44.5, 39.7, 38.8, 38.3, 36.7, were added AzmbOH (106 mg, 0.60 mmol), EDCI (153 mg, 0.80
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mmol), and DMAP (97 mg, 0.80 mmol) under argon atmosphere. reactant was completely consumed. The reaction mixture was
The mixture was stirred for 12 h, and diluted with CH2Cl2 fol- diluted with EtOAc, washed with saturated aqueous NaHCO3
lowed by washing with 1 M HCl, saturated aqueous NaHCO3, and brine. The organic phase was dried over Na2SO4, ltered and
and brine. The organic phase was dried over Na2SO4, ltered and concentrated under reduced pressure. The residue was puried
concentrated. The residue was puried by silica gel column by silica gel column chromatography (petroleum ether/CH2Cl2/
chromatography (petroleum ether/EtOAc ¼ 7/1) to give 6 (239 EtOAc ¼ 20/5/1) to give 3 (300 mg, 0.38 mmol, 92%). [a]D24
¼
mg, 0.36 mmol, 91%). [a]2D4 ¼ +33.4 (c 1.00, CHCl3); 1H NMR (500 ꢀ29.1 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) d 8.04 (d, J ¼
MHz, CDCl3) d 7.98 (dd, J ¼ 8.2, 1.0 Hz, 2H), 7.92 (dd, J ¼ 7.8, 1.0 7.4 Hz, 2H), 7.82–7.75 (m, 1H), 7.75–7.66 (m, 3H), 7.57 (t, J ¼ 7.4
Hz, 1H), 7.79–7.71 (m, 1H), 7.69–7.59 (m, 3H), 7.59–7.53 (m, 1H), Hz, 1H), 7.50–7.34 (m, 5H), 5.37 (t, J ¼ 7.0 Hz, 1H), 5.18 (d, J ¼ 2.6
7.51–7.33 (m, 8H), 7.30 (dd, J ¼ 8.4, 1.5 Hz, 1H), 7.28–7.22 (m, Hz, 1H), 4.81 (d, J ¼ 12.2 Hz, 1H), 4.78 (d, J ¼ 12.2 Hz, 1H), 4.60
1H), 7.11 (d, J ¼ 8.0 Hz, 2H), 5.62 (t, J ¼ 8.1 Hz, 1H), 5.27 (t, J ¼ (d, J ¼ 5.2 Hz, 1H), 4.14 (dd, J ¼ 12.1, 3.8 Hz, 1H), 3.78–3.71 (m,
8.3 Hz, 1H), 4.95 (d, J ¼ 8.4 Hz, 1H), 4.78 (d, J ¼ 12.2 Hz, 1H), 4.72 1H), 3.71–3.65 (m, 1H), 3.51 (dd, J ¼ 12.0, 7.2 Hz, 1H), 3.18 (dd, J
(d, J ¼ 12.2 Hz, 1H), 4.64 (d, J ¼ 14.8 Hz, 1H), 4.54 (d, J ¼ 14.8 Hz, ¼ 11.7, 3.4 Hz, 1H), 2.87 (d, J ¼ 6.3 Hz, 1H), 0.97 (s, 3H), 0.96 (s,
1H), 4.32 (dd, J ¼ 11.9, 4.7 Hz, 1H), 3.90–3.76 (m, 1H), 3.58 (dd, J 3H), 0.91–0.84 (m, 15H), 0.64 (s, 3H); 13C NMR (126 MHz, CDCl3)
¼ 11.9, 8.9 Hz, 1H), 2.33 (s, 3H); 13C NMR (126 MHz, CDCl3) d 166.1, 145.1, 135.0, 133.31, 133.26, 133.2, 130.1, 129.9, 128.5,
d 165.7, 165.3, 138.6, 137.6, 135.0, 133.5, 133.4, 133.21, 133.15, 128.4, 128.0, 127.8, 127.0, 126.3, 126.2, 125.9, 116.7, 104.7, 90.0,
133.0, 131.3, 130.1, 130.0, 129.41, 129.35, 128.7, 128.6, 128.4, 74.1, 73.1, 72.6, 71.3, 61.7, 52.1, 51.0, 50.6, 47.3, 44.5, 39.7, 39.0,
128.20, 128.15, 128.0, 127.8, 126.9, 126.3, 126.2, 125.8, 86.9, 74.4, 38.3, 36.7, 36.6, 35.4, 32.3, 32.2, 28.5, 28.2, 27.8, 26.3, 25.0, 24.3,
74.1, 73.0, 70.7, 66.6, 52.8, 21.3; HRMS (ESI): m/z calcd for C38- 23.0, 22.9, 22.7, 20.2, 19.1, 16.6, 16.2, 14.3; HRMS (ESI): m/z calcd
H33O6N3SNa [M + Na]+ 682.1988, found 682.2000.
for C53H72O6Na [M + Na]+ 827.5221, found 827.5230.
Lanost-7-en-3b-yl 2-O-[2-(azidomethyl)benzoyl]-3-O-benzoyl-4-
O-(2-naphthylmethyl)-b-D-xylopyranoside (25)
p-Tolyl 3-O-acetyl-2,4-di-O-benzyl-1-thio-b-D-xylopyranoside
(27)
A solution of alcohol 5 (24 mg, 0.057 mmol) and thioglycoside 6 26 (100 mg, 0.39 mmol) was allowed to react with acetic anhy-
(50 mg, 0.074 mmol) in dry CH2Cl2 (2 mL) was stirred vigorously dride (41 mL, 0.43 mmol) in dry acetonitrile (1.5 mL) at 40 ꢁC for
˚
in the presence of activated 4 A molecular sieves (200 mg) for 20 12 h in the presence of tetrabutylammonium acetate (35 mg,
min. The mixture was cooled to 0 ꢁC, then NIS (26 mg, 0.114 0.12 mmol). The solution was concentrated in vacuo and directly
mmol) and TMSOTf (1 mL, 0.0057 mmol) were added. Aer stir- puried by ash column chromatography (petroleum ether/
ring for 2 h, the reaction mixture was quenched with Et3N, and EtOAc ¼ 1.5/1). The resulting residue was dissolved in pyridine
the solid was ltered off. The ltrate was washed with saturated (2 mL) and then benzoyl chloride (111 mL, 0.93 mmol) and DMAP
aqueous Na2S2O3 and brine. The organic phase was dried over (3 mg, 0.023 mmol) were added. Aer the reaction went to
Na2SO4, ltered and concentrated. The residue was puried by completion, the mixture was concentrated in vacuo. The residue
silica gel column chromatography (petroleum ether/EtOAc ¼ 17/ was diluted with CH2Cl2 and washed with 1 M HCl, saturated
1) to give 25 (51 mg, 0.052 mmol, 91%). [a]2D4 ¼ +45.6 (c 1.00, aqueous solution of NaHCO3 and brine. The combined organic
1
CHCl3); H NMR (500 MHz, CDCl3) d 7.94 (d, J ¼ 7.4 Hz, 3H), phase dried over Na2SO4, ltered and concentrated. The ob-
7.77–7.71 (m, 1H), 7.70–7.59 (m, 3H), 7.53 (t, J ¼ 7.4 Hz, 1H), tained residue was puried by silica gel column chromatography
7.50–7.39 (m, 4H), 7.36 (t, J ¼ 7.8 Hz, 2H), 7.32–7.27 (m, 2H), 5.62 (petroleum ether/EtOAc ¼ 8/1) to afford 27 (116 mg, 0.23 mmol,
(t, J ¼ 8.8 Hz, 1H), 5.30 (dd, J ¼ 9.0, 7.2 Hz, 1H), 5.13 (d, J ¼ 5.3 Hz, 59% for two steps). [a]2D4 ¼ ꢀ52.1 (c 1.00, CHCl3); 1H NMR (500
1H), 4.77 (d, J ¼ 12.3 Hz, 1H), 4.74–4.68 (m, 2H), 4.62 (s, 2H), 4.14 MHz, CDCl3) d 8.03 (d, J ¼ 7.4 Hz, 2H), 8.00 (d, J ¼ 7.5 Hz, 2H),
(dd, J ¼ 11.9, 4.9 Hz, 1H), 3.90–3.80 (m, 1H), 3.50 (dd, J ¼ 11.8, 9.5 7.62–7.53 (m, 2H), 7.47–7.33 (m, 6H), 7.12 (d, J ¼ 7.9 Hz, 2H),
Hz, 1H), 3.12 (dd, J ¼ 11.7, 3.5 Hz, 1H), 0.94 (s, 3H), 0.90–0.84 (m, 5.54 (t, J ¼ 7.7 Hz, 1H), 5.26 (t, J ¼ 7.6 Hz, 1H), 5.21–5.13 (m, 1H),
9H), 0.83 (s, 3H), 0.76 (s, 3H), 0.72 (s, 3H), 0.61 (s, 3H); 13C NMR 5.01 (d, J ¼ 7.6 Hz, 1H), 4.54 (dd, J ¼ 11.9, 4.6 Hz, 1H), 3.64 (dd, J
(126 MHz, CDCl3) d 165.9, 165.1, 145.0, 137.9, 135.1, 133.4, ¼ 11.9, 8.0 Hz, 1H), 2.34 (s, 3H), 1.97 (s, 3H); 13C NMR (126 MHz,
133.23, 133.17, 133.0, 131.3, 130.0, 129.6, 129.2, 128.50, 128.45, CDCl3) d 169.9, 165.6, 165.2, 138.7, 133.62, 133.56, 133.54, 130.1,
128.0, 127.9, 127.8, 127.0, 126.3, 126.2, 125.9, 116.7, 103.1, 90.2, 130.0, 129.9, 129.4, 129.3, 128.7, 128.65, 128.60, 86.9, 71.4, 70.3,
75.0, 73.7, 73.1, 72.2, 63.4, 52.9, 52.1, 51.0, 50.6, 47.3, 44.5, 39.7, 69.2, 65.0, 21.3, 20.8; HRMS (ESI): m/z calcd for C28H30O7NS [M +
38.8, 38.2, 36.7, 36.6, 35.4, 32.3, 32.2, 28.15, 28.13, 27.7, 26.2, 24.9, NH4]+ 524.1737, found 524.1723.
24.3, 23.0, 22.9, 22.7, 20.2, 19.1, 16.4, 16.2, 14.2; HRMS (ESI): m/z
calcd for C61H77O7N3Na [M + Na]+ 986.5659, found 986.5671.
p-Tolyl 2,4-di-O-benzoyl-1-thio-b-D-xylopyranoside (7a)
To a solution of 27 (2.86 g, 5.65 mmol) in 50 mL of MeOH/CH2Cl2
Lanost-7-en-3b-yl 3-O-benzoyl-4-O-(2-naphthylmethyl)-b-D-
(v/v ¼ 1/2) was added acetyl chloride (2.0 mL) dropwise at 0 ꢁC.
xylopyranoside (3)
The reaction mixture was stirred for 24 h, and then quenched
To a solution of 25 (400 mg, 0.41 mmol, 1 equiv.) in THF (10 mL) with Et3N. The volatile was removed in vacuo. The resulting
were added Bu3P (815 mL, 3.26 mmol, 8 equiv.) and water (0.40 residue was puried by silica gel column chromatography
mL) under argon atmosphere. The reaction mixture was stirred (petroleum ether/EtOAc ¼ 6/1) to afford 7a (2.58 g, 5.37 mmol,
for 1 h at 50 ꢁC, when TLC monitoring indicated that the 95%). [a]2D4 ¼ ꢀ59.3 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3)
5450 | RSC Adv., 2016, 6, 5442–5455
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d 8.06 (d, J ¼ 8.1 Hz, 2H), 8.02 (d, J ¼ 8.1 Hz, 2H), 7.65–7.50 (m, 7.63–7.51 (m, 2H), 7.48–7.34 (m, 4H), 6.96 (d, J ¼ 9.0 Hz, 2H),
2H), 7.49–7.31 (m, 6H), 7.11 (d, J ¼ 7.8 Hz, 2H), 5.19–5.06 (m, 6.80 (d, J ¼ 9.0 Hz, 2H), 5.60 (t, J ¼ 7.6 Hz, 1H), 5.47 (dd, J ¼ 7.6,
2H), 5.00 (d, J ¼ 7.5 Hz, 1H), 4.48 (dd, J ¼ 11.9, 4.4 Hz, 1H), 4.14 5.8 Hz, 1H), 5.31–5.20 (m, 2H), 4.45 (dd, J ¼ 12.2, 4.4 Hz, 1H),
(t, J ¼ 7.5 Hz, 1H), 3.61 (dd, J ¼ 11.8, 8.0 Hz, 1H), 2.34 (s, 3H); 13
C
3.75 (s, 3H), 3.70 (dd, J ¼ 12.2, 7.3 Hz, 1H), 2.02 (s, 3H); 13C NMR
NMR (126 MHz, CDCl3) d 166.3, 138.6, 133.63, 133.58, 133.52, (126 MHz, CDCl3) d 170.0, 165.6, 165.3, 155.7, 150.8, 133.7,
130.2, 130.0, 129.9, 129.57, 129.55, 128.9, 128.61, 128.59, 86.4, 133.6, 130.04, 130.02, 129.31, 129.29, 128.7, 128.6, 118.8, 114.7,
73.1, 72.4, 71.7, 64.6, 21.4; HRMS (ESI): m/z calcd for C26H25O6S 99.9, 70.5, 70.3, 69.3, 61.9, 55.8, 20.9; HRMS (ESI): m/z calcd for
[M + H]+ 465.1366, found 465.1353.
C
28H26O9Na [M + Na]+ 529.1469, found 529.1458.
2,4,6-Tri-O-benzoyl-3-O-methyl-a-D-glucopyranosyl
trichloroacetimidate (8)
4-Methoxyphenyl 2,4-di-O-benzoyl-b-D-xylopyranoside (7b)
Following the procedure for the preparation of 7a, 7b (85 mg,
To a solution of hemiacetal 28 (2.90 g, 5.73 mmol) in CH2Cl2 (50 0.18 mmol, 93%), puried by silica gel column chromatography
mL) were added Cl3CCN (5.75 mL, 57.3 mmol) and DBU (0.17 (CH2Cl2/EtOAc ¼ 10/1), was prepared from compound 31 (100
1
mL, 1.15 mmol). The resulting mixture was stirred at room mg, 0.20 mmol). [a]2D4 ¼ ꢀ49.0 (c 1.00, CHCl3); H NMR (500
temperature for 6 h followed by concentration in vacuo. The MHz, CDCl3) d 8.04 (d, J ¼ 8.0 Hz, 2H), d 8.03 (d, J ¼ 8.0 Hz, 2H),
residue was puried by silica gel ash column chromatography 7.62–7.50 (m, 2H), 7.44–7.30 (m, 4H), 7.02 (d, J ¼ 8.9 Hz, 2H),
(petroleum ether/EtOAc ¼ 7/1) to give 8 (3.53 g, 5.44 mmol, 95%). 6.83 (d, J ¼ 8.9 Hz, 2H), 5.41 (d, J ¼ 4.1 Hz, 1H), 5.34 (t, J ¼ 4.9
[a]2D4 ¼ +81.5 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) d 8.60 (s, Hz, 1H), 5.24–5.15 (m, 1H), 4.45 (dd, J ¼ 12.8, 3.4 Hz, 1H), 4.25
1H), 8.16–7.95 (m, 6H), 7.67–7.50 (m, 3H), 7.51–7.34 (m, 6H), (t, J ¼ 5.6 Hz, 1H), 3.81 (dd, J ¼ 12.8, 5.0 Hz, 1H), 3.77 (s, 3H); 13
C
6.71 (d, J ¼ 3.7 Hz, 1H), 5.58 (t, J ¼ 9.8 Hz, 1H), 5.43 (dd, J ¼ 9.8, NMR (126 MHz, CDCl3) d 166.2, 166.0, 155.8, 150.4, 133.6, 133.5,
3.8 Hz, 1H), 4.59 (dd, J ¼ 12.2, 2.4 Hz, 1H), 4.44–4.54 (m, 1H), 130.1, 130.0, 129.7, 129.4, 128.5, 118.6, 114.8, 99.0, 71.5, 71.1,
4.39 (dd, J ¼ 12.2, 5.2 Hz, 1H), 4.18 (t, J ¼ 9.6 Hz, 1H), 3.50 (s, 3H); 69.4, 60.4, 55.8; HRMS (ESI): m/z calcd for C26H24O8Na [M + Na]+
13C NMR (126 MHz, CDCl3) d 166.1, 165.3, 165.1, 160.4, 133.5, 487.1363, found 487.1355.
133.5, 133.1, 129.9, 129.8, 129.7, 129.6, 129.2, 129.2, 128.5, 128.5,
128.3, 93.4, 79.0, 72.10, 70.6, 70.0, 62.7, 60.8; HRMS (ESI): m/z 4,6-Di-O-benzoyl-3-O-methyl-a-D-glucopyranose-1,2-diyl (4-
calcd for C30H26O9NCl3Na [M + Na]+ 672.0565, found 672.0555. methoxyphenyl 2,4-di-benzoyl b-D-xylopyranoside)-3-yl
orthobenzoate (32)
p-Tolyl 2,4,6-tri-O-benzoyl-3-O-methyl-1-thio-b-D-
glucopyranoside (29)
Following the procedure for the preparation of compound 29, the
coupling of 7b (38 mg, 0.083 mmol) and 8 (70 mg, 0.108 mmol) in
A solution of compound 7a (38 mg, 0.082 mmol) and 8 (80 mg, CH2Cl2 in the presence of TMSOTf (1.5 mL, 0.0083 mmol) fur-
0.12 mmol) in anhydrous CH2Cl2 (2 mL) was stirred vigorously in nished 32 (28 mg, 0.029 mmol, 35%) aer purication by silica gel
the presence of activated 4 A molecular sieves (2 g) for 20 min. column chromatography (toluene/EtOAc ¼ 20/1). [a]2D4 ¼ ꢀ5.3 (c
˚
The mixture was cooled to 0 ꢁC and TMSOTf (1.5 mL, 0.0082 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) d 7.99 (d, J ¼ 7.6 Hz, 2H),
mmol) was added. Aer 1 h, the reaction mixture was quenched 7.94 (d, J ¼ 7.6 Hz, 2H), 7.85 (d, J ¼ 6.9 Hz, 2H), 7.83 (d, J ¼ 6.9 Hz,
with Et3N, and the solid was ltered off. The ltrate was 2H), 7.69 (d, J ¼ 7.4 Hz, 2H), 7.58 (t, J ¼ 7.5 Hz, 1H), 7.54 (t, J ¼ 7.5
concentrated in vacuo and the resulting residue was puried by Hz, 1H), 7.48 (t, J ¼ 7.4 Hz, 1H), 7.42 (t, J ¼ 7.5 Hz, 3H), 7.38–7.28
silica gel column chromatography (petroleum ether/EtOAc ¼ 7/ (m, 7H), 7.17 (t, J ¼ 7.6 Hz, 2H), 6.95 (d, J ¼ 9.0 Hz, 2H), 6.78 (d, J ¼
1) to afford 29 (28 mg, 0.046 mmol, 56%). [a]2D4 ¼ +9.4 (c 1.25, 9.0 Hz, 2H), 6.04 (d, J ¼ 5.2 Hz, 1H), 5.37 (t, J ¼ 4.6 Hz, 1H), 5.28 (m,
CHCl3); 1H NMR (500 MHz, CDCl3) d 8.15–8.08 (m, 2H), 8.03 (m, 1H), 5.21–5.15 (m, 1H), 5.12 (d, J ¼ 8.9 Hz, 1H), 4.91–4.84 (m, 1H),
4H), 7.65–7.54 (m, 3H), 7.51–7.40 (m, 6H), 7.35 (d, J ¼ 8.1 Hz, 4.39 (dd, J ¼ 12.4, 3.3 Hz, 1H), 4.28–4.17 (m, 2H), 4.11 (t, J ¼ 5.3 Hz,
2H), 6.88 (d, J ¼ 8.0 Hz, 2H), 5.41 (t, J ¼ 9.6 Hz, 1H), 5.28 (t, J ¼ 1H), 3.86–3.78 (m, 1H), 3.75 (s, 3H), 3.68 (dd, J ¼ 12.5, 5.2 Hz, 1H),
9.4 Hz, 1H), 4.84 (d, J ¼ 10.0 Hz, 1H), 4.64 (dd, J ¼ 12.1, 2.7 Hz, 3.59 (s, 3H), 3.55 (s, 1H); 13C NMR (126 MHz, CDCl3) d 166.1, 165.5,
1H), 4.40 (dd, J ¼ 12.1, 6.3 Hz, 1H), 4.05–3.96 (m, 1H), 3.86 (t, J ¼ 165.4, 165.2, 155.4, 150.8, 135.5, 133.5, 133.4, 133.3, 133.0, 130.0,
9.1 Hz, 1H), 3.38 (s, 3H), 2.24 (s, 3H); 13C NMR (126 MHz, CDCl3) 129.90, 129.87, 129.81, 129.78, 129.76, 129.51, 129.49, 128.5, 128.4,
d 166.3, 165.2, 165.1, 138.4, 133.6, 133.5, 133.4, 133.2, 130.0, 128.34, 128.29, 126.7, 122.0, 118.4, 114.7, 98.7, 97.9, 77.1, 73.3,
129.97, 129.96, 129.8, 129.7, 129.4, 128.7, 128.6, 128.50, 128.48, 70.8, 70.5, 69.4, 68.5, 67.4, 64.5, 60.6, 58.6, 55.8; HRMS (ESI): m/z
86.6, 83.5, 76.3, 71.9, 70.6, 63.5, 60.1, 21.2; HRMS (ESI): m/z calcd calcd for C54H52O16N [M + NH4]+ 970.3281, found 970.3283.
for C35H36O8NS [M + NH4]+ 630.2156, found 630.2149.
4-Methoxyphenyl 2,4,6-tri-O-benzoyl-3-O-methyl-a-D-
4-Methoxyphenyl 3-O-acetyl-2,4-di-O-benzoyl-b-D-
xylopyranoside (31)
glucopyranosyl-(1/3)-2,4-di-O-benzoyl-b-D-xylopyranoside
(33a) and 4-methoxyphenyl 2,4,6-tri-O-benzoyl-3-O-methyl-b-
D-glucopyranosyl-(1/3)-2,4-di-O-benzoyl-b-D-xylopyranoside
(33b)
Following the procedure for the preparation of compound 27,
30 (1.35 mg, 5.27 mmol) was converted into 31 (1.6 mg, 3.16
mmol, 60%) over two steps by purication with silica gel According to the protocol for the synthesis of 29, TBSOTf (6.0 mL,
column (petroleum ether/EtOAc ¼ 6/1). [a]2D4 ¼ ꢀ34.2 (c 0.90, 0.025 mmol)-catalyzed glycosylation of 7b (38 mg, 0.083 mmol)
1
CHCl3); H NMR (500 MHz, CDCl3) d 8.03 (d, J ¼ 7.7 Hz, 4H), and 8 (70 mg, 0.108 mmol) in anhydrous CH2Cl2 (2 mL) to afford
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33a (18 mg, 0.019 mmol, 23%) and 33b (31 mg, 0.032 mmol, backlled with hydrogen (1 atm). The mixture was stirred at 50
39%) with the purication of silica gel column chromatography ꢁC for 24 h, at this stage TLC indicated the reaction was
(toluene/EtOAc ¼ 30/1) 33a: [a]2D4 ¼ +66.8 (c 1.00, CHCl3); 1H completed. The mixture was ltered through a pad of Celite.
NMR (500 MHz, CDCl3) d 8.04 (d, J ¼ 7.3 Hz, 2H), 7.99 (d, J ¼ 7.2 The ltrate was concentrated and the residue was puried by
Hz, 2H), 7.95 (d, J ¼ 7.3 Hz, 2H), 7.89 (d, J ¼ 7.2 Hz, 2H), 7.79 (d, J silica gel column chromatography (petroleum ether/EtOAc ¼
¼ 7.3 Hz, 2H), 7.63–7.42 (m, 7H), 7.39 (s, 2H), 7.35–7.27 (m, 6H), 2.5/1) to afford the desired hemiacetal as a white foam which
7.00 (d, J ¼ 9.1 Hz, 2H), 6.81 (d, J ¼ 9.1 Hz, 2H), 5.64 (d, J ¼ 3.7 was directly used in the next step. To a soln of the above
Hz, 1H), 5.60–5.54 (m, 1H), 5.46 (t, J ¼ 9.7 Hz, 1H), 5.27 (d, J ¼ 4.9 hemiacetal (1.91 g, 2.26 mmol) and Cl3CCN (2.3 mL, 22.6 mmol)
Hz, 1H), 5.19–5.04 (m, 2H), 4.47–4.28 (m, 4H), 4.07 (t, J ¼ 9.7 Hz, in CH2Cl2 (2.5 mL) was added DBU (171 mL, 1.15 mmol) at 0 ꢁC.
1H), 3.91 (dd, J ¼ 12.2, 4.0 Hz, 1H), 3.77 (s, 3H), 3.56 (dd, J ¼ 12.3, The mixture was stirred overnight at ambient temperature, and
6.2 Hz, 1H), 3.44 (s, 3H); 13C NMR (126 MHz, CDCl3) d 166.2, then concentrated in vacuo. The resulting residue was puried
165.4, 165.2, 165.0, 155.6, 150.8, 133.8, 133.52, 133.49, 133.1, by silica gel column chromatography (petroleum ether/EtOAc ¼
129.98, 129.93, 129.86, 129.85, 129.5, 129.22, 129.21, 129.0, 3.5/1) to afford 35 (2.02 g, 2.04 mmol, 74% over two steps).
128.7, 128.6, 128.53, 128.46, 128.4, 118.5, 114.8, 99.3, 96.9, 78.8, [a]2D4 ¼ ꢀ15.7 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) d 8.47
73.9, 72.8, 70.7, 70.6, 70.5, 68.7, 62.5, 60.9, 60.8, 55.8; HRMS (s, 1H), 8.11 (d, J ¼ 7.5 Hz, 2H), 8.01 (d, J ¼ 8.5 Hz, 2H), 7.99 (d, J
(ESI): m/z calcd for C54H52O16N [M + NH4]+ 970.3281, found ¼ 8.5 Hz, 2H), 7.93 (d, J ¼ 7.5 Hz, 2H), 7.71–7.54 (m, 4H), 7.54–
970.3261. 33b: [a]2D4 ¼ ꢀ35.6 (c 0.75, CHCl3); 1H NMR (500 MHz, 7.45 (m, 5H), 7.42 (t, J ¼ 7.7 Hz, 2H), 7.39–7.28 (m, 4H), 7.19 (t, J
CDCl3) d 8.04 (d, J ¼ 7.6 Hz, 2H), 8.00 (d, J ¼ 7.5 Hz, 2H), 7.95– ¼ 7.7 Hz, 2H), 6.49 (d, J ¼ 3.4 Hz, 1H), 5.38–5.30 (m, 1H), 5.30–
7.89 (m, 6H), 7.60–7.40 (m, 6H), 7.36–7.22 (m, 7H), 7.12 (t, J ¼ 7.7 5.17 (m, 3H), 5.04 (d, J ¼ 8.0 Hz, 1H), 4.60 (t, J ¼ 9.2 Hz, 1H), 4.54
Hz, 2H), 6.73 (d, J ¼ 9.1 Hz, 2H), 6.67 (d, J ¼ 9.1 Hz, 2H), 5.52– (dd, J ¼ 12.0, 2.9 Hz, 1H), 4.29–4.17 (m, 2H), 4.12–4.04 (m, 1H),
5.42 (m, 2H), 5.32 (s, 1H), 5.24 (s, 1H), 5.19–5.12 (m, 2H), 4.57 3.87 (t, J ¼ 10.8 Hz, 1H), 3.70 (t, J ¼ 9.3 Hz, 1H), 3.23 (s, 3H); 13
C
(dd, J ¼ 12.0, 2.9 Hz, 1H), 4.50–4.37 (m, 3H), 4.15–4.08 (m, 1H), NMR (126 MHz, CDCl3) d 166.4, 165.5, 165.3, 164.9, 164.8, 160.5,
3.89 (t, J ¼ 9.2 Hz, 1H), 3.78–3.71 (m, 4H), 3.39 (s, 3H); 13C NMR 133.73, 133.65, 133.5, 133.4, 133.1, 129.98, 129.95, 129.7, 129.6,
(126 MHz, CDCl3) d 166.3, 165.5, 165.3, 165.2, 165.1, 155.1, 129.5, 129.30, 129.29, 129.0, 128.7, 128.6, 128.42, 128.38, 101.6,
150.3, 133.6, 133.5, 133.2, 133.1, 132.9, 130.00, 129.97, 129.81, 93.7, 81.8, 77.2, 75.4, 72.6, 72.55, 72.48, 70.7, 68.8, 64.0, 61.7,
129.78, 129.72, 129.4, 129.3, 128.7, 128.5, 128.4, 128.33, 128.27, 59.3; HRMS (ESI): m/z calcd for C49H46O15N2Cl3 [M + NH4]+
118.5, 114.4, 110.1, 101.2, 97.2, 82.0, 73.0, 72.69, 72.68, 70.7, 1007.1958, found 1007.1957.
69.1, 68.7, 63.6, 59.6, 58.9, 55.8; HRMS (ESI): m/z calcd for
C54H52O16N [M + NH4]+ 970.3281, found 970.3288.
p-Tolyl 2,3-di-O-benzoyl-6-deoxy-6-iodo-1-thio-b-D-
glucopyranoside (37)
Benzyl 2,4,6-tri-O-benzoyl-3-O-methyl-b-D-glucopyranosyl-(1/
3)-2,4-di-O-benzoyl-a-D-xylopyranoside (34)
To a solution of 36 (1.13 g, 2.29 mmol), Ph3P (1.20 g, 4.58 mmol)
and imidazole (0.62 g, 9.16 mmol) in anhydrous THF (20 mL)
Following the procedure for the preparation of compound 29, the was added a solution of I2 (0.76 g, 2.98 mmol) in anhydrous THF
coupling of 7c (1.38 g, 3.07 mmol) and 8 (3.0 g, 4.61 mmol) in (3 mL). Aer stirring for 1 h, monitoring by TLC indicated that
anhydrous CH2Cl2 (20 mL) in the presence of TMSOTf (56 mL, the reaction went to completion. The mixture was ltered and
0.022 mmol) afford 34 (2.30 g, 2.46 mmol, 80%) by silica gel the ltrate was concentrated in vacuo. The residue was puried
column chromatography (toluene/EtOAc ¼ 30/1). [a]2D4 ¼ +1.0 (c by silica gel column chromatography to give 37 (petroleum
1.00, CHCl3); 1H NMR (500 MHz, CDCl3) d 8.06 (d, J ¼ 7.2 Hz, 2H), ether/EtOAc ¼ 5/1, 1.26 g, 2.08 mmol, 91%). [a]D24 ¼ +52.4 (c
1
8.02–7.95 (m, 4H), 7.93 (d, J ¼ 7.2 Hz, 2H), 7.69 (t, J ¼ 7.4 Hz, 1H), 1.00, CHCl3); H NMR (500 MHz, CDCl3) d 7.98 (d, J ¼ 8.0 Hz,
7.63–7.50 (m, 5H), 7.49–7.35 (m, 6H), 7.33–7.22 (m, 3H), 7.20– 2H), 7.94 (d, J ¼ 8.0 Hz, 2H), 7.57–7.45 (m, 4H), 7.44–7.32 (m,
7.12 (m, 5H), 7.12–7.04 (m, 2H), 5.30 (t, J ¼ 9.5 Hz, 1H), 5.27–5.19 4H), 7.13 (d, J ¼ 7.9 Hz, 2H), 5.45–5.31 (m, 2H), 4.89 (d, J ¼ 9.1
(m, 2H), 5.11 (d, J ¼ 3.5 Hz, 1H), 5.06 (d, J ¼ 8.0 Hz, 1H), 4.96 (dd, Hz, 1H), 3.79–3.65 (m, 2H), 3.47 (dd, J ¼ 10.7, 6.4 Hz, 1H), 3.42–
J ¼ 9.4, 3.6 Hz, 1H), 4.69 (d, J ¼ 12.3 Hz, 1H), 4.60 (t, J ¼ 9.1 Hz, 3.34 (m, 1H), 3.21 (s, 1H), 2.35 (s, 3H); 13C NMR (126 MHz,
1H), 4.48–4.39 (m, 2H), 4.31 (dd, J ¼ 11.9, 5.9 Hz, 1H), 4.08–3.98 CDCl3) d 168.0, 165.3, 138.9, 134.4, 133.9, 133.5, 130.2, 130.0,
(m, 2H), 3.78 (t, J ¼ 10.6 Hz, 1H), 3.70 (t, J ¼ 9.3 Hz, 1H), 3.24 (s, 129.8, 129.4, 128.7, 128.6, 128.5, 127.5, 86.0, 79.0, 78.4, 73.3,
3H); 13C NMR (126 MHz, CDCl3) d 166.4, 165.6, 165.2, 165.1, 70.0, 21.4, 5.6; HRMS (ESI): m/z calcd for C27H29O6NIS [M +
164.9, 137.0, 133.6, 133.3, 133.2, 133.0, 130.0, 129.93, 129.88, NH4]+ 622.0755, found 622.0743.
129.79, 129.77, 129.68, 129.62, 129.59, 129.40, 129.35, 128.6,
128.5, 128.38, 128.35, 128.34, 128.0, 127.8, 101.5, 95.1, 81.9, 75.5,
73.9, 72.7, 72.2, 70.8, 69.9, 69.7, 63.9, 59.5, 59.2; HRMS (ESI): m/z
calcd for C54H52O15N [M + NH4]+ 954.3331, found 954.3329.
p-Tolyl 2,3-di-O-benzoyl-6-deoxy-1-thio-b-D-glucopyranoside (9)
To a solution of 19 (1.38 g, 2.28 mmol) in anydrous N,N-dime-
thylformamide (45 mL) was added 10% Pd/C (700 mg) and
NaHCO3 (633 mg, 7.53 mmol). The reaction vessel was evacu-
ated and backlled with hydrogen (1 atm). The mixture was
stirred at 40 ꢁC for 24 h. The solid was ltered on Celite and the
2,4,6-Tri-O-benzoyl-3-O-methyl-b-D-glucopyranosyl-(1/3)-2,4-
di-O-benzoyl-a-D-xylopyranosyl trichloroacetimidate (35)
To a solution of 34 (2.58 mg, 2.75 mmol) in EtOH (70 mL) was ltrate was concentrated. The crude product was puried by
added 10% Pd/C (1 g). The reaction vessel was evacuated and silica gel column chromatography (petroleum ether/EtOAc ¼ 5/
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1) to give 9 (904 mg, 1.89 mmol, 83%). [a]2D4 ¼ +89.7 (c 1.00, 7.60–7.49 (m, 5H), 7.49–7.43 (m, 5H), 7.43–7.35 (m, 8H), 7.32–
1
CHCl3); H NMR (500 MHz, CDCl3) d 8.02–7.90 (m, 4H), 7.56– 7.24 (m, 8H), 7.18 (t, J ¼ 7.8 Hz, 2H), 7.14 (dd, J ¼ 8.4, 1.2 Hz,
7.48 (m, 2H), 7.42–7.33 (m, 6H), 7.11 (d, J ¼ 8.1 Hz, 2H), 5.40 (t, J 1H), 5.36–5.23 (m, 4H), 5.21 (s, 1H), 5.16 (t, 8.1 Hz, 1H), 5.03–
¼ 9.6 Hz, 1H), 5.32 (t, J ¼ 9.0 Hz, 1H), 4.83 (d, J ¼ 9.9 Hz, 1H), 4.97 (m, 1H), 4.97–4.93 (m, 1H), 4.87 (d, J ¼ 7.8 Hz, 1H), 4.71 (d, J
3.65–3.49 (m, 2H), 2.93 (d, J ¼ 4.4 Hz, 1H), 2.34 (s, 3H), 1.46 (d, J ¼ 7.9 Hz, 1H), 4.64 (d, J ¼ 4.0 Hz, 1H), 4.59–4.46 (m, 3H), 4.42
¼ 5.8 Hz, 3H); 13C NMR (126 MHz, CDCl3) d 167.9, 165.4, 138.6, (dd, J ¼ 12.0, 3.2 Hz, 1H), 4.28 (dd, J ¼ 11.9, 6.3 Hz, 1H), 4.17 (t, J
133.7, 133.6, 133.4, 130.1, 129.9, 129.8, 129.5, 129.0, 128.6, ¼ 5.6 Hz, 1H), 4.04–3.90 (m, 2H), 3.86–3.75 (m, 2H), 3.67 (t, J ¼
128.50, 128.49, 86.3, 78.8, 74.7, 70.6, 21.3, 18.0; HRMS (ESI): m/z 9.2 Hz, 1H), 3.52–3.61 (m, 1H), 3.39–3.31 (m, 2H), 3.29 (s, 3H),
calcd for C27H30O6NS [M + NH4]+ 496.1788, found 496.1786.
3.25–3.16 (m, 1H), 3.09 (dd, J ¼ 11.7, 3.6 Hz, 1H), 3.05 (dd, J ¼
12.6, 5.0 Hz, 1H), 2.04–1.88 (m, 4H), 1.82–1.71 (m, 2H), 1.04 (s,
3H), 1.02–0.97 (m, 6H), 0.91–0.83 (m, 15H), 0.64 (s, 3H); 13C
NMR (126 MHz, CDCl3) d 166.2, 165.6, 165.5, 165.3, 165.2, 164.8,
164.7, 145.1, 135.2, 133.6, 133.42, 133.40, 133.2, 133.1, 133.04,
133.00, 132.8, 132.7, 130.1, 130.0, 129.97, 129.93, 129.90,
129.87, 129.8, 129.7, 129.6, 129.4, 129.2, 128.7, 128.6, 128.5,
128.4, 128.3, 128.23, 128.19, 128.0, 127.7, 126.8, 126.1, 126.0,
125.9, 116.8, 103.7, 101.5, 100.5, 100.4, 90.2, 83.1, 81.7, 76.4,
75.2, 74.6, 74.4, 73.7, 72.70, 72.68, 72.4, 72.1, 71.0, 70.9, 70.6,
69.1, 63.7, 62.5, 60.2, 59.3, 52.1, 51.0, 50.7, 47.3, 44.5, 39.7, 39.2,
38.3, 36.7, 36.6, 35.4, 32.32, 32.26, 28.2, 27.8, 26.3, 25.0, 24.3,
23.0, 22.7, 20.2, 19.1, 17.6, 16.4, 16.2, 14.2; HRMS (ESI): m/z
calcd for C120H130O26Na [M + Na]+ 2009.8743, found 2009.8736.
p-Tolyl 2,4,6-tri-O-benzoyl-3-O-methyl-b-D-glucopyranosyl-
(1/3)-2,4-di-O-benzoyl-b-D-xylopyranosyl-(1/4)-2,3-di-O-
benzoyl-6-deoxy-1-thio-b-D-glucopyranoside (4)
A solution of 35 (1.24 g, 1.25 mmol) and 9 (400 mg, 0.84 mmol) in
anhydrous CH2Cl2 (12 mL) was stirred vigorously in the presence
˚
of activated 4 A molecular sieves (1 g) for 20 min. The mixture
was cooled to 0 ꢁC and TMSOTf (15 mL, 0.084 mmol) were added.
Aer 1 h, the reaction mixture was quenched with Et3N and
ltered. The ltrate was concentrated in vacuo. The residue was
puried by silica gel column chromatography (petroleum ether/
EtOAc ¼ 3/1) to give 4 (756 mg, 70%). [a]2D4 ¼ +2.6 (c 1.00, CHCl3);
1H NMR (500 MHz, CDCl3) d 8.01 (s, 2H), 7.98 (s, 2H), 7.96 (d, J ¼
7.7 Hz, 2H), 7.93 (d, J ¼ 7.7 Hz, 2H), 7.89 (d, J ¼ 7.8 Hz, 4H), 7.80
(d, J ¼ 7.7 Hz, 2H), 7.60–7.07 (m, 24H), 5.48 (t, J ¼ 9.2 Hz, 1H),
5.37 (t, J ¼ 9.4 Hz, 1H), 5.32 (t, J ¼ 8.3 Hz, 1H), 5.23 (t, J ¼ 9.7 Hz,
1H), 5.03–4.97 (m, 1H), 4.97–4.88 (m, 2H), 4.74 (d, J ¼ 2.8 Hz,
1H), 4.63 (d, J ¼ 10.1 Hz, 1H), 4.47 (dd, J ¼ 11.9, 3.0 Hz, 1H), 4.33
(dd, J ¼ 12.0, 6.3 Hz, 1H), 4.21 (t, J ¼ 4.5 Hz, 1H), 4.06–3.96 (m,
1H), 3.93 (dd, J ¼ 12.7, 2.4 Hz, 1H), 3.73 (t, J ¼ 9.2 Hz, 1H), 3.42 (t,
J ¼ 9.2 Hz, 1H), 3.32 (s, 3H), 3.22–3.15 (m, 1H), 3.11 (dd, J ¼ 12.7,
4.0 Hz, 1H), 2.35 (s, 3H), 1.10 (t, J ¼ 6.0 Hz, 3H); 13C NMR (126
MHz, CDCl3) d 166.2, 165.6, 165.5, 165.3, 165.2, 164.9, 164.7,
138.4, 133.6, 133.44, 133.37, 133.27, 133.26, 133.19, 133.00,
132.95, 130.02, 129.94, 129.91, 129.8, 129.7, 129.6, 129.4, 129.2,
129.0, 128.63, 128.59, 128.5, 128.43, 128.40, 128.32, 128.27,
101.2, 100.0, 86.2, 82.7, 81.7, 75.4, 74.8, 74.0, 72.7, 72.5, 71.5,
70.6, 70.3, 68.8, 63.7, 59.6, 18.0; HRMS (ESI): m/z calcd for
C74H70O20NS [M + NH4]+ 1324.4206, found 1324.4198.
Lanost-7-en-3b-yl 2,4,6-tri-O-benzoyl-3-O-methyl-b-D-
glucopyranosyl-(1/3)-2,4-di-O-benzoyl-b-D-xylopyranosyl-
(1/4)-2,3-di-O-benzoyl-6-deoxy-b-D-glucopyranosyl-(1/2)-3-
O-benzoyl-b-D-xylopyranoside (38)
To a solution of 2 (100 mg, 0.05 mmol) in CH2Cl2 (2.80 mL) and
MeOH (0.80 mL) was added DDQ (34 mg, 0.15 mmol) in three
portions at half an hour interval. Aer 5 h, the reaction was
completed and the volatile was removed by evaporation. The
residue was taken up in dichloromethane and washed with
saturated aqueous NaHCO3 and brine. The collected organic
phase was dried over Na2SO4, ltered and concentrated under
reduced pressure. The residue was puried by silica gel column
chromatography (petroleum ether/EtOAc ¼ 2.5/1) to give 38 (81
mg, 88%). [a]2D4 ¼ ꢀ2.5 (c 1.05, CHCl3); 1H NMR (500 MHz,
CDCl3) d 8.11–7.97 (m, 6H), 7.96–7.83 (m, 8H), 7.79 (d, J ¼ 7.3 Hz,
2H), 7.66–7.53 (m, 3H), 7.52–7.38 (m, 10H), 7.38–7.19 (m, 9H),
7.15 (t, J ¼ 7.8 Hz, 2H), 5.48 (t, J ¼ 9.4 Hz, 1H), 5.42–5.31 (m, 2H),
5.26–5.20 (m, 1H), 5.18 (s, 1H), 5.03–4.98 (m, 1H), 4.98–4.95 (m,
1H), 4.94 (d, J ¼ 7.8 Hz, 1H), 4.88 (t, J ¼ 4.0 Hz, 1H), 4.82 (s, 1H),
4.76–4.67 (m, 2H), 4.47 (dd, J ¼ 12.0, 3.2 Hz, 1H), 4.34 (dd, J ¼
Lanost-7-en-3b-yl 2,4,6-tri-O-benzoyl-3-O-methyl-b-D-
glucopyranosyl-(1/3)-2,4-di-O-benzoyl-b-D-xylopyranosyl-
(1/4)-2,3-di-O-benzoyl-6-deoxy-b-D-glucopyranosyl-(1/2)-3-
O-benzoyl-4-O-(2-naphthylmethyl)-b-D-xylopyranoside (2)
A solution of 3 (62 mg, 0.076 mmol) and 4 (150 mg, 0.115 mmol) 12.0, 6.3 Hz, 1H), 4.25 (dd, J ¼ 10.1, 1.8 Hz, 1H), 4.22 (t, J ¼ 4.7
in anhydrous CH2Cl2 (2 mL) was stirred vigorously in the Hz, 1H), 4.04–3.97 (m, 1H), 3.94 (dd, J ¼ 12.6, 2.6 Hz, 1H), 3.90 (s,
˚
presence of activated 4 A molecular sieves (200 mg) for 20 min. 1H), 3.75 (t, J ¼ 9.2 Hz, 1H), 3.64–3.56 (m, 1H), 3.53 (dd, J ¼ 12.3,
ꢁ
The mixture was cooled to 0 C and NIS (34 mg, 0.152 mmol) 2.9 Hz, 1H), 3.43 (t, J ¼ 9.2 Hz, 1H), 3.33 (s, 3H), 3.19–3.03 (m,
and TMSOTf (2 mL, 0.008 mmol) were added. Aer stirring for 2 4H), 1.01 (d, J ¼ 6.0 Hz, 3H), 0.97 (s, 3H), 0.91–0.85 (m, 12H), 0.84
h, the reaction mixture was quenched with Et3N, and the solid (s, 3H), 0.67 (s, 3H), 0.64 (s, 3H); 13C NMR (126 MHz, CDCl3)
was ltered off. The ltrate was washed with saturated aqueous d 166.2, 166.04, 166.00, 165.5, 165.3, 165.2, 164.9, 164.7, 145.2,
Na2S2O3 and brine. The organic phase was dried over Na2SO4, 133.6, 133.6, 133.5, 133.4, 133.2, 133.2, 133.1, 133.0, 130.1,
ltered and concentrated. The residue was puried by silica gel 130.00, 129.96, 129.9, 129.78, 129.75, 129.74, 129.6, 129.42,
column chromatography (petroleum ether/EtOAc ¼ 3.5/1) to 129.38, 129.2, 128.7, 128.6, 128.5, 128.44, 128.43, 128.33, 128.29,
give 2 (134 mg, 67%). [a]D24 ¼ +10.6 (c 0.75, CHCl3); 1H NMR (500 116.6, 102.1, 101.3, 101.0, 100.1, 89.6, 82.9, 81.7, 77.4, 73.9, 73.7,
MHz, CDCl3) d 8.00 (d, J ¼ 7.3 Hz, 2H), 7.94–7.81 (m, 10H), 7.78 73.2, 72.72, 72.69, 72.5, 71.2, 70.6, 70.3, 68.8, 67.1, 63.7, 61.7,
(d, J ¼ 7.3 Hz, 2H), 7.74–7.65 (m, 3H), 7.62 (t, J ¼ 7.4 Hz, 1H), 59.6, 59.3, 52.1, 51.0, 50.5, 47.3, 44.5, 39.7, 39.1, 38.3, 36.7, 36.6,
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35.4, 32.3, 32.2, 28.3, 28.2, 27.8, 26.2, 25.0, 24.3, 23.00, 22.98, pyridine-d5) d 145.8, 117.7, 106.0, 105.9, 105.7, 89.6, 88.5, 87.6,
22.7, 20.2, 19.1, 17.5, 16.3, 16.2, 14.3; HRMS (ESI): m/z calcd for 86.5, 84.0, 78.7, 76.8, 76.2, 76.1, 75.8, 75.6, 74.3, 72.3, 71.1, 69.4,
C
109H126O26N [M + NH4]+ 1864.8563, found 1864.8521.
67.1, 64.9, 62.5, 61.4, 52.8, 51.7, 51.4, 48.0, 45.2, 40.3, 40.0, 38.8,
37.33, 37.27, 36.0, 33.1, 32.9, 28.8, 28.7, 28.4, 27.5, 25.5, 25.0,
23.7, 23.5, 23.2, 20.8, 19.7, 18.5, 17.1, 16.8, 14.9; HRMS (ESI): m/z
calcd for C53H89O21S [M ꢀ Na]ꢀ 1093.5621, found 1093.5625.
Lanost-7-en-3b-yl 2,4,6-tri-O-benzoyl-3-O-methyl-b-D-
glucopyranosyl-(1/3)-2,4-di-O-benzoyl-b-D-xylopyranosyl-
(1/4)-2,3-di-O-benzoyl-6-deoxy-b-D-glucopyranosyl-(1/2)-3-
O-benzoyl-4-O-sulfo-b-D-xylopyranoside (39)
Acknowledgements
To a mixture of alcohol 38 (60 mg, 0.032 mmol) in anhydrous
pyridine (2.0 mL) was added sulfur trioxide/pyridine complex
(103 mg, 0.65 mmol). The sealed Pyrex tube was irradiated in
the microwave (100 W, CEM corporation, Matthews, North
Carolina, USA) at 100 ꢁC for 2 h. Aer cooling, water (1 mL) was
added to the mixture, which was then concentrated in vacuo.
The residue was puried by silica gel column chromatography
(CH2Cl2/MeOH ¼ 13/1) to give 39 (60 mg, 0.03 mmol, 94%).
[a]2D4 ¼ +2.8 (c 1.00, CHCl3); 1H NMR (500 MHz, CDCl3) d 8.04 (d,
J ¼ 5.4 Hz, 2H), 7.99 (d, J ¼ 7.5 Hz, 2H), 7.97 (d, J ¼ 7.5 Hz, 2H),
7.93 (d, J ¼ 7.6 Hz, 2H), 7.87 (d, J ¼ 6.5 Hz, 4H), 7.79 (d, J ¼ 7.5
Hz, 2H), 7.63 (d, J ¼ 7.6 Hz, 2H), 7.60–7.52 (m, 3H), 7.50 (t, J ¼
7.3 Hz, 1H), 7.47–7.30 (m, 11H), 7.29–7.19 (m, 4H), 7.15 (t, J ¼
7.6 Hz, 2H), 7.10–7.00 (m, 1H), 6.73–6.54 (m, 2H), 5.46 (t, J ¼ 9.0
Hz, 1H), 5.39–5.24 (m, 3H), 5.19 (s, 1H), 5.04–4.97 (m, 2H), 4.97–
4.81 (m, 3H), 4.72 (s, 1H), 4.61 (d, J ¼ 7.8 Hz, 1H), 4.52–4.39 (m,
2H), 4.34 (d, J ¼ 11.9 Hz, 1H), 4.29 (dd, J ¼ 11.8, 6.1 Hz, 1H), 4.20
(t, J ¼ 4.8, 1H), 3.99–3.88 (m, 2H), 3.88–3.78 (m, 2H), 3.76–3.60
(m, 1H), 3.49 (t, J ¼ 9.0 Hz, 1H), 3.29 (s, 3H), 3.16–3.08 (m, 1H),
3.08–2.98 (m, 2H), 1.00 (d, J ¼ 5.5 Hz, 3H), 0.98 (s, 3H), 0.83 (s,
3H), 0.64 (s, 3H), 0.62 (s, 3H); 13C NMR (126 MHz, CDCl3)
d 166.2, 165.7, 165.4, 165.3, 165.2, 164.9, 164.7, 145.1, 133.5,
133.4, 133.3, 133.2, 133.0, 130.3, 130.03, 129.93, 129.88, 129.71,
129.70, 129.6, 129.5, 129.4, 129.2, 128.9, 128.64, 128.60, 128.5,
128.4, 128.3, 128.0, 127.9, 116.6, 102.16, 102.14, 101.1, 100.5,
90.0, 82.6, 81.7, 75.0, 74.4, 73.7, 72.8, 72.7, 72.4, 71.4, 71.2, 70.7,
70.6, 68.8, 63.7, 62.9, 60.0, 59.3, 52.1, 51.0, 50.5, 47.3, 44.5, 39.7,
39.1, 38.3, 36.7, 36.6, 35.4, 32.3, 32.2, 32.1, 30.3, 29.8, 29.7, 29.5,
28.5, 28.1, 27.8, 26.1, 25.0, 24.3, 23.0, 22.8, 22.7, 20.2, 19.1, 17.5,
16.2, 16.2, 14.2; HRMS (ESI): m/z calcd for C109H122O29S [M ꢀ
Na]ꢀ 1926.7787, found 1926.7743.
We are grateful for the nancial support from NSFC-Shandong
Joint Fund (U1406402); National Science Funding of China
(21272220); Project on Scientic development in Shandong
Province (2012GHY11526) and Fundamental Research Funds
for the Central Universities. We also thank Dr Patrick Chaffey
and Dr Zhongping Tan at the University of Colorado Boulder for
their revisions of this manuscript.
Notes and references
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Sodium salt of lanost-7-en-3b-yl 3-O-methyl-b-D-
glucopyranosyl-(1/3)-b-D-xylopyranosyl-(1/4)-6-deoxy-b-D-
glucopyranosyl-(1/2)-4-O-sulfo-b-D-xylopyranoside (1)
To a solution 39 (50 mg, 0.026 mmol) in 9 mL of anhydrous
methanol/CH2Cl2 (v/v ¼ 2/1) was added a solution of sodium
methoxide (1.04 mL, 1.04 mmol, 1 M) in methanol. Aer the
resulting mixture was stirred at rt for 30 h, it was diluted with
water, and then concentrated under reduced pressure. The
residue was dialyzed against water followed by lyophilization to
afford 1 (25 mg, 86%). [a]2D4 ¼ ꢀ7.0 (c 0.25, H2O); 1H NMR (500
MHz, pyridine-d5) d 5.40 (d, J ¼ 7.6 Hz, 1H), 5.35 (s, 1H), 5.26–
4.90 (m, 4H), 4.87 (d, J ¼ 7.3 Hz, 1H), 4.81–4.63 (m, 2H), 4.49 (d, J
¼ 10.6 Hz, 1H), 4.40–4.19 (m, 4H), 4.18–3.93 (m, 7H), 3.88 (s,
3H), 3.82–3.53 (m, 5H), 3.26 (d, 1H), 1.74 (d, J ¼ 5.4 Hz, 3H), 1.26
(s, 3H), 1.19 (s, 3H), 1.11 (s, 3H), 0.99 (d, J ¼ 8.6 Hz, 3H), 0.98 (s,
3H), 0.92 (d, J ¼ 6.5 Hz, 6H), 0.76 (s, 3H); 13C NMR (126 MHz,
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