Studies towards the synthesis of the β-D-Xyl-(1→ 3)-L-ara disaccharide moiety of OSW-1 from Ornithogalum saundersiae

Article abstract of DOI:10.1081/CAR-200029997

The OSW-1 disaccharide having 2-O-p-methoxybenzoyl-β-D-xylopyranosyl- (1 → 3)-L-arabinopyranoside structure was obtained as the benzylated 4-O-acetyl derivative 19. Also, the 4,2′-di-O-acetate 18 was synthesized by a short synthetic approach. The arabinos

Full text of DOI:10.1081/CAR-200029997

This article was downloaded by: [University of Saskatchewan Library]
On: 17 October 2012, At: 22:19
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Carbohydrate Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lcar20
Studies Towards the Synthesis of the
β‐D‐Xyl‐(1 → 3)‐L‐ara Disaccharide
Moiety of OSW‐1 from Ornithogalum
saundersiae
René Suhr a & Joachim Thiem a
a Institute of Organic Chemistry, University of Hamburg,
Martin‐Luther‐King‐Platz 6, D‐20146, Hamburg, Germany
Version of record first published: 18 Aug 2006.
To cite this article: René Suhr & Joachim Thiem (2004): Studies Towards the Synthesis of the
β‐D‐Xyl‐(1 → 3)‐L‐ara Disaccharide Moiety of OSW‐1 from Ornithogalum saundersiae , Journal of
Carbohydrate Chemistry, 23:5, 261-276
To link to this article: http://dx.doi.org/10.1081/CAR-200029997
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 23, No. 5, pp. 261–276, 2004
Studies Towards the Synthesis of the b-D-Xyl-
(1!3)-L-ara Disaccharide Moiety of OSW-1 from
Ornithogalum saundersiae1
*
´
Rene Suhr and Joachim Thiem
Institute of Organic Chemistry, University of Hamburg, Hamburg, Germany
CONTENTS
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
I. INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
II. RESULTS AND DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . 262
A. Synthesis of D-Xylopyranose Donors . . . . . . . . . . . . . . . . . 262
B. Preparation of Benzyl 4-O-Acetyl-2-O-benzyl-b-L-arabino-
pyranose as Acceptor . . . . . . . . . . . . . . . . . . . . . . . . . . 264
C. Formation of b-D-Xyl-(1 ! 3)-L-ara Disaccharides . . . . . . . . . 264
III. CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
IV. EXPERIMENTAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
A. General Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
1This paper is dedicated to Professor Karsten Krohn on the occasion of his 60th birthday.
*
Correspondence: Joachim Thiem, Institute of Organic Chemistry, University of Hamburg, Martin-
Luther-King-Platz 6, D-20146 Hamburg, Germany; E-mail: thiem@chemie.uni-hamburg.de.
261
DOI: 10.1081/CAR-200029997
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

262
Suhr and Thiem
ACKNOWLEDGMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
ABSTRACT
The OSW-1 disaccharide having 2-O-p-methoxybenzoyl-b-D-xylopyranosyl-(1 ! 3)-
L-arabinopyranoside structure was obtained as the benzylated 4-O-acetyl derivative 19.
Also, the 4,20-di-O-acetate 18 was synthesized by a short synthetic approach. The ara-
binose acceptor 15 was obtained in a three step-one pot sequence from easily available
benzyl b-L-arabinopyranoside.
Key Words: Saponin glycosides; Arabinopyranose acceptor; Xylopyranose donor;
b–D –Xyl–(1–3)–L –ara disaccharide.
INTRODUCTION
Natural products of plants show a broad spectrum of biological activities with a high
potential for medicinal applications. A structurally diversified class of compounds are the
saponins, complex glycosides with a steroid, a steroid alkaloid or triterpene aglycon.[1–4]
Several groups perform systematic research on the constitution and biological effects
of this interesting class of compounds. Kubo et al. and Mimaki et al. described OSW-1 (1)
and some of its derivatives with a variation in the benzoyl part and showed their high cyto-
static potential concurrent with a low effect on non-transformed cells.[5,6] OSW-1 was
tested in vitro (IC50 ¼ 0.25 nM, leukemia HL-60 cell line) and in vivo (mice P388,
enhanced life span by single application of 0.1 mg/kg: 59%). This activity is 10–100
times better than prominent cancer therapeutics presently in use, whereas the toxicity
against non-transformed cells is low.
The synthesis of the aglycon part was performed by Guo and Fuchs in 1998[7,8] and
the total synthesis of 1 was published by Deng et al.[9] Several other groups work on
synthetic projects concerning this highly interesting compound.[10–13] As a part of our
research on saponin chemistry,[14–17] our interest focused on alternative pathways
and glycosylation studies towards the disaccharide moiety.
RESULTS AND DISCUSSION
Synthesis of D-Xylopyranose Donors
The xylopyranoside part of OSW-1 contains a 2-O-p-methoxybenzoyl group, whereas
related compounds are substituted by other electron-rich benzoyl substituents such as
cinnamoyl or 3,4-dimethoxybenzoyl (veratryl). These latter two OSW-1 derivatives are
rare: they were isolated more recently and showed an even higher cytostatic activity than
OSW-1 itself. Therefore, a variation of the 2-O-benzoyl substitution is of particular interest.

Ornithogalum saundersiae
263
The introduction of the modified benzoate can occur on the level of the xylose donor, on the
level of the disaccharide, or even on the level of the saponin. In order to obtain b-glycosidic
bonds selectively, a neighboring participating group in the 2 position is required.
Scheme 1 shows the synthesis of two donors applying the orthoester methodology,
which was introduced and investigated extensively by Kochetkov et al.[18–20] This group
demonstrated the advantage of using orthoesters as efficient donors as well as intermediates,
which are differentiated in the 2-position. Starting from acetobromoxylopyranose 2,[21,22]
ethanethiol or ethanol was reacted in the presence of sym-collidine as a hindered base in
acetonitrile under catalysis of tetrabutylammonium bromide to give 3 and 6,[23] respectively.
´
The remaining acetates in 3- and 4-position were cleaved by the Zemplen method, and the
resulting hydroxyl groups were benzylated. This short synthetic sequence with good to sat-
isfactory yields for each step led to thioorthoester 5 as a b-selective donor.
To obtain a 2-O-p-methoxybenzoylated xylopyranose donor, the ethyl orthoester 8
was not isolated. The orthoester group was cleaved in 95% acetic acid, and the resulting
hydroxyl groups were reacetylated by a standard procedure. The 1,2-diacetate 9 was
obtained from 7 in 74% yield over three steps. The following thiomethylation at the
anomeric position occurred with methylthiotrimethylsilane (TMSSMe) under TMSOTf
´
catalysis and the remaining 2-O-acetate was transesterified under Zemplen conditions.
The selectively dibenzylated thiomethyl xylopyranoside 10 was obtained as a mixture
of anomers in 52% yield.
The acylation of the 2-O-position with p-methoxybenzoyl chloride was performed in
pyridine to give donor 11. TLC monitoring showed a different reactivity of the two
anomers, of which the a-anomer appeared to be more reactive. In comparison, it may
be noted that Deng et al.[9] obtained a selective 2-O-benzoylation of the benzyl a-D-xylo-
pyranoside.
The synthetic flexibility of the thioglycosides allowed a facile preparation of the
highly reactive trichloroacetimidate 13 in good yield, which was subjected to the glyco-
sylation of the arabinose acceptor.
Preparation of Benzyl 4-O-Acetyl-2-O-benzyl-b-L-arabinopyranose
as Acceptor
Fischer glycosylation of L-arabinose with benzyl alcohol led to benzyl b-L-arabino-
pyranoside 14[24,25] in high yield. Whereas the b-L-arabinopyranosides are preferentially
4
found as C1 conformers (96%), the a-anomers undergo a rapid conformational change
1
with a high amount of the less reactive C4 form.[26] In order to obtain an acceptor with
a free 3-hydroxyl group for differentiation of the 2-, 3-, and 4-position of the L-arabino-
pyranoside an easy three step-one pot procedure was chosen (Sch. 2). The 3,4-diol was
protected as an orthoacetate, followed by benzylation of the 2 position. The orthoester
group was selectively rearranged with 95% acetic acid to give the acceptor arabino-
pyranose derivative 15 with a free 3-hydroxyl group in high yield.
Under mild basic conditions an acetate migration to the 3 position occurred to give 16,
which might offer a pathway to other arabinose acceptors. In such a case, compound 15
could be obtained by deacetylation, to give 17[27] followed by orthoacetate protection
and orthoacetate rearrangement as described earlier (Sch. 2).

264
Suhr and Thiem

Ornithogalum saundersiae
265

266
Suhr and Thiem

Ornithogalum saundersiae
Formation of b-D-Xyl-(1 ! 3)-L-ara Disaccharides
267
The xylose donors 13 and 5 were successfully reacted with benzyl 4-O-acetyl-2-O-
benzyl-b-L-arabinopyranoside (15) to give the disaccharides 18 and 19 with b-D-xyl-
(1!3)-b-L-ara structure. Thiol activation of 5 by NIS with a catalytic amount of TfOH
to rearrange intermediate orthoesters[28] was performed in diethylether/dichloromethane,
because glycosylations were slower and milder than in pure dichloromethane.[29] The dis-
accharide 18 with acetyl and benzyl protecting groups was obtained in 61% yield.
An even better yield was obtained with the trichloroacetimidate donor 13 in CH2Cl2
through activation with BF3–etherate. By this reaction the 20-O-p-methoxybenzoyl
substituted disaccharide 19 resulted in 74% yield (Sch. 3).
CONCLUSIONS
In this work facile syntheses of both xylopyranose donors as well as the arabinopyra-
nose acceptor could be favorably elaborated. Further, optimized glycosylations led to the
title compound 2-O-p-methoxybenzoyl-b-D-xylopyranosyl-(1!3)-L-arabinopyranoside
in form of a partially protected derivative.
EXPERIMENTAL
General Procedures
1H NMR spectra (400 MHz) and 13C NMR spectra (100.67 MHz) were recorded with
the Bruker AMX-400 (400 MHz 1H, 100.67 MHz 13C) or DRX-500 (500 MHz 1H,
125.77MHz 13C) spectrometers. Melting points were determined with an Olympus BH-2
polarizing microscope with a Mettler FP 82 heating desk. Optical rotations were
determined with a Perkin–Elmer 241 polarimeter. Thin layer chromatography (TLC)
was performed on precoated plates of silica gel 60 (GF254 by Merck or ALUGRAM
SIL G/UV254 by Machery-Nagel), detection occurred by UV-absorption or spraying
with 15% ethanolic sulfuric acid and subsequent heating. Column chromatography was
performed by the flash technique on silica gel 230–400 mesh (Merck). Elemental analyses
were performed in the Microanalytical Laboratory of the Institute of Organic Chemistry of
the University of Hamburg.
3,4-Di-O-acetyl-1,2-O-(1-ethylthioethylidene)-a-D-xylopyranose (3). In a 500 mL
round bottom flask acetobromoxylose (2, 55.50 g, 164 mmol)[21,22] was dissolved in anhy-
drous acetonitrile (170 mL) under argon. Then sym-collidine (28.0 mL, 25.0g, 210mmol)
and tetrabutylammonium bromide (5.60 g, 17.0 mmol) were added. The round bottom
flask was closed with a septum and an argon filled balloon was attached. Ethanethiol
(16.0 mL, 13.0 g, 220 mmol) was added via a syringe and the reaction mixture was stirred
for 21 hr at room temperature (RT) until TLC [petroleum ether (PE)/ethyl acetate (EA)
1 : 1, Rf (2) ¼ 0.44] showed complete conversion of the starting material. The solvent was
removed under reduced pressure and the remainder was coevaporated four times with
toluene, dissolved in diethylether and washed seven times with water to remove collidinium

268
Suhr and Thiem
hydrobromide. After flash chromatography with PE/EA 3 : 1 þ 1% pyridine 3 (34.30 g,
1
107 mmol, 65%) was obtained as a mixture of diastereomers (exo/endo ꢁ 5: 1 by H
NMR). Slightly yellow oily mass; TLC (PE/EA 1 : 1): Rf ¼ 0.80 (PE/EA 3 : 1, þ1% pyri-
dine): Rf ¼ 0.34; (H2SO4); 1H NMR (500 MHz, CDCl3): dexo ¼ 5.59 (d, 1H, H-1,
3
3
3J1,2 ¼ 4.7Hz), 5.40 (d, 1H, H-1endo, J1,2 ¼ 3.4 Hz), 5.25 (dd ꢀ t, 1H, H-3, J2,3 ¼ 2.8,
3J3,4 ¼ 2.5Hz), 4.90 (m, 1H, H-4), 4.39 (m, 1H, H-2), 3.95 (dd, 1H, H-5a, J4,5a ¼ 6.6,
3
2J5a,5b ¼ 12.0 Hz), 3.63 (dd, 1H, H-5b, J4,5a ¼ 8.5, J5a,5b ¼ 12.0 Hz), 2.63 (q, 2H,
SCH2CH3, 3J ¼ 7.5 Hz), 2.09, 2.12 (2ꢂ s, ꢂ3H, CH3COO), 1.96 (s, 3H, endo-CH3C[OR]2-
SEtexo), 1.26 (t, 3H, SCH2CH3, 3J ¼ 7.5 Hz) ppm; 13C NMR (100.67 MHz, CDCl3):
dexo ¼ 169.92, 169.21 (2ꢂ CH3COO), 116.59 (CH3C[OR]2SEtexo), 96.82 (C-1), 90.33 (C-
3
2
1
endo), 73.58, 69.18, 67.90 (C-2, C-3, C-4), 58.97 (C-5), 27.66 (endo-CH3C[OR]2SEtexo),
24.78 (SCH2CH3), 20.83, 20.75 (CH3COO), 15.04 (SCH2CH3) ppm.
(S)-1,2-O-(1-Ethylthioethylidene)-a-D-xylopyranose (4). In a 500mL round bottom
flask acetobromoxylose (2, 30.91 g, 91.1 mmol),[21,22] was dissolved in anhydrous. aceto-
nitrile (100 mL) under argon. Then sym-collidine (15.6 mL, 117.4 mmol) and tetra-
butylammonium bromide (2.97 g, 9.1mmol) were added. The round bottom flask was
closed with a septum and an argon filled balloon was attached. Ethanethiol (11.2mL,
151 mmol) was added via a syringe, and the reaction mixture was stirred overnight at RT
until TLC (PE/EA 1 : 1, Rf (2) ¼ 0.44) showed complete conversion of the starting material.
The solvent was removed under reduced pressure, and the remainder was coevaporated four
times with toluene, dissolved in diethylether and washed seven times with water to remove
collidinium hydrobromide. The slightly yellow syrup was dissolved in anhydrous. methanol
(120 mL), and a 1 M methanolic sodium methanolate solution (3.0 mL, 3 mmol) was added.
The reaction mixture was stirred for 10 min at RT until TLC showed complete conversion of
the starting material. The solvent was evaporated and the remainder was coevaporated with
toluene. After crystallization from toluene (no heating!) at 2308C compound 4 (19.64 g,
83.1mmol, 91%) was obtained as pure exo-derivative. Colorless needles; mp: 67.5–
68.58C; [a]2D0 ¼ þ46.5 (c ¼ 0.4, MeOH); TLC (PE/EA 1 : 1 þ 1% pyridine): Rf ¼ 0.36
1
3
(H2SO4); H NMR (400 MHz, CDCl3): dexo ¼ 5.55 (d, 1H, H-1, J1,2 ¼ 3.6Hz), 4.26
3
3
(dd ꢀ t, 1H, H-2, J1,2 ¼ 3.6 Hz), 4.03 (m, 1H, H-3), 3.91 (dd, 1H, H-5a, J4,5a ¼ 6.4,
2J5a,5b ¼ 14.0 Hz), 3.72–3.64 (m, 2H, H-4, H-5b), 3.56 (bs, 2H, 3-OH, 4-OH), 2.65 (q, 2H,
SCH2CH3, 3J ¼ 7.4Hz), 1.95 (s, 3H, CH3C(SEt)OR2), 1.26 (t, 3H, SCH2CH3, 3J ¼ 7.4 Hz)
ppm; 13C NMR (100.67 MHz, CDCl3): dexo ¼ 116.79 (CH3C[OR]2SEtexo), 97.28 (C-1),
77.06, 79.85, 68.01 (C-2, C-3, C-4), 63.67 (C-5), 28.88 (endo-CH3C[OR]2SEtexo), 24.78
(SCH2CH3), 15.00 (SCH2CH3) ppm.
3,4-Di-O-benzyl-1,2-O-(1-ethylthioethylidene)-a-D-xylopyranose (5). In a 1 L three
neck round bottom flask with condenser and dropping funnel compound 4 (11.45 g,
48.45 mmol) was dissolved in anhydrous DMF (100 mL) and sodium hydride (3.48g,
145 mmol) was cautiously added in small portions (gas development, solution became
yellow). The suspension was stirred for 25 min until the gas development decreased. The
reaction mixture was cooled in an ice bath and benzyl bromide (12.7 mL, 106.6 mmol)
was added slowly via the dropping funnel. Stirring continued for 48 hr at RT until TLC
showed complete conversion of the starting material. The mixture was again cooled in an
ice bath and water (3 mL) was added slowly and stirring continued for 1/2hr. The volume
of the solvent was reduced under high vacuum, the remainder was dissolved in diethylether
and was washed five times with water. After flash chromatography with PE/EA 5 : 1 com-
pound 5 (10.48 g, 25.16 mmol, 52%) was obtained. Slightly yellow syrup; [a]2D0 ¼ 216.2

Ornithogalum saundersiae
269
(c ¼ 0.5, CHCl3); TLC (PE/EA 5 : 1): Rf ¼ 0.30 (UV, H2SO4); 1H NMR (400 MHz, CDCl3):
3
dexo ¼ 7.47–7.25 (m, 10H, 2ꢂ C6H5CH2O), 5.67 (d, 1H, H-1, J1,2 ¼ 5.6 Hz), 4.85–4.49
(m, 5H, C6H5CH2O, H-2), 3.93 (dd ꢀ t, 1H, H-3, 3J3,4 ¼ 3.1 Hz), 3.81–3.59 (m, 3H, H-4,
H-5a, H-5b), 2.61 (m, 2H, SCH2CH3), 1.98 (s, 1H, endo-CH3C[OR]2SEtexo), 1.36 (t, 3H,
3
SCH2CH3, J ¼ 7.4 Hz); 13C NMR (100.67MHz, CDCl3): dexo ¼ 138.35, 137.99, 137.6,
128.99–128.08 (C6H5CH2O), 116.19 (CH3C[OR]2SEt), 98.24 (C-1), 78.20, 75.80, 75.07
(C-2, C-3, C-4), 72.47, 72.29 (C6H5CH2O), 63.18 (C-5), 28.45 (endo-CH3C[OR]2SEtexo),
25.22 (SCH2CH3), 15.63 (SCH2CH3).
1,2-Di-O-acetyl-3,4-di-O-benzyl-D-xylopyranose (9). In a 1 L three neck round
bottom flask with condenser and dropping funnel compound 7[23] (4.0 g, 18.2 mmol)
was dissolved in anhydrous DMF (250 mL), and sodium hydride (1.7 g, 70.8 mmol) was
cautiously added in small portions (gas development, solution became yellow). The sus-
pension was stirred for 10 min until the gas development decreased. The reaction mixture
was cooled in an ice bath and benzyl bromide (6.7 mL, 56.4 mmol) was added slowly via
the dropping funnel. Stirring was continued for 1 hr at RT until TLC showed complete
conversion of the starting material. The mixture was again cooled in an ice bath, and
methanol (5 mL) was added slowly, and stirring was continued for 15 min. The volume
of the solvent was reduced under high vacuum, and the remainder was dissolved in
ethyl acetate and was washed five times with water. The crude 8 (PE/EA 3 : 1,
Rf ¼ 0.46) was dissolved in 95% acetic acid (10 mL) and the solution was left for 1 hr
at RT. The solution was concentrated and coevaporated three times with toluene. Then
the remainder was dissolved in pyridine (20 mL) and acetic acid anhydride (10 mL) was
added. Stirring was continued overnight at RT. The reagents were removed under high
vacuum and the crude product was purified by flash chromatography with PE/EA 3 : 1
to give 9 (5.57 g, 13.4 mmol, 74%) as a mixture of anomers. Colorless solid; TLC (PE/
1
EA 3 : 1): Rf ¼ 0.34, 0.29 (UV, H2SO4); H NMR (400 MHz, CDCl3): da ¼ 7.37–7.25
3
(m, 10H, 2ꢂ C6H5CH2O), 6.18 (dd, 1H, H-1, J1,2 ¼ 1.0, 3.6 Hz), 4.96 (ddd, 1H, H-2,
3
3J1,2 ¼ 1.0, 3.6, J2,3 ¼ 9.7 Hz), 4.88 (d, 1H, C6H5CH2O, 2J ¼ 11.7 Hz), 4.77–4.73
2
(m, 2H, C6H5CH2O), 4.63 (d, 1H, C6H5CH2O, J ¼ 11.2 Hz), 3.90 (dd ꢀ t, 1H, H-3,
3
3
3
3J2,3 ¼ 9.2, J3,4 ¼ 8.7 Hz), 3.81 (dd, 1H, H-5eq, J4,5eq ¼ 4.3, J5eq,5ax ¼ 9.4 Hz),
3.74–3.61 (m, 2H, H-4, H-5aꢂ), 2.13, 1.98 (2ꢂ s, 2ꢂ 3H, 2ꢂ CH3COO) ppm.
Methyl 3,4-Di-O-benzyl-1-thio-b-D-xylopyranoside (10b) and methyl 3,4-di-O-
benzyl-1-thio-a-D-xylopyranoside (10a). In a 250 mL round bottom flask diacetate 9
(5.57 g, 13.4 mmol) was dissolved in anhydrous dichloromethane (50 mL) under argon.
The round bottom flask was closed with a septum and an argon filled balloon was attached.
Then methylthiotrimethylsilane (TMSSMe, 2.48 mL, 17.5 mmol) was added, and the reac-
tion mixture was cooled in an ice bath. TMSOTf (2.43 mL, 13.46 mmol) was added and
stirring was continued over night with the temperature rising to RT until TLC (PE/EA
3 : 1) showed complete conversion. Then under cooling in an ice bath triethylamine
(10 mL) was added, stirred for 10 min, and the solvent was removed under reduced pres-
sure. The residue was coevaporated with toluene three times, dissolved in diethylether and
washed twice with water, once with 10% aqueous NaHCO3 solution and once again with
water. The organic phase was dried over sodium sulfate, filtered, and evaporated. The
crude product was dissolved in methanol (50 mL) and solid sodium methoxide was
added until pH 9 was reached. The reaction mixture was stirred for 5 hr until TLC
showed complete conversion, neutralized with Amberlite IR 120 (Hþ), and the solvent
was removed under reduced pressure. After crystallization from Et2O/PE compound

270
Suhr and Thiem
10b (868 mg, 2.41 mmol, 18%) and a mixture of the anomers 10b and 10a (1.600 g,
4.43 mmol, 33%) were obtained. 10b: Fine needles; mp: 107.8–108.58C; [a]2D0 ¼ 261.8
1
(c ¼ 0.6, CHCl3); TLC (PE/EA 3 : 1): Rf ¼ 0.24 (UV, H2SO4); H NMR (400 MHz,
CDCl3): d ¼ 7.28–7.20 (m, 10H, 2ꢂC6H5CH2O), 4.77, 4.72 (2ꢂ d, 2ꢂ 1H, C6H5CH2O,
2
2J ¼ 11.4 Hz), 4.62, 4.57 (2ꢂ d, 2ꢂ 1H, C6H5CH2O, J ¼ 11.4 Hz), 4.37 (d, 1H, H-1,
3
2
3J1,2 ¼ 7.1 Hz), 4.08 (dd, 1H, H-5eq, J4,5eq ¼ 3.7, J5eq,5ax ¼ 12.0 Hz), 3.58–3.45
(m, 3H, H-2, H-3, H-4), 3.32 (dd, 1H, H-5ax, 3J4,5ax ¼ 7.8, 2J5eq,5ax ¼ 12.0 Hz), 2.35 (bs,
1H, 2-OH), 2.10 (s, 3H, SCH3) ppm; 13C NMR (100.62 MHz, CDCl3): d ¼ 138.44,
128.66–128.62, 128.11–127.97 (2ꢂ C6H5CH2O), 87.04 (C-1), 81.61, 76.69, 71.34 (C-2,
C-3, C-4), 74.45, 72.91 (C6H5CH2O), 65.35 (C-5), 13.03 (SCH3) ppm.
Anal. calcd for C20H24O4S (360.46): C 66.64, H 6.71. Found: C 66.30, H 6.51.
1
10a: TLC (PE/EA 3 : 1): Rf ¼ 0.19 (UV, H2SO4); H NMR (400 MHz, CDCl3):
3
d ¼ 7.28–7.20 (m, 10H, 2ꢂ C6H5CH2O), 4.95 (d, 1H, H-1, J1,2 ¼ 3.6 Hz), 4.72–4.58
3
2
(m, 4H, 2ꢂ C6H5CH2O), 4.04 (dd, 1H, H-5eq, J4,5eq ¼ 3.6, J5eq,5ax ¼ 12.2 Hz), 3.88–
3.48 (m, 4H, H-2, H-3, H-4, H-5ax), 3.18 (m, 1H, 2-OH), 2.21 (s, 3H, SCH3) ppm.
Methyl 3,4-Di-O-benzyl-2-O-p-methoxybenzoyl-1-thio-a-D-xylopyranoside (11a)
and
methyl
3,4-di-O-benzyl-2-O-p-methoxybenzoyl-1-thio-b-D-xylopyranoside
(11b). Compound 10 (210 mg, 0.58 mmol) was dissolved in pyridine (2 mL). The solution
was cooled in an ice bath and p-methoxybenzoyl chloride (0.16 mL, 200 mg, 1.17 mmol)
was added in portions and stirred for 14 hr at RT. Then another portion of p-methoxyben-
zoyl chloride (0.08 mL, 100 mg, 0.59 mmol) was added, and stirring continued for another
24 hr at RT. The reaction was stopped by cooling in an ice bath, addition of methanol
(1 mL) and stirring for 1 hr. The crude product was purified by flash chromatography
with PE/EA 3 : 1 to give the a-anomer 11a (45 mg, 0.09 mmol, 16%), the b-anomer
11b (99 mg, 0.20 mmol, 36%) and a mixture of the anomers (83 mg, 0.17 mmol, 29%);
total yield of 11: 227 mg (0.46 mmol, 79%). 11a: colorless solid; mp: 99.6–100.38C;
[a]2D0 ¼ 218.9 (c ¼ 0.4, CHCl3); TLC (PE/EA 3 : 1): Rf ¼ 0.36 (UV, H2SO4); 1H
NMR (400 MHz, CDCl3): d ¼ 7.98 (ddd, 2H, b-CH3OC6H4COO, 3J ¼ 9.2,
4J ¼ 2.0 Hz), 7.34–7.18 (m, 10H, 2ꢂ C6H5CH2O), 6.91 (ddd, 2H, g-CH3OC6H4COO,
4
3
3
3J ¼ 9.2, J ¼ 2.0 Hz), 5.46 (d, 1H, H-1, J1,2 ¼ 5.6 Hz), 5.21 (dd, 1H, H-2, J1,2 ¼ 5.1,
3J2,3 ¼ 9.2 Hz), 4.82 (d, 1H, C6H5CH2O, 2J ¼ 11.2 Hz), 4.78 (d, 1H, C6H5CH2O,
2J ¼ 11.2 Hz), 4.74 (d, 1H, C6H5CH2O, 2J ¼ 11.7 Hz), 4.64 (d, 1H, C6H5CH2O,
2J ¼ 11.7 Hz), 4.03–3.93 (m, 2H, H-3, H-5a), 3.86 (s, 3H, CH3OC6H4COO), 3.77–3.64
(m, 2H, H-4, H-5b), 2.03 (s, 3H, SCH3) ppm; 13C NMR (100.67 MHz, CDCl3):
d ¼ 165.45 (CH3OC6H4COO), 163.79 (d-CH3OC6H4COO), 138.30 (quart-C6H5CH2O),
132.12 (b-CH3OC6H4COO), 128.59, 128.45, 128.06, 127.97, 127.93, 127.78
(2ꢂ C6H5CH2O), 122.16 (a-CH3OC6H4COO), 113.89 (g-CH3OC6H4COO), 83.99
(C-1), 79.19 (C-3), 77.79 (C-4), 75.34, 73.47 (2ꢂ C6H5CH2O), 73.05 (C-2), 60.92 (C-
5), 55.61 (CH3OC6H4COO), 12.92 (SCH3) ppm. 11b: Colorless needles; mp: 177.2–
178.08C; [a]2D0 ¼ þ 40.7 (c ¼ 0.8, CHCl3); TLC (PE/EA 3:1): Rf ¼ 0.27 (UV,
1
3
H2SO4); H NMR (400 MHz, CDCl3): d ¼ 7.98 (ddd, 2H, b-CH3OC6H4COO, J ¼ 8.7,
4J ¼ 3.1, 2.0 Hz), 7.34–7.13 (m, 10H, 2ꢂ C6H5CH2O), 6.91 (ddd, 2H, g-CH3OC6H4-
3
4
3
3
COO, J ¼ 9.2, J ¼ 2.5, 2.0 Hz), 5.23 (dd ꢀ t, 1H, H-2, J1,2 ¼ 8.7, J2,3 ¼ 8.6 Hz),
2
2
4.77 (d, 1H, C6H5CH2O, J ¼ 11.2 Hz), 4.72 (d, 1H, C6H5CH2O, J ¼ 8.6 Hz), 4.69
2
2
(d, 1H, C6H5CH2O, J ¼ 8.1 Hz), 4.63 (d, 1H, C6H5CH2O, J ¼ 11.7 Hz), 4.44 (d, 1H,
3
3
2
H-1, J1,2 ¼ 8.7 Hz), 4.14 (dd, 1H, H-5eq, J4,5eq ¼ 4.6, J5eq,5ax ¼ 11.7 Hz), 3.86
(s, 3H, CH3OC6H4COO), 3.78–3.67 (m, 2H, H-3, H-4), 3.38 (dd, 1H, H-5ax,

Ornithogalum saundersiae
271
2
3J4,5ax ¼ 9.2, J5eq,5ax ¼ 11.7 Hz), 2.14 (s, 3H, SCH3) ppm; 13C NMR (100.67 MHz,
CDCl3): d ¼ 165.03 (CH3OC6H4COO), 163.71 (d-CH3OC6H4COO), 138.12 (quart-
C6H5CH2O), 132.11 (b-CH3OC6H4COO), 128.63, 128.38, 128.14, 128.06, 128.00,
127.75 (2ꢂ C6H5CH2O), 122.35 (a-CH3OC6H4COO), 113.81 (g-CH3OC6H4COO),
84.05 (C-1), 81.96, 77.52 (C-3, C-4), 74.88, 73.38 (2ꢂ C6H5CH2O) 70.96 (C-2), 67.34
(C-5), 55.61 (CH3OC6H4COO), 11.90 (SCH3) ppm.
3,4-Di-O-benzyl-2-O-p-methoxybenzoyl-D-xylopyranose (12). Thioglycoside 11
(689 mg, 1.39 mmol) was dissolved in acetonitrile (15 mL) and water (0.2 mL,
11.1 mmol) was added. The mixture was cooled in an ice bath, and NBS (545 mg,
3.06 mmol) was added in portions and the solution became yellow–brown. The reaction
was monitored by TLC with PE/EA 1 : 1 and was complete after 30 min. A tenfold
excess of diethylether was added and the solution was washed with saturated
NaHCO3 and H2O, dried over sodium sulfate and evaporated to dryness. The crude
product was crystallized from isopropanol to give 12 (510 mg, 1.10 mmol, 79%, a/
b ꢁ 5 : 4 by 1H NMR). Colorless solid; TLC (PE/EA 1 : 1): Rf ¼ 0.50–0.36; (UV,
1
H2SO4); H NMR (400 MHz, CDCl3): d ¼ 8.03–7.94 (m, 4H, 2ꢂ b-CH3OC6H4COO),
7.34–7.18 (m, 20H, 4ꢂ C6H5CH2O), 6.93–6.87 (m, 4H, 2ꢂ g-CH3OC6H4COO), 5.42
3
3
3
(d, 1H, H-1a, J1,2 ¼ 3.6 Hz), 5.03 (dd, 1H, H-2a, J1,2 ¼ 3.6, J2,3 ¼ 9.2 Hz), 4.99
3
3
(dd ꢀ t, 1H, H-2b, J1,2 ¼ 8.1, J2,3 ¼ 9.2 Hz), 4.87–4.60 (m, 9H, H-1b,
3
3
4ꢂ C6H5CH2O), 4.14, (dd ꢀ t, 1H, H-3a, J2,3 ¼ 8.1, J3,4 ¼ 9.2 Hz), 4.07 (dd, 1H,
3
2
H-5eqb, J4,5eq ¼ 5.1, J5eq,5ax ¼ 12.2 Hz), 3.92–3.65 (2ꢂm, 2H, 5H, 2ꢂ H-3, 2ꢂ H-
3
4, 3ꢂ H-5), 3.86 (s, 3H, CH3OC6H4COO), 3.41 (dd, 1H, H-5axb, J4,5ax ¼ 9.2,
2J5eq,5ax ¼ 12.2 Hz), 2.45 (m, 2H, 2 ꢂ 1-OH) ppm; 13C NMR (100.67 MHz, CDCl3):
d ¼ 166.63, 165.67 (2ꢂ CH3OC6H4COO), 163.80, 163.63 (2ꢂ d-CH3OC6H4COO),
138.25, 138.13 (2ꢂ quart-C6H5CH2O), 132.07, 131.94 (2ꢂ b-CH3OC6H4COO),
128.49–127.63 (4ꢂ C6H5CH2O), 122.02, 121.69 (2ꢂ a-CH3OC6H4COO), 113.72
(2ꢂ g-CH3OC6H4COO), 96.06, 90.90 (2ꢂ C-1), 79.74, 78.20, 77.58, 77.06, 74.60,
73.26 (je 2ꢂ C-2, C-3, C-4), 75.16, 74.83, 73.28, 73.14 (2ꢂ C6H5CH2O), 63.16, 60.48
(C-5), 55.48, 55.47 (2ꢂ CH3OC6H4COO) ppm.
O-(3,4-Di-O-benzyl-2-O-p-methoxybenzoyl-D-xylopyranosyl)-trichloroacetim-
idate (13). In a 100 mL round bottom flask compound 12 (516 mg, 1.11 mmol) was co-
evaporated three times with toluene and residual solvent was removed in vacuo. Then
the remainder was dissolved under argon atmosphere in anhydrous CH2Cl2 (30 mL).
The round bottom flask was closed with a septum and an argon filled balloon was attached.
Trichloroacetonitrile (1.11 mL, 11.10 mmol) and DBU (16 mL, 0.11 mmol) were added via
a syringe. The reaction was monitored by TLC with PE/EA 1 : 1. Because there was no
reaction after stirring for 20 hr, another ten drops of DBU were added and stirring contin-
ued for 8.5 hr. The product was purified by flash chromatography with PE/EA 4 : 1 þ 0.1%
triethylamine to give 13 (411 mg, 0.67 mmol, a/b ꢁ 1 : 6 by 1H NMR, 60%). Syrup; TLC
1
(PE/EA 1 : 1): Rf ¼ 0.71 (UV, H2SO4); H NMR (400 MHz, CDCl3): d ¼ 8.60 (s, 1H,
NHb), 8.50 (s, 1H, NHa), 7.97–7.90 (m, 2ꢂ 2H, 2ꢂ b-CH3OC6H4COO), 7.34–7.18
(m, 2ꢂ 10H, 4ꢂ C6H5CH2O), 6.88, 6.85 (2ꢂ m, 2ꢂ 2H, 2ꢂ g-CH3OC6H4COO), 6.48
3
3
(d, 1H, H-1a, J1,2 ¼ 3.6 Hz), 6.03 (d, 1H, H-1b, J1,2 ¼ 5.1 Hz), 5.43 (dd ꢀ t, 1H,
3
3
3
3
H-2b, J1,2 ¼ 5.6, J2,3 ¼ 6.6 Hz), 5.26 (dd, 1H, H-2a, J1,2 ¼ 3.6, J2,3 ¼ 10.2 Hz),
3
4.90–4.56 (m, 2ꢂ 4H, 4ꢂ C6H5CH2O), 4.19 (dd, 1H, H-5ab, J4,5a ¼ 3.6,
2J5a,5b ¼ 11.7 Hz), 3.92–3.72 (m, 5H, 6H, 2ꢂ H-3, 2ꢂH-4, 2ꢂ CH3OC6H4COO), 3.69
(dd, 1H, H-5bb, J4,5b ¼ 6.6, J5a,5b ¼ 11.7 Hz) ppm; 13C NMR (100.62 MHz, CDCl3):
3
2

272
Suhr and Thiem
d ¼ 164.97 (CH3OC6H4COO), 163.73 (d-CH3OC6H4COO), 161.36 (CCl3C(OR)55NH),
137.91 132.10 (b-CH3OC6H4COO), 128.60–127.79
(2ꢂ quart-C6H5CH2O),
(2ꢂ C6H5CH2O), 122.06 (a-CH3OC6H4COO), 113.77 (2ꢂ g-CH3OC6H4COO), 96.46
(C-1b), 90.90 (C-1a), 77.56, 75.72, 69.60 (C-2, C-3, C-4), 73.73, 72.17
(2ꢂ C6H5CH2O), 63.16 (C-5), 55.56 (CH3OC6H4COO) ppm.
Benzyl 4-O-acetyl-2-O-benzyl-b-L-arabinopyranoside (15), benzyl 3-O-acetyl-2-
O-benzyl-b-L-arabinopyranoside (16), and benzyl 2-O-benzyl-b-L-arabinopyranoside
(17). In a 500 mL round bottom flask benzyl b-L-arabinopyranoside (14)[24,25] (10.00g,
41.62 mmol), triethyl orthoacetate (19.0 mL, 104 mmol), and p-toluene sulfonic acid
(370mg, 1.95mmol) were suspended in anhydrous dichloromethane (250mL) and stirred
at RT for 1 hr, whereby the reaction mixture clarified. When TLC [PE/EA 1 : 1, Rf
(14) ¼ 0, Rf (3,4-orthoacetate) ¼ 0.52] showed complete conversion of the starting material,
sodium hydride (100 mg) was added, the volatile reagents and the solvent were evaporated.
The remainder was coevaporated with toluene four times. The yellow syrup was dissolved in
DMF (100mL), and sodium hydride (1.50 g, 62.5mmol) was added in small portions (gas
development!). The suspension was stirred for 2.5 hr at RT. Then benzyl bromide
(5.5mL, 45.8mmol) was added dropwise at RT, and stirring was continued overnight
until TLC [Rf (2-O-benzyl-3,4-orthoacetate) ¼ 0.75] showed complete conversion of the
starting material. The mixture was cooled in an ice bath, water (3 mL) was added slowly,
and stirring was continued for 1/2 hr. The volume of the solvent was reduced under high
vacuum, the remainder was dissolved in diethylether and was washed five times with
water. The solvent was removed, the crude product was dissolved in glacial acetic acid
(15 mL) and water (1mL). Stirring continued over night until TLC showed complete and
selective conversion of the starting material to 15. After evaporation of the volatile reagents
under high vacuum slightly brown crystals of 15 were obtained. During the crystallization
from diethylether, a partial migration of the acetate function occurred supposedly caused
by acid impurities in the solvent. After flash chromatography with PE/EA 2 : 1 ! 1 : 1 com-
pound 15 (3.696g, 9.92mmol, 24%) and 16 with trace impurities of 17 (2.371g, 6.37mmol,
15%) and 17[27] (2.185g, 6.61mmol, 16%) as well as a mixture of 15 and 16 (532mg,
´
1.43mmol, 3%) were obtained. All impure fractions were deacetylated by the Zemplen
method to give 17. Compound 15: colorless solid; mp: 74.5–77.28C; [a]2D0 ¼ þ 180.3
(c ¼ 0.8, CHCl3); TLC (PE/EA 1 : 1): Rf ¼ 0.31 (UV, H2SO4); 1H-NMR (400MHz,
CDCl3): d ¼ 7.41–7.23 (m, 10H, 2ꢂ C6H5CH2O), 5.20 (dd ꢀ m, 1H, H-4), 4.95 (d, 1H,
3
2
H-1, J1,2 ¼ 3.6 Hz), 4.72 (d, 1H, C6H5CH2O, J ¼ 12.2Hz), 4.59 (d, 1H, C6H5CH2O,
2J ¼ 11.7Hz), 4.53 (d, 1H, C6H5CH2O, 2J ¼ 11.7Hz), 4.48 (d, 1H, C6H5CH2O,
3
3
2J ¼ 12.2Hz), 4.21 (dd, 1H, H-3, J2,3 ¼ 9.9, J3,4 ¼ 3.6 Hz), 3.84 (dd, 1H, H-5a,
3J4,5a ¼ 0, 2J5a,5b ¼ 13.0Hz), 3.75 (dd, 1H, H-2, 3J1,2 ¼ 3.3, 3J2,3 ¼ 9.9 Hz), 3.66 (dd, 1H,
3
2
H-5b, J4,5b ¼ 1.8, J5a,5b ¼ 13.0Hz), 2.24 (bs, 1H, 3-OH), 2.14 (s, 3H, CH3COO); 13C
NMR (100.67MHz, CDCl3): d ¼ 170.88 (CH3COO), 137.86, 137.08, 128.49–127.93
(2ꢂ C6H5CH2O), 95.56 (C-1), 76.88 (C-2), 72.47 (C6H5CH2O), 71.34 (C-4), 69.33
(C6H5CH2O), 67.16 (C-3), 60.78 (C-5), 21.16 (CH3COO).
Anal. calcd for C21H24O6 (372.41): C 67.73, H 6.50. Found: C 67.46, H 6.51.
1
Compound 16: TLC (PE/EA 1 : 1): Rf ¼ 0.21 (UV, H2SO4); H NMR (400 MHz,
3
CDCl3): d ¼ 7.38–7.18 (m, 10H, 2ꢂ C6H5CH2O), 5.29 (dd, 1H, H-3, J2,3 ¼ 10.5,
3
3J3,4 ¼ 3.2 Hz), 4.87 (d, 1H, H-1, J1,2 ¼ 3.6 Hz), 4.75–4.45 (m, 4H, 2ꢂC6H5CH2O),
3
4.08 (m, 1H, H-4), 3.92–3.83 (m, 2H, H-2, H-5a), 3.59 (dd, 1H, H-5b, J4,5b ¼ 2.3,
2J5a,5b ¼ 11.8 Hz), 2.27 (bs, 1H, 4-OH), 2.06 (s, 3H, CH3COO); 13C NMR

Ornithogalum saundersiae
273
(100.67 MHz, CDCl3): d ¼ 170.21 (CH3COO), 138.24, 137.98, 128.50–127.93
(2ꢂC6H5CH2O), 96.42 (C-1), 73.75 (C-2), 72.80 (C6H5CH2O), 71.99 (C-3), 69.27
(C6H5CH2O), 68.25 (C-3), 62.42 (C-5), 21.33 (CH3COO) ppm.
Benzyl
2-O-acetyl-3,4-di-O-benzyl-b-D-xylopyranosyl-(1!3)-4-O-acetyl-2-O-
benzyl-b-L-arabinopyranoside (18). Donor 5 (1.380 g, 3.31 mmol) and acceptor 15
(1.357g, 3.64 mmol) were coevaporated twice in a 100 mL round bottom flask and dissolved
in freshly anhydrous diethylether (20mL) and freshly anhydrous dichloromethane (20mL).
˚
Then freshly activated MS 4 A was added and the mixture was stirred under argon for 1 hr
at RT. Then N-iodosuccinimide (745 mg, 3.31 mmol) was added by which the colorless
solution became violet, and stirring was continued for 5.5 hr. For orthoester rearrangement
triflic acid (29 mL, 0.33mmol) was added, and the reaction was stirred for another 16hr at
RT. The reaction was monitored by TLC with PE/EA 2 : 1 [Rf (5) ¼ 0.67, Rf (15) ¼ 0.13].
The molecular sieves were removed by filtration over celite, and the solid was washed with
dichloromethane (200 mL). The red filtrate was decolorized with 10% aqueous sodium disul-
fite solution, washed once with saturated NaHCO3, and dried over sodium sulfate. The solvent
was removed, and the crude product was purified by flash chromatography to give 18 (1.463 g,
2.01 mmol, 61%). Colorless solid; mp: 67.2–68.68C; [a]2D0 ¼ þ 64.2 (c ¼ 0.6, CHCl3); TLC
(PE/EA2: 1):Rf ¼ 0.28 (UV, H2SO4); 1H NMR (500 MHz, CDCl3): d ¼ 7.39–7.23 (m, 20H,
3
3
4ꢂC6H5CH2O), 5.22 (dd, 1H, H-4, J3,4 ¼ 3.2, J4,5 ¼ 1.6, 0 Hz), 4.95 (dd, 1H, H-20,
3
2
J1 ,2 ¼ 7.1, 3J2 ,3 ¼ 8.7Hz), 4.80 (d, 1H, C6H5CH2O-30a, J ¼ 11.4 Hz), 4.79 (d, 1H, H-1,
0
0
0
0
3
3
J1,2 ¼ 4.1 Hz), 4.69, 4.69 (2ꢂ d, 2ꢂ 1H, H-10, J1 ,2 ¼ 6.9, C6H5CH2O-1a, 2J ¼ 12.3 Hz),
0
0
4.67–4.58 (m, 4H, 4ꢂ C6H5CH2O), 4.50 (d, 1H, C6H5CH2O-1b, 2J ¼ 12.3 Hz), 4.41 (d, 1H,
C6H5CH2O-2b, 2J ¼ 12.0 Hz), 4.12 (dd, 1H, H-3, 3J2,3 ¼ 10.1, 3J3,4 ¼ 3.8 Hz), 3.95 (dd, 1H,
3
2
3
H-50 eq, J4 ,5
¼ 5.0, J5 eq,5 ax ¼ 12.0Hz), 3.84 (dd, 1H, H-5eq, J4,5eq ¼ 0,
0
0
0
0
eq
2J5a,5b ¼ 12.6 Hz), 3.75 (dd, 1H, H-2, J1,2 ¼ 3.5, J2,3 ¼ 10.1 Hz), 3.66 (ddd, 1H, H-40,
3
3
3
2
3
3
3
0
0
0
0
0
0
J3 ,4 ¼ 8.2, J4 ,5 ax ¼ 8.5, J4 ,5 eq ¼ 5.1 Hz), 3.61 (dd, 1H, H-5ax, J4,5ax ¼ 1.7,
3
3
J5ax,5eq ¼ 13.1 Hz), 3.55 (dd ꢀ t, 1H, H-30, J2 ,3 ¼ 8.8, J3 ,4 ¼ 8.2 Hz), 3.26 (dd, 1H,
0
0
0
0
3
2
H-50ax, J4 ,5 ax ¼ 8.8, J5 ax,5 eq ¼ 11.7Hz), 2.15 (s, 3H, 4-CH3COO), 1.90 (s, 3H, 20-
0
0
0
0
13
CH3COO); C NMR (100.67 MHz, CDCl3): d ¼ 171.03 (4-CH3COO), 169.85 (20-
CH3COO), 138.82–137.40, 128.90–128.01 (4ꢂC6H5CH2O), 102.03 (C-10), 96.09 (C-1),
80.70 (C-30), 77.56 (C-40), 75.88 (C-2), 74.46 (C-3), 74.34 (C6H5CH2O-30), 73.19
(C6H5CH2O-2), 72.98 (C6H5CH2O-40), 72.39 (C-20), 71.61 (C-4), 69.17 (C6H5CH2O-1),
63.13 (C-50), 60.73 (C-5), 21.08, 20.91 (2ꢂCH3COO).
Anal. calcd for C42H46O11 (726.80): C 69.41, H 6.38. Found: C 68.94, H 6.40.
Benzyl 2-O-p-methoxybenzoyl-3,4-di-O-benzyl-b-D-xylopyranosyl-(1!3)-4-O-
acetyl-2-O-benzyl-b-L-arabinopyranoside (19). Donor 13 (347 mg, 0.57 mmol) and
acceptor 15 (254mg, 0.68mmol) were dissolved under argon in freshly anhydrous dichloro-
˚
methane (40 mL), and MS 4 A (one spatula) was added. The round bottom flask was
closed with a septum, an argon filled balloon was attached, and the mixture was
stirred for 1 hr at RT. Boron trifluoride–etherate (7 mL) was added via a syringe and
the reaction mixture was stirred for 2.5 hr at RT. To stop the reaction, one drop of tri-
ethylamine was added, and stirring was continued for 5 min. The molecular sieves were
removed by filtration over celite, and the solvent was evaporated. The crude product was
purified by flash chromatography with PE/EA 2 : 1 to give 19 (345 mg, 0.42 mmol,
74%). Colorless solid; mp: 116–117.58C; [a]2D0 ¼ þ 63.0 (c ¼ 0.3, CHCl3); TLC
1
(PE/EA 1 : 1): Rf ¼ 0.60 (UV, H2SO4); H NMR (500 MHz, CDCl3): d ¼ 7.91 (d, 2H,
3
b-CH3OC6H4COO, J ¼ 8.8 Hz), 7.35–7.27 (m, 10H, C6H5CH2O), 7.19–7.12 (m, 8H,

274
Suhr and Thiem
C6H5CH2O), 6.96 (d, 2H, C6H5CH2O), 6.78 (d, 2H, g-CH3OC6H4COO, 3J ¼ 8.8 Hz), 5.25
3
(ddd ꢀ m, 1H, H-4), 5.22 (dd ꢀ t, 1H, H-20, J1 ,2 ¼ 7.3, 3J2 ,3 ¼ 7.9 Hz), 4.87 (d, 1H, H-10,
0
0
0
0
3
2
J1 ,2 ¼ 6.9 Hz), 4.74 (d, 1H, C6H5CH2O-30a, J ¼ 11.4 Hz), 4.69–4.59 (m, 5H, H-1,
0
0
2
C6H5CH2O-1a, -30b, -40a,b), 4.44 (d, 1H, C6H5CH2O-1b, J ¼ 12.3 Hz), 4.41 (d, 1H,
2
2
C6H5CH2O-2a, J ¼ 12.3 Hz), 4.19 (d, 1H, C6H5CH2O-2b, J ¼ 12.6 Hz), 4.14 (dd, 1H,
H-3, 3J2,3 ¼ 9.8, 3J3,4 ¼ 3.5 Hz), 4.01 (dd, 1H, H-50eq, J4 ,5 eq ¼ 4.1, 2J5 eq,5 ax ¼ 12.0 Hz),
3
0
0
0
0
3
2
), 3.84 (dd ꢀ d, 1H, H-5a, J4,5a ¼ 0, J5a,5b ¼ 12.9 Hz), 3.80 (s, 3H, CH3OC6H4COO),
3
3
3.76–3.67 (m, 2H, H-30, H-40), 3.63 (dd, 1H, H-2, J1,2 ¼ 3.5, J2,3 ¼ 10.1 Hz), 3.59
3
2
3
(dd ꢀ d, 1H, H-5b, J4,5b ¼ 0, J5a,5b ¼ 12.9 Hz), 3.35 (dd, 1H, H-50ax, J4 ,5 ax ¼ 8.4,
0
0
J5 eq,5 ax ¼ 11.8 Hz), 2.08 (s, 3H, CH3COO); 13C NMR (100.67 MHz, CDCl3):
d ¼ 170.76 (CH3COO), 164.87 (CH3OC6H4COO), 163.42 (d-CH3OC6H4COO), 138.41,
138.06, 137.99, 136.94 (quart-C6H5CH2O), 131.82 (b-CH3OC6H4COO), 128.48–127.30
(4ꢂ C6H5CH2O), 122.31 (a-CH3OC6H4COO), 113.61 (g-CH3OC6H4COO), 102.21 (C-10),
96.29 (C-1), 80.39 (C-30), 77.53 (C-40), 75.82 (C-2), 74.36 (C-3), 74.28 (C6H5CH2O-30),
73.28 (C6H5CH2O-2), 72.97 (C6H5CH2O-40), 72.52 (C-20), 71.72 (C-4), 69.14 (C6H5CH2O-
1), 63.07 (C-50), 60.72 (C-5), 55.40 (CH3OC6H4COO), 21.09 (CH3COO).
2
0
0
ACKNOWLEDGMENT
Support of this work by the Fonds der Chemischen Industrie is gratefully
acknowledged.
REFERENCES
1. Hostettmann, K.; Marston, A. Saponins; Cambridge University Press: Cambridge,
1995; 548.
2. Tschesche, R.; Wulff, G. Chemie und Biologie der Saponine. Prog. Chem. Org. Nat.
Prods. 1972, 30, 461–606.
3. Schwarz, M.W. Saponins. Ullmanns Encyclopedia Indus. Chem. 1993, A 23, 485–498.
4. Kofler, L. Die Saponine; Julius Springer Verlag: Wien, 1927; 278.
5. Kubo, S.; Mimaki, Y.; Terao, M.; Sashida, Y.; Nikaido, T.; Ohmoto, T. Acylated
cholestane glycosides from the bulbs of Ornithogalum saundersiae. Phytochemistry
1992, 31 (11), 3969–3973.
6. Mimaki, Y.; Kuroda, M.; Kameyama, A.; Sashida, Y.; Maekawa, R.; Wada, T.;
Sugita, K.; Beutler, J.A. Cholestane glycosides with potent cytostatic activities on
various tumor cells from Ornithogalum saundersiae bulbs. Bioorg. Med. Chem.
Lett. 1997, 7 (5), 633–636.
7. Guo, C.; Fuchs, P.L. The first synthesis of the aglycone of the potent anti-tumor
steroidal saponin OSW-1. Tetrahedron Lett. 1998, 39, 1099–1102.
8. Guo, C.; LaCour, T.G.; Fuchs, P.L. On the relationship of OSW-1 to the cephalo-
statins. Bioorg. Med. Chem. Lett. 1999 (9), 419–424.
9. Deng, S.; Yu, B.; Lou, Y.; Hui, Y. First total synthesis of an exceptionally potent
antitumor saponin, OSW-1. J. Org. Chem. 1999, 64, 202–208.

Ornithogalum saundersiae
275
10. Ma, X.; Yu, B.; Hui, Y.; Xiao, D.; Ding, J. Synthesis of glycosides bearing the disac-
charide of OSW-1 or its 1 ! 4 linked analogue and their antitumor activities. Carbo-
hydr. Res. 2000, 329, 495–505.
11. Ma, X.; Yu, B.; Hui, Y.; Miao, Z.; Ding, J. Synthesis of steroidal glycosides bearing
the disaccharide moiety of OSW-1 and their antitumor activities. Carbohydr. Res.
2001, 334, 159–164.
12. Yu, W.; Jin, Z. A new strategy for the stereoselective introduction of steroid side chain
via alpha-alkoxy vinyl cuprates: total synthesis of highly potent antitumor natural
product OSW-1. J. Am. Chem. Soc. 2001, 123, 3369–3370.
13. Matsuya, Y.; Itoh, T.; Nemoto, H. Total synthesis of A-nor B-aromatic OSW-1
aglycon: a highly effective approach to optically active trans-4,5-benzhydrindane.
Eur. J. Org. Chem. 2003, 2221–2224.
14. Suhr, R. University of Hamburg: Hamburg, 2001. Abstract: http://www.sub.
uni-hamburg.de/disse/848/zusammen.pdf; Full text: http://www.sub.uni-hamburg.
de/disse/848/dissertation.pdf; Thesis.
¨
15. Lahmann, M.; Gyback, H.; Garegg, P.J.; Oscarson, S.; Suhr, R.; Thiem, J. A facile
approach to diosgenin and furostan type saponins bearing a 3-chacotriose moiety.
Carbohydr. Res. 2002, 337 (21–23), 2153–2159.
16. Suhr, R.; Lahmann, M.; Oscarson, S.; Thiem, J. Synthesis of dihydrodiosgenin glyco-
sides as mimetics of bidesmosidic steroidal saponins. Eur. J. Org. Chem. 2003 (20),
4003–4011.
17. Suhr, R.; Pfefferkorn, P.; Weingarten, S.; Thiem, J. Synthesis of rhamnosylated dios-
genyl glucosides as mimetics of cytostatic steroidal saponins from Ornithogalum
saundersiae and Galtonia candicans. Org. Biomol. Chem. 2003, 1 (24), 4373–4379.
18. Kochetkov, N.K.; Khorlin, A.J.; Bochkov, A.F. A new method of glycosylation.
Tetrahedron 1967, 23, 693–707.
19. Kochetkov, N.K.; Bochkov, A.F.; Sokolovskaya, T.A.; Snyatkova, V.J. Modifications
of the orthoester method of glycosylation. Carbohydr. Res. 1971, 16, 17–27.
20. Kochetkov, N.K.; Backinowsky, L.V.; Tsvetkov, Y.E. Sugar thio orthoesters as
glycosylating agents. Tetrahedron Lett. 1977, 41, 3681–3684.
21. Hudson, C.S.; Johnson, J.M. The isomeric tetraacetates of xylose, and observations
regarding the acetates of melibiose, trehalose and sucrose. J. Am. Chem. Soc 1915,
37, 2748–2753.
22. Finan, P.A.; Warren, C.D. The purification of acetylglycosyl bromides. J. Chem. Soc.
1962, 2823–2824.
` ´ ´
23. Utille, J.-P.; Gagnaire, D. Synthese en serie xylopyranose: tri-O-acetyl-D-xyloses et
´ ´ ´ ´
derives chloroacetyles. Carbohydr. Res. 1982, 106, 43–57.
24. Wold, F. The L-glyceric acid monophosphates. J. Org. Chem. 1961, 26, 197–199.
25. Franzkowiak, M.; Thiem, J. Synthesen von Agrocinopin A und B. Liebigs Ann.
Chem. 1987, 1065–1071.
26. Durette, P.L.; Horton, D. Conformational studies on pyranoid sugar derivatives. The
conformational equilibria of the D-aldopentopyranose tetraacetates and benzoates.
J. Org. Chem. 1971, 36 (18), 2658–2669.
27. Liptak, A.; Szurmai, Z.; Harangi, J.; Nanasi, P. 13C NMR study of methyl and benzyl
ethers of L-arabinose and oligosaccharides having L-arabinose at the reducing end.
Acta Chim. Acad. Sci. Hung. 1981, 108 (4), 333–342.

276
Suhr and Thiem
28. Zuurmond, H.M.; van der Marel, G.A.; van Boom, J.H. Potential usefulness of sugar
1,2-thio-orthoesters in iodonium-promoted glycosylation. Recl. Trav. Chim. Pays-Bas
1993, 112, 507–510.
29. Lahmann, M.; Oscarson, S. One-pot oligosaccharide synthesis exploiting solvent
reactivity effects. Org. Lett. 2000, 2 (24), 3881–3882.
Received November 26, 2003
Accepted March 30, 2004