Synthesis of naturally occurring arsenic-containing carbohydrates

Article abstract of DOI:10.1071/CH08461

We report the synthesis of (S)-2′-hydroxy-3′-sulfonylpropyl 5-deoxy-5-dimethylarsinoyl-β-D-riboside ammonium salt and (S)-2′-hydroxy-3′-sulfooxypropyl 5-deoxy-5-dimethylarsinoyl-β- d-riboside ammonium salt, two common naturally occurring arsenicals.

Full text of DOI:10.1071/CH08461

RESEARCH FRONT
Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2009, 62, 538–545
www.publish.csiro.au/journals/ajc
Synthesis of Naturally Occurring Arsenic-Containing
Carbohydrates
Pedro Traar,A Alice Rumpler,A Tobias Madl,B Gerald Saischek,A
and Kevin A. FrancesconiA,C
AInstitute of Chemistry, Karl-Franzens University Graz, Universitaetsplatz 1, 8010 Graz, Austria.
BInstitute of Structural Biology, Helmholtz Zentrum Muenchen; and Biomolecular
NMR-Spectroscopy, Department Chemie, Technische Universitaet Muenchen,
Lichtenbergstrasse 4, 85747 Garching, Germany.
CCorresponding author. Email: kevin.francesconi@uni-graz.at
We report the synthesis of (S)-2ꢀ-hydroxy-3ꢀ-sulfonylpropyl 5-deoxy-5-dimethylarsinoyl-β-d-riboside ammonium salt
and (S)-2ꢀ-hydroxy-3ꢀ-sulfooxypropyl 5-deoxy-5-dimethylarsinoyl-β-d-riboside ammonium salt, two common naturally
occurring arsenicals.
Manuscript received: 24 October 2008.
Final version: 7 January 2009.
Introduction
compounds intensified, however, as a result of human health
issues related to the ingestion of arsenosugars contained in edi-
ble algae and molluscs. The major arsenical metabolite in the
urine of humans eating algae or molluscs was shown[9,10] to be
dimethylarsinate, the same arsenical produced from arsenate, a
proven human carcinogen that can be a contaminant of drinking
water as a result of natural geological processes.[11] These obser-
vations led to a more detailed study[12] of metabolic pathways
using pure synthesized compound 1, the arsenosugar most read-
ily accessible by synthesis.[13–15] A subsequent related study,
however, showed that the four major arsenosugars are likely to
have different metabolic behaviour, and hence would need to be
assessed independently.[16]
The human health concern regarding arsenic in foods has cre-
ated a need for quantities of pure arsenosugars for toxicological
assessment. We report a synthetic scheme able to deliver arseno-
sugars 1, 2, and 3, together with their thio-analogues. A novel
aspect of the scheme is the use of sulfur as a pseudo-protecting
group for arsenic, thereby overcoming the otherwise recalcitrant
behaviour of intermediates that contain the arsinoyl group dur-
ing the synthesis. A preliminary account of this work has been
reported.[17]
Arsenic-containing ribosides (arsenosugars) were first identi-
fied in the brown alga Ecklonia radiata almost 30 years ago,[1]
and they were subsequently shown to be common constituents
of algae and animals feeding on algae such as oysters and
mussels.[2] Arsenosugars are considered key compounds in the
cycling and transformation of arsenic in marine systems: they
are biosynthesized as a result of arsenate being taken up by
algae directly from seawater (because algae cannot distinguish
arsenate from phosphate), and they might be the precursors to
arsenobetaine, the predominant arsenical compound found in
marine animals.[2]
Although 17 arsenosugars have been identified,[3] four com-
pounds clearly dominate (Fig. 1). These compounds (dimethyl-
arsinoyl, Me2As(O)−, derivatives) have also recently been
shown to have thio-analogues (Me2As(S)−).The thio-analogues
are trace constituents of algae[4] but can occur in significant
quantities in molluscs, possibly as a result of metabolic changes
that take place within the animal.[5–8]
Fundamental aspects such as the biosynthesis of arseno-
sugars and their possible biochemical roles in organisms have
encouraged continuing studies over several years. Interest in the
2؅
Me
1؅
3؅
O
O
OH
O
O
SO3NH4
O
5
O
As
R
OH
OH
O
OSO3NH4
1
2
4
R ꢀ
1
Me
O
P
OH
3
3
2
O
OH
OH
OH
OH
ONH4
OH
4
Fig. 1. Major arsenosugars present in algae.
© CSIRO 2009
10.1071/CH08461
0004-9425/09/060538

RESEARCH FRONT
Synthesis of As-Containing Carbohydrates
539
Results and Discussion
the nucleophile was initiated by reaction of dimethyliodoarsine
with lithium to give tetramethyldiarsine ((Me2As)2),[21,22] which
was cleaved in situ upon addition of finely cut sodium pieces.
Reaction of the chloro compound 9 with sodium dimethyl-
arsenide gave the trialkylarsine 10; this compound, which is
difficult to handle, was not isolated but directly converted into
the arsine oxide 11 (Scheme 2). Removal of the acetal group in
acidic medium gave compound 1, and its subsequent treatment
with H2S provided its sulfur analogue 12 (Scheme 3). This com-
pound had previously been prepared by a different route by Liu
et al.[23]
The strategy from this point was to acetylate the residual
hydroxy groups of compound 11, and then remove the iso-
propylidene group on the aglycone to give a diol suitable for
introduction of the desired functional groups. Surprisingly, the
arsine oxide 11 could not be acetylated – it remained steadfastly
unreactive under standard acetylation conditions. Acetylation of
the arsine 10, however, gave the desired protected product. This
result indicated that the polar dimethylarsinoyl group might be
interfering with the reaction, and suggested to us that the arsine
sulfide could be a more suitable substrate. Arsine sulfides are
considerably less polar than their oxide analogues, they are easy
to handle (in contrast to arsines), and they can readily be changed
back to the oxide by treatment with H2O2.[5] Thus, sulfur might
act as a pseudo-protecting group for the arsenic, allowing func-
tionalization on the rest of the molecule, before being changed
back to the arsine oxide in the final step. With this in mind,
the oxide 11 was treated with H2S to form the arsine sulfide 13,
which was readily acetylated to give 14; removal of the isopropy-
lidene group yielded the diol 15 (Scheme 3) which promised
to serve as the key intermediate in the synthesis of the acidic
derivatives 2 and 3.
Our approach was to prepare the arsenosugar with the glyc-
erol aglycone, compound 1, followed by functionalization of the
aglycone to provide compounds 2 and 3. The glycoside 7 was
obtained in a three step procedure from commercially available
tetraacetyl ribose and (S)-2,3-di-O-benzylglycerol[18] essen-
tiallyaccordingtothemethodofMcAdametal.[13] Wefoundthat
the reported glycosidation could be improved by using the cata-
lyst BF3·OEt2 and initiating the reaction at −25◦C with subse-
quent warming of the reaction mixture to room temperature.The
dibenzylated glycoside 5 was hydrogenated over Pd/C to give the
diol 6, which was converted into the acetonide 7 (Scheme 1).
Removal of acetyl groups gave the triol 8, which was selec-
tively chlorinated at the primary hydroxy group using Ph3P and
CCl4 according to the method of Whistler and Anisuzzaman.[19]
The product 9 was used directly in the arsenylation procedure
since previous work had shown that free secondary hydroxy
groups do not interfere with the arsenylation reaction.[20]
The arsenic group has been successfully introduced at C5 by
nucleophilic substitution with sodium dimethylarsenide formed
from dimethyliodoarsine and sodium.[13] We found, however,
that the combined use of lithium and sodium to form the nucleo-
phile gave more consistent and higher yields.Thus, generation of
AcO
OAc
AcO
O
OR
O
O
OR
(a)
OAc OAc
OAc OAc
5 R ꢀ Bn
6 R ꢀ H
(b)
According to the method of Martinelli et al.[24] compound 15
was converted into the tosylate 16, which was then simultane-
ously deprotected and sulfonated by treatment with Na2SO3 in
water/MeOH (2/1, v/v) to yield the sulfonate 17 (Scheme 4).
Regeneration of the arsine oxide moiety was achieved on
treatment of the arsine sulfide with 30% H2O2 to give the
product 2.
(c)
AcO
O
O
OH
O
OBn
O
Me
Me
OBn
(S)-2,3-di-O-benzylglycerol
OAc OAc
Treatment of the key intermediate 15 with sulfur trioxide
triethylamine complex gave the sulfuric acid ester 18, subse-
quent removal of acetyl groups (NaOMe) delivered compound
19 (Scheme 4). Regeneration of the arsine oxide as described for
compound 2 gave the product 3.
7
Scheme 1. (a) (S)-2,3-Di-O-benzylglycerol, BF3·OEt2, MeCN, 85%.
(b) Pd/C 5%, MeOH, 82%. (c) 2,2-Dimethoxypropane, p-TsOH,
CH2Cl2, 85%.
AcO
O
R1
O
O
O
O
O
O
Me
O
Me
(a)
Me
Me
OAc OAc
OR2 OR2
7
8 R1 ꢀ OH, R2 ꢀ H
9 R1 ꢀ Cl, R2 ꢀ H
(b)
(c)
Me
Me
As
Me
O
As
O
Me
O
O
O
O
O
O
Me
O
Me
(d)
Me
Me
OH
OH
OH
OH
11
10
Scheme 2. (a) OH− resin, MeOH, 82%. (b) Ph3P, CCl4, pyridine, 68%. (c) Li, Me2AsNa, THF,
Na, crude. (d) THF, H2O2, 66% for steps (c) and (d).

RESEARCH FRONT
540
P. Traar et al.
Me
As
O
O
O
O
Me
O
Me
Me
OH
11
OH
(c)
(a)
Me
As
Me
As
O
O
S
O
OH
O
O
O
Me
Me
OH
O
Me
Me
OH
OH
OH
OH
1
13
(d)
(b)
Me
As
Me
As
S
O
S
O
OH
O
O
O
Me
Me
OH
O
Me
Me
OH
OH
OAc OAc
14
12
(e)
Me
As
S
O
O
OH
Me
OH
OAc OAc
15
Scheme 3. (a) CF3COOH/water, 85%. (b) H2S, water, 93%. (c) H2S, pyridine, 84%. (d) Ac2O, pyridine,
77% based on compound 11. (e) CF3COOH/water, MeCN, 82%.
Me
S
As
O
OH
O
Me
OH
OAc OAc
(a)
(c)
15
Me
As
Me
S
O
OTs
O
S
As
O
OSO3NH4
O
Me
OH
Me
OH
OAc OAc
OAc OAc
16
18
(b)
(d)
Me
As
Me
As
S
O
O
OSO3NH4
S
O
O
SO3NH4
Me
Me
OH
OH
OH
19
OH
OH
OH
17
Scheme 4. (a) p-TsCl, Et3N, Bu2SnO, CH2Cl2, 72%. (b) Na2SO3, water/MeOH, NH+4 resin, 69%.
(c) Et3N:SO3, pyridine, NH+4 resin, 58%. (d) NaOMe, MeOH, NH+4 resin, 80%.

RESEARCH FRONT
Synthesis of As-Containing Carbohydrates
541
O
O
P
1 × 8, from Fluka (Buchs, Switzerland). Cation exchange resin
referstoDowex50WX8–200suppliedbySigma–Aldrich(Stein-
heim, Germany). Melting points (uncorrected) were recorded
on a Mettler FP62 melting point apparatus, from Mettler–
Toledo (Giessen, Germany). Rotation values were measured on
a Perkin–Elmer Polarimeter 341, from Perkin–Elmer (Ueberlin-
gen, Germany) at ambient temperature (λ 589 nm). Elemental
analyses were performed on a Carlo Erba/Fisons 1108 Ele-
mental Analyzer, Fisons Instruments (Milan, Italy). 1H and
13C NMR spectra were recorded with Varian (400 MHz) or
Bruker (360 and 500 MHz) instruments. Chemical shifts are
given in ppm and are referenced to partially protonated sol-
vent or internal standard: 1H NMR: D2O 4.83 ppm, CDCl3
7.24 ppm, TMS 0 ppm. 13C NMR: CDCl3 77 ppm. Electro-
spray ionization mass spectra were recorded on an Agilent 1100
LC/MSD series single quadrupole mass spectrometer, Agilent
Technologies (Waldbronn, Germany) with flow injection.
O
Cl
P
Cl
OBn
O
O
O
O
O
OBn
(a), (b)
Cl
Cl
20
Scheme 5. (a) (S)-2,3-Di-O-benzylglycerol, pyridine, CH2Cl2, 0◦C to rt,
crude. (b) (R,S)-2,3-O-Isopropylideneglycerol, 55% for steps (a) and (b).
We also attempted the synthesis of the phosphoric acid
diester 4. First, we prepared the model compound 20 by the
phosphotriester approach (Scheme 5).[25,26] However, attempts
to phosphorylate the diol 15 in an analogous fashion were
unsuccessful. Further attempts will consider protecting the sec-
ondary hydroxy group of compound 15, and include alternative
phosphorylation reactions.[25]
(R)-2ꢀ,3ꢀ-Dihydroxypropyl 2,3,5-Tri-O-acetyl-β-D-riboside 6
(i) BF3·OEt2 (7.4 g, 52 mmol) was added at −25◦C to a mix-
ture of 1,2,3,5-tetra-O-acetyl-β-d-ribose (15.0 g, 47 mmol) and
(S)-2,3-di-O-benzylglycerol (14.0 g, 51 mmol) in acetonitrile
(MeCN, 300 mL). The reaction mixture was allowed to warm
to room temperature and then poured into a saturated NaHCO3
solution under vigorous stirring. The product was extracted
into dichloromethane (CH2Cl2) and after usual workup and
removal of the organic layer, the residue was subjected to column
chromatography (silica, cyclohexane/ethyl acetate (EtOAc), 4/1,
v/v) to yield (R)-2ꢀ,3ꢀ-di-O-benzylpropyl 2,3,5-tri-O-acetyl-β-
d-riboside 5 (21.2 g, 85%) as a pale yellow oil. δH (500 MHz,
CDCl3) 7.32 (10H, m, Ar), 5.31, 5.23 (2H, 2 × d, J 4.9, H2, 3),
5.00 (1H, s, H1), 4.65, 4.62 (2H, 2 × d, J 11.7, CH2Ar), 4.53,
4.50 (2H, 2 × d, J 12.0, CH2Ar), 4.28, 4.11 (3H, 2 × m, H4,5),
3.82 (1H, dd, J 10.4, 5.5, H1ꢀ), 3.72 (1H, m, H2ꢀ), 3.57 (3H, m,
H1ꢀ,3ꢀ), 2.06, 2.02, 2.00 (9H, 3 × s, OAc). δC (125 MHz, CDCl3)
170.2, 169.3, 169.2 (CO), 138.2–127.3 (Ar), 105.1 (C1), 78.3
(C4), 76.4 (C2ꢀ), 74.4, 73.1, 71.9, 71.3 (C2, C3, CH2Ar), 69.4,
67.4 (C1ꢀ, C3ꢀ), 64.3 (C5), 20.4, 20.2, 20.1 (OAc). m/z (ESI) 569
[M + K]+, 553 [M + Na]+.
The 1H and 13C NMR data and chromatographic behaviour
for the synthetically prepared compounds 1, 2, and 3 are in good
agreement with those reported for the natural products.[27,28] The
described synthetic scheme provides the previously synthesized
compound 1 in 17% overall yield in 7 steps and delivers two
new synthetic products, sulfonic acid 2 and sulfuric acid ester
3, each in 5% overall yield in 10 steps. The sulfur analogues 12,
17, and 19 are also obtained during this reaction sequence.
Experimental
All chemicals and solvents were purchased from Lactan/Roth
(Graz, Austria), Sigma–Aldrich (Vienna, Austria), or Acros
Chemicals (Geel, Belgium) and were used in the synthetic
procedures without further purification. TLC was performed
on silica gel 60 F254 (plastic sheets or glass plates), from
Merck (Darmstadt, Germany). Compounds were visualized by
UV254 detection or by dipping the TLC plates in a solu-
tion of vanillin (1.5 g)/H2SO4 (20 mL)/water (150 mL)/ethanol
(125 mL) and subsequently heating the plate to 140◦C. The
procedure described by the term ‘usual workup’ contained the
following steps: The organic layer, which contained the prod-
uct, was washed successively with water, 5% H2SO4, saturated
NaHCO3, and water. The organic layer was then dried over
MgSO4 or Na2SO4. Similarly, the term ‘workup’ refers to
this same series of steps except that the acidic washing step
(5% H2SO4) was omitted. Column chromatography was per-
formed on silica gel 60, 63–100 µm, from Merck (Darmstadt,
Germany). Size exclusion chromatography was performed on
Sephadex G-15 (26 × 600 mm2, water as eluent) or Sephadex
LH-20 (26 × 300 mm2, MeOH as eluent) both supplied by
Amersham Pharmacia Biotech AB (Uppsala, Sweden). Before
the compounds were applied to Sephadex G-15, the column
was pretreated with 0.1 M NH4OH followed by equilibration
with water. Anion exchange chromatography was performed
on DEAE (diethylaminoethyl) Sephadex A-25 (16 × 300 mm2),
AmershamBiosciencesAB(Uppsala, Sweden)using0.05 MTris
(tris(hydroxymethyl)aminomethan) buffer, pH 8.0, as the elu-
ent. Before compounds were applied, the column was washed
with 0.5 M Tris buffer, pH 8.0, followed by equilibration with
the eluent. Ion exchange resins were used after washing and
cycling to constant titre with 5% (w/v) NaOH or NH4OH (1 M)
and 5% (w/v) HCl. Anion exchange resin refers to Dowex
(ii) The glycoside 5 (15.0 g, 28 mmol) was dissolved in
methanol (MeOH, 200 mL) and hydrogenated over Pd/C (5%,
7.5 g) for 3 h. Filtration and evaporation gave an oil, which
was subjected to column chromatography (silica, cyclohexane/
EtOAc, 1/4, v/v), to deliver the diol 6 (8.1 g, 82% based on com-
pound 5). [α]D −21.0◦ (c. 2.4 MeOH). (Found: C 47.9, H 6.3.
C14H22O10 requires C 48.0, H 6.3%.) δH (500 MHz, CDCl3)
5.32 (1H, m, H3), 5.27 (1H, d, J 5.0, H2), 5.05 (1H, s, H1), 4.32
(2H, m, H4,5), 4.21 (1H, dd, J 12.8, 6.8, H5), 3.86 (1H, m, H2ꢀ),
3.74 (1H, dd, J 10.4, 6.5, H1ꢀ), 3.69 (1H, dd, J 11.4, 4.1, H3ꢀ),
3.63 (1H, dd, J 10.5, 4.0, H1ꢀ), 3.59 (1H, dd, J 11.4, 5.9, H3ꢀ),
2.12, 2.11, 2.07 (9H, 3 × s, OAc). δC (125 MHz, CDCl3) 170.8,
169.8, 169.7 (CO), 105.6 (C1), 78.5 (C4), 74.6 (C2), 71.1 (C3),
70.6 (C2ꢀ), 70.1 (C1ꢀ), 64.2 (C5), 63.4 (C3ꢀ), 20.7, 20.5, 20.4
(OAc). m/z (ESI) 389 [M + K]+, 373 [M + Na]+.
(S)-2ꢀ,3ꢀ-O-Isopropylidenepropyl
2,3,5-Tri-O-acetyl-β-D-riboside 7
The diol 6 (6.6 g, 19 mmol) in CH2Cl2 (120 mL) together with
2,2-dimethoxypropane (5.2 g, 50 mmol) and p-toluenesulfonic
acid (p-TsOH) monohydrate (190 mg, 1.0 mmol) was stirred
for 1 h. Workup and evaporation of the organic phase gave
an oil, which was purified by column chromatography (silica,

RESEARCH FRONT
542
P. Traar et al.
cyclohexane/EtOAc, 4/1, v/v) to deliver the glycoside 7 (6.28 g,
85%) as a colourless oil. [α]D −17.5◦ (c. 2.9 MeOH). (Found: C
52.1, H 6.7. C17H26O10 requires C 52.3, H 6.7%.) δH (400 MHz,
CDCl3) 5.33 (1H, m, H3), 5.26 (1H, d, J 4.8, H2), 5.05 (1H, s,
H1), 4.31 (2H, m, H4,5), 4.24 (1H, m, H2ꢀ), 4.15 (1H, m, H5),
4.05 (1H, dd, J 8.2, 6.7, H3ꢀ), 3.77 (2H, m, H1ꢀ,3ꢀ), 3.46 (1H,
dd, J 10.2, 5.6, H1ꢀ), 2.11, 2.10, 2.06 (9H, 3 × s, OAc), 1.40,
1.36 (6H, 2 × s, CMe2). δC (100 MHz, CDCl3) 170.5, 169.6,
169.5 (CO), 109.4 (CMe2), 105.4 (C1), 78.6 (C4), 74.6 (C2),
74.2 (C2ꢀ), 71.4 (C3), 68.4 (C1ꢀ), 66.5 (C3ꢀ), 64.5 (C5), 26.6,
25.3 (CMe2), 20.7, 20.4, 20.3 (OAc). m/z (ESI) 429 [M + K]+,
413 [M + Na]+.
dry tetrahydrofuran (THF, 15 mL) under an argon atmosphere.
The suspension was stirred overnight whereupon all the lithium
was dissolved. Sodium (396 mg, 17 mmol), cut into small pieces,
was then added and the reaction mixture was stirred for 3 h.
MeOH was added to the reaction mixture, which was then diluted
with EtOAc and washed with water. The organic layer, contain-
ing the trialkylarsine 10, was filtered through a plug of silica and
the filtrate evaporated to dryness. The residue was taken up in
THF (30 mL), cooled to 0◦C, and treated with 30% H2O2 (3 mL).
After stirring for 15 min, the solvent was removed and the residue
subjected to column chromatography (silica, EtOAc/MeOH, 2/1,
v/v) to give the arsine oxide 11 (1.03 g, 66%) as a brown oil. [α]D
−2.5◦ (c. 2.3 MeOH). (Found: C 40.5, H 6.7. C13H25O7As·H2O
requires C 40.4, H 7.0%.) δH (500 MHz, CDCl3) 4.93 (1H, s,
H1), 4.34 (1H, m, H4), 4.22 (1H, m, H2ꢀ), 4.05 (3H, m, H2,3,3ꢀ),
3.70 (2H, m, H1ꢀ,3ꢀ), 3.42 (1H, dd, J 10.0, 5.6, H1ꢀ), 2.59 (1H,
dd, J 13.2, 5.2, H5), 2.27 (1H, dd, J 13.2, 8.8, H5), 1.77, 1.75
(6H, 2 × s,AsMe2), 1.40, 1.35 (6H, 2 × s, CMe2). δC (125 MHz,
CDCl3) 109.4 (CMe2), 108.0 (C1), 77.1 (C4), 76.2 (C3), 75.0
(C2), 74.3 (C2ꢀ), 68.7 (C1ꢀ), 66.6 (C3ꢀ), 37.1 (C5), 26.7, 25.2
(CMe2), 16.1, 15.3 (AsMe2). m/z (ESI) 407 [M + K]+, 391
[M + Na]+, 369 [M + H]+.
(S)-2ꢀ,3ꢀ-O-Isopropylidenepropyl β-D-Riboside 8
This material was prepared essentially according to the method
of Stick and coworkers.[13] An anion exchange resin (10.0 g,
Dowex 1, OH−) was added to a solution of the glycoside 7 (5.0 g,
13 mmol) in MeOH (100 mL). The suspension was heated to
45◦C and stirred for 1.5 h after which the reaction mixture was
cooled and the resin filtered off. The solvent was evaporated
and the residue subjected to column chromatography (silica,
cyclohexane/EtOAc, 1/4, v/v) to yield the triol 8 (2.78 g, 82%) as
a colourless oil. [α]D −41.5◦ (c. 3.4 MeOH). (Found: C 48.4, H
7.6. C11H20O7·0.5H2O requires C 48.4, H 7.7%.) δH (500 MHz,
D2O) 5.07 (1H, s, H1), 4.46 (1H, m, H2ꢀ), 4.27 (1H, dd, J 7.0,
4.7, H3), 4.19 (1H, dd, J 8.4, 7.0, H3ꢀ), 4.12 (1H, d, J 4.7, H2),
4.07 (1H, m, H4), 3.82 (3H, m, H5,1ꢀ,3ꢀ), 3.68 (2H, m, H5,
1ꢀ), 1.50, 1.43 (6H, 2 × s, CMe2). δC (125 MHz, D2O) 109.8
(CMe2), 106.5 (C1), 82.4 (C4), 74.0, 73.9 (C2,2ꢀ), 70.4 (C3),
67.5 (C1ꢀ), 64.9 (C3ꢀ), 62.4 (C5), 25.2, 23.8 (CMe2). m/z (ESI)
303 [M + K]+, 287 [M + Na]+, 299 [M + Cl]−.
(R)-2ꢀ,3ꢀ-Dihydroxypropyl 5-Deoxy-
5-dimethylarsinoyl-β-D-riboside 1
This material was prepared essentially according to the method
of Stick and coworkers.[13] The diol 11 (441 mg, 1.2 mmol) was
dissolved in a mixture of CF3COOH/water (3 mL, 9/1, v/v)
and stirred for 10 min. The solution was concentrated and co-
evaporated several times with NH4OH (1 M). The residue thus
obtained was dissolved in water and passed through a column
of anion exchange resin (Dowex 1, OH−) to give the tetrol 1
(335 mg, 85%) as a brown oil. δH (400 MHz, D2O) 5.06 (1H, s,
H1), 4.29 (2H, m, H3,4), 4.17 (1H, d, J 4.0, H2), 3.94 (1H, m,
H2ꢀ), 3.79 (1H, dd, J 10.6, 6.2, H1ꢀ), 3.64 (3H, m, H1ꢀ,3ꢀ), 2.69
(1H, dd, J 13.8, 3.0, H5), 2.54 (1H, dd, J 13.8, 10.3, H5), 1.92,
1.89 (6H, 2 × s, AsMe2). δC (90 MHz, D2O) 109.4 (C1), 78.9
(C4), 77.7 (C3), 76.2 (C2), 72.0 (C2ꢀ), 70.7 (C1ꢀ), 64.2 (C3ꢀ),
37.8 (C5), 16.3, 15.9 (AsMe2). m/z (ESI) 351 [M + Na]+, 329
[M + H]+.
(S)-2ꢀ,3ꢀ-O-Isopropylidenepropyl 5-Chloro-
5-deoxy-β-D-riboside 9
The triol 8 (2.0 g, 7.6 mmol) was dissolved in pyridine (40 mL)
and Ph3P (6.0 g, 23 mmol) together with CCl4 (11.6 g, 76 mmol)
were added. The colourless solution turned brown; it was
stirred at 45◦C for 1.5 h by which time TLC analysis (silica,
petroleum/acetone, 7/3, v/v) indicated the reaction to be com-
plete. The solution was then diluted with MeOH, stirred for
5 min after which the solvent was evaporated to give a semicrys-
talline mass. The residue was suspended under vigorous stirring
in slightly basic water (pH 8.0, NH4OH), whereupon the product
dissolved in water. The suspension was filtered and the filtrate
extracted several times with CH2Cl2. The organic layers were
combined and concentrated to give an oil, which was subjected
to column chromatography (silica, cyclohexane/EtOAc, 1/4, v/v)
to deliver the chloride 9 (1.46 g, 68%) as a pale yellow oil. [α]D
−40.0◦ (c. 2.5 MeOH). (Found: C 47.2, H 6.9. C11H19O6Cl
requires C 46.8, H 6.7%.) δH (500 MHz, CDCl3) 4.99 (1H, s,
H1), 4.33 (1H, m, H3), 4.27 (1H, m, H2ꢀ), 4.14 (1H, m, H4),
4.09 (1H, d, J 4.8, H2), 4.05 (1H, dd, J 8.4, 6.6, H3ꢀ), 3.76
(2H, m, H1ꢀ,3ꢀ), 3.69 (2H, m, H5), 3.47 (1H, dd, J 10.5, 4.7,
H1ꢀ), 1.42, 1.36 (6H, 2 × s, CMe2). δC (125 MHz, CDCl3) 109.6
(CMe2), 107.2 (C1), 82.7 (C4), 75.1 (C2), 74.2 (C2ꢀ), 73.1 (C3),
68.2 (C1ꢀ), 66.2 (C3ꢀ), 45.5 (C5), 26.5, 25.3 (CMe2). m/z (ESI)
305 [M + Na]+, 317 [M + Cl]−.
(R)-2ꢀ,3ꢀ-Dihydroxypropyl 5-Deoxy-
5-dimethylarsinothioyl-β-D-riboside 12
This material was prepared by an alternative procedure as
described in the literature.[23] The tetrol 1 (50 mg, 0.15 mmol)
was dissolved in water and H2S was passed through the solution
for 1 min. After stirring for 15 min, the solvent was evaporated
and the residue passed through Sephadex G-15/water to give the
arsine sulfide 12 (48 mg, 93%) as a brown oil. δH (500 MHz,
D2O) 5.04 (1H, s, H1), 4.39 (1H, m, H4), 4.31 (1H, dd, J 6.8,
4.6, H3), 4.17 (1H, d, J 4.6, H2), 3.93 (1H, m, H2ꢀ), 3.79 (1H,
dd, J 10.6, 6.1, H1ꢀ), 3.67 (1H, dd, J 11.6, 4.9, H3ꢀ), 3.62 (1H,
dd, J 10.6, 4.1, H1ꢀ), 3.61 (1H, dd, J 11.6, 6.5, H3ꢀ), 2.59 (2H, m,
H5), 1.98, 1.96 (6H, 2 × s, AsMe2). δC (125 MHz, D2O) 107.1
(C1), 77.6 (C4), 75.3 (C3), 74.0 (C2), 70.0 (C2ꢀ), 68.7 (C1ꢀ), 62.2
(C3ꢀ), 37.4 (C5), 17.6, 17.5 (AsMe2). m/z (ESI) 367 [M + Na]+,
345 [M + H]+.
(S)-2ꢀ,3ꢀ-O-Isopropylidenepropyl 5-Deoxy-
5-dimethylarsinoyl-β-D-riboside 11
(S)-2ꢀ,3ꢀ-O-Isopropylidenepropyl 5-Deoxy-
5-dimethylarsinothioyl-β-D-riboside 13
Elemental lithium (120 mg, 17 mmol) was added to the chloride
Hydrogen sulfide was passed through a solution of the arsine
9 (1.2 g, 4.3 mmol) and dimethyliodoarsine (2.0 g, 8.6 mmol) in
oxide 11 (40 mg, 0.11 mmol) in pyridine for 30 s. After stirring

RESEARCH FRONT
Synthesis of As-Containing Carbohydrates
543
the mixture for 10 min, the solvent was evaporated and the
residue subjected to column chromatography (silica, EtOAc) to
give the arsine sulfide 13 (35 mg, 84%) as a brown oil. [α]D
+5.7◦ (c. 1.6 MeOH). (Found: C 40.3, H 6.6. C13H25O6AsS
requires C 40.6, H 6.5%.) δH (400 MHz, CDCl3) 4.97 (1H, s,
H1), 4.29 (2H, m, H3,4), 4.24 (1H, m, H2ꢀ), 4.11 (1H, d, J 3.8,
H2), 4.05(1H, dd, J 8.4, 6.6, H3ꢀ), 3.70(2H, m, H1ꢀ,3ꢀ), 3.45(1H,
dd, J 10.8, 5.3, H1ꢀ), 2.44 (2H, m, H5), 1.88, 1.86 (6H, 2 × s,
AsMe2), 1.41, 1.36 (6H, 2 × s, CMe2). δC (100 MHz, CDCl3)
109.5 (CMe2), 107.5 (C1), 78.3 (C4), 75.4, 75.1 (C2,3), 74.3
(C2ꢀ), 68.7 (C1ꢀ), 66.5 (C3ꢀ), 38.9 (C5), 26.7, 25.2 (CMe2), 19.4,
18.6 (AsMe2). m/z (ESI) 423 [M + K]+, 407 [M + Na]+.
(S)-2ꢀ-Hydroxy-3ꢀ-O-tosylpropyl 5-Deoxy-5-
dimethylarsinothioyl-2,3-di-O-acetyl-β-D-riboside 16
The diol 15 (200 mg, 0.47 mmol) in CH2Cl2 (4 mL) together with
p-tosyl chloride (96 mg, 0.5 mmol), Et3N (51 mg, 0.5 mmol),
and Bu2SnO (5 mg, 0.02 mmol) was stirred at 35◦C for 1.5 h.
The reaction mixture was then diluted (CH2Cl2) and filtered.
After usual workup of the filtrate, the organic layer was evapo-
rated and the residue was subjected to column chromatography
(silica, EtOAc) to give the tosylate 16 (200 mg, 72%) as a
yellow oil. [α]D −1.8◦ (c. 1.4 MeOH). (Found: C 42.5, H
5.5. C21H31O10AsS2·0.5H2O requires C 42.6, H 5.4%.) δH
(500 MHz, CDCl3) 7.78, 7.38 (4H, 2d, J 8.2, Ar), 5.25 (2H,
m, H2,3), 5.00 (1H, s, H1), 4.72 (1H, m, H4), 4.10 (1H, dd, J
9.8, 6.4, H3ꢀ), 3.98 (1H, m, H2ꢀ), 3.91 (1H, dd, J 9.8, 5.4, H3ꢀ),
3.84 (1H, dd, J 10.0, 4.4, H1ꢀ), 3.52 (1H, dd, J 10.0, 3.8, H1ꢀ),
2.50 (1H, dd, J 13.2, 11.2, H5), 2.46 (3H, s, ArMe), 2.30 (1H,
dd, J 13.2, 2.0, H5), 2.11, 2.07 (6H, 2 × s, OAc), 1.92, 1.84
(6H, 2 × s, AsMe2). δC (125 MHz, CDCl3) 169.9, 169.7 (CO),
145.3–127.9 (Ar), 105.3 (C1), 76.1 (C4), 74.7, 74.3 (C2,3), 69.2
(C3ꢀ), 67.6 (C1ꢀ,2ꢀ), 38.3 (C5), 21.6 (ArMe), 20.5 (OAc), 19.7,
19.2 (AsMe2). m/z (ESI) 605 [M + Na]+, 583 [M + H]+, 567
[M − Me]+.
(S)-2ꢀ,3ꢀ-O-Isopropylidenepropyl 5-Deoxy-5-
dimethylarsinothioyl-2,3-di-O-acetyl-β-D-riboside 14
The arsine oxide 11 (1.0 g, 2.7 mmol) was dissolved in pyridine
(10 mL) and H2S was passed through the solution for 1 min.
After stirring for 15 min, TLC analysis (silica, EtOAc/MeOH,
4/1, v/v) indicated the conversion to the sulfur analogue 13 to be
complete. Acetic anhydride (5 mL) was added and stirring was
continued for 2 h. The reaction mixture was poured into aque-
ous NaHCO3 solution under vigorous stirring. Extraction with
CH2Cl2, workup, and evaporation of the organic layer gave a
syrup, which was subjected to column chromatography (silica,
EtOAc) to give the fully protected arsine sulfide 14 (970 mg,
77%) initially as an oil, which slowly crystallized. Recrystal-
lization was performed from a mixture of hexane/ether/MeOH
to give white needles. Mp (hexane/ether/MeOH) 96◦C (dec.).
[α]D −7.1◦ (c. 1.9 MeOH). (Found: C 43.5, H 6.2. C17H29O8AsS
requires C 43.6, H 6.2%.) δH (500 MHz, CDCl3) 5.19 (2H, m,
H2,3), 4.97 (1H, s, H1), 4.59 (1H, m, H4), 4.17 (1H, m, H2ꢀ),
3.99 (1H, dd, J 8.2, 6.6, H3ꢀ), 3.64 (2H, m, H1ꢀ,3ꢀ), 3.42 (1H, dd,
J 10.0, 5.6, H1ꢀ), 2.30 (2H, m, H5), 2.05, 2.00 (6H, 2 × s, OAc),
1.83, 1.76 (6H, 2 × s, AsMe2), 1.33, 1.29 (6H, 2 × s, CMe2).
δC (125 MHz, CDCl3) 169.9, 169.7 (CO), 109.6 (CMe2), 105.5
(C1), 76.1 (C4), 74.7, 74.3 (C2,3), 74.1 (C2ꢀ), 69.0 (C1ꢀ), 66.4
(C3ꢀ), 39.0 (C5), 26.7, 25.3 (CMe2), 20.5, 20.4 (OAc), 19.5,
19.4 (AsMe2). m/z (ESI) 507 [M + K]+, 491 [M + Na]+, 469
[M + H]+.
(S)-2ꢀ-Hydroxy-3ꢀ-sulfonylpropyl 5-Deoxy-
5-dimethylarsinoyl-β-D-riboside, Ammonium Salt 2
(i) The tosylate 16 (240 mg, 0.41 mmol) was dissolved in a
mixture of MeOH/water (1/1, v/v, 2 mL) and heated to 40◦C.
Na2SO3 (104 mg, 0.83 mmol) in water (1 mL) was added and
the solution was stirred for 6 h at 40◦C. The solution was
then concentrated and the residue subjected to anion exchange
chromatography (DEAE Sephadex/0.05 M Tris buffer, pH 8.0,
16 × 300 mm2, elution volume 360 mL) followed by size exclu-
sion chromatography (Sephadex G-15/water, 26 × 600 mm2,
elution volume 160 mL) to yield the sulfonic acid as the Tris
salt. This procedure was repeated twice. Conversion into the
ammonium salt was performed by passage through cation
exchange resin (Dowex 50, NH+4 ). Subsequent size exclu-
sion chromatography (Sephadex G-15/water) delivered (S)-
2ꢀ-hydroxy-3ꢀ-sulfonylpropyl 5-deoxy-5-dimethylarsinothioyl-
β-d-riboside, ammonium salt 17 (120 mg, 69%). δH (500 MHz,
D2O) 5.07 (1H, s, H1), 4.41 (1H, m, H4), 4.33 (2H, m, H3,2ꢀ),
4.20 (1H, d, J 4.4, H2), 3.86 (1H, dd, J 10.6, 5.6, H1ꢀ), 3.69 (1H,
dd, J 10.6, 3.6, H1ꢀ), 3.21 (1H, dd, J 14.4, 5.0, H3ꢀ), 3.10 (1H, dd,
J 14.4, 6.9, H3ꢀ), 2.64 (1H, dd, J 13.5, 10.2, H5), 2.58 (1H, dd,
J 13.5, 3.2, H5), 2.00, 1.97 (6H, 2 × s, AsMe2). δC (125 MHz,
D2O) 107.2 (C1), 77.6 (C4), 75.4 (C3), 74.1 (C2), 70.5 (C1ꢀ),
66.2 (C2ꢀ), 53.6 (C3ꢀ), 37.4 (C5), 17.7, 17.5 (AsMe2). m/z (ESI)
407 [M − NH4]−.
(R)-2ꢀ,3ꢀ-Dihydroxypropyl 5-Deoxy-5-dimethylarsinothioyl-
2,3-di-O-acetyl-β-D-riboside 15
The fully protected arsine sulfide 14 (900 mg, 1.9 mmol) was dis-
solved in MeCN (25 mL) and a mixture of CF3COOH/H2O (8/2,
v/v, 1 mL) was added. The solution was stirred for 15 min, after
which it was neutralized (NH4OH). The solvent was removed
under reduced pressure and the obtained residue subjected to
column chromatography (silica, EtOAc/MeOH, 4/1, v/v) to give
the diol 15 (676 mg, 82%) as a yellow oil. [α]D −10.2◦ (c. 1.8
MeOH). (Found: C 38.9, H 5.6. C14H25O8AsS requires C 39.3,
H 5.8%.) δH (500 MHz, CDCl3) 5.26 (2H, m, H2,3), 5.02 (1H,
s, H1), 4.62 (1H, m, H4), 3.89 (1H, m, H2ꢀ), 3.74 (1H, dd, J
10.0, 6.4, H1ꢀ), 3.68 (1H, dd, J 11.2, 3.6, H3ꢀ), 3.57 (1H, dd,
J 11.2, 6.4, H3ꢀ), 3.53 (1H, dd, J 10.0, 4.0, H1ꢀ), 2.50 (1H, dd,
J 13.2, 11.2, H5), 2.36 (1H, dd, J 13.2, 2.0, H5), 2.12, 2.07
(6H, 2 × s, OAc), 1.89, 1.85 (6H, 2 × s, AsMe2). δC (125 MHz,
CDCl3) 170.3, 170.1 (CO), 105.4 (C1), 76.1 (C4), 75.0, 74.4
(C2,3), 70.4 (C2ꢀ), 69.3 (C1ꢀ), 63.1 (C3ꢀ), 38.8 (C5), 20.5 (OAc),
19.3 (AsMe2). m/z (ESI) 467 [M + K]+, 451 [M + Na]+, 429
[M + H]+.
(ii) Compound 17 (65 mg, 0.15 mmol) was dissolved in water
(5 mL) and treated with 30% H2O2 (0.1 mL) at 0◦C.The solution
was stirred for 10 min after which the solvent was evaporated
and the residue subjected to anion chromatography (DEAE
Sephadex/0.05 MTrisbuffer, pH8.0, 16 × 300 mm2, elutionvol-
ume 250 mL) followed by desalting on Sephadex G-15/water
(26 × 600 mm2, elution volume 160 mL). The sulfonic acid was
obtained as the Tris salt and passage through a column of cation
exchange resin (Dowex 50, NH+4 ) delivered the sulfonic acid
2 as the ammonium salt which was further purified by size
exclusion chromatography (Sephadex G-15/water) to deliver the
sulfonic acid, ammonium salt 2 (53 mg, 87%) as a colourless
oil. [α]D +2.5◦ (c. 1.4 MeOH). (Found: C 28.5, H 6.2, N 3.0.
C10H24O9AsNS·0.5H2O requires C 28.7, H 6.0, N 3.3%.) δH

RESEARCH FRONT
544
P. Traar et al.
(360 MHz, D2O) 5.06 (1H, s, H1), 4.29 (3H, m, H3,4,2ꢀ), 4.17
(1H, d, J 3.0, H2), 3.83 (1H, dd, J 10.6, 5.6, H1ꢀ), 3.67 (1H, dd,
J 10.6, 3.4, H1ꢀ), 3.18 (1H, dd, J 14.4, 5.4, H3ꢀ), 3.06 (1H, dd,
J 14.4, 6.7, H3ꢀ), 2.76 (1H, dd, J 13.8, 2.7, H5), 2.63 (1H, dd,
J 13.8, 10.1, H5), 1.99, 1.96 (6H, 2 × s, AsMe2). δC (90 MHz,
D2O) 108.2 (C1), 77.3 (C4), 76.4 (C3), 74.9 (C2), 71.3 (C1ꢀ),
67.0 (C2ꢀ), 54.4 (C3ꢀ), 36.7 (C5), 15.1, 14.8 (AsMe2). m/z (ESI)
391 [M − NH4]−.
Tris buffer, pH 8.0, 16 × 300 mm2, elution volume 300 mL) fol-
lowed by size exclusion chromatography (Sephadex G-15/water,
26 × 600 mm2, elution volume 190 mL) to give the sulfuric
acid ester as the Tris salt. Passage through a column of cation
exchange resin (Dowex 50, NH+4 ) followed by size exclusion
chromatography delivered the sulfuric acid ester, ammonium
salt 3 (55 mg, 85%) as a colourless oil, which slowly solidi-
fied. [α]D +1.0◦ (c. 1.4 MeOH). (Found: C 27.9, H 5.8, N 3.1.
C10H24O10AsNS requires C 28.2, H 5.6, N 3.3%.) δH (360 MHz,
D2O) 5.05 (1H, s, H1), 4.29 (2H, m, H3,4), 4.17 (1H, d, J 3.4,
H2), 4.09 (3H, m, H2ꢀ,3ꢀ), 3.85 (1H, dd, J 10.6, 4.4, H1ꢀ), 3.64
(1H, dd, J 10.6, 3.2, H1ꢀ), 2.75 (1H, dd, J 13.9, 2.9, H5), 2.60
(1H, dd, J 13.9, 10.1, H5), 1.98, 1.94 (6H, 2 × s, AsMe2). δC
(90 MHz, D2O) 108.3 (C1), 77.5, 76.7, 75.2 (C2,3,4), 69.2, 68.9,
68.6 (C1ꢀ,2ꢀ,3ꢀ), 36.9 (C5), 15.3, 15.1 (AsMe2). m/z (ESI) 407
[M − NH4]−.
(S)-2ꢀ-Hydroxy-3ꢀ-sulfooxypropyl 5-Deoxy-
5-dimethylarsinothioyl-2,3-di-O-acetyl-β-D-riboside 18
A solution of the diol 15 (200 mg, 0.47 mmol) in pyridine (4 mL)
and Et3N:SO3 (136 mg, 0.75 mmol) was stirred for 24 h at room
temperature. The pyridine was then concentrated and the residue
subjected to column chromatography (silica, MeOH/EtOAc, 1/2,
v/v) to give the crude sulfuric acid ester. The compound was dis-
solved in water and passed through a column of cation exchange
resin (Dowex 50, NH+4 ) to give the sulfuric acid ester as the
ammoniumsalt. Passage through Sephadex LH-20/MeOH deliv-
ered the sulfuric acid ester, ammonium salt 18 (142 mg, 58%) as
a yellow oil. [α]D −11.0◦ (c. 1.4 MeOH). (Found: C 30.9, H 5.3,
N 2.6. C14H28O11AsNS2·H2O requires C 30.9, H 5.5, N 2.6%.)
δH (500 MHz, D2O) 5.50 (2H, m, H2,3), 5.32 (1H, s, H1), 4.80
(2H, m, H4,2ꢀ), 4.37 (1H, dd, J 10.7, 5.5, H3ꢀ), 4.33 (1H, dd, J
10.7, 4.6, H3ꢀ), 4.08 (1H, dd, J 11.0, 5.5, H1ꢀ), 3.95 (1H, dd, J
11.0, 3.7, H1ꢀ), 2.87 (1H, dd, J 13.4, 11.0, H5), 2.60 (1H, dd,
J 13.4, 2.7, H5), 2.28, 2.21 (6H, 2 × s, OAc), 2.09, 2.00 (6H,
2 × s, AsMe2). δC (125 MHz, D2O) 172.8, 172.7 (CO), 104.9
(C1), 76.3 (C4), 75.6 (C3), 75.0 (C2ꢀ), 74.7 (C2), 66.1, 66.0
(C1ꢀ,3ꢀ), 36.7 (C5), 20.5 (OAc), 18.2, 17.7 (AsMe2). m/z (ESI)
507 [M − NH4]−.
(R,S)-2,3-O-Isopropylidenepropyl-(R)-5,6-
di-O-benzylpropyl-2-chlorophenyl Phosphate 20
The alcohol (S)-2,3-di-O-benzylglycerol (110 mg, 0.4 mmol) in
CH2Cl2 (0.5 mL) was slowly added to an ice-cold solution
that contained 2-chlorophenyl phosphorodichloridate (100 mg,
0.41 mmol) and pyridine (160 mg, 2.0 mmol) in CH2Cl2
(1.5 mL) under an argon atmosphere. After complete addition
of the alcohol, the reaction mixture was stirred for 1 h at 0◦C,
and then allowed to warm to room temperature and stirred for
an additional hour. TLC analysis (silica, cyclohexane/EtOAc,
2/1, v/v) indicated the formation of a less polar product. The
alcohol (R,S)-2,3-O-isopropylideneglycerol (70 mg, 0.53 mmol)
in CH2Cl2 (0.5 mL) was added to the solution that contained
the presumed diester and the reaction mixture was stirred for
2 h. After workup, the organic layer was evaporated and the
residue subjected to column chromatography (silica, cyclohex-
ane/EtOAc, 2/1, v/v) to give 20 (128 mg, 55%) as a colourless
oil. δH (360 MHz, CDCl3) 7.32, 7.14 (14H, 2 × m, Ar), 4.63,
4.51 (4H, 2 × s, 2CH2Ar), 4.41–3.58 (10H, 6 × m, H1–6), 1.37,
1.32 (6H, 2 × s, CMe2). δC (90 MHz, CDCl3) 146.6–121.5 (Ar),
109.9 (CMe2), 76.4, 73.8, 73.5, 72.3, 68.9, 68.3, 66.1 (C1–6,
CH2Ar), 26.7, 25.3 (CMe2). δP (145.8 MHz, CDCl3) −11.6. m/z
(ESI) 599 [M + Na]+, 577 [M + H]+.
(S)-2ꢀ-Hydroxy-3ꢀ-sulfooxypropyl 5-Deoxy-
5-dimethylarsinoyl-β-D-riboside, Ammonium Salt 3
(i)The partially protected arsine sulfide 18 (165 mg, 0.31 mmol)
was dissolved in MeOH (5 mL) and NaOMe in MeOH (1 M,
0.7 mL) was added. After complete deacetylation (10 min) the
solution was adjusted to pH 8.0 (CH3COOH). The solvent
was evaporated and the residue subjected to anion exchange
chromatography (DEAE Sephadex/0.05 M Tris buffer, pH 8.0,
16 × 300 mm2, elution volume 500 mL) followed by size exclu-
sion chromatography (Sephadex G-15/water, 26 × 600 mm2,
elution volume 190 mL). This procedure was repeated twice.
The obtained Tris salt was passed through a column of
cation exchange resin (Dowex 50, NH+4 ) to give the sulfuric
acid ester as the ammonium salt. Subsequent size exclusion
chromatography (Sephadex G-15/water) delivered (S)-2ꢀ-
hydroxy-3ꢀ-sulfooxypropyl 5-deoxy-5-dimethylarsinothioyl-β-
d-riboside, ammonium salt 19 (110 mg, 80%) as a colourless
oil. δH (500 MHz, D2O) 5.06 (1H, s, H1), 4.43 (1H, m, H4),
4.35 (1H, dd, J 7.0, 4.5, H3), 4.20 (1H, d, J 4.5, H2), 4.15
(3H, m, H2ꢀ,3ꢀ), 3.88 (1H, dd, J 10.6, 4.4, H1ꢀ), 3.66 (1H, dd,
J 10.6, 3.2, H1ꢀ), 2.64 (1H, dd, J 13.5, 10.3, H5), 2.58 (1H, dd,
J 13.5, 3.2, H5), 2.02, 1.99 (6H, 2 × s, AsMe2). δC (125 MHz,
D2O) 107.1 (C1), 77.6 (C4), 75.4 (C3), 74.1 (C2), 68.2, 67.8,
67.6 (C1ꢀ,2ꢀ,3ꢀ), 37.2 (C5), 17.8, 17.5 (AsMe2). m/z (ESI) 423
[M − NH4]−.
Acknowledgements
The Austrian Science Fund (FWF P16816) and the Austrian Academy of
Sciences (DOC Scholarship) are thanked for financial support. Robert V.
Stick, Rudolf Pietschnig, and Wolfram Wielandt are gratefully thanked for
helpful and supportive discussions.
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