Preparation of 5-selenopentopyranose sugars from pentose starting materials by Samarium(II) iodide or (phenylseleno)formate mediated ring closures

Article abstract of DOI:10.1016/S0040-4020(00)00299-4

2,3,4-Tri-O-benzyl-1,5-dideoxy-5-seleno-D-pentopyranose sugars (16, 23,24) are readily prepared by thermolysis of 2,3,4-tri-O-benzyl-5- benzylseleno-D-ribit-1-yl formate, 2,3,4-tri-O-benzyl-5-benzylseleno-D-xylit- 1-yl formate and 2,3,4-tri-O-benzyl-5-ben

Full text of DOI:10.1016/S0040-4020(00)00299-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3995±4000
Preparation of 5-Selenopentopyranose Sugars from Pentose
Starting Materials by Samarium(II) Iodide or
(Phenylseleno)formate Mediated Ring Closures
²
*
Mathew A. Lucas, Oanh T. K. Nguyen, Carl H. Schiesser and Shi-Long Zheng
School of Chemistry, The University of Melbourne, Victoria 3010, Australia
Received 10 December 1999; revised 20 March 2000; accepted 6 April 2000
AbstractÐ2,3,4-Tri-O-benzyl-1,5-dideoxy-5-seleno-d-pentopyranose sugars (16, 23, 24) are readily prepared by thermolysis of 2,3,4-tri-O-
benzyl-5-benzylseleno-d-ribit-1-yl formate, 2,3,4-tri-O-benzyl-5-benzylseleno-d-xylit-1-yl formate and 2,3,4-tri-O-benzyl-5-benzylseleno-
d-arabit-1-yl formate (13, 21, 22) in transformations which involve intramolecular nucleophilic attack of the benzylseleno moiety with
concomitant loss of carbon dioxide and phenylselenoate. In a complementary procedure, treatment of 2,3,4-tri-O-benzyl-5-benzylseleno-5-
deoxyribose (19) with samarium(II) iodide in THF affords 2,3,4-tri-O-benzyl-5-deoxy-5-seleno-d-ribopyranose (26) in 50% isolated yield in
a process most likely involving intramolecular homolytic substitution at the selenium atom in the selenosugar. q 2000 Elsevier Science Ltd.
All rights reserved.
Introduction
acid (7) which provides an effective treatment for Kwashio-
kor, a protein-malnutrition disorder,10 selenacephalosporins
(8) which were patented by Hoffman La Roche as antibio-
tics,11 selenazine (9) which is reported to be effective
against Methiciline resistant Staphylococcus aureus,8
(MRS) and Ebselen (10), which is currently undergoing
clinical trials as a non-steroidal antiin¯ammatory (Fig. 1).7
It is well accepted that carbohydrates play an important role
in a vast array of biological processes. Modi®ed carbohy-
drates such as nitrogen, phosphorus and sulfur containing
monosaccharides are of interest due to their wide variety of
pharmacological activity and physiochemical properties.
Examples include 5-deoxy-5-thio-d-glucose (1) which has
been shown to be a potent inhibitor of cellular d-glucose
transport and also selectively toxic to hypoxic tumor cells,1
nojirimycin (2), deoxynojirimycin (3) and the butylated
analogue (4) which are well known to show antibacterial
activity and have been proposed as chemotherapeutic agents
to treat HIV infection.2 Selenium analogues of these impor-
tant compounds (e.g. 5, 6) may also be expected to show
interesting properties.
It is well established that selenium is an essential trace
element and selenium dietary supplements are commonly
available, especially in countries such as France and New
Zealand, which are soil selenium de®cient.12
There are very few reports of carbohydrates containing sele-
nium in the ring position.13 Those that have been reported
(e.g. 6) were prepared in very poor yield.13 Given the biome-
dical importance of selenium-containing organic molecules,
and the scarcity of (ring) selenium-modi®ed carbohydrates,
it is clear that a synthetically useful method for the prepara-
tion of selenium-containing carbohydrates is required.
There can be no doubt that selenium-containing organic
molecules have played and continue to play an important
role in biology and medicine.3 The mythology surrounding
the `high toxicity' of organic selenides, which itself can be
traced to the voyages of Marco Polo,4 and, more recently,
the American civil war,5 has largely been dispelled, and a
wide range of organic selenides are now accepted as useful
antioxidants,6 anti-in¯ammatory agents,7 antibiotics8 and
anti-viral agents.9 Examples include the diselenovaleric
As part of ongoing investigations, we were interested in the
preparation of novel selenium-containing carbohydrates
related to 5. Given our recent successes in the preparation
of selenium-containing higher heterocycles through the use
of intramolecular free-radical homolytic substitution chem-
istry as well as ionic chemistry,14,15 we began to explore the
possibility of constructing the carbohydrates of interest
through appropriate extensions of previous work.
Keywords: carbohydrate; selenium; free-radical; samarium iodide; ring
closure.
* Corresponding author. Tel.: 161-3-8344-4180; fax: 161-3-9347-5180;
e-mail: c.schiesser@chemistry.unimelb.edu.au
Current address: West China University of Medical Sciences, Chengdu,
We now report that 2,3,4-tri-O-benzyl-1,5-dideoxy-5-sele-
no-d-pentopyranose sugars (16, 23, 24) can be prepared by
thermolysis of suitable selenoformate derivatives of pentose
²
China.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00299-4

3996
M. A. Lucas et al. / Tetrahedron 56 (2000) 3995±4000
Figure 1.
carbohydrates, while 2,3,4-tri-O-benzyl-5-deoxy-5-seleno-
d-pentopyranose analogues (26, 28, 29) can be prepared
by treatment of suitable precursor aldopentose derivatives
with samarium(II) iodide in THF/HMPA.
To our delight, when selenoformate (13) was heated to
1508C in benzene (0.27 M solution) in a sealed tube, H
1
NMR spectroscopy revealed an almost quantitative conver-
sion into the required product; 2,3,4-tri-O-benzyl-1,5-
dideoxy-5-seleno-d-arabinopyranose (16: [a]2D2ˆ241) was
isolated in 81% yield after chromatography. Presumably, 16
is formed from 13 in an analogous manner to the transfor-
mations depicted in Scheme 1. When the complete sequence
depicted in Scheme 2 was repeated using l-arabinose as
starting material, 2,3,4-tri-O-benzyl-1,5-dideoxy-5-seleno-
l-arabinopyranose, the enantiomer of 16 ([a]2D2ˆ145)
was isolated in 74% yield from the corresponding l-seleno-
formate.
Results and Discussion
We reported recently that 1-(benzylseleno)alkyl (phenyl-
telluro)formates (11, YˆTePh), as well as the (phenylsele-
no)formate and chloroformate analogues, upon thermolysis,
react to provide the selenium-containing rings (12) in excel-
lent yield.15 The mechanism of these transformations has
been shown to involve intramolecular nucleophilic attack
of the benzylseleno moiety with concomitant loss of carbon
dioxide and phenylchalcogenide or chloride (Scheme 1).15
The procedure reported by Quiclet-Sire for the preparation
of 14,16 when applied to the analogous ribose and xylose
substrates, proved to be fraught with dif®culties. In particu-
lar, the ribose and xylose analogues of 14 proved to be
unstable and a preparative sequence that avoided their
preparation was required. We found that the known dithioa-
cetals17 (17, 18) derived from d-ribose and d-xylose respec-
tively, are readily mesylated. Further treatment with sodium
benzylselenoate followed by mercuric chloride deprotection
afforded the benzylseleno aldehydes (19, 20) in excellent
yields (Scheme 3). Further sodium borohydride reduction
and conversion of the resultant alcohols into the selenofor-
mates (21, 22) was achieved as described for the preparation
of 13. To our delight, both selenoformates (21, 22) provided
their respective (optically-inactive) cyclic selenosugar,
namely 2,3,4-tri-O-benzyl-1,5-dideoxy-5-seleno-d-ribopyr-
anose (23) and 2,3,4-tri-O-benzyl-1,5-dideoxy-5-seleno-d-
xylopyranose (24) in 56 and 96% yield respectively
(Scheme 3).
Given these previous observations, it seemed appropriate to
explore similar chemistry involving aldopentose starting
materials; selenoformate (13) derived from d-arabinose
appeared to be a reasonable initial target. To that end d-
arabinose was converted into 2,3,4-tri-O-benzyl-5-O-
methanesulfonylarabinose (14) following the procedure of
Barton and Quiclet-Sire.16 Subsequent reduction with
sodium borohydride followed by reaction with sodium
benzylselenoate14 afforded the benzylselenoarabitol (15) in
55% yield after ¯ash chromatography (Scheme 2). Follow-
ing our previously published procedure,15 15 was treated
with a solution of phosgene in toluene followed by sodium
phenylselenoate to give the required selenoformate (13) in
71% yield after chromatography.
Given our recent successes in the application of intramole-
cular homolytic substitution chemistry to the synthesis of
selenium and tellurium containing heterocycles,6,14 we felt
that this approach might be amenable to the preparation of
selenosugars in which the `anomeric' centre is oxygenated.
Samarium (II) iodide mediated radical ring-closure seemed
Scheme 1.

M. A. Lucas et al. / Tetrahedron 56 (2000) 3995±4000
3997
Scheme 2.
Scheme 3.
appropriate chemistry to explore,18 although we were
unaware of any reports of SmI2 mediated homolytic substi-
tution reactions at the outset of this work.
molecular homolytic substitution of the radical centre in 27,
generated by the reaction of the aldehyde moiety in 19 with
SmI2, at the selenium atom with expulsion of the benzyl
group (Scheme 4). It should be noted that selenosugar
(26) was isolated as a pair of anomers, as evidenced by H
NMR spectroscopy.
1
Aldehyde (14) was readily converted into the required
benzylseleno derivative (25) by treatment with sodium
benzylselenoate. With the required precursors (19, 20, 25)
in hand, we began to explore the SmI2 ring-closure chem-
istry. When 19 was treated with 2.5 equiv. of samarium(II)
iodide in THF/HMPA, TLC analysis revealed the absence of
starting material (19) after 20 min. To our delight, separa-
tion of the crude reaction mixture by ¯ash chromatography
afforded 2,3,4-tri-O-benzyl-5-deoxy-5-seleno-d-ribopyra-
nose (26) in 50% yield. Presumably, 26 is formed by intra-
Unfortunately, treatment of 2,3,4-tri-O-benzyl-5-benzyl-
seleno-5-deoxyxylose (20) and 2,3,4-tri-O-benzyl-5-
benzylseleno-5-deoxyarabinose (25) with samarium(II)
iodide in THF/HMPA gave a complex mixture of
compounds as evidenced by TLC. Careful ¯ash chromato-
graphy of each of these mixtures afforded impure samples
2,3,4-tri-O-benzyl-5-deoxy-5-seleno-d-xylopyranose (28)
Scheme 4.

3998
M. A. Lucas et al. / Tetrahedron 56 (2000) 3995±4000
and
2,3,4-tri-O-benzyl-5-deoxy-5-seleno-d-arabinopyra-
s), 3.85 (1H, m), 3.97 (2H, m), 4.16 (1H, t, Jˆ4.6 Hz),
4.30 (1H, dd, Jˆ6.6, 11 Hz), 4.41 (1H, dd, Jˆ3.1,
11 Hz), 4.56±4.76 (5H, m), 4.90 (1H, m), 7.30±7.36
(15H, m).
nose (29). Despite the impurity of these samples, the
formation of 28 and 29 was con®rmed by HRMS in each
case.20
To the best of our knowledge, these transformations repre-
sent the ®rst examples of SmI2 mediated homolytic substi-
tution chemistry and complement the selenoformate
mediated entry routes into rare 5-selenopentopyranose
carbohydrates.
Standard protocol A for the preparation of benzylseleno
sugars: 2,3,4-tri-O-benzyl-5-benzylseleno-d-arabitol (15).
Sodium borohydride (0.04 g, 1.06 mmol) was added to a
solution of dibenzyl diselenide (0.12 g, 0.35 mmol) in dry
ethanol (20 mL) and the solution was purged with nitrogen
and allowed to react for 1 h. A solution of 2,3,4-tri-O-benzyl-
5-O-methanesulfonyl-d-arabitol (0.34 g, 0.59 mmol) in
ethanol (2 mL) was syringed into the benzylselenoate solu-
tion and the mixture was stirred for a further 18 h. The
reaction solvent was removed in vacuo, and the residue
dissolved in dichloromethane (40 mL). This organic solu-
tion was washed with saturated NaCl (10 mL) separated,
dried (Na2SO4) and the solvent removed in vacuo. The
title compound was puri®ed by ¯ash chromatography
(hexane/ethyl acetate 80:20) affording 15 as a pale yellow
solid, (0.24 g, 61%), mp 83±848C. 1H NMR d (CDCl3) 2.12
(1H, sbr), 2.91 (2H, d, Jˆ5.4 Hz), 3.74 (2H, d, Jˆ3.4 Hz),
3.57±3.85 (5H, m), 4.42±4.67 (6H, m), 7.23±7.32 (20H,
m). 13C NMR d 25.18, 27.90, 61.80, 72.37, 72.89, 74.01,
79.81, 79.99, 80.18, 126.66, 127.68, 127.85, 127.90, 128.02,
128.33, 128.39, 128.44, 128.93, 138.05, 138.32, 138.37,
139.47. 77Se NMR d (CDCl3) 222.36. IR(nujol) nmax
3485 cm21. [a]D27 (cˆ1.0, CHCl3)ˆ24.1. Anal. Calcd for
C33H36O4Se: C, 68.9; H, 6.3. Found: C, 68.9; H, 6.4.
Experimental
All reagents used were obtained from commercial suppliers.
Dibenzyl diselenide was prepared according to published
procedure.19 All melting points are uncorrected. Elemental
analyses were carried out by Chemical and Micro Analytical
Services Pty. Ltd.
2,3,4-Tri-O-benzyl-5-O-methanesulfonyl-d-arabitol.
Sodium borohydride (180 mg, 4.8 mmol) was added with
stirring at 08C to a solution of 2,3,4-tri-O-benzyl-5-O-
methanesulfonyl-arabinose (14)16 (0.80 g, 1.6 mmol) in
4:1 dichloromethane±methanol (25 mL). The system was
¯ushed with nitrogen. After stirring for 4 h at 08C, the
solvent was removed in vacuo, and the residue dissolved
in ether (30 mL). The resultant solution was washed with
water (5 mL), dried (MgSO4), and the solvent removed. The
title compound was isolated after ¯ash chromatography
(70:30 hexane±ethyl acetate) as a white crystalline solid
of suf®cient purity for further use (0.47 g, 59%), mp 58±
2,3,4-Tri-O-benzyl-5-benzylseleno-d-ribose diethyl di-
thioacetal was prepared from 2,3,4-tri-O-benzyl-5-O-
methanesulfonyl-d-ribose diethyl dithioacetal following
standard protocol A as a light yellow viscous oil (42%).
1H NMR d (CDCl3) 1.18 (6H, m), 2.57±2.68 (5H, m),
2.89 (1H, dd, Jˆ7.8, 13.0 Hz), 3.71 (2H, d, Jˆ4.1 Hz),
3.93±3.98 (1H, m), 3.87 (1H, dd, Jˆ3.2, 7.6 Hz), 4.17
(2H, m), 4.61 (4H, m), 4.76 (1H, m), 4.87 (1H, m), 7.19±
7.34 (20H, m). 13C NMR d (CDCl3) 14.42, 24.99, 26.35,
27.97, 53.94, 72.35, 73.41, 74.52, 79.84, 80.79, 82.41,
126.52, 127.48, 127.57, 127.85, 128.01, 128.25, 128.29,
128.37, 128.87, 138.07, 138.37, 139.58. 77Se NMR d
(CDCl3) 230.25. MS (ESI) m/z 703.4 (M1Na)1. [a]D28
(cˆ1.0, CHCl3)ˆ15.1. Anal. Calcd for C37H44O3S2Se: C,
65.4; H, 6.5. Found: C, 65.5; H, 6.4.
1
598C. H NMR d (CDCl3) 1.79 (1H, sbr), 2.88 (3H, s),
3.66±3.81 (3H, m) 3.85 (1H, t, Jˆ4.5 Hz), 3.94 (1H, m),
4.42 (1H, dd, Jˆ5.8 Hz), 4.49±4.75 (7H, m), 7.29±7.34
(15H, m). 13C NMR d 36.83, 60.70, 69.25, 72.27, 72.31,
74.06, 77.43, 78.06, 78.71, 127.52, 127.62, 127.64, 127.86,
128.15, 137.29, 137.51, 137.81. IR(nujol) nmax 3480 cm21
[a]2D7 (cˆ1.0, CHCl3)ˆ24.2.
.
2,3,4-Tri-O-benzyl-5-O-methanesulfonyl-d-ribose diethyl
dithioacetal. 4-Dimethylaminopyridine (12 mol%, 0.04 g,
0.334 mmol) was added to a solution of 17 in dry dichloro-
methane (15 mL) and dry pyridine (6 mL) at 08C. After
stirring at 08C for 15 min, methanesulfonyl chloride
(0.32 mL, 4.18 mmol) was added, and the mixture was stir-
red at room temperature for a further 4 h. The solvent was
removed in vacuo, and the residue was dissolved in ethyl
acetate (50 mL), washed with saturated NaHCO3 (20 mL),
dilute HCl (2£20 mL), water (2£50 mL) and saturated NaCl
(20 mL), dried (Na2SO4), and the solvent removed in vacuo
to afford the title compound as a green, unstable oil of
2,3,4-Tri-O-benzyl-5-benzylseleno-d-xylose diethyl di-
thioacetal was prepared from 2,3,4-tri-O-benzyl-5-O-
methanesulfonyl-d-xylose diethyl dithioacetal following
standard protocol A as a light yellow viscous oil (40%).
1H NMR d (CDCl3) 1.18 (6H, m), 2.51 (2H, m), 2.68 (2H,
m), 2.82 (1H, dd, Jˆ7.0, 12.5 Hz), 3.63 (1H, m), 3.74 (2H,
s), 3.80 (1H, d, Jˆ3.6 Hz), 4.01 (1H, dd, Jˆ3.5, 6.8 Hz),
4.20 (1H, dd, Jˆ3.6, 7.0 Hz), 4.40 (1H, m), 4.52±4.86 (6H,
m), 7.27±7.34 (20H, m). 13C NMR d (CDCl3) 14.33, 14.43,
23.44, 25.01, 25.34, 27.62, 53.54, 71.75, 74.96, 75.14,
78.66, 80.48, 82.83, 16.68, 127.17, 127.29, 127.50,
127.64, 127.68, 127.76, 127.83, 127.91, 128.04, 128.10,
128.20, 128.29, 128.43, 128.92, 137.88, 138.43, 138.55,
139.08. 77Se NMR d (CDCl3) 224.28. MS (ESI) m/z
703.1 (M1Na)1. [a]D28 (cˆ1.0, CHCl3)ˆ214.3. Anal.
Calcd for C37H44O3S2Se: C, 65.4; H, 6.5. Found: C,
65.2; H, 6.5.
1
suf®cient purity for further use (1.45 g, 86%). H NMR d
(CDCl3) 1.17±1.26 (6H, m), 2.59±2.68 (4H, m), 2.77 (3H,
s), 3.92 (1H, dd, Jˆ3.9, 6.6 Hz), 4.09±4.17 (3H, m), 4.35
(2H, m), 4.60±4.78 (5H, m), 4.96 (1H, d, Jˆ11 Hz), 7.29
(15H, m).
2,3,4-Tri-O-benzyl-5-O-methanesulfonyl-d-xylose diethyl
dithioacetal was prepared by the procedure described
above for the ribose analogue and isolated as an unstable
orange viscous oil of suf®cient purity for further use (85%)
1H NMR d (CDCl3) 1.20 (6H, m), 2.61 (4H, m), 2.80 (3H,

M. A. Lucas et al. / Tetrahedron 56 (2000) 3995±4000
3999
Standard protocol B for the deprotection of dithioacetals:
2,3,4-tri-O-benzyl-5-benzylseleno-aldehydo-d-ribose 19.
Calcium carbonate (0.86 g, 8.56 mmol) and mercuric (II)
chloride (2.32 g, 8.56 mmol) was added to a solution of
2,3,4-tri-O-benzyl-5-benzylseleno-d-ribose diethyl dithio-
acetal (1.18 g, 1.95 mmol) in acetonitrile-water (9:1,
15 mL). The mixture was stirred at room temperature for
4 h. The solution was then ®ltered through a Celite pad,
and the ®ltrate was evaporated in vacuo. The residue was
dissolved in dichloromethane and the solution was washed
with 30% potassium iodide (20 mL), 30% sodium thiosulfate
(20 mL) and saturated NaCl (20 mL) solutions. The organic
phase was separated, dried (Na2SO4) and the solvent
removed in vacuo to afford the title compound as a yellow
72.69, 74.53, 78.63, 79.18, 79.35, 126.70, 127.73, 127.75,
127.80, 127.90, 128.04, 18.15, 128.15, 128.33, 128.35,
128.38, 128.43, 128.90, 137.78, 138.01, 138.12, 139.14.
77Se NMR d (CDCl3) 224.71. IR(neat) nmax 3466 cm21
.
MS (ESI) (M1Na)1 m/z 599.0. [a]2D7 (cˆ1.0,
CHCl3)ˆ211.0. Anal. Calcd for C33H36O4Se: C, 68.9; H,
6.3. Found: C, 68.9; H, 6.4.
Standard protocol C for the preparation of (phenylseleno)
formates: (phenylseleno) 2,3,4-tri-O-benzyl-5-benzyl-
seleno-d-arabit-1-yl formate 13. Sodium borohydride
(16 mg, 38 mmol) was added with stirring to a solution of
diphenyl diselenide (39 mg, 13 mmol), in dry THF (10 mL).
The reaction vessel was purged with nitrogen and dry
methanol (ca. 250 mL) was added dropwise until the yellow
solution turned colorless (ca. 10 min). In a separate reaction
vessel a 20% solution of phosgene in toluene (0.4 mL,
200 mmol) was added via syringe to a solution of 15
(120 mg, 21 mmol) in dry THF (10 mL) under nitrogen.
The solution was stirred for 1 h and concentrated to approxi-
mately half the original volume in vacuo. After purging with
nitrogen, the solution of the chloroformate was cannulated
into the solution containing the sodium phenylselenoate and
the resulting solution was stirred at room temperature under
nitrogen overnight. The mixture was diluted with ether
(30 mL) was washed with water (5 mL). The combined
organic layers were dried (Na2SO4), and the solvent
removed in vacuo. The selenoformate 13 was obtained as
a yellow viscous oil after ¯ash chromatography (hexane/
1
viscous oil in quantitative yield. H NMR d (CDCl3) 2.76
(1H, dd, Jˆ4.5, 12.8 Hz), 2.96 (1H, dd, Jˆ3.9, 12.9 Hz), 3.73
(2H, d, Jˆ7.5 Hz), 3.92±4.01 (2H, m), 4.07 (1H, m), 4.43
(1H, m), 4.54 (2H, q, Jˆ4.1 Hz), 4.64±4.71 (3H, m), 7.15±
7.35 (20H, m), 9.47 (1H, s). 13C NMR d (CDCl3) 25.32,
27.62, 72.17, 72.64, 72.96, 76.47, 81.93, 82.53, 126.55,
127.56, 127.69, 127.77, 127.80, 127.89, 128.23, 128.32,
128.39, 128.78, 137.22, 137.37, 137.50, 139.29, 201.04.
77Se NMR d (CDCl3) 204.33. IR(neat) nmax 1731 cm21
.
[a]2D9 (CHCl3)ˆ116.0. HRMS (ESI) Calcd for
C33H34O4SeNa (M1Na)1 597.1520. Found: 597.1518.
2,3,4-Tri-O-benzyl-5-benzylseleno-aldehydo-d-xylose 20
was prepared from 2,3,4-tri-O-benzyl-5-benzylseleno-d-
xylose diethyl dithioacetal following standard protocol B
1
1
as a yellow viscous oil (72%). H NMR d (CDCl3) 2.54
ethyl acetate 90:10), (110 mg, 71%). H NMR d (C6D6)
(1H, dd, Jˆ5.1, 12.7 Hz), 2.74 (1H, dd, Jˆ8.5, 12.6 Hz),
3.68 (3H, m), 3.82 (d, 1H, Jˆ5.3 Hz), 4.04 (1H, dd, Jˆ3.2,
5.3 Hz), 4.31±4.76 (6H, m), 7.21±7.37 (20H, m), 9.65 (1H,
s). 13C NMR d (CDCl3) 23.10, 27.63, 72.41, 72.80, 73.84,
77.32, 79.34, 80.68, 126.74, 127.65, 127.93, 137.97, 128.0,
128.20, 128.27, 128.38, 128.40, 18.43, 128.81, 137.13,
137.15, 37.47, 138.82, 200.22. 77Se NMR d (CDCl3)
2.86 (2H, m), 3.52 (2H, d, Jˆ7.3 Hz), 3.79±3.89 (3H, m),
4.25±4.49 (8H, m), 6.69±7.33 (23H, m), 7.56 (2H, m). 13C
NMR d (C6D6) 25.10, 27.64, 63.15, 71.92, 73.13, 74.02,
78.94, 79.11, 125.82, 126.54, 127.56, 127.61, 127.70,
127.74, 127.80, 127.90, 128.21, 128.32, 128.78, 129.03,
129.16, 135.66, 137.85, 137.87, 139.26, 160.39, 166.39.
77Se NMR d (C6D6) 219.69, 506.57. IR(neat) nmax
1727 cm21. [a]D29 (cˆ1.0, CHCl3)ˆ212.4. Anal. Calcd for
C40H40O5Se2: C, 63.3; H, 5.3. Found: C, 63.1; H, 5.3.
219.90. IR(neat) nmax 1729 cm21
.
[a]2D7 (cˆ1.0,
CHCl3)ˆ220.8. HRMS (ESI) Calcd for C33H34O4SeNa
(M1Na)1 597.1520. Found: 597.1527.
(Phenylseleno) 2,3,4-tri-O-benzyl-5-benzylseleno-d-ribit-
1-yl formate 21 was prepared from 2,3,4-tri-O-benzyl-5-
benzylseleno-d-ribitol following standard protocol C as a
2,3,4-Tri-O-benzyl-5-benzylseleno-d-ribitol was prepared
from 19 following the same procedure as described for
2,3,4-tri-O-benzyl-5-O-methanesulfonyl-d-arabitol (above)
1
light yellow viscous oil, yield (71%). H NMR d (CDCl3)
1
as a light yellow viscous oil (82%). H NMR d (CDCl3)
2.75 (2H, m), 3.72 (2H, d, Jˆ7.5 Hz), 3.75±3.84 (3H, m),
4.34 (1H, dd, Jˆ2.7, 12.0 Hz), 4.45±4.61 (7H, m), 7.21±
7.36 (23H, m), 7.59 (2H, d, Jˆ7.8 Hz). 13C NMR d (CDCl3)
24.77, 27.79, 67.21, 72.09, 72.15, 73.68, 77.43, 78.75,
79.14, 125.91, 126.55, 127.59, 127.62, 127.84, 127.91,
127.97, 128.26, 128.34, 128.81, 129.02, 19.17, 135.74,
137.72, 137.89, 139.36, 166.61. 77Se d (CDCl3) 219.90,
2.46 (1H, sbr), 2.80±3.00 (2H, m), 3.73±3.95 (6H, m),
4.03±4.06 (1H, m), 4.60±4.78 (6H, m), 7.33±7.45 (20H,
m). 13C NMR d (CDCl3) 24.61, 27.73, 61.12, 71.68,
72.17, 73.72, 78.6, 79.20, 79.62, 126.50, 17.56, 127.62,
127.66, 127.76, 127.82, 17.93, 128.21, 128.25, 128.29,
128.31, 137.81, 137.84, 137.94, 139.30. 77Se NMR d
(CDCl3) 224.28. IR(neat) nmax 3466 cm21. MS (ESI)
(M1Na)1 m/z 599.4. [a]D27 (cˆ1.0, CHCl3)ˆ213.1. Anal.
Calcd for C33H36O4Se: C, 68.9; H, 6.3. Found: C, 68.9; H,
6.2.
512.01. IR(neat) nmax 1729 cm21
.
[a]2D6 (cˆ1.0,
CHCl3)ˆ215.6. HRMS (ESI) Calcd for C40H40O5Se2Na
(M1Na)1 783.1104. Found: 783.1115.
(Phenylseleno) 2,3,4-tri-O-benzyl-5-benzylseleno-d-xylit-
1-yl formate 22 was prepared from 2,3,4-tri-O-benzyl-5-
benzylseleno-d-ribitol following standard protocol C as a
2,3,4-Tri-O-benzyl-5-benzylseleno-d-xylitol was prepared
from 20 following the same procedure as described for
2,3,4-tri-O-benzyl-5-O-methanesulfonyl-d-arabitol (above)
1
light yellow viscous oil (68%). H NMR d (C6D6) 2.55
1
as a light yellow viscous oil (67%). H NMR d (CDCl3)
(1H, dd, Jˆ5.6, 12.5 Hz), 2.82 (1H, dd, Jˆ6.9, 12.7 Hz),
3.47 (2H, d, Jˆ5.4 Hz), 3.71 (1H, m), 3.82 (2H, m), 4.22±
4.61 (8H, m), 6.92±7.26 (25H, m). 13C NMR d (C6D6)
27.71, 68.08, 72.52, 73.12, 74.74, 77.74, 79.23, 79.35,
2.64 (1H, dd, Jˆ6.1, 12.7 Hz), 2.80 (1H, dd, Jˆ6.8 Hz),
3.48±3.84 (7H, m), 4.41±4.73 (6H, m), 7.24±7.33 (20H,
m). 13C NMR d (CDCl3) 23.91, 27.69, 61.58, 72.45,

4000
M. A. Lucas et al. / Tetrahedron 56 (2000) 3995±4000
126.93, 127.79, 18.08, 128.12, 128.55, 128.70, 129.10,
129.38, 129.40, 136.09, 138.75, 138.78, 138.84, 139.73,
166.32. 77Se NMR d (C6D6) 227.91, 509.02. IR(neat) nmax
1728 cm21 (CvO). MS (ESI) m/z (M1Na)1 783.9. [a]2D5
(cˆ1.0, CHCl3)ˆ225.5. Anal. Calcd for C40H40O5Se2: C,
63.4; H, 5.3. Found: C, 63.5; H, 5.3.
extracted with ether, the combined organic layers dried
(MgSO4) and the solvent removed in vacuo. The residue
was separated by ¯ash chromatography (10% ethyl acetate
in petrol) to afford 26 as a mixture of anomers (40 mg,
1
50%). H NMR d 2.4±2.9 (2H, m), 3.1±4.3 (4H, m), 4.5±
4.9 (6H, m), 5.38 (0.5H, m, anomer A), 5.42 (0.5H, m,
anomer B), 7.18±7.40 (15H, m). [a]2D5 (cˆ1.0,
CHCl3)ˆ111.48C. HRMS (ESI) Calcd for C26H28O4SeNa
(M1Na)1 507.1046. Found 507.1051.
Standard protocol D for the preparation of 2,3,4-tri-O-
benzyl-1,5-dideoxy-5-selenopentopyranose sugars: 2,3,4-
tri-O-benzyl-1,5-dideoxy-5-seleno-d-arabinopyranose 16.
A solution of 13 (102 mg, 13.6 mmol) dissolved in dry
benzene (0.5 mL, 0.27 M) in a vacuum sealed tube, was
thermolised at 1658C in a silicon oil bath for 27 h, shielded
from background light. Removal of the solvent in vacuo and
puri®cation via ¯ash chromatography (hexane/ethyl acetate
90:10) afforded the title compound as a pale yellow viscous
Acknowledgements
We thank the Australian Research Council for ®nancial
support and the China Scholarship Council for the award
of a scholarship to S.-L. Z.
1
oil, (52 mg, 81%). H NMR d (C6D6) 2.19 (1H, dd, Jˆ4.2,
13.2 Hz), 2.28 (1H, dd, Jˆ3.4, 11.5 Hz), 3.07 (1H, dd, Jˆ2,
13.2 Hz), 3.22 (1H, t, Jˆ11 Hz), 3.70 (1H, m), 3.80 (1H, m),
4.09 (2H, m), 4.13±4.17 (1H, m), 4.30 (2H, m), 4.44 (1H, d,
Jˆ12 Hz), 4.70 (1H, d, Jˆ12 Hz), 7.04±7.24 (15H, m) 13C
NMR d (C6D6) 16.55, 17.84, 70.56, 70.846, 73.65, 76.49,
76.80, 77.78, 126.61, 126.76, 126.94, 127.25, 129.30,
133.07, 138.94, 139.42. 77Se NMR d (C6D6) 69.37. MS
(ESI) m/z 491.5 (M1Na)1. [a]2D2ˆ241. Anal. Calcd for
C26H28O3Se: C, 66.8; H, 6.1. Found: C, 66.8; H, 5.7.
References
1. Whistler, R. L.; Lake, W. C. Biochem. J. 1970, 130, 919; Kim,
J. H.; Kim, S. H.; Hahn, W. W. Science 1978, 200, 206; Hughes,
A. B.; Rudge, A. J. Nat. Prod. Rep. 1994, 135.
2. Schewe, T. Gen. Pharmacol. 1995, 26, 1153.
3. May, S. W. Expert Opin. Invest. Drugs 1999, 8, 1017.
4. Marsden, W.; Wright, T. The Travels of Marco Polo; Liveright:
New York, 1926.
2,3,4-Tri-O-benzyl-1,5-dideoxy-5-seleno-d-ribopyranose
23 was prepared from 21 following standard protocol D.
Thermolysis at 180±1908C for 11 days afforded the title
compound (after workup) as a light yellow viscous oil
5. Coolidge, R. H. Statistical Report on Illness and Mortality in
the Army of the United States, January 1857±January 1860, US
Congress 26th Session, Senate Exch. Doc., 52, 37.
È
6. Engman, L.; Laws, M. J.; Malmstrom, J.; Schiesser, C. H.;
Zugaro, L. M. J. Org. Chem. 1999, 64, 6764.
1
(32 mg, 56%). H NMR d (C6D6) 2.27 (2H, dd, Jˆ3.2,
11.2 Hz), 3.52 (1H, dd, Jˆ1.5, 3.9 Hz), 3.57 (1H, dd,
Jˆ1.5, 3.9 Hz), 4.13±4.35 (6H, m), 4.71 (1H, m), 4.97
(2H, m), 7.12±7.53 (15H, m). 13C NMR d (C6D6) 16.69,
7054, 74.73, 78.28, 81.78, 127.47, 127.79, 128.18, 128.35,
128.52, 128.58, 129.25, 129.31, 132.74, 139.16. 77Se NMR
d (C6D6) 85.27. HRMS (ESI) Calcd for C26H28O3SeNa
(M1Na)1 491.1101. Found: 491.1084.
7. Seiyaku, D. Drugs Future 1995, 20, 1057.
8. Mamoru, K.; Hideharu, I.; Masahiro, H. Res. Commun. Mol.
Pathol. Pharmacol. 1998, 101, 179.
9. Kirsi, J. J. Antimicrob. Agents Chemother. 1983, 24, 353.
10. Schwarz, K. Fed. Proc. 1961, 666.
11. Reiner, R.; Weiss, U. Eur. Pat. Appl. EP 49855.
12. For useful additional information, visit: http://www.blackmor-
es.com
2,3,4-Tri-O-benzyl-1,5-dideoxy-5-seleno-d-xylopyranose
24 was prepared from 22 following standard protocol D.
Thermolysis at 1658C for 2 days afforded the title
compound (after workup) as a light yellow viscous oil
13. Van Es, T.; Rabelo, J. J. Carbohydr. Res. 1977, 59, 351.
14. Schiesser, C. H; Sutej, K. J. Chem. Soc., Chem. Commun.
1992, 57; Schiesser, C. H.; Sutej. K. Tetrahedron Lett. 1992, 33,
5137; Benjamin, L. J.; Schiesser, C. H.; Sutej, K. Tetrahedron
1993, 49, 2557; Fong, M. C.; Schiesser, C. H. Tetrahedron Lett.
1993, 34, 4347; Fong, M. C.; Schiesser, C. H. Tetrahedron Lett.
1995, 36, 7329; Fong, M. C.; Schiesser, C. H. J. Org. Chem. 1997,
62, 3103.
1
(47.9 mg, 96%). H NMR d (C6D6) 2.36 (4H, m), 3.19
(1H, t, Jˆ8.7 Hz), 3.67 (2H, q, Jˆ8.6 Hz), 4.42 (4H, q,
Jˆ11.7 Hz), 4.91 (2H, s), 7.12±7.27 (15H, m). 13C NMR
d (C6D6) 22.07, 72.57, 76.29, 83.49, 87.23, 127.42, 127.63,
127.83, 128.11, 128.34, 128.47, 139.32, 139.94. 77Se NMR
d (C6D6) 86.33. HRMS (ESI) Calcd for C26H28O3SeNa
(M1Na)1 491.1101. Found: 491.1124.
15. Lucas, M. A.; Schiesser, C. H. J. Org. Chem. 1998, 63, 3032.
16. Barton, H. H. R.; Gero, S. D.; Holliday, P.; Quiclet-Sire, B.
Tetrahedron 1996, 52, 8233.
17. Tadano, K.; Maeda, H.; Hoshino, M.; Iimura, Y.; Suami, T.
J. Org. Chem. 1987, 52, 1946.
18. Molander, G. A. Chem. Rev. 1992, 92, 29.
2,3,4-Tri-O-benzyl-5-deoxy-5-seleno-d-ribopyranose 26.
Dry HMPA (0.4 mL) was added to a stirred solution of
SmI2 in THF (5 mL, 0.1 M) and the solution ¯ushed with
nitrogen. 2,3,4-Tri-O-benzyl-5-benzylseleno-5-deoxyribose
(19) (100 mg, 0.17 mmol) in THF (3 mL) was added via
syringe and the resultant solution stirred for 4 h. A further
aliquot of SmI2 (5 mL) was added and the solution stirred
overnight at which time TLC analysis indicated the absence
of 19. Saturated NaHCO3 (20 mL) was added, the mixture
19. Reich, H. J.; Jasperse, C. P.; Renga, J. M. J. Org. Chem. 1986,
51, 2981.
20. 2,3,4-Tri-O-benzyl-5-deoxy-5-seleno-d-xylopyranose (28):
HRMS (ESI) Calcd for C26H28O4SeNa (M1Na)1 507.1046.
Found 507.1050. 2,3,4-Tri-O-benzyl-5-deoxy-5-seleno-d-arabino-
pyranose (29): HRMS (ESI) Calcd for C26H28O4SeNa (M1Na)1
507.1046. Found 507.1048.