Synthesis of phenylseleno sugars from epoxides and of α,β- unsaturated carbonyl derivatives for the study of their insecticidal activity

Article abstract of DOI:10.1081/CAR-200030077

This work reports the synthesis of sugar epoxides and their derivatives obtained by reaction with the dianion of phenyl selenoacetic acid. Approaches to the introduction of α,β-unsaturated carbonyl units in pyranoid systems were investigated. Preparation

Full text of DOI:10.1081/CAR-200030077

JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 23, No. 4, pp. 239–251, 2004
Synthesis of Phenylseleno Sugars from Epoxides and
of a,b-Unsaturated Carbonyl Derivatives for the
Study of Their Insecticidal Activity
1,
Amelia P. Rauter, Tana Canda, Jorge Justino,
2
3
*
´
4
Maria I. Ismael, and Jose A. Figueiredo
4
´
1
´
´
ˆ
Departamento de Quımica e Bioquımica, Faculdade de Ciencias da
Universidade de Lisboa, Ed. C8, Campo Grande, Lisboa, Portugal
2Universidade Agostinho Neto, Luanda, Angola
3
´ ´ ´
Escola Superior Agraria - Instituto Politecnico de Santarem, Complexo Andaluz,
´
Santarem, Portugal
´
Departamento de Quımica da Universidade da Beira Interior,
4
ˆ
Unidade I&D de Materiais Texteis e Papeleiros,
Covilha˜, Portugal
CONTENTS
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
I. INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240
II. RESULTS AND DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . 241
III. EXPERIMENTAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
A. General Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
*
´ ´ ´
Correspondence: Amelia P. Rauter, Departamento de Quımica e Bioquımica, Faculdade de
ˆ
Ciencias da Universidade de Lisboa, Ed. C8, 58 Piso, Campo Grande, 1749-016, Lisboa, Portugal;
E-mail: aprauter@fc.ul.pt.
239
DOI: 10.1081/CAR-200030077
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

240
Rauter et al.
ACKNOWLEDGMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
ABSTRACT
This work reports the synthesis of sugar epoxides and their derivatives obtained by
reaction with the dianion of phenyl selenoacetic acid. Approaches to the introduction
of a,b-unsaturated carbonyl units in pyranoid systems were investigated. Preparation
of a protected D-glycero-hex-3-enepyranosid-2-ulose and of a D-erythro-hex-2-
enono-1,5-lactone is described. Some of the synthesized compounds possess insectici-
dal activity against fruit flies, house flies, and white flies.
Key Words: Sugar epoxides; Phenylseleno sugars; a,b-Unsaturated carbonyl moiety;
Insecticidal activity.
INTRODUCTION
Sugarepoxidesareversatileintermediatesinorganicsynthesis,[1,2] duetotheeaseoftheir
preparation from a variety of starting materials and to their susceptibility to reactions, for
example, with electrophiles, nucleophiles, acids and bases. Furthermore, epoxides are part
ofagroupofcompoundsrecognizedasactiveprinciples, withbiologicalandpharmacological
activities. Referencecanbemadetocytotoxic metabolites, namelycrotepoxide, pipoxide, and
senepoxide, the latter playing an important role as an antifeedant agent in plants.[3]
Methods for the preparation of epoxides use halohydrins as intermediate com-
pounds,[4] and also alkenes,[5] vicinal diols,[6,7] glycals,[8,9] carbonyl compounds,[10]
among others. Epoxides have been reported as starting materials for the synthesis of
phenylseleno lactones, key intermediates for the preparation of butenolides.[11–13]
Recently, the sugar phenylseleno lactones 6a, b and analogs to these compounds, their
corresponding butenolides, as well as compound 22 have shown efficacy as insecticides
with high toxicity to fruit fly (Drosophila melanogaster), white fly (Trialeurodes vaporar-
iorum), and house fly (Musca domestica). The evaluation of the toxicity to fruit flies and
house flies was determined by topical treatment, whereas the toxicity to the white fly was
investigated by foliar treatment of glasshouse white fly. For fruit flies, the LD50 (mg per
insect) ¼ 1.5 ꢀ 1024 (6a, b) and 1.6 ꢀ 1024 (22) are interesting results, when compared
to LD50 ¼ 1.25 ꢀ 1022 of imidacloprid, the reference insecticide for fruit flies. These com-
pounds were not toxic to brine shrimps (Artemia salina), the reference organisms in assays
to evaluate the potential toxicity hazard to organisms in ecosystems. These tests were
performed using the immersion bioassay of brine shrimp larvae in brine.[14]
Inthiswork, wereportthesynthesisofnewepoxides,theirphenylselenosugarderivatives,
and new pyranoid compounds, containing an a,b-unsaturated carbonyl moiety. The structural
diversity of these compounds will enable a further investigation of the bioactive groups and of
thestructural units tolerated bythesystems, in what concerns theinfluence ofthe presence ofan
oxirane, its orientation and position in the ring, the presence of a phenylselenolactone, or other
phenylseleno groups and that of a a,b-unsaturated carbonyl unit in pyranoid structures.

Synthesis of Phenylseleno Sugars
RESULTS AND DISCUSSION
241
The synthesis of the epimer in C-5 of the diepoxide 4 was accomplished starting from
methyl 2,3-anhydro-b-D-mannofuranoside, which after partial tosylation at OH-6 and
treatment with sodium methoxide gave the target molecule in 53% yield.[15] We have pre-
pared the diepoxide 4 starting from methyl 2,5-di-O-tosyl-b-D-glucofuranoside (2),[13]
which was obtained by reduction of 1.[16] Reaction of 2 with potassium hydroxide in
THF/H2O solution at rt for 12 hr gave 4 in 97% yield.[13] In the presence of NaOH/
dried methanol at rt,[17] compound 2 gave the epoxide 3 in 51% yield after 30 min,
while the diepoxide 4 was formed in 61% yield by changing the reaction time to 1 hr
30 min (Sch. 1).
Reaction of diepoxide 4 with phenylselenoacetic acid or phenylselenopropionic acid/
n-butyllithium, diisopropylamine in THF at 08C gave the phenylselenolactones 5a, b and
6a, b[13] in 16% and 32%, yield respectively. The formation of the five-membered lactone
in 5 was confirmed by the IR band of its carbonyl group at 1774 cm21. The presence of the
oxirane ring was detected by the chemical shifts of C-2 and C-3 at d 54.7 and 53.4, respect-
ively, when compared to the corresponding C-2 at d 83.3 and C-3 at d 73.5 of the precursor
molecule 2. The bioactivity of the diastereoisomers 5a, b will be investigated, since they
are close related analogs to compounds 6a, b, which showed potent insecticidal activity
against fruit flies.
Scheme 1. Synthesis of sugar epoxides from methyl 2,5-di-O-tosyl-a-D-glucofuranurono-6,3-
lactone (1):[16] (a) LiBH4, THF, 2108C (1 hr), 148C (16 hr), 94%;[16] (b) NaOH 4N, THF, rt,
30 min, 51%; (c) NaOH 4N, THF, rt, 1 hr 30 min, 61%; (d) KOH 1.25 N, THF, rt, 12 hr, 97%;[13]
(e) LDA, PhSeCHRCO2H, 08C (1 hr), rt (16 hr), R ¼ H, 16%, R ¼ Me, 32%.

242
Rauter et al.
Scheme 2. Phenylseleno derivatives from a sugar epoxide: (a) MeCOCl, MeOH, 608C, 48 hr, 96%;
(b) NaOMe, MeOH, rt, 1 hr, 65% for 9, 35% for 10; (c) LDA, PhSeCH2CO2H, 08C (1 hr), rt (16 hr),
40% for 11, 17.5% for 12, based upon the reacted starting material, recovered in 2.5% yield.

Synthesis of Phenylseleno Sugars
243
Preparation of 2,3-anhydroallofuranose derivatives was reported in the literature as
early as 1976.[18] We report now the synthesis of the allofuranosides 9 and 10 by reaction
of the 3-O-tosyl derivative 7 with acetyl chloride in methanol to give the 2-hydroxy deriva-
tives 8a, b in 96% yield (Sch. 2), which were treated with sodium methoxide in methanol at
rt affording the target molecules 9 and 10 in 65% and 35% yield, respectively. The anomeric
configuration of these compounds was established by NOESY, considering the interaction
of the methyl group of 9 with H-2, H-3, H-5, H-6a, H-6b, while in compound 10 these inter-
actions were not observed, being detected the interaction of H-1 with H-6a and H-6b.
Treatment of the epoxide 9 with the dianion of phenylselenoacetic acid gave the
phenylselenoacid 11 in 40% yield, together with the secondary product 12, obtained in
16% yield. The presence of the moieties bound to C-3 in 11 and C-2 in 12 was detected
by the signal of H-30 at d 3.68 with J3,3 ¼ 6.9 Hz in 11, while H-20a, H-20b of 12 are included
0
in a multiplet at d 3.73–3.56, as confirmed by COSY and NOESY experiments.13C NMR,
DEPT, and HMQC spectra allowed to assign the signals corresponding to C-30 at d50.6 in 11
and to C-20 at d 30.0 in 12. The signal of the carbonyl group appeared at d 167.7 in 11. Both
compounds presented IR bands confirming the presence of hydroxyl groups at 3432 cm21
,
while 11 showed the expected band due to the carbonyl group at 1728 cm21. The formation
[19]
¨
of secondary products such as 12 was previously reported by Fraser-Reid and Benko.
When the epoxide 14 (Sch. 3) was treated under the same reaction conditions as the
epoxides 4 and 9, the phenylseleno acid 15 and the secondary product 16 were obtained.
Scheme 3. Synthesis of phenylseleno sugars starting from the 3-O-allyl derivative 13: (a)
m-CPBA, NaOAc, CH2Cl2, rt, 45 hr, 58% based on reacted starting material, recovered in 5%
yield; (b) LDA, PhSeCH2CO2H, 08C (1 hr), rt (16 hr), 11% for 15, 25% for 16.

244
Rauter et al.
The synthesis of 14 was first accomplished by phase transfer catalyzed epoxy alkylation of
1,2:5,6-di-O-isopropylidene-a-D-glucofuranose with epichlorohydrin.[20] We have syn-
thesized 14 by treatment of 3-O-allyl-1,2;5,6-di-O-isopropylidene-a-D-glucofuranose
(13)[21] with m-chloroperbenzoic acid in dichloromethane at rt in 58% yield based on
reacted starting material, recovered in 5% yield.
We have previously found that a,b-unsaturated five-membered ring lactones bound to
sugars demonstrated fungicidal[12] and insecticidal activities.[14] We report now the syn-
thesis of compounds 19 and 22, which contain an a,b-unsaturated carbonyl group in
their structure, in order to be able to evaluate the bioactivity of these pyranoid structures.
The synthesis and reactions of sugar enolones were reported in the literature by
Lichtenthaler.[22] We describe now the preparation of the keto sugar 19 in 33% yield
by treating with the base (Me3Si)2NLi,[23] the a-acetoxy ketone 18 (Sch. 4), obtained
by acetylation of methyl 2,6-di-O-pivaloyl-a-D-ribo-hexopyranosid-3-ulose.[24]
The expected intramolecular cyclization to give 20 did not occur and deacetylation
gave 17 in 67% yield. The mechanism proposed for the synthesis of 19 is based on
enolate formation, followed by transesterification to give the pyvaloate at position 3,
tautomerism of the enol to the carbonyl compound, and elimination of acetic acid. The
presence of the double bond was confirmed by the resonance of H-4 at d 6.55 as a
doublet with J4,5 ¼ 1.5 Hz, together with13C NMR signals of C-3 and C-4 at d 142.2
and 132.1, respectively. Two pivaloyl groups were detected by their resonances at d
1.24 and 1.25 together with the signals of the corresponding carbonyl groups at d 178.1
Scheme 4. Synthesis of the a,b-unsaturated keto sugar 19: (a) (Me3Si)2NLi, 2708C, 1 hr 30 min,
33% for 19, 67% for 17.

Synthesis of Phenylseleno Sugars
245
and 175.7. H-1 appeared as a singlet at d 4.89 and the signal of C-2 was assigned at d
182.4.
Reaction of the glycal 21 with NBS in THF/H2O at rt, followed by oxidation of the
˚
intermediate 2-bromolactol with PCC in the presence of molecular sieve powder 3 A, gave
the biologically active a,b-unsaturated lactone 22 in 37% overall yield (Sch. 5). The
lactone functionality was confirmed by the IR band at 1752 cm21, and by the signal of
its carbonyl group at d 157.1 in the13C NMR spectrum. The double bond gave the expected
IR band at d 1632 cm21. The 1H NMR and 13C NMR spectra exhibited the olefinic proton
H-3 at d 7.01 as a doublet with J3,4 ¼ 3.9 Hz and the resonances of C-2 and C-3 at d 116.4
and 142.3, respectively.
EXPERIMENTAL
General Methods
Reactions were monitored by TLC performed on aluminum sheets Kieselgel 60 F254
(Merck) with detection by UV light, than charring with 3% vanillin–sulfuric acid solution.
Column chromatography (CC) was conducted under low pressure by elution of columns
with silica gel (0.040–0.063 mm Merck). Melting points were determined with a Leica
Galen III apparatus and are uncorrected. Optical rotations were measured with a
Perkin–Elmer 343 polarimeter, IR spectra were recorded with a Hitachi 270-50, and
UV spectra with a Shimadzu UV-160 TCC-240 spectrophotometer. NMR spectra were
carried out in CDCl3 using a Varian Unity 300 MHz spectrometer and 13C NMR
spectra were recorded at 75.43 MHz. Chemical shifts are expressed in parts per million
downfield from TMS.
Methyl 2,3-anhydro-5-O-tosyl-b-D-mannofuranoside (3). A solution of 2[13]
(1.78 g, 3.78 mmol) in THF (22 mL) was cooled to 08C. Then NaOH 4 N (4.4 mL) was
added dropwise and the mixture was stirred at rt for 30 min. Diethyl ether (225 mL)
was added and the mixture was washed with water (155 mL). The organic phase was
dried over sodium sulfate. Evaporation of the solvent under reduced pressure gave a
residue which was purified by CC eluted with ethyl acetate/toluene (1 : 1) to give 3 as a
syrup (600 mg, 51%); [a]D20 ¼ 258 (c 1.0, CH2Cl2); IR (neat) 3404 cm21 (OH),
1
1298 cm21 (C-O, epoxide); H NMR: d 7.84 (d, 2H, Ph), 7.34 (d, 2H, Ph), 4.97 (s, 1H,
H-1), 4.68–4.65 (m, 1H, H-5), 4.10 (d, 1H, H-4, J4,5 ¼ 8.0 Hz), 3.89 (m, 1H, H-6a,
J6a,6b ¼ 11.4 Hz), 3.78 (m, 1H, H-6b), 3.65, 3.51 (each d, 1H, H-2, H-3, J2,3 ¼ 2.7 Hz),
Scheme 5. Synthesis of the a,b-unsaturated lactone 22: (a) NBS, THF/H2O, rt, 12 hr; (b) PCC,
˚
CH2Cl2, molecular sieve powder 3 A, rt, 16 hr, 37% overall yield for (a) and (b).

246
Rauter et al.
2.49 (s, 3H, CH3, Ts); 13C NMR: d 145.1, (Cq, Ph), 132.9 (Cq, Ph), 129.9, 127.8 (CH, Ph),
102.3 (C-1), 79.6 (C-5), 73.7 (C-4), 61.6 (C-6), 56.8 (OCH3), 56.1, 54.5 (C-2, C-3), 21.5
(CH3, Ts).
Anal. Calcd for C14H18O7S (330.35): C, 50.90; H, 5.49; S, 9.71. Found: C, 51.04; H,
6.00; S, 9.34.
Methyl 2,3:5,6-dianhydro-a-L-gulofuranoside (4). Methyl-2,5-di-O-tosyl-b-D-
glucofuranoside (2) (3.12 g, 6.21 mmol) gave 4 (600 mg, 61%), following the experimen-
tal procedure described above for 3, stirring the reaction mixture at rt for 1 hr 30 min; mp
127–1288C; physical and spectroscopy data were in full agreement with those given in
literature.[13]
7(R)-, 7(S)-2,3-Anhydro-6,7-dideoxy-7-phenylselenyl-a-L-gulo-octofuranurono-
8,5-lactone (5a, b). n-Butyl lithium 1.6 M in hexane (2.75 mL, 4.4 mmol) was added
dropwise to a solution of diisopropylamine (0.62 mL, 4.4 mmol) in anhydrous THF
(8 mL) at 08C under argon. The reaction mixture was stirred at 08C for 25 min. A solution
of phenylselenoacetic acid (430 mg, 2 mmol) in anhydrous THF (2 mL) was added drop-
wise and the reaction mixture was stirred at 08C for 1 hr. The solution of the diepoxide 4
(316 mg, 2 mmol) in anhydrous THF (1 mL) was dropped to the reaction mixture, which
was stirred at 08C for 1 hr and at rt for 16 hr. After acidification with 50% acetic acid
(5 mL), the mixture was heated at 758C for 6 hr, cooled to rt, neutralized with NaHCO3
saturated solution, and extracted with diethyl ether (3 ꢀ 10 mL). The organic phase was
washed with water, dried with sodium sulfate and evaporated. The residue was purified
by CC with ethyl acetate/n-hexane (1 : 2) to give 5a, b as a syrup (113.7 mg, 16%; ratio
1
5a/5b ¼ 1 : 1); IR (neat) 1774 cm21; H NMR: d 7.61–7.50 (m, 2H, Ph), 7.32–7.28
(m, 3H, Ph), 4.99 (s, 1H, H-1), 4.21 (d, 1H, H-4, J4,5 ¼ 4.8 Hz), 4.10–4.09 (m, 1H,
H-5), 3.74–3.15 (m, 8H, OCH3, H-6a, H-6b, H-2, H-3, H-7); 13C NMR: d 176.6
(C55O), 133.4, 129.3, 128.0 (CH, Ph), 102.0 (C-1), 77.1 (C-4), 70.4 (C-5), 59.0 (C-7),
55.8 (OCH3), 54.7 (C-2), 53.4 (C-3), 27.4 (C-6).
Anal. Calcd for C15H16O5Se (355.24): C, 50.71; H, 4.54. Found: C, 49.76; H, 4.55.
Methyl 5,6-di-O-benzyl-3-O-tosyl-a,b-D-glucofuranoside (8a, b). A solution
of 5,6-di-O-benzyl-1,2-O-isopropylidene-3-O-tosyl-a-D-glucofuranose (7) (600 mg,
1.08 mmol) in MeOH (3.25 mL) and AcCl (0.04 mL) was heated at 608C and stirred for
30 hr.[25] The reaction mixture was cooled to rt, neutralized with AgCO3, stirred for
2 hr, filtered and concentrated under vacuum. The residue was purified by CC eluted
with ethyl acetate/n-hexane (1 : 3) to give 8a, b (560 mg, 96%); [a]2D0 ¼ 2188 (c 1.0,
1
CHCl3); IR (neat): 3472 cm21 (OH); H NMR: d 7.79–7.74 (m, 4H, Ph), 7.32–7.28
(m, 24H, Ph); 4.93–4.91 (m, 4H, H-1a, H-1b, H-3a, H-3b), 4.78–4.30 (m, 8H, 4
OCH2Ph, H-2a, H-2b, H-4a, H-4b), 3.85–3.80 (m, 4H, H-5a, H-5b, H-6aa, H-6ab),
3.66 (m, 2H, H-6ba, H-6bb), 3.43, 3.34 (each s, 3H, OCH3); 2.37, 2.36 (each s, 3H,
CH3, Ts); 13C NMR: d 145.0, 138.4 (each Cq, Ph), 129.8, 128.3, 128.2, 127.8, 127.5
(CH, Ph), 109.2 (C-1b); 101.4 (C-1a); 85.2, 83.3 (C-3a, C-3b); 78.9, 78.3 (C-5a,
C-5b); 76.3, 76.0 (C-4a, C-4b), 75.4 (C-2a, C-2b), 73.4, 72.0 (OCH2 Ph), 69.8 (C-6a,
C-6b), 55.8 (OCH3); 21.6 (CH3, Ts).
Anal. Calcd for C28H32O8S (528.61): C, 63.62; H, 6.10; S, 6.07. Found: C, 63.19; H,
5.90; S, 5.83.
Methyl 2,3-anhydro-5,6-di-O-benzyl-b-D-allofuranoside (9) and methyl 2,3-
anhydro-5,6-di-O-benzyl-a-D-allofuranoside (10). A solution of 8a, b (940 mg,
1.78 mmol) in NaOMe 1 M in MeOH (28 mL) was stirred at rt for 1 hr. The reaction

Synthesis of Phenylseleno Sugars
247
mixture was diluted with water (55 mL) and concentrated in a rotary evaporator. The
concentrated solution was extracted with CHCl3 and the inorganic phase was dried and
evaporated. The residue was purified by CC eluted with ethyl acetate/n-hexane (1 : 5)
to give 9 (420 mg, 65%) and 10 (230 mg, 35%). Data for 9: [a]2D0 ¼ 2888 (c 1.0,
1
CHCl3); IR (neat): 1286 cm21 (C–O, epoxide); H NMR: d 7.34–7.23 (m, 10H, 2Ph),
4.86 (s, 1H, H-1), 4.78, 4.74 (1H, part A of AB system, JA,B ¼ 12 Hz, OCH2Ph), 4.54–
4.48 (m, 3H, part B of AB, OCH2Ph), 4.17 (d, 1H, H-4, J4,5 ¼ 9.3 Hz), 3.84–3.77
(m, 2H, H-3, H-6a), 3.62-3.53 (m, 3H, H-2, H-5, H-6b), 3.25 (s, 3H, OCH3); 13C NMR:
d 137.9 (Cq, Ph), 128.0, 127.3, 127.2, 127.1 (CH, Ph), 102.4 (C-1), 78.1 (C-5), 76.5 (C-
4), 72.8, 72.0 (OCH2 Ph), 69.5 (C-6), 55.3 (C-2), 55.4 (OCH3), 55.0 (C-3).
Anal. Calcd for C21H24O5 (356.41): C, 70.77; H, 6.79. Found: C, 70.89; H, 6.97.
Data for 10: [a]2D0 ¼ 2288 (c 1.0, CHCl3); IR (neat): 1296 cm21 (C–O, epoxide);1H
NMR: d 7.33–7.26 (m, 10H, 2Ph), 5.06 (s, 1H, H-1), 4.73, 4.69 (1H, part A of AB system,
JA,B ¼ 12 Hz, OCH2Ph), 4.56–4.52 (m, 3H, part B of AB system, OCH2Ph), 4.37 (d, 1H,
H-4, J4,5 ¼ 3.9 Hz), 3.83 (d, 1H, H-3, J2,3 ¼ 2.7 Hz), 3.70–3.57 (m, 4H, H-2, H-5, H-6a,
H-6b), 3.45 (s, 3H, OCH3); 13C NMR: d 137.8, 137.6 (Cq, Ph), 128.2, 127.5, 127.5, 127.4
(CH, Ph), 102.5 (C-1), 78.7 (C-5), 78.7 (C-4), 73.2, 72.4 (OCH2Ph), 68.7 (C-6), 56.0 (C-2),
56.1 (C-3), 56.5 (OCH3).
Anal. Calcd for C21H24O5 (356.41): C, 70.77; H, 6.79. Found: C, 70.89; H, 6.97.
2(R)-, 2(S)-Phenylselenyl-2-(methyl 5,6-di-O-benzyl-3-deoxy-b-D-glucofurano-
sid-3-yl)ethanoic acid (11) and methyl 5,6-di-O-benzyl-2-deoxy-2-C-phenylseleno-
methyl-b-D-altrofuranoside (12). Starting from
9
(408 mg, 1.14 mmol), the
experimental procedure described for 5a, b gave 11 (255 mg, 40%) and 12 (103 mg,
17.5%) based on reacted starting material recovered in 2.5% yield, after purification by
CC eluted with ethyl acetate/n-hexane 1 : 3. Data for 11: IR (neat) 3432 cm21 (OH),
1728 cm21 (C55O); 1H NMR: d 7.53–7.49 (m, 2H, Ph), 7.33–7.08 (m, 13H, Ph),
4.78–4.74 (m, 2H, H-10, part A of AB system, OCH2Ph), 4.64–4.52 (m, 6H, H-20,
H-30, H-40, part B of AB system, OCH2Ph), 4.04–3.92 (m, 2H, H-50, H-60a), 3.77 (dd,
1H, H-60b, J6 a,6 b ¼ 12.9 Hz; J5,6 b ¼ 5.4 Hz), 3.68 (d, 1H, H-2, J2,3 ¼ 6.9 Hz); 3.34
(s, 3H, OCH3); 13C NMR: d 167.7 (C55O), 138.3, 138.2 (Cq, Ph), 132.5, 128.9, 128.7,
128.2, 127.9 (CH, Ph), 109 (C-10), 82.6 (C-40), 79.8 (C-20), 78.0 (C-50, C-30), 73.3, 71.7
(OCH2 Ph), 70.1 (C-60), 55.3 (OCH3), 50.6 (C-2).
0
0
0
0
Anal. Calcd for C29H32O7Se (571.52): C, 60.94; H, 5.63. Found: C, 60.49; H, 6.01.
1
Data for 12: IR (neat) 3432 cm21 (OH); H NMR: d 7.69–7.65 (m, 2H, Ph), 7.34–
7.23 (m, 13H, Ph), 4.97 (d, 1H, H-1, J1,2 ¼ 5.7 Hz), 4.79, 4.75 (part A of AB system,
JAB ¼ 12 Hz, OCH2Ph), 4.68–4.58 (m, 4H, H-4 part B of AB system, OCH2Ph), 3.89–
3.79 (m, 2H, H-5, H-6a), 3.73–3.56 (m, 5H, H-6b, H-2, H-20a, H-20b, H-3), 3.32 (s, 3H,
OCH3); 13C NMR: d 138.3, 137.8 (Cq, Ph), 133.5, 129.0, 128.4, 127.7, 127.2 (CH, Ph),
104.9 (C-1), 83.5 (C-5), 80.3 (C-2, C-3), 78.9 (C-4), 73.6, 72.8 (OCH2 Ph), 70.1 (C-6),
55.3 (OCH3), 30.0 (C-20).
Anal. Calcd for C28H32O5Se (527.51): C, 63.75; H, 6.14. Found: C, 63.51; H, 6.36.
3-O-[20(S), 30-, 20(R), 30-Anhydropropyl]-1,2:5,6-di-O-isopropylidene-a-D-gluco-
furanose (14). A solution of 13 (1.07 mg, 3.56 mmol) in CH2Cl2 (75 mL) was treated
with m-CPBA (2.85 g, 16.53 mmol) and sodium acetate (1.36 g, 16.53 mmol). The reaction
mixture was stirred at rt for 45 hr. A saturated solution of NaHCO3 was added and the
mixture was extracted with CH2Cl2.The organic phase was washed with sodium thio-
sulfate solution, then with NaCl solution and dried with sodium sulfate. Evaporation of

248
Rauter et al.
the solvent gave a residue which was purified by CC with ethyl acetate/toluene (1 : 1) to
give 14 (550 mg, 58%, based on reacted starting material, recovered in 5% yield); ratio
14a/14b: 2 : 1; IR (neat): 1380 cm21 (C–O, isop.), 1262 cm21 (C–O, epoxide); 1H
NMR: d 5.89–5.87 (m, 2H, H-1), 4.60 (d, 1H, H-2, J1,2 ¼ 3.4 Hz, minor), 4.55 (d, 1H,
H-2, J1,2 ¼ 3.6 Hz, major), 4.31 (m, 2H, H-4), 4.11–4.07 (m, 6H, H-3, H-6a, H-6b),
4.00–3.85 (m, 3H, H-5, H-10a, minor), 3.88 (dd, 1H, H-10a, J1 a, 2 ¼ 3.0 Hz, major),
0
0
3.63 (dd, 1H, H-10b, J1 a, 1 b ¼ 12.0 Hz, J1 b,2 ¼ 5.1 Hz, major), 3.47 (dd, 1H, H-10b,
0
0
0
0
J1 a,1 b ¼ 11.4 Hz; J1 b,2 ¼ 6.3 Hz, minor), 3.15 (m, 2H, H-20), 2.84–2.77 (m, 2H,
H-30a), 2.65–2.61 (m, 2H, H30b), 1.49 (s, 6H, CH3, isop.), 1.42 (s, 6H, CH3, isop.),
1.35 (s, 6H, CH3, isop.), 1.32 (s, 6H, CH3, isop.); 13C NMR: d 111.6 (Cq, isop. 1, 2),
108.8 (Cq, isop. 5, 6), 105.0 (C-1), 82.6 (C-2, major), 82.4 (C-2, minor), 82.3 (C-5),
80.9 (C-3), 72.2 (C-4), 71.8 (C-10, minor), 70.4 (C-10, major), 67.1 (C-6), 50.5 (C-20,
minor), 50.3 (C-20, major), 44.2 (C-30, minor), 43.8 (C-30, major), 26.6, 26.0, 25.2
(CH3, isop.).
0
0
0
0
Anal. Calcd for C15H24O7 (316.35): C, 56.95; H, 7.65. Found: C, 56.76; H, 7.70.
2(R,S)-Phenylselenyl-4(R,S)-hydroxy-5-(1,2:5,6-di-O-isopropylidene-a-D-glu-
cofuranos-3-oxy)pentanoic acid (15) and 1,2;5,6-di-O-isopropylidene-3-O-[20(S)-
,20(R)-hydroxy-30-phenylselenyl]propyl-a-D-glucofuranose (16). Starting from 14
(536 mg, 1.7 mM) and following the procedure described for 5a, b, compounds 15
(100 mg, 11%) and 16 (203 mg, 25%) were obtained after purification by CC eluted
with ethyl acetate/n-hexane (1 : 2); Data for 15: IR (neat) 3452 cm21 (OH), 1382 cm21
(C–O, isop.), 1736 cm21 (C55O); 1H NMR: d 7.64–7.60 (m, 4H, Ph), 7.36–7.25
(m, 6H, Ph), 5.92–5.87 (m, 2H, H-10), 4.54–4.52 (m, 2H, H-20), 4.31–4.29 (m, 2H,
H-40), 4.17–3.52 (m, 20H, H-30, H-50, H-60a, H-60b, H-2, H-3a, H-3b, H-4 H-5a, H-5b),
1.53, 1.44 (each s, 12H, 4CH3, isop.), 1.36, 1.32 (s, 12H, 4CH3, isop.); 13C NMR: d
ppm (CDCl3): d 177.6, 173.5 (C55O), 137.3 (Cq, Ph), 135.7, 131.5, 129.1, 128.6, 127.1
(CH, Ph), 112.0, 109.4 (Cq, isop.), 105.6 (C-10), 84.4 (C-50), 83.0, 82.5 (C-20), 81.2 (C-
30), 73.0 (C-40), 72.4, 70.7 (C-5a, C-5b), 69.2 (C-4), 67.7 (C-60), 65.2 (C-3), 36.8 (C-2),
26.8, 26.2, 25.1 (CH3, isop.).
Anal. Calcd for C23H32O9Se (531.45): C, 51.98; H, 6.06. Found: C, 51.40; H, 6.05.
Data for 16: IR (neat) 3460 cm21 (OH), 1380 cm21 (C-O, isop.); 1H NMR: d 7.63–
7.47 (m, 4H, Ph), 7.31–7.21 (m, 6H, Ph), 5.88–5.81 (m, 2H, H-1), 4.47 (d, 1H, H-2,
J1,2 ¼ 3.6 Hz), 4.42 (d,1H, H-2, J1,2 ¼ 3.6 Hz), 4.28–3.80 (m, 16H, H-3, H-4, H-5,
H-6a, H-6b, H-10a, H-10b, H-20), 3.06–2.97 (m, 4H, H-30a, H-30b), 1.48, 1.43 (each s,
12H, 4CH3, isop.), 1.42, 1.35 (s, 12H, 4CH3, isop.); 13C NMR: d ppm (CDCl3): d 137.3
(Cq, Ph), 132.6, 129.1, 127.1 (CH, Ph), 111.9 (Cq, isop.), 109.3 (Cq, isop.), 105.6,
105.5 (C-1), 84.3 (C-5), 83.0, 82.4 (C-2), 81.3 (C-3), 74.6, 72.4 (C-10), 72.8, 72.7 (C-4),
70.2, 69.2 (C-20), 67.8 (C-6), 30.6, 30.4 (C-30), 26.8, 26.2, 25.1 (CH3, isop.).
Anal. Calcd for C21H30O7Se (473.39): C, 53.28; H, 6.38. Found: C, 53.39; H, 6.70.
Methyl 4-deoxy-3,6-di-O-pivaloyl-a-D-glycero-hex-3-enepyranosid-2-ulose (19). To
a solution of (Me3Si)2NLi 1 M in THF (1.43 mL), anhydrous THF (2.4 mL) was added and
cooled to 2708C under argon atmosphere. A solution of 18[24] (240 mg, 0.60 mmol) in
THF (38 mL) was slowly added (35 min) and the reaction mixture was stirred at 2708C
for 1 hr 30 min. The reaction mixture was then added to HCl 2N (1.9 mL), stirred until
reaching the rt and extracted with ethyl acetate. A saturated solution of NaCl was
added to the organic phase under stirring. Filtration and concentration of the filtrate
gave a residue, which was solved in CH2Cl2 and dried with sodium sulfate. Evaporation

Synthesis of Phenylseleno Sugars
249
of the solvent and purification of the residue by CC eluted with ethyl acetate/toluene (1 : 8)
gave 19 (36 mg, 33%) and 17 (80.5 mg, 67%), based on reacted starting material, recov-
ered in 43% yield. The physical and spectroscopic data of 17 were in full agreement with
those given in the literature.[19]
Data for 19: [a]2D0 ¼ þ388 (c 1.0, CH2Cl2); IR (neat) 1766 cm21 (C55O), 1726 cm21
1
(C55O), 1663 cm21 (C55C); H NMR: d 6.55 (d, 1H, H-4, J4,5 ¼ 1.5 Hz), 4.94 (td, 1H,
H-5), 4.89 (s, 1H, H-1), 4.41 (dd, 1H, H-6a, J5,6a ¼ 5.7 Hz, J6a,6b ¼ 11.7 Hz), 4.23 (dd,
1H, H-6b, J5,6 ¼ 5.1 Hz), 3.55 (s, 3H, OCH3), 1.25 (s, 9H, CH3, Piv), 1.24 (s, 9H, CH3,
Piv); 13C NMR: d 182.4 (C-2), 178.1, 175.7 (C55O, Piv), 142.2 (C-3), 132.1 (C-4),
99.1 (C-1), 67.6 (C-5), 64.3 (C-6), 56.9 (OCH3), 39.0 (Cq, Piv), 27.1 (CH3, Piv).
Anal. Calcd for C17H26O7 (342.38): C, 59.64; H, 7.65. Found: C, 59.55; H, 7.87.
4,6-Di-O-acetyl-2-bromo-2,3-dideoxy-D-erythro-hex-2-enono-1,5-lactone (22). NBS
(780 mg, 4.88 mmol) was added to a solution of 3,4,6-tri-O-acetyl-D-glucal (1 g,
3.67 mmol) in THF (370 mL) and water (92 mL) and the reaction mixture was stirred
for 16 hr at rt, then it was poured in ice water, extracted with diethyl ether and the
organic phase dried with sodium sulfate. Evaporation of the solvent gave a residue,
˚
which was added to a suspension of molecular sieve powder 3 A (6.8 g) in a solution of
PCC (4.37 g, 15.64 mmol). The reaction mixture was stirred at rt for 16 hr. Ethyl ether
(100 mL) was added and the mixture stirred for 10 min and filtered. The filtrate was filtered
over florisil and evaporated to give (22) as a syrup (760 mg, 67%); [a]2D0 ¼ þ 1218 (c 1.0,
CH2Cl2); IR (neat) 1752 cm21 (C55O), 1632 cm21 (C55C); 1H NMR: d 7.01 (d, 1H, H-3,
J3,4 ¼ 3.9 Hz), 5.30 (dd, 1H, H-4, J4,5 ¼ 6.6 Hz), 4.194, 4.179, 4.152, 4.138 (H-6a, part of
AB system, J6a,6b ¼ 12.6 Hz, J5,6a ¼ 4.5 Hz), 4.10, 4.08, 4.06, 4.04 (H-6b, part of AB
system, J5,6b ¼ 3.6 Hz), 1.91 (s, 3H, Ac), 1.85 (s, 3-H, Ac); 13C NMR: d 170.1, 169.0
(C55O, Ac), 157.1 (C-1), 142.3 (C-3), 116.4 (C-2), 77.7 (C-4), 64.8 (C-5), 61.6 (C-6),
20.4 (CH3, Ac).
Anal. Calcd for C10H11BrO6 (307.09): C, 39.11; H, 3.61. Found: C, 39.13; H, 3.62.
ACKNOWLEDGMENT
This work was supported by the Treaty of Windsor Programme under the auspice of
´ ˆ
the British Council and the Ministerio da Ciencia e do Ensino Superior.
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