Preparation of O-, S- and N-benzyl derivatives of 1,6-anhydro-β-D-hexopyranoses via aziridine ring opening

Article abstract of DOI:10.1135/cccc20021805

The aziridine ring opening of N-tosylepimino carbohydrates 1-6 having D-allo, D-manno, D-galacto and D-talo configurations with benzyl alcohol, benzylamine and phenylmethanethiol afforded 2-, 3- and 4-O-benzyl-, benzylsulfanyl and benzylamino derivatives of 1,6-anhydro-β-D-hexopyranoses of D-gluco, D-galacto and D-manno configurations 7-23 in 44-99% yields. Hexenopyranoses 24-26 were prepared from tosylepimino carbohydrates 1, 4 and 5 by intramolecular rearrangement of the aziridine ring.

Full text of DOI:10.1135/cccc20021805

1,6-Anhydro-β-D-hexopyranoses
1805
PREPARATION OF O-, S- AND N-BENZYL DERIVATIVES OF
1,6-ANHYDRO-β-D-HEXOPYRANOSES via AZIRIDINE RING OPENING
b
c
Jiří KROUTILa1,*, Jindřich KARBAN , Tomáš TRNKAa2, Miloš BUDĚŠÍNSKÝ and
a3
Miloslav ČERNÝ
a
Department of Organic Chemistry, Charles University, 128 43 Prague 2, Czech Republic;
1
2
3
e-mail: kroutil@natur.cuni.cz, trnka@natur.cuni.cz, mila@natur.cuni.cz
Institute of Chemical Processes Fundamentals, Academy of Sciences of the Czech Republic,
165 02 Prague 6, Czech Republic; e-mail: karban@icpf.cas.cz
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
166 10 Prague 6, Czech Republic; e-mail: milos.budesinsky@uochb.cas.cz
b
c
Received July 31, 2002
Accepted October 5, 2002
Th e aziridin e rin g open in g of N-tosylepim in o carboh ydrates 1–6 h avin g D-allo, D-manno,
D-galacto an d D-talo con figuration s with ben zyl alcoh ol, ben zylam in e an d ph en ylm eth an e-
th iol afforded 2-, 3- an d 4-O-ben zyl-, ben zylsulfan yl an d ben zylam in o derivatives of
1,6-an h ydro-β-D-h exopyran oses of D-gluco, D-galacto an d D-manno con figuration s 7–23 in
44–99% yields. Hexen opyran oses 24–26 were prepared from tosylepim in o carboh ydrates 1, 4
an d 5 by in tram olecular rearran gem en t of th e aziridin e rin g.
Keyw ord s: Carboh ydrates; Rin g open in g reaction s; Stereospecific syn th esis; NMR spectro-
scopy; Aziridin es; Am in o sugars; An h ydro sugars; Nucleoph ilic addition s.
Epim in o derivatives of 1,6-an h ydro-β-D-h exopyran oses con stitute an im -
portan t class of com poun ds poten tially useful as startin g com poun ds for
th e preparation of substituted am in o derivatives of 1,6-an h ydroh exoses
an d th e correspon din g h exoses. In th e presen t paper, we perform ed open -
in g reaction s of th e aziridin e rin g of N-tosylated epim in o derivatives of
1,6-an h ydro-β-D-h exopyran oses with ben zyl n ucleoph iles (Bn OH, Bn SH,
Bn NH2) exploitin g th e tem porary protective fun ction of th e ben zyl group.
Th e ben zyl group is frequen tly used for protection of OH, SH an d NH2
groups, especially in carboh ydrate ch em istry1–3. Deprotection of th e ben zyl
group can be preferen tially effected by h ydrogen olysis over palladium cata-
lysts1,2 or by reduction with sodium in liquid am m on ia4,5. In som e cases,
selective deprotection of OBn or NBn group is also possible (h ydrogen ation
un der acidic con dition s6 an d treatm en t with diisopropyl azodicarboxylate7
favours N-deben zylation ). Th us, th e orth ogon al protection by ben zyl group
Collect. Czech. Chem. Commun. (Vol. 67) (2002)
doi: 10.1135/cccc20021805

1806
Kroutil et al.:
is applicable8,9. Ben zylam in e, ben zyl alcoh ol an d ph en ylm eth an eth iol are
better n ucleoph iles th an am m on ia, water an d h ydrogen sulfide, due to th eir
en h an ced reactivity even un der m ilder reaction con dition s, in th e rin g
open in g of oxiran es10–14 an d aziridin es15–17. Moreover, th e products th us
obtain ed are m ore stable, e.g. towards oxidation .
Th e open in g of th e aziridin e rin g is a com m on m eth od exten sively used
for n on -sugar aziridin es (cf. refs18,19), but sporadically for th e derivatives of
epim in o carboh ydrates20. Th e m ain reason is m uch lower reactivity an d
poor regioselectivity of th e rin g open in g of th e latter com poun ds. Th e de-
velopm en t of n ew procedures is, th erefore, still n eeded.
For th ese reason s we decided to prepare O-, S- an d N-ben zyl protected
1,6-an h ydro-β-D-h exopyran oses of th e D-gluco, D-galacto an d D-manno con -
figuration s via aziridin e rin g open in g in N-tosylepim in o carboh ydrates 1–6
h avin g a rigid structure. N-Tosyl group was used to en h an ce low rin g-
reactivity of un substituted epim in o com poun ds. Recen tly we h ave foun d
out th at N-tosylepim in o carboh ydrates react with h alides by trans-diaxial
cleavage with h igh regioselectivity21 in con trast to oth er sugar aziridin es22.
RESULTS AND DISCUSSION
Th e epim in o derivatives 1–6 were prepared by lith ium alum in ium h ydride
reduction of vicin al azidotosylates an d subsequen t tosylation followin g lit-
erature procedures21,23. O-Ben zyl an d S-ben zyl derivatives were obtain ed by
th e reaction of tosylepim in o carboh ydrates 1–6 with Bn ONa in DMSO at
100 °C an d with Bn SNa in refluxin g m eth an ol, respectively. Th e reaction of
tosylepim in o carboh ydrates with n eat ben zylam in e at 150 °C was used for
th e in troduction of NHBn group (Sch em e 1). All perform ed cleavage reac-
tion s were optim ised with respect to a particular n ucleoph ile. Th e open in g
of th e aziridin e rin g catalysed by Lewis acids (BF3·OEt2 or titan ium
isopropoxide) in reaction s of tosylepim in o carboh ydrates with Bn SH an d
NHTs
BnO
BnONa / DMSO
100 oC
OBn
NHTs
BnO
BnO
Ts
N
BnSNa / CH3OH
reflux
BnO
SBn
NHTs
BnNH2
150 oC
NHBn
SCHEME 1
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1,6-Anhydro-β-D-hexopyranoses
1807
Bn OH in toluen e or with Bn ONa in Bn OH at 150 °C afforded m ain ly un -
iden tifiable products.
Th e epim in o derivatives 1, 3, 4 an d 6 wh en reacted with Bn ONa, Bn SNa
an d Bn NH2 gave th e correspon din g di-O-ben zyl derivatives 7–9 (both
epim in o derivatives 3 an d 6 afforded th e sam e product 8 by th e action of
Bn ONa) in 58–74% yields, ben zylsulfan yl derivatives 10–13 in 62–97%
yields an d ben zylam in o derivatives 14–17 in 44–99% yields, respectively.
Com poun ds 7–17 were of D-gluco con figuration . Th e D-talo epim in o deriva-
tives 2 an d 5 afforded D-galacto derivatives 18–20 an d D-manno derivatives
21–23, respectively. Yields were 91 an d 80% for th e di-O-ben zyl derivatives
18 an d 21, 70 an d 71.5% for th e ben zylsulfan yl derivatives 19 an d 22, an d
76 an d 96% for th e ben zylam in es 20 an d 23, respectively. Th e rin g open in g
of th e epim in o derivatives proceeded with 100% regioselectivity an d fol-
lowed th e Fürst–Plattn er rule24 (trans-diaxial aziridin e rin g open in g).
O
O
7, R = OBn
R
10, R = SBn
14, R = NHBn
BnO
BnO
O
O
NHTs
O
BnO
O
N
Ts
24
1
NHTs
O
O
R1
NHTs
R2
R1
R1
R2
R3
O
O
Ts
N
8
11
15
18
19
20
H
OBn
OBn
OBn
H
OBn
SBn
NHBn
OBn
SBn
NHBn
H
R2
H
R3
OBn
OBn
OBn
2, R1 = OBn, R2 = H
3, R1 = H, R2 = OBn
H
H
SCHEME 2
Th e reaction s of epim in o derivatives 4 an d 5 with Bn ONa in DMSO gave
a m ixture of ben zyl derivatives 9 an d 21 togeth er with un saturated
tosylam in es 25 an d 26, from wh ich 9 an d 21 could n ot be separated in
pure form by colum n ch rom atograph y on silica gel. Pure com poun ds 9 an d
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1808
Kroutil et al.:
21 were prepared by altern ative reaction s of tosylepim in o carboh ydrates 4
an d 5 with Bn ONa in ben zyl alcoh ol. Un der th ese con dition s, th e un satu-
rated derivatives were n ot form ed. Tosylepim in o carboh ydrates 1, 4, an d 5
with th e cis arran gem en t of th e aziridin e rin g an d n eigh bourin g O-ben zyl
group gave rise to un saturated tosylam in es (com poun ds 24–26) wh en
treated with a base. Th eir form ation was depen den t on th e base an d th e
solven t used. Th e best yields viz. 57, 44 an d 35% for 24, 25 an d 26, respec-
tively, were obtain ed wh en th e appropriate tosylam in e was treated with po-
tassium tert-butoxide in THF at room tem perature. Wh en sodium h ydride
in DMSO was used, th en n o un saturated, but on ly un iden tifiable products
were form ed.
O
O
9, R = OBn
R
12, R = SBn
16, R = NHBn
TsHN
O
O
OBn
O
O
TsN
OBn
25
4
TsHN
OBn
O
O
R1
R2
R3
8
13
17
21
22
23
H
OBn
OBn
OBn
H
OBn
SBn
NHBn
OBn
SBn
NHBn
Ts
H
NH
R1
O
O
H
R3
OBn
OBn
OBn
R2
Ts
N
H
R1
H
R2
O
O
5, R1 = OBn, R2 = H
6, R1 = H, R2 = OBn
TsHN
26
OBn
SCHEME 3
Th e 2,3-epim in o com poun d 2 yielded on ly polym eric products an d th e
correspon din g un saturated tosylam in e was n ot isolated. Oth er epim in o de-
rivatives (3 an d 6) did n ot react with potassium tert-butoxide at all. We as-
sum e th at th e form ation of un saturated tosylam in es requires base-catalysed
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

1,6-Anhydro-β-D-hexopyranoses
1809
abstraction of th e h ydrogen atom , wh ich is trans orien ted to th e aziridin e
rin g. Molecular m odellin g (MM2+) of th e epim in o derivative 1 predicted
th e dih edral an gle H(4)–C(4)–C(3)–N of ca 169°. Th e E2 elim in ation is,
th erefore, sterically favoured. Th e m ech an ism is an alogous to th e rearran ge-
m en t of th e dian h ydro derivative 27 in to th e allylic alcoh ol 28 (Sch em e 4)
by th e reaction with potassium tert-butoxide in 2-m eth ylpropan -2-ol25, but
can n ot accoun t for th e sm ooth elim in ation alon e (cf. N-ben zylated or
un substituted epim in o derivatives with appropriate con figuration did n ot
provide th e correspon din g un saturated am in es). Th us, th e presen ce of
N-tosyl substituen t likely plays th e dom in an t role.
O
O
O
O
t-BuOK
BnO
BnO
X
XH
1, X = NTs
27, X = O
24
28
SCHEME 4
Th e structure of prepared com poun ds h as been determ in ed from 1H an d
13C NMR spectra (Tables I–III). Th e D-gluco con figuration in com poun ds
7–17 is con firm ed by sm all vicin al couplin gs J(1,2), J(2,3), J(3,4) an d J(4,5)
in th e ran ge 1.1–2.4 Hz in accordan ce with equatorial position s of all corre-
spon din g proton s. Th e D-galacto con figuration in derivatives 18–20 is m an i-
fested by relatively large values of couplin gs J(3,4) ≈ 6.15–6.6 an d J(4,5) ≈
4.0–4.3 Hz an d by lon g-ran ge couplin g J(4,6ex) ≈ 1.0–1.1 Hz. Th e D-manno
con figuration in derivatives 21–23 is eviden ced by large values of couplin g
J(2,3) ≈ 6.15–6.5 Hz wh ilst oth er couplin gs J(1,2), J(3,4) an d J(4,5) are rela-
tively sm all (1.4–1.8 Hz). Th e structure of un saturated tosylam in es 24–26
was deduced on th e basis of 13C NMR data – ch em ical sh ifts of th e olefin ic
carbon atom s in –CH=C(–OBn )– fragm en t ap p eared in th e ran ge δ
89.1–90.1 ppm (C-3) an d δ 156.3–157.6 ppm (C-4 in 24 an d C-2 in 25–26).
CONCLUSION
Rin g-open in g reaction s of N-tosylepim in o derivatives of 1,6-an h ydro-
β-D-h exopyran oses with ben zyl n ucleoph iles viz. Bn OH, Bn SH, Bn NH2 were
elaborated with respect to th e form ation of a sin gle isom er of th e product.
Its con figuration could be predicted usin g th e Fürst–Plattn er rule24. An un -
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1810
Kroutil et al.:
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

1,6-Anhydro-β-D-hexopyranoses
1811
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1812
Kroutil et al.:
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1,6-Anhydro-β-D-hexopyranoses
1813
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1814
Kroutil et al.:
usual rearran gem en t of tosylepim in o carboh ydrates in to h exen opyran oses
was also observed.
EXPERIMENTAL
Meltin g poin ts were determ in ed on a Boëtius m eltin g-poin t m icroapparatus an d are un -
corrected. Th e optical rotation s were m easu red on an Au top ol III (Ru d olp h Research ,
Flan ders, NJ, U.S.A.) polarim eter at 23 °C; [α]D values are given in 10–1 deg cm 2 g–1. Th e 1H
an d 13C NMR spectra were m easured on a Varian INOVA-400 (1H at 400 MHz an d 13C at
100 MHz) or on a Varian UNITY-500 (1H at 500 MHz an d 13C at 125.7 MHz) in strum en t in
CDCl3 (TMS referen ce for 1H an d th e ch loroform sign al at δ 77.0 ppm for 13C) at 25 °C.
Ch em ical sh ifts are given in ppm (δ-scale), couplin g con stan ts (J) in Hz. Th e 1H-1H-COSY
an d 1H-13C-HMQC tech n iques were used for th e structural assign m en ts. High -resolution
m ass spectra were recorded on a ZAB-EQ (VG An alytical, U.K.) in strum en t usin g th e FAB
m eth od (Xe ion isation ). TLC was carried out on MERCK DC Alufolien with Kiesegel F254
with th e followin g solven t system s: S1, h exan e–eth yl acetate 3:2; S2, h exan e–eth yl acetate
1:1; S3, h exan e–eth yl acetate 3:1. TLC plates were visualised by UV detection at 254 n m , io-
din e vapours an d an isaldeh yde solution in sulfuric acid. Colum n ch rom atograph y was per-
form ed on silica gel 60 MERCK (70–230 m esh ASTM) with h exan e–eth yl acetate gradien t
elution . Th e solven ts were evaporated on a vacuum rotary evaporator at 40 °C (un less stated
oth erwise). Toluen e an d dieth yl eth er were dried over sodium , m eth an ol an d eth an ol over
m agn esium . Petroleum eth er refers to th e 40–60 °C distillation fraction . DMF an d DMSO
were purch ased from Aldrich an d were used as supplied. All oth er ch em icals were of com -
m on grade an d were used with out furth er purification . Reaction s were carried out un der
argon atm osph ere. Th e 1H NMR spectral param eters are given in Tables I an d II, an d
th ose of 13C NMR spectra in Table III. For preparation of tosylepim in o carboh ydrates 1, 3, 4
an d 6, see ref.21
Preparation of Tosylepim in o Carboh ydrates 2 an d 5
Th e tosylepim in o carboh ydrates 2 an d 5 were prepared by tosylation of free epim in o deriva-
tives accordin g to th e literature procedures21,23
.
1,6-Anhydro-4-O-benzyl-2,3-dideoxy-2,3-(N-tosylepimino)-β-D-talopyranose (2). Prepared from
1,6-an h ydro-3-azido-4-O-ben zyl-3-deoxy-2-O-tosyl-β-D-galactopyran ose23 (1.053 g, 2.44 m m ol),
LiAlH4 (433 m g, 11.41 m m ol) an d tosyl ch loride (1.147 g, 6.01 m m ol). Yield 0.746 g (79%),
m .p. 189–190 °C, [α]D –123.4 (c 0.28, CHCl3). For C20H21NO5S (387.5) calculated: 62.00% C,
5.46% H, 3.62% N, 8.28% S; foun d: 61.93% C, 5.38% H, 3.61% N, 8.14% S.
1,6-Anhydro-2-O-benzyl-3,4-dideoxy-3,4-(N-tosylepimino)-β-D-talopyranose (5). Prepared from
1,6-an h ydro-3-azido-2-O-ben zyl-3-deoxy-4-O-tosyl-β-D-m an n opyran ose23 (0.928 g, 2.15 m m ol),
LiAlH4 (163 m g, 4.30 m m ol) an d tosyl ch loride (0.546 g, 2.86 m m ol). Yield 0.397 g (48%),
m .p. 156–157 °C, [α]D +103.1 (c 0.26, CHCl3). For C20H21NO5S (387.5) calculated: 62.00% C,
5.46% H, 3.62% N, 8.28% S; foun d: 61.87% C, 5.46% H, 3.65% N, 8.26% S.
Reaction of Tosylepim in o Carboh ydrates with Ben zyl alcoh ol. Gen eral Procedure
Ben zyl alcoh ol (140 µl, 1.35 m m ol) was successively added in to a suspen sion of sodium h y-
dride (50 m g of 60% oil-suspen sion , 1.25 m m ol) in DMSO (4 m l) un der argon . Th e m ixture
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

1,6-Anhydro-β-D-hexopyranoses
1815
was stirred at room tem perature for 1 h an d gave a clear yellow solution of ben zyl
alcoh olate. To th is, a solution of tosylepim in o carboh ydrate (100 m g, 0.258 m m ol) in
DMSO (1–2 m l) was added an d th e m ixture was h eated to 100 °C wh ile stirred. After con -
sum ption of startin g epim in o derivative, th e m ixture was poured on to crush ed ice an d th e
resultin g suspen sion was extracted with dich lorom eth an e (3 × 20 m l). Th e organ ic layer was
wash ed with water, dried over an h ydrous Na2SO4 an d evaporated to dryn ess. Residue (oil or
solid) was furth er purified by colum n ch rom atograph y an d/or crystallized to afford th e
di-O-ben zyl derivatives (7–9, 18, 21).
1,6-Anhydro-3,4-di-O-benzyl-2-deoxy-2-(N-tosylamino)-β-D-glucopyranose (7). Prepared from 1
followin g th e gen eral procedure (24 h h eatin g). Ch rom atograph y on silica gel (50 g, eluen t
S2) gave an oil (103 m g, 80.5%), wh ich was crystallized from an eth an ol–dieth yl eth er–
petroleum eth er m ixture. Yield 74.3 m g (58%), m .p. 65–66 °C, [α]D –30 (c 0.29, CHCl3). For
C
27H29NO6S (495.6) calculated: 65.44% C, 5.90% H, 2.83% N, 6.47% S; foun d: 65.34% C,
5.95% H, 2.89% N, 6.48% S.
1,6-Anhydro-2,4-di-O-benzyl-3-deoxy-3-(N-tosylamino)-β-D-glucopyranose (8)
Method A. Prepared from 3 followin g th e gen eral procedure (2 h h eatin g). It was th en
purified on silica gel (25 g, eluen t S3) an d crystallized from an eth an ol–dieth yl eth er–
petroleum eth er m ixture. Yield 90 m g (70%), m .p. 134–135 °C, [α]D +31.5 (c 0.25, CHCl3).
For C27H29NO6S (495.6) calculated: 65.44% C, 5.90% H, 2.83% N, 6.47% S; foun d: 65.41% C,
6.02% H, 2.82% N, 6.35% S.
Method B. Prepared from 6 followin g th e gen eral procedure (2 h h eatin g). Purification on
silica gel (25 g, eluen t S3) an d crystallization from an eth an ol–dieth yl eth er–petroleum eth er
m ixture yielded 8 (92 m g, 72%), m .p. 136–136.5 °C, wh ich was iden tical with th e sam ple
prepared from 3.
1,6-Anhydro-2,3-di-O-benzyl-4-deoxy-4-(N-tosylamino)-β-D-glucopyranose (9)
Method A. Prepared from 4 followin g th e gen eral procedure (2 h h eatin g). Th e oil was
purified on silica gel (25 g, eluen t S3) an d crystallized from an eth an ol–dieth yl eth er–
petroleum eth er m ixture. Yield 104 m g (81%) of im pure 9, m .p. 112–115 °C. Th e m ain im -
purity was th e un saturated tosylam in e 25 (40%, based on 1H NMR spectrum by in tegration
of H-1 sign als).
Method B. Tosylepim in o carboh ydrate 4 (100 m g, 0.258 m m ol) was m ixed with a 0.1 M so-
lution of sodium ben zyloxide in ben zyl alcoh ol (2.5 m l, 0.25 m m ol) an d h eated with stir-
rin g at 150 °C for 33 h . After th is tim e, th e startin g epim in o derivative was n early
con sum ed. Acetic acid (0.5 m l) an d water (50 m l) were added an d th e reaction m ixture was
distilled to collect ca 50 m l of distillate. Th e residue was th en evaporated to dryn ess an d
ch rom atograph ed on silica gel (25 g, eluen t S1) to afford pure 9, wh ich was crystallized from
an eth an ol–dieth yl eth er–petroleum eth er m ixture. Yield 95 m g (74%), m .p. 115–116 °C,
[α]D +21.3 (c 0.30, CHCl3). For C27H29NO6S (495.6) calculated: 65.44% C, 5.90% H, 2.83% N,
6.47% S; foun d: 65.31% C, 6.00% H, 2.85% N, 6.39% S.
1,6-Anhydro-2,4-di-O-benzyl-3-deoxy-3-(N-tosylamino)-β-D-galactopyranose (18). Prepared
from 2 (2 h h eatin g). Th e oil obtain ed was th en purified on silica gel (25 g, eluen t S1). Yield
117 m g (91%), [α]D –48.2 (c 0.54, CHCl3). HRMS (FAB), m/z: foun d 495.1803 (M+);
C
27H29NO6S requires 495.1716.
1,6-Anhydro-2,4-di-O-benzyl-3-deoxy-3-(N-tosylamino)-β-D-mannopyranose (21)
Method A. Prepared from 5 followin g th e gen eral procedure (2 h h eatin g). Th e oil was
purified on silica gel (25 g, eluen t S1) an d crystallized from an eth an ol–dieth yl eth er–
petroleum eth er m ixture. Yield 102 m g (80%) of im pure 21, m .p. 48–51 °C. Th e m ain im pu-
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

1816
Kroutil et al.:
rity was th e un saturated tosylam in e 26 (60%, based on 1H NMR spectrum by th e in tegration
of H-1 sign als).
Method B. Tosylepim in o carboh ydrate 5 (100 m g, 0.258 m m ol) was m ixed with a 0.1 M so-
lution of sodium ben zyloxide in ben zyl alcoh ol (2.5 m l, 0.25 m m ol) an d h eated un der stir-
rin g at 150 °C for 24 h . After th is tim e, th e startin g epim in o derivative was all con sum ed.
Acetic acid (0.5 m l) an d water (50 m l) were added, an d th e reaction m ixture was distilled to
collect ca 50 m l of distillate. Th e residue was evaporated to dryn ess an d ch rom atograph ed
on silica gel (25 g, eluen t S1) to afford pure 21, wh ich was crystallized from an eth an ol–
dieth yl eth er–petroleum eth er m ixture. Yield 89 m g (69%), m .p. 99–100 °C, [α]D +94.8
(c 0.27, CHCl3). For C27H29NO6S (495.6) calculated: 65.44% C, 5.90% H, 2.83% N, 6.47% S;
foun d: 65.42% C, 5.88% H, 2.71% N, 6.45% S.
Reaction of Tosylepim in o Carboh ydrates with Ph en ylm eth an eth iol. Gen eral Procedure
A 1 M solution of sodium m eth oxide in m eth an ol (500 µl, 0.5 m m ol) was added in to th e
m ixture of tosylepim in o carboh ydrate (100 m g, 0.258 m m ol), ph en ylm eth an eth iol (61 µl,
0.52 m m ol) an d m eth an ol (8 m l) an d th e resultin g solution was refluxed for a given tim e.
After con sum ption of tosylepim in o carboh ydrate, th e m ixture was poured on to crush ed ice
an d extracted with dich lorom eth an e (3 × 20 m l). Th e organ ic layer was wash ed with water,
dried over an h ydrous Na2SO4 an d stirred with ch arcoal. After filtration , th e solution was
evaporated to obtain oil (coevaporation with toluen e was n ecessary to rem ove th e th iol).
Ben zylsulfan yl derivatives (10–13, 19, 22) were obtain ed as colourless oils (dried over P2O5
un der vaccum ) or as crystals (from an eth an ol–dieth yl eth er–petroleum eth er m ixture).
1,6-Anhydro-4-O-benzyl-3-benzylsulfanyl-2-deoxy-2-(N-tosylamino)-β-D-glucopyranose (10).
Prepared from 1 followin g th e gen eral procedure (reflux 23 h ). Yield 82 m g (62%), m .p.
126–128 °C, [α]D –188 (c 0.31, CHCl3). For C27H29NO5S2 (511.7) calculated: 63.38% C,
5.71% H, 2.74% N, 12.53% S; foun d: 63.25% C, 5.56% H, 2.68% N, 12.33% S.
1,6-Anhydro-4-O-benzyl-2-benzylsulfanyl-3-deoxy-3-(N-tosylamino)-β-D-glucopyranose (11).
Prepared from 3 followin g th e gen eral procedure (reflux 22.5 h ). Yield 104 m g (78%) of oily
11, [α]D –28 (c 0.72, CHCl3). HRMS (FAB), m/z: foun d 511.1409 (M+); C27H29NO5S2 requires
511.1487.
1,6-Anhydro-2-O-benzyl-3-benzylsulfanyl-4-deoxy-4-(N-tosylamino)-β-D-glucopyranose (12).
Prepared from 4 followin g th e gen eral procedure (reflux 20 h ). Yield 115 m g (87%), m .p.
114–115 °C, [α]D +102 (c 0.20, CHCl3). For C27H29NO5S2 (511.7) calculated: 63.38% C,
5.71% H, 2.74% N, 12.53% S; foun d: 63.23% C, 5.76% H, 2.69% N, 12.42% S.
1,6-Anhydro-2-O-benzyl-4-benzylsulfanyl-3-deoxy-3-(N-tosylamino)-β-D-glucopyranose (13).
Prepared from 6 followin g th e gen eral procedure (reflux 25 h ). Yield 129 m g (97%) of oily
13, [α]D +91.6 (c 0.95, CHCl3). HRMS (FAB), m/z: foun d 511.1385 (M+); C27H29NO5S2 re-
quires 511.1487.
1,6-Anhydro-4-O-benzyl-2-benzylsulfanyl-3-deoxy-3-(N-tosylamino)-β-D-galactopyranose (19).
Prepared from 2 followin g th e gen eral procedure (reflux 18 h ). Yield 91 m g (70%) after
recrystallization from an eth yl acetate–petroleum eth er m ixture, m .p. 41–43 °C (dec.), [α]D
–102.5 (c 0.08, CHCl3). For C27H29NO5S2 (511.7) calculated: 63.38% C, 5.71% H, 2.74% N,
12.53% S; foun d: 63.17% C, 5.69% H, 2.66% N, 12.25% S.
1,6-Anhydro-2-O-benzyl-4-benzylsulfanyl-3-deoxy-3-(N-tosylamino)-β-D-mannopyranose (22).
Prepared from 5 followin g th e gen eral procedure (reflux 18 h ). Yield 93 m g (71.5%) after
recrystallization from an eth yl acetate–petroleum eth er m ixture, m .p. 48–50 °C (dec.), [α]D
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1,6-Anhydro-β-D-hexopyranoses
1817
+212.2 (c 0.28, CHCl3). For C27H29NO5S2 (511.7) calculated: 63.38% C, 5.71% H, 2.74% N,
12.53% S; foun d: 63.15% C, 5.66% H, 2.72% N, 12.52% S.
Reaction of Tosylepim in o Carboh ydrates with Ben zylam in e. Gen eral Procedure
Tosylepim in o carboh ydrate an d ben zylam in e were m ixed an d h eated at 150 °C for a given
tim e. After con sum in g th e startin g epim in o derivative, th e m ixture was cooled to –18 °C
yieldin g crystals, if n ot th en m ixture was ch rom atograph ed on silica gel (25–50 g, eluen t S2)
to rem ove excess ben zylam in e. Ben zylam in o derivatives (14–17, 20, 23) were obtain ed as
colourless oils (dried over P2O5 un der vaccum ) or crystals (from an eth an ol–dieth yl eth er–
petroleum eth er m ixture).
1,6-Anhydro-4-O-benzyl-3-(benzylamino)-2,3-dideoxy-2-(N-tosylamino)-β-D-glucopyranose (14).
Prepared from 1 (100 m g, 0.258 m m ol) an d ben zylam in e (300 µl, 2.7 m m ol) followin g th e
gen eral procedure (23 h h eatin g). Yield 87 m g (69%), m .p. 135–136 °C, [α]D –45.5 (c 0.22,
CHCl3). For C27H30N2O5S (494.6) calculated: 65.57% C, 6.11% H, 5.66% N, 6.48% S; foun d:
65.68% C, 6.23% H, 5.57% N, 6.36% S.
1,6-Anhydro-4-O-benzyl-2-(benzylamino)-2,3-dideoxy-3-(N-tosylamino)-β-D-glucopyranose (15).
Prepared from 3 (100 m g, 0.258 m m ol) an d ben zylam in e (600 µl, 5.4 m m ol) followin g th e
gen eral procedure (64 h h eatin g). Yield 55.4 m g (44%, after recrystallization 30 m g, 24%),
m .p. 49–52 °C, [α]D +71.4 (c 0.15, CHCl3). For C27H30N2O5S (494.6) calculated: 65.57% C,
6.11% H, 5.66% N, 6.48% S; foun d: 65.51% C, 6.29% H, 5.46% N, 6.49% S.
1,6-Anhydro-2-O-benzyl-3-(benzylamino)-3,4-dideoxy-4-(N-tosylamino)-β-D-glucopyranose (16).
Prepared from 4 (100 m g, 0.258 m m ol) an d ben zylam in e (700 µl, 6.3 m m ol) followin g th e
gen eral procedure (50 h h eatin g). Yield 110 m g (99%, after recrystallization 74 m g, 57%),
m .p. 83–85 °C, [α]D –5 (c 0.12, CHCl3). For C27H30N2O5S (494.6) calculated: 65.57% C,
6.11% H, 5.66% N, 6.48% S; foun d: 65.56% C, 6.08% H, 5.56% N, 6.39% S.
1,6-Anhydro-2-O-benzyl-4-(benzylamino)-3,4-dideoxy-3-(N-tosylamino)-β-D-glucopyranose (17).
Prepared from 6 (200 m g, 0.516 m m ol) an d ben zylam in e (1 m l, 9.2 m m ol) followin g th e
gen eral procedure (64 h h eatin g). Yield 247 m g (97%) of oily 17, [α]D +6.6 (c 1.57, CHCl3).
HRMS (FAB), m/z: foun d 495.1806 (M+ + H); C27H31N2O5S requires 495.1954.
1,6-Anhydro-4-O-benzyl-2-(benzylamino)-2,3-dideoxy-3-(N-tosylamino)-β-D-galactopyranose
(20). Prepared from 2 (100 m g, 0.258 m m ol) an d ben zylam in e (300 µl, 2.7 m m ol) fol-
lowin g th e gen eral procedure (reflux 10 h ). Yield 97 m g (76%, after crystallization from a
m eth an ol–dieth yl eth er–petroleum eth er m ixture), m .p. 109–111 °C, [α]D +16.4 (c 0.28,
CHCl3). For C27H30N2O5S (494.6) calculated: 65.57% C, 6.11% H, 5.66% N, 6.48% S; foun d:
65.47% C, 6.23% H, 5.62% N, 6.65% S.
1,6-Anhydro-2-O-benzyl-4-(benzylamino)-3,4-dideoxy-3-(N-tosylamino)-β-D-mannopyranose
(23). Prepared from 5 (100 m g, 0.258 m m ol) an d ben zylam in e (300 µl, 2.7 m m ol) followin g
th e gen eral procedure (14 h h eatin g). Yield 123 m g (96%, after recrystallization 100 m g,
78%), m .p. 126.5–127 °C, [α]D +62.6 (c 0.31, CHCl3). For C27H30N2O5S (494.6) calculated:
65.57% C, 6.11% H, 5.66% N, 6.48% S; foun d: 65.34% C, 6.35% H, 5.52% N, 6.65% S.
Preparation of Un saturated Tosylam in es. Gen eral Procedure
A solution of tosylepim in o carboh ydrate (100 m g, 0.258 m m ol) in THF (5 m l) was added to
a stirred suspen sion of potassium tert-butoxide (140 m g, 1.25 m m ol) in THF (5 m l). Durin g
th e addition , potassium tert-butoxide gradually dissolved an d th e reaction m ixture turn ed
yellow. Th e reaction m ixture was stirred at room tem perature for a given tim e. After con -
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1818
Kroutil et al.:
sum in g th e startin g epim in o derivative, Dowex 50X8 (H-cycle, air-dried) an d eth yl acetate
(50 m l) was added to adjust pH to 6. Th e resultin g suspen sion was filtered an d th e filtrate
evaporated. Th e residue was dissolved in th e solven t system S1 (30 m l) an d th e solution
passed th rough silica gel (2 g) to rem ove polym eric im purities. Silica gel was furth er eluted
with an oth er portion of solven t system S1 (50 m l). Com bin ed eluates were evaporated an d
th e solid was crystallized from an eth yl acetate–dieth yl eth er–petroleum eth er m ixture to ob-
tain pure product.
1,6-Anhydro-4-O-benzyl-2,3-dideoxy-2-(N-tosylamino)-β-D-erythro-hex-3-enopyranose (24).
Prepared from 1 followin g th e gen eral procedure (7 h ). Yield 57 m g (57%), m .p. 175–177 °C,
[α]D –77.9 (c 0.23, CHCl3). For C20H21NO5S (387.5) calculated: 62.00% C, 5.46% H, 3.62% N,
8.28% S; foun d: 61.72% C, 5.55% H, 3.53% N, 8.02% S.
1,6-Anhydro-2-O-benzyl-3,4-dideoxy-4-(N-tosylamino)-β-D-erythro-hex-2-enopyranose (25).
Prepared from 4 followin g th e gen eral procedure (48 h ). Yield 44 m g (44%), m .p. 118–119 °C,
[α]D +60.4 (c 0.30, CHCl3). For C20H21NO5S (387.5) calculated: 62.00% C, 5.46% H, 3.62% N,
8.28% S; foun d: 62.01% C, 5.58% H, 3.55% N, 8.39% S.
1,6-Anhydro-2-O-benzyl-3,4-dideoxy-4-(N-tosylamino)-β-D-threo-hex-2-enopyranose (26).
Prepared from 5 (95 m g, 0.245 m m ol) followin g th e gen eral procedure (13 h ). Yield 33 m g
(35%), m .p. 124–126 °C, [α]D –32.7 (c 0.31, CHCl3). For C20H21NO5S (387.5) calculated:
62.00% C, 5.46% H, 3.62% N, 8.28% S; foun d: 61.96% C, 5.66% H, 3.88% N, 8.01% S.
This work was supported by the Grant Agency of the Czech Republic (grant No. 203/01/0862) and
by the Ministry of Education, Youth and Sports of the Czech Republic (MSM 113100001). Authors are
also indebted to Ms B. Šperlichová for the measurement of optical rotation.
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