Synthesis and NMR spectra of 1,6-anhydro-2,3-dideoxy-2,3-epimino- and 1,6-anhydro-3,4-dideoxy-3,4-epimino-β-D-hexopyranoses

Article abstract of DOI:10.1135/cccc20010799

A complete series of 2,3-dideoxy-2,3-epimino-and 3,4-dideoxy-3,4-epimino-1,6-anhydro-β-D-hexopyranoses were prepared by lithium aluminum hydride reduction of the corresponding trans-azido tosylates or trans-azido epoxides of 1,6-anhydro-β-D-hexopyranoses. The structure of the epimino derivatives was confirmed by ¹H and ¹³C NMR spectra.

Full text of DOI:10.1135/cccc20010799

Synthesis of Epimino Derivatives
799
SYNTHESIS AND NMR SPECTRA OF 1,6-ANHYDRO-2,3-DIDEOXY-2,3-EPIMINO-
AND 1,6-ANHYDRO-3,4-DIDEOXY-3,4-EPIMINO-β-D-HEXOPYRANOSES
a,
b
c1
c2
Jindřich KARBAN *, Miloš BUDĚŠÍNSKÝ , Miloslav ČERNÝ and Tomáš TRNKA
a
Institute of Chemical Process 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,
b
166 10Prague 6, Czech Republic; e-mail: milos.budesinsky@uochb.cas.cz
c
Department of Organic Chemistry, Charles University, 128 40Prague 2, Czech Republic;
1
2
e-mail: mila@mail.natur.cuni.cz, trnka@mail.natur.cuni.cz
Received Jan uary 5, 2001
Accepted April 5, 2001
A com plete series of 2,3-dideoxy-2,3-epim in o- an d 3,4-dideoxy-3,4-epim in o-1,6-an h ydro-
β-D-h exopyran oses were prepared by lith ium alum in um h ydride reduction of th e corre-
spon din g trans-azido tosylates or trans-azido epoxides of 1,6-an h ydro-β-D-h exopyran oses.
Th e structure of th e epim in o derivatives was con firm ed by 1H an d 13C NMR spectra.
Keyw ord s: Carboh ydrates; Am in osugars; An h ydrosugars; 1,6-An h ydro-β-D-h exopyran oses;
Azides; Aziridin es; Reduction s; NMR spectroscopy.
Recen tly, as a part of our program m e focused on syn th esis of epim in o de-
rivatives of 1,6-an h ydro-β-D-aldoh exopyran oses as versatile syn th etic in ter-
m ediates, we h ave reported1 th e syn th esis of 1,6-an h ydro-2,3-(N-ben zyl-
epim in o)-2,3-dideoxy-β-D-h exopyran ose of th e allo-con figuration an d
1,6-an h ydro-3,4-(N-ben zylepim in o)-3,4-dideoxy-β-D-h exopyran oses of th e
allo-, talo- an d galacto-con figuration . Th is syn th esis em ployed th e
Mitsun obu reaction of 2-, 3- an d 4-(ben zylam in o)-2-, 3- an d 4-deoxy deriva-
tives of 1,6-an h ydro-β-D-h exopyran oses obtain ed by trans-diaxial cleavage
of suitable 1,6:2,3- an d 1,6:3,4-dian h ydro-β-D-h exopyran oses with ben zyl-
am in e. A m ajor drawback of th is procedure con sists in th e low reactivity of
th e dian h ydro derivatives (h avin g th e oxiran e rin g exo-orien ted) with
ben zylam in e, wh ich ren ders th is m eth od rath er in con ven ien t for syn th esis
of all possible isom ers. Th erefore, we h ave exam in ed th e possibility of syn -
th esisin g th e com plete series of 2,3-dideoxy-2,3-epim in o an d 3,4-dideoxy-
3,4-epim in o derivatives of 1,6-an h ydro-β-D-h exopyran oses by lith ium alu-
m in um h ydride reduction of th e correspon din g vicin al trans-azido tosylates
or vicin al trans-azido epoxides of 1,6-an h ydro-β-D-h exopyran oses. Form at-
Collect. Czech. Chem. Commun. (Vol. 66) (2001)
doi: 10.1135/cccc20010799

800
Karban, Buděšínský, Černý, Trnka:
ion of th e aziridin e rin g from azido tosylates by reaction of LiAlH4 is a stan -
dard m eth od in carboh ydrate ch em istry based on in tram olecular
substitution of tosyloxy group with am in o group form ed in situ from azido
group2. Form ation of vicin al h ydroxy epim in es from azido epoxides on re-
action with LiAlH4 takes advan tage of th e kn own 3 isom erisation of vicin al
trans-am in o epoxides in to h ydroxy epim in es in alkalin e solution .
RESULTS AND DISCUSSION
Azido tosylates an d azido epoxides suitable for aziridin e rin g closure were
prepared startin g from 1,6:2,3-dian h ydro derivatives 1a (ref.4), 1b (ref.4), 2a
(ref.5), 2b (ref.5), 2c (ref.3b), 2d (ref.6), 3a (ref.7) an d 1,6:3,4-dian h ydro deriv-
atives 4a (ref.8), an d 5a (ref.9) of β-D-h exopyran oses. Ben zylation of com -
poun ds 3a an d 4a yielded O-ben zyl derivatives 3b an d 4b. Treatm en t of
dian h ydro derivatives 1a, 1b, 2a, 3b, 4b an d 5a with sodium azide an d am -
m on ium ch loride in 2-m eth oxyeth an ol–H2O at 110–120 °C (see e.g. ref.10)
gave azido derivatives 6a (ref.11), 6b, 6c (ref.12), 7a, 8a an d 6d (ref.13) in
good yields, in m ost cases above 70%. Th e oxiran e rin g open in g proceeded
with h igh regio- an d stereoselectivity affordin g products th at h ave azido
an d h ydroxy groups trans-diaxially orien ted. Th is stereoch em ical course is
in accordan ce with gen eral stereoch em ical rules con trollin g reactivity of
dian h ydro derivatives with n ucleoph iles14. Dian h ydro derivatives 3b an d
4b reacted with sodium azide to give 7a an d 8a m ore slowly th an th e oth er
suggestin g th at th e steric h in dran ce caused by th e 1,6-an h ydro bridge an d
ben zyloxy group m ay play an im portan t role in con trollin g th e reaction
rate.
Azido tosylates 6e (ref.11), 6f, 6g, 7b an d 8b were obtain ed from com -
poun ds 6a, 6c, 6d , 7a an d 8a by treatm en t with tosyl ch loride in pyridin e.
Th e tosylation of 6c an d 6d required tem peratures about 80–100 °C, wh ich
is con sisten t with th e low reactivity of th e axial h ydroxy group14a at C-3.
Azido tosylate 6h was prepared from azido derivative 6b by reaction with
ben zyl brom ide an d sodium h ydride in tetrah ydrofuran . Azidolysis of
epoxides 1a, 2a, 3b, 4b an d 5a an d subsequen t tosylation are sh own in
gen eral Sch em e 1.
O
OR
OR
OR
HO
N3
TsO
N3
(i)
(ii)
R = Bn
(i) NaN3, NH4Cl; (ii) TsCl, py
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Synthesis of Epimino Derivatives
801
1
Th e structure of all azido derivatives was con firm ed by H an d 13C NMR
spectra (see Tables I–III). Th e presen ce of azido group is in directly m an i-
fested in 13C NMR spectra by th e observation of th e upfield sh ifted sign al of
>CH–N3 carbon in th e ran ge δ 58.9–62.8. Oth er substituen ts (OH, OBn an d
OTs) provide ch aracteristic sign als in 1H NMR spectra (Table I) an d last two
substituen ts also in 13C NMR spectra (Table III). Th e gluco-, galacto- an d
manno-con figuration of azido derivatives 6–8 an d th e con form ation of th eir
pyran ose rin g is reflected by vicin al in terproton couplin g con stan ts
(Table II). In agreem en t with th e ch air form 1C4 com m on for 1,6-an h ydro-
h exopyran oses m ost of th e gluco-derivatives 6 (with equatorial h ydrogen s
in position 2, 3 an d 4) sh ow sm all values of J(2,3) an d J(3,4) con stan ts
(≤ 2.5 Hz). Som ewh at h igh er J-values ≈ 3.5 Hz in com poun ds 6c, 6d an d 6k
O
O
O
O
RO
O
O
O
O
RO
O
R
RO
O
O
O
2a, R = OBn
2b, R = OH
2c, R = N3
1a, R = Bn
1b, R = Ts
3a, R = H
3b, R = Bn
4a, R = H
4b, R = Bn
2d, R = OTs
O
O
O
O
R3
O
O
R
R2
R2
O
R3
R1
R1
R3
5a, R = OBn
5b, R = NH2
5c, R = N3
6
a
b
c
d
e
f
R1
R2
N3
N3
OH
7
a
b
R1
R2 R3
OBn
OTs
OBn
N3
OH
OH
N3
OH N3 OBn
OTs N3 OBn
OBn OH
OTs N3
O
O
OBn
OBn
N3
N3
OTs
R2
R1
g
h
i
OBn OTs
OBn N3
NH2 OH
R3
OTs
OH
8
a
b
R1
R2 R3
OH
j
N3
N3
N3
N3
OH
OH
OTs
OH
OBn N3 OH
OBn N3 OTs
OTs
OTs
N3
k
l
m
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

802
Karban, Buděšínský, Černý, Trnka:
TABLE I
1H NMR ch em ical sh ifts (ppm , δ-scale) of azido derivatives 6a–6h , 6j–6l, 7a, 7b, 8a, 8b in CDCl3
Com -
poun d
H-1
H-2
H-3
H-4
H-5
H-6en
H-6ex
Oth er proton s
6a
5.44 bt
3.59 dm
3.84 dq
3.31 ddt
4.58 dm
4.04 dd
3.74 ddd
Bn : 4.68 d, 4.65 d,
7.32–7.40 m (5 H);
OH: 2.72 d
6b
6c
6d
6e
5.42 t
3.52 vbd
3.23 dm
3.30 m
3.63 m
3.90 um
3.88 um
3.71 tt
4.24 m
4.65 m
4.04 dd
3.94 dd
4.01 dd
3.70 bdd
3.75 dd
3.70 dd
3.75 dd
3.59 ddd
Ts: 2.48 s (3 H),
7.84 m (2 H), 7.41 m
(2 H); OH:
Bn : 4.70 d, 4.68 d,
7.30–7.40 m (5 H);
OH: 2.45 bd
Bn : 4.70 d, 4.67 d,
7.30–7.39 m (5 H);
OH: 2.41 bd
Bn : 4.65 d, 4.60 d,
7.30–7.39 m (5 H);
Ts: 2.46 s (3 H),
7.83 m (2 H), 7.36 m
(2 H)
a
5.47 bt
5.49 bt
5.37 bs
3.38 dm
3.34 dm
3.21 bdd
4.62 dq
4.59 dm
4.51 dm
4.07 dd
6f
5.44 t
3.06 q
4.60 p
3.49 q
4.56 dm
3.98 dd
3.71 dd
Bn : 4.72 d, 4.54 d,
7.31–7.38 m (5 H);
Ts: 2.47 s (3 H),
7.80 m (2 H), 7.38 m
(2 H)
6g
6h
5.36 t
5.38 s
3.29 m
3.18 d
4.55 p
3.61 t
3.37 m
4.62 m
4.68 dt
4.02 dd
3.82 dd
3.77 dd
3.67 dd
Bn : 4.55 d, 4.29 d,
7.20–7.35 m ; Ts:
2.47 s (3 H), 7.79 m
(2 H), 7.38 m (2 H)
Bn : 4.65 d, 4.60 d,
7.30–7.38 m (5 H);
Ts: 2.46 s (3 H),
7.82 m (2 H), 7.35 m
(2 H)
4.10 dd
6j
5.51 bt
5.44 bt
3.52 m
3.89 dm
3.91 tt
3.66 dm
4.44 ddt
4.58 dm
4.64 dq
4.22 dd
4.06 dd
3.80 bdd
3.72 ddd
3-OH: 2.45 d; 4-OH:
2.61 d
Ts: 2.46 s (3 H),
7.85 m (2 H), 7.38 m
(2 H)
6k
3.26 dm
6l
5.44 m
3.13 m
4.53 dt
4.52 dd
4.63 m
4.07 dd
3.75 dd
2 × Ts: 2.48 s (3 H),
2.47 s (3 H), 7.83 m
(2 H), 7.78 m (2 H),
7.39 m (4 H)
7a
7b
5.31 t
3.76 bdt
4.28 t
4.00 dq
3.96 ddd
4.42 m
4.40 m
4.45 dd
4.38 bd
3.67 ddd
3.59 dd
Bn : 4.71 d, 4.63 d,
7.32–7.40 m (5 H); OH:
2.10 d
Bn : 4.68 d, 4.60 d,
7.32–7.40 m (5 H); Ts:
2.47 s (3 H), 7.80 m (2 H),
7.38 m (2 H)
5.81 um
≈3.98 m
≈3.98 m
8a
8b
5.43 t
5.41 t
3.71 ddd
3.72 ddd
3.97 dq
3.89 dq
3.79 um
4.42 bt
4.42 m
4.39 m
4.25 dd
4.13 dd
3.77 dd
3.70 dd
Bn : 4.71 d, 4.68 d,
7.30–7.40 m (5 H); OH:
2.39 d
Bn : 4.66 d, 4.64 d,
7.30–7.37 m (5 H); Ts:
2.48 s (3 H), 7.80 m (2 H),
7.39 m (2 H)
a
Not observed.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Synthesis of Epimino Derivatives
803
in dicate a certain population of boat form B3,O wh ich becom es th e pre-
ferred con form ation in com poun ds 6e, 6h with bulky substituen ts OBn an d
OTs in position 2, 4 (J(2,3) ≈ J(3,4) = 5.0–6.6 Hz). Th e h igh er values of J(3,4) ≈
5.5 Hz in galacto derivatives 7 an d J(2,3) ≈ 5.5–5.9 Hz in th e manno deriva-
tives 8 can be explain ed by th e presen ce of axial h ydrogen atom s in posi-
tion s 4 an d 2, respectively, in th e preferred ch air form 1C4. Th e presen ce of
azido group in azido derivatives was also in dicated in th eir IR spectra by th e
absorption ban d ν(N3) at 2 106–2 121 cm –1
.
Th e azido tosylates 6e, 6f, 6g, 6h , 7b an d 8b were con verted in to
epim in es 11, 9a, 13, 15b, 12a an d 16, respectively, by th e treatm en t with
lith ium alum in um h ydride in tetrah ydrofuran (see Sch em e 2).
TABLE II
1H NMR couplin g con stan ts (in Hz) of azido derivatives 6a–6h , 6j–6l, 7a, 7b, 8a an d 8b in CDCl3
Com -
J(1,2)
J(2,3)
J(3,4)
J(4,5)
J(5,6en )
J(5,6ex)
J(6en ,6ex) J(1,3)
J(2,4)
J(3,5)
poun da
6ab
6bc
6cd
6d e
6ef
6f
≈1.5
≈1.5
1.1
1.5
0.9
≈1.6
1.6
0
2.2
≈2.65
3.5
2.0
≈2.65
3.5
2.1
≈3.0
1.6
1.6
1.4
≈2.1
1.5
1.2
2.2
1.5
3.3
3.9
3.6
2.0
2.0
0.9
1.0
0.9
0.8
0.9
1.1
1.0
1.0
0.9
1.0
1.1
≈0.6
0.8
1.0
1.0
5.6
5.5
5.4
5.2
5.2
5.7
5.6
5.1
5.4
5.5
5.7
5.1
5.1
5.6
5.6
7.6
8.1
7.6
7.6
7.6
7.8
7.8
7.8
7.7
7.9
8.1
7.5
7.7
7.7
8.0
1.4
≈1.5
1.3
1.3
0.6
≈1.6
1.2
≈0
1.3
≈0.7
0.8
0.8
≈0.3
≈1.5
1.4
≈0
1.7
≈1.5
1.3
1.2
0.8
≈1.5
1.4
≈0
3.1
3.5
5.0
5.2
≈1.5
1.5
≈1.5
1.5
6gg
6h
6.0
6.6
6jh
6ki
6lj
7ak
7bl
8am
8b
2.0
1.3
1.8
≈1.7
1.9
1.8
1.8
2.0
2.2
1.7
1.0
1.6
≈1.5
1.2
1.5
1.4
1.2
0.7
≈0
1.7
1.3
0.9
≈1.4
1.4
1.8
1.8
3.6
3.7
2.1
1.7
≈1.6
1.5
5.5
≈0
5.6
≈0
5.5
1.6
0.5
0.4
5.9
1.6
a
Gem in al couplin g of ben zyl proton s appears in th e ran ge 11.8–12.4 Hz. Addition al couplin g con stan ts:
b
c
d
J(OH,2) = 11.6, J(1,4) = 0.8, J(2,5) = 0.6, J(1,6ex) = 0.5; J(2,OH) ≈ 8.5; J(1,4) = 0.4, J(1,6en ) ≈ 0.2,
e
f
J(1,6ex) ≈ 0.3, J(3,OH) ≈ 8.5; J(3,OH) ≈ 4.8, J(2,5) = 0.5, J(1,4) = 0.5, J(1,5) <0.3; J(1,4) <0.3, J(1,6en ) ≈ 0.2,
J(1,6ex) = 0.4; J(1,6en ) ≈ J(1,6ex) <0.3, J(1,4) <0.5, J(1,5) <0.3; J(3,OH) = 7.1, J(4,OH) = 10.4, J(2,5) =
g
h
i
j
0.6, J(1,4) = 0.7, J(1,6ex) = 0.3; J(1,4) = 0.5, J(1,6en ) ≈ 0.2, J(1,6ex) = 0.4, J(2,5) = 0.5; J(1,6ex) <0.5;
k
l
J(2,OH) = 9.4, J(4,6ex) = 1.3. J-Values were obtain ed from CDCl3–C6D6 (9 : 1): J(4,6ex) = 1.0, J(1,6en ) ≈
m
J(1,6ex) <0.3, J(1,5) <0.5;
J(3,OH) = 9.2.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

804
Karban, Buděšínský, Černý, Trnka:
TABLE III
13C NMR ch em ical sh ifts (in ppm , δ-scale) of azido derivatives 6a–6h , 6j–6l, 7a, 7b, 8a an d 8b in CDCl3
Com -
poun d
C-1
C-2
C-3
C-4
C-5
C-6
Oth er carbon s
6a
101.44
101.50
68.13
68.94
60.30
61.20
75.51
76.95
74.07
74.79
65.30
65.55
Bn : 136.74, 128.71 (2), 128.32 127.93
(2), 71.58
Ts: 145.92, 132.72, 130.29 (2),
127.94
6b
(2), 21.70
6c
6d
6e
101.05
101.19
100.02
62.76
77.80
77.76
70.45
70.12
60.37
78.59
62.44
77.76
75.03
74.85
75.10
66.26
66.89
66.67
Bn : 137.33, 128.60 (2), 128.10,
127.91 (2), 71.86
Bn : 137.26, 128.60 (2), 128.13,
127.96 (2), 72.29
Bn : 136.80, 128.67 (2), 128.29,
128.04 (2), 72.08; Ts: 145.48, 132.89,
130.02 (2), 128.07 (2), 21.69
6f
99.62
100.10
101.02
58.98
73.42
79.04
75.44
75.31
60.74
74.16
59.33
80.05
74.29
73.76
75.56
64.98
65.66
67.06
Bn : 136.88, 128.58 (2), 128.15,
127.90 (2), 71.52; Ts: 145.73, 132.91,
130.27 (2), 128.04 (2), 21.68
6g
6h
Bn : 136.78, 128.52 (2), 128.12,
127.84 (2), 71.96; Ts: 145.68, 132.92,
130.24 (2), 127.96 (2), 21.68
Bn : 136.76, 128.61 (2), 128.26,
128.01 (2), 72.49; Ts: 145.59, 132.85,
130.03 (2), 128.08 (2), 21.70
6j
100.42
100.94
61.88
62.45
71.74
70.10
70.86
79.46
76.74
74.92
65.64
66.02
Ts: 145.56, 132.95, 130.05 (2),
127.84
(2), 21.66
6k
6l
99.77
58.92
74.07
75.19
74.16
64.91
2 × Ts: 146.00, 145.70, 132.75,
132.22, 130.29 (2), 130.12 (2), 128.08
(2), 128.05 (2), 21.72 (2)
7a
7b
100.71
98.54
70.93
76.36
61.28
59.29
71.68
71.63
72.96
72.33
64.13
64.18
Bn : 137.19, 128.69 (2), 128.32,
127.73 (2), 71.83
Bn : 137.00, 128.69 (2), 128.36,
127.72 (2), 72.15; Ts: 145.80, 132.54,
130.24 (2), 127.98 (2), 21.67
8a
8b
100.02
99.62
73.83
73.99
61.44
59.24
70.89
77.72
76.01
74.09
65.01
65.02
Bn : 137.19, 128.62 (2), 128.22,
127.88 (2), 71.92
Bn : 136.99, 128.60 (2), 128.24,
127.84 (2), 72.23; Ts: 145.72, 132.89,
130.22 (2), 127.84 (2), 21.70
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Synthesis of Epimino Derivatives
805
OBn
OBn
TsO
N3
(i)
N
H
(i) LiAlH4, THF
SCHEME 2
Th e reaction proceeded at room tem perature an d th e yields of epim in o
derivatives were m ostly in th e n arrow ran ge 58–64% except epim in o deriv-
ative 16 obtain ed in 81% yield. Epim in o derivatives 11, 13 an d 16 were sta-
ble crystallin e com poun ds, wh ile derivatives 9a an d 12a were isolated as
slowly crystallisin g com poun ds wh ich were ch aracterised as th e N-tosyl de-
rivatives 9b an d 12b, respectively. Epim in o derivative 15b was isolated as
un stable syrupy substan ce wh ich , after a few weeks of storin g in a refrigera-
tor at –20 °C con tain ed several products of decom position accordin g to TLC
an d NMR. Epim in e 15b was th erefore ch aracterised as stable crystallin e
N-tosyl derivative 15c. Altern atively, un substituted epim in e 15a was ob-
tain ed as a stable crystallin e com poun d by lith ium alum in um h ydride re-
duction of azido derivative 6b.
O
O
O
O
R2O
BnO
O
O
O
O
NR
NH
BnO
BnO
NR1
NR
10a, R1 = H, R2 = H
10b, R1 = H, R2 = Bn
10c, R1 = Bn, R2 = H
10d, R1 = Bn, R2 = Bn
9a, R = H
9b, R = Ts
11
12a, R = H
12b, R = Ts
O
O
O
O
O
R1O
O
NR2
O
BnO
NH
O
R2N
HN
OR1
OBn
15a, R1 = H, R2 = H
15b, R1 = Bn, R2 = H
15c, R1 = Bn, R2 = Ts
14a, R1 = H, R2 = H
14b, R1 = Bn, R2 = H
14c, R1 = Bn, R2 = Bn
14d, R1 = Bn, R2 = Ns
13
16
Bn, benzyl; Ns, 4-nitrobenzenesulfonyl; Ts, 4-methylbenzenesulfonyl
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

806
Karban, Buděšínský, Černý, Trnka:
Epim in o derivative 10a h as already been prepared15 by isom erisation of
am in o epoxide 5b in 5% aqueous potassium h ydroxide at 90–110 °C. How-
ever, th is reaction is in con ven ien t for th e preparation of epim in e 10a on a
larger scale sin ce th e predom in an t product is am in o sugar 6i form ed by
h ydrolysis of th e oxiran e rin g15. Attem pts to perform isom erisation of 5b
usin g potassium tert-butoxide in dioxan at 100 °C or potassium h ydroxide
in eth an ol at 100 °C failed. Neverth eless, 68% yield of epim in e 10a was ob-
tain ed by lith ium alum in um h ydride reduction of azido epoxide 5c in
tetrah ydrofuran . Th is reaction likely in volves reduction of th e azido group
followed by isom erisation (see Sch em e 3). No products of reductive cleav-
age of th e oxiran e rin g of 5c were foun d in th e reaction m ixture.
O
HO
(i)
N3
(i) LiAlH4, THF
N
H
SCHEME 3
Startin g azido epoxide 5c was prepared by th e followin g reaction se-
quen ce: Dian h ydro derivative5 2b reacted with sodium azide to give azido
diol16 6j wh ose tosylation yielded m on otosylate17 6k togeth er with a sm all
am oun t of ditosylate 6l; m on otosylate 6k provided azido epoxide 5c by th e
action of sodium m eth oxide in m eth an ol–ch loroform . No isom erisation of
dian h ydro derivative 2b to altro-epoxide 4a was observed durin g azidolysis
of 2b, despite th e fact th at com poun d 2b is pron e to isom erise in th e pres-
en ce of n ucleoph iles6. Attem pts to prepare azido epoxide 5c on a larger
scale by azidolysis of 2d followed by th e oxiran e rin g closure at position s
3,4 accordin g to th e procedure described in literature17 failed due to rapid
form ation of com poun d 5c durin g azidolysis an d its furth er reaction with
azide an ion to give diazide17 6m as th e m ain product of azidolysis.
Azido epoxide3b 2c reacted with lith ium alum in um h ydride in a sim ilar
way as azido epoxide 5c an d un substituted epim in e18 14a was obtain ed in
38% yield. Treatm en t of epim in es 10a an d 14a with ben zyl brom ide in th e
presen ce of sodium h ydride in tetrah ydrofuran –N,N-dim eth ylform am ide
gave predom in an tly O-ben zyl derivatives 10b an d 14b . On ly a sm all
am oun t of N,O-diben zyl derivative 14c was isolated as a by-product after
ben zylation of 14a; traces of N-ben zyl derivative 10c an d N,O-diben zyl de-
rivative 10d were detected by TLC in ben zylation of 10b. Prelim in ary ex-
perim en ts revealed th at addition of tetrabutylam m on ium iodide to th e
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Synthesis of Epimino Derivatives
807
reaction m ixture (see e.g. ref.19) sign ifican tly in creased N-ben zylation .
Epim in o derivative 10b is a stable crystallin e com poun d wh ereas isom er 14b
was obtain ed as a syrupy com poun d ch aracterised as N-(4-n itroben zen e-
sulfon yl) derivative 14d .
Th e structure of all epim in o derivatives 9–16 was con firm ed by 1H an d
13C NMR spectra (see Tables IV–VI). Th e presen ce of th e aziridin e rin g is
supported by ch aracteristic upfield sh ifted sign als for >CH–NR proton s
(δ 2.16–2.97 for R = H, δ 1.7–1.8 for R = Bn an d δ 2.98–3.49 for R = Ts or Ns
(4-n itroben zen esulfon yl) – see Table IV) an d also by >CH–NR carbon s
(δ 28.2–35.5 for R = H, δ 36.7–39.6 for R = Bn and δ 33.5–45.7 for R = Ts or Ns –
see Table VI). Vicin al couplin g con stan ts of aziridin e-rin g proton s appear in
th e ran ge 5.0–6.6 Hz if R = H or Bn an d 7.0–7.4 Hz if R = Ts or Ns (Table V)
an d th ey are sign ifican tly h igh er th an th e correspon din g con stan ts in
epoxides (J ≈ 4 Hz, e.g. com poun ds 3b, 4b – for data see Experim en tal).
Con form ation of th e pyran ose rin g is determ in ed by th e aziridin e rin g lead-
in g to flatten ed h alf-ch air con form ation 5HO(D) for 2,3-epim in es an d flat-
ten ed h alf-ch air con form ation 1HO(D) for 3,4-epim in es, repectively (MM2
calculated en ergy m in im ised con form ation s of epim in es 9–16 sh owed vari-
ation s of all pyran ose rin g torsion an gles with in 20°). Th e con figuration at
position 2 an d 4 in th e wh ole series of com poun ds 9–16 is clearly distin -
guish ed by J(1,2) an d J(4,5) couplin gs: sm all values J(1,2) = 0.9–1.3 Hz an d
J(4,5) = 0.8–1.7 Hz in dicate H2β- an d H4β-con figuration s wh ile h igh er val-
ues of J(1,2) = 2.9–4.0 Hz an d J(4,5) = 5.2–6.9 Hz correspon d to H2α- an d
H4α-con figuration . We sh ould still n otice a ch aracteristic differen ce be-
tween J(5,6en ) an d J(5,6ex) values in 2,3-epim in es 9–12 (J(5,6en ) =
1.2–2.2 Hz, J(5,6ex) = 5.4–6.9 Hz) an d 3,4-epim in es 13–16 (J(5,6en ) =
0–0.5 Hz, J(5,6ex) = 4.2–4.6 Hz). Th is observation is in agreem en t with
th eoretically calculated torsion an gles H5/H6en , H5/H6ex for epim in es
with aziridin e rin g 2,3-exo- (ca 114°, –13°), 2,3-endo-position (ca 103°, –23°)
on on e side an d 3,4-exo- (ca 94°, –34°) an d 3,4-endo-position (ca 90°, –37°)
on th e oth er side.
Th e structures of aziridin e derivatives 9a, 10a, 11, 12a, 13, 14a, 15a an d
16 were also proved by X-ray an alysis20. IR spectra of un substituted
epim in es 10a, 14a an d 15a an d O-ben zyl epim in es 9a, 10b, 11, 12a, 13,
14b, 15b an d 16 exh ibit absorption in th e 3 285–3 330 cm –1 region corre-
spon din g to th e valen ce vibration of th e im in o group21
.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

808
Karban, Buděšínský, Černý, Trnka:
TABLE IV
1H NMR ch em ical sh ifts (in ppm , δ-scale) of epim in o derivatives 9a, 9b, 10a, 10b, 11, 12a, 12b, 13,
14a–14d , 15a–15c an d 16 in CDCl3
Com -
poun d
H-1
H-2
H-3
H-4
H-5
H-6en
H-6ex
Oth er proton sa
9a
9b
5.63 bs
5.55 bs
2.16 dd
2.98 dd
2.33 m
3.23 m
3.52 dd
3.48 dd
4.43 m
4.45 m
3.67 ddd 3.88 ddd Bn : 4.86 d, 4.62 d,
7.30–7.42 m (5 H)
3.63 dd
3.88 dd
Bn : 4.57 d, 4.42 d,
7.27–7.34 m (5 H);
Ts: 2.40 s (3 H),
7.91 m (2 H), 7.22 m
(2 H)
10ab
10bc
5.61 um 2.32 dt
2.26 dd
4.29 dt
4.39 m
4.25 m
4.26 ddd 3.81 ddd
5.50 bs
5.80 bd
5.75 d
5.63 d
2.17 dt
2.75 dd
2.81 dd
2.19 ddd 3.85 dt
4.20 ddd 3.68 bdd Bn : 4.63 d, 4.44 d,
7.24–7.33 m ( 5 H)
11b
2.36 dd
2.42 t
3.61 bs
4.19 dd
4.52 m
3.62 dd
3.64 dd
3.45 dd
3.55 dd
Bn : 4.74 d, 4.71 d,
7.29–7.40 m (5 H)
Bn : 4.84 d, 4.62 d,
7.30–7.39 m (5 H)
Bn : 4.60 d, 4.42 d,
7.28–7.34 m (5 H);
Ts: 2.39 s (3 H),
7.88 m (2 H), 7.19 m
(2 H)
12ab
12b
4.39 ddd 4.01 dd
4.38 tm 4.12 dd
3.48 bdd 3.19 bdd 4.02 dd
13
5.24 m
3.53 dd
3.83 dd
2.24 m
2.16 dd
4.67 dm 3.96 dd
3.80 dd
Bn : 4.83 d, 4.60 d,
7.29–7.40 m (5 H)
14ab
14bb
5.30 dd
2.16 ddd 2.38 dt
2.20 bdd 2.33 dt
4.17 dm 4.12 dd
4.67 dm 4.19 dd
3.92 dd
3.92 dd
5.29 bdd 3.59 dd
Bn : 4.75 d, 4.64 d,
7.29–7.39 m (5 H)
2 × Bn: 4.64 d, 4.52 d,
3.62 d, 3.46 d,
7.30–7.40 m (10 H)
Bn : 4.64 d, 4.57 d,
7.32 m (3 H), 7.25 m
(2 H); Ns: 8.11 m (2 H),
8.37 m (2 H)
14c
14d
5.24 t
5.27 t
3.56 d
3.47 d
1.72 dd
3.05 dd
1.80 dd
3.14 dd
4.66 bd
4.65 bd
4.05 d
4.16 d
3.80 dd
3.86 dd
15ab
15b
15c
5.24 t
3.78 bs
3.50 d
2.33 dd
2.30 bd
2.93 dd
2.88 t
4.84 dd
4.82 dd
4.81 dd
4.01 d
4.01 d
3.78 d
3.50 dd
3.44 dd
3.41 dd
Bn : 4.71 d, 4.68 d,
7.27–7.39 m (5 H)
Bn : 4.67 d, 4.59 d,
7.27–7.36 m (5 H);
Ts: 2.47 s (3 H),
7.76 m (2 H), 7.30 m
(2 H)
5.29 t
2.83 bt
3.49 dd
5.26 dd
3.37 bs
16b
5.24 dd
3.69 dd
2.44 ddd 2.97 t
4.81 dd
3.98 d
3.54 dd
Bn : 4.80 d, 4.72 d,
7.28–7.42 m (5 H)
a
b
Sign als of NH an d OH proton s appear as broad sin glets in th e δ ran ge of 0.8–1.7; data obtain ed after
c
addition of 2–3 drops of CD3COOD; data obtain ed after addition of 2–3 drops of CD3COOD + 10%
C6D6.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Synthesis of Epimino Derivatives
809
EXPERIMENTAL
Th e m eltin g poin ts were determ in ed with a Boëtius m eltin g poin t m icroapparatus an d were
n ot corrected. Th e optical rotation s were m easured with a Ben dix–Ericsson ETL-143 A
polarim eter at 21 °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 with a Varian -UNITY-500 apparatus (1H at 500 MHz, 13C at 125.7 MHz) in
CDCl3 solution s at 20 °C. Hom on uclear 2D-COSY spectra were used for th e assign m en t of
proton s. Proton 1D spectra with a selective decouplin g of H-1 allowed to determ in e sm all
lon g-ran ge couplin gs. Th e sign als of proton bearin g carbon s were structurally assign ed from
2D-1H,13C-HMQC spectra. Ch em ical sh ifts are given in ppm (δ-scale), couplin g con stan ts (J)
in Hz. Mass spectra were recorded on a VG-7070E spectrom eter usin g electron ion isation
(70 eV, trap curren t 50 µA, acceleratin g voltage 6 kV, ion source tem perature 150 °C). In fra-
red spectra (waven um bers in cm –1) were recorded on a PE684 in ch loroform solution . In fra-
red spectra of epim in o derivatives were m easured in tetrach lorom eth an e at con cen tration s
lower th an 4.2 · 10–3 m ol dm –3 in order to avoid in term olecular association s. Preparative
TABLE V
1H NMR couplin g con stan ts (Hz) of epim in o derivatives 9a, 9b, 10a, 10b, 11, 12a, 12b, 13, 14a–14d ,
15a–15c, 16 in CDCl3
Com -
J(1,2)
J(2,3)
J(3,4)
J(4,5)
J(5,6en )
J(5,6ex)
J(6en ,6ex)
J(1,3)
J(2,4)
J(3,5)
poun da
9ab
9b
10ac,d
10be,f
11d
1.3
1.1
1.3
1.3
4.0
3.8
3.7
0.9
3.4
5.0
7.0
5.6
6.6
6.0
5.8
7.2
5.5
≈0
5.8
5.7
≈0
0.8
0.8
5.5
5.2
≈1
2.2
2.2
2.1
2.1
1.8
1.2
1.7
0.5
0.5
0.5
≈0
6.8
6.9
6.3
6.3
5.9
5.4
6.1
4.4
4.4
4.3
4.2
4.2
4.4
4.6
4.6
4.3
7.9
8.2
8.2
8.1
7.7
7.7
7.3
7.0
7.3
7.2
7.2
7.7
6.8
6.2
6.6
7.0
0.9
0.6
<0.3
0.6
<1
≈0
≈0
0.9
0.9
≈0
≈0
≈0
≈0
1.0
0.9
≈0
≈0
≈0
≈0
≈0
≈0
1.6
1.2
1.7
1.7
1.4
≈0
≈0
≈0.5
5.0
4.4
5.2
5.6
5.7
6.5
7.1
6.4
6.5
7.4
6.4
12ad
6.9
6.1
1.7
1.6
1.2
1.0
1.3
6.3
6.2
6.1
6.1
≈0
12b
13g
14ad
14bd,h 3.0
<0.5
1.8
2.0
2.0
1.8
1.9
1.6
1.1
1.5
1.0
<1
0.9
0.6
<0.5
≈0
≈0
14c
14d i
15ad
15b
15c
16d
2.9
2.9
0.9
1.2
1.0
3.6
≈0
≈0
≈0
≈0
≈0
≈0
≈0
≈0.6
≈0
≈0
≈0
≈0
≈0
4.8
≈0
≈0
a
Gem in al couplin g of O-ben zyl proton s appears in th e ran ge 11.5–12.3 Hz; J(gem ) of N-ben zyl proton s in
b
c
14c is 13.6 Hz. Addition al couplin g con stan ts: J(1,5) = 0.2, J(1,6en ) = 0.5, J(1,6ex) = 0.4; J(1,5) <0.3,
J(1,6en ) = 0.6, J(1,6ex) <0.3, J(4,6ex) = 0.8; e J(1,5) <0.2, J(1,6ex) <0.3, J(4,6ex) = 0.7; J(1,5) ≈ 0.7, J(1,6ex)
g
h
i
d
f
<0.5; J(1,5) ≈ 0.5; J(1,5) <0.5 Hz; data obtain ed after addition of 2–3 drops of CD3COOD; data ob-
tain ed after addition of 2–3 drops of CD3COOD + 10% C6D6.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

810
Karban, Buděšínský, Černý, Trnka:
TABLE VI
13C NMR ch em ical sh ift (in ppm , δ-scale) of epim in o derivatives 9a, 9b, 10a, 10b, 11, 12a, 12b, 13,
14a–14d , 15a–15c an d 16 in CDCl3
Com -
poun d
C-1
C-2
C-3
C-4
C-5
C-6
Oth er carbon s
9a
9b
97.99
96.29
31.13
36.58
28.16
35.10
71.89
70.78
76.28
75.21
65.44
65.64
Bn : 137.40, 128.52 (2), 127.95 (3), 70.27
Bn : 137.05, 128.39 (2), 128.33 (2), 127.86,
69.90; Ts: 145.07, 134.40, 129.80 (2),
127.81 (2), 21.70
10a
10b
97.75
98.05
30.97
32.96
64.50
73.52
72.24
62.82
63.27
30.74a 30.66a 71.66
Bn : 137.56, 128.55 (2), 128.03, 127.63 (2),
71.49
11
98.53
97.88
95.72
34.51
38.77
45.68
26.96
26.53
35.05
74.50
71.48
69.29
72.02
69.11
69.37
65.80
62.74
63.22
Bn : 137.68, 128.53 (2), 127.92, 127.74 (2),
71.55
12a
12b
Bn : 137.82, 128.52 (2), 127.97, 127.80 (2),
70.43
Bn : 137.22, 128.43 (2), 127.96, 127.82 (2),
70.31; Ts: 144.75, 134.85, 128.71 (2),
127.72 (2), 21.62
13
101.45 71.33
27.23
31.28
69.56
67.15
Bn : 137.52, 128.50 (2), 127.98, 127.95 (2),
70.70
14a
14b
14c
99.44
98.49
98.05
65.64
72.90
73.31
31.32
29.10
36.71
31.32
31.40
39.60
70.30
70.44
70.69
68.87
69.04
68.77
Bn : 137.45, 128.52 (2), 128.01 (3), 71.58
2 × Bn : 138.30, 137.43, 128.44 (2), 128.41
(2), 128.16 (2), 127.95, 127.88 (2), 127.20,
71.40, 62.75
14d
97.94
71.54
38.54
39.34
69.53
68.29
Bn : 136.57, 128.66 (2), 128.37, 128.06 (2),
71.83; Ns: 150.74, 143.70, 129.13 (2),
124.41 (2)
15a
15b
100.85 66.28
29.69
27.52
31.96
32.04
72.31
72.04
65.60
65.06
99.04
73.12
Bn : 137.67, 128.51, 128.48 (2), 127.90 (2),
72.32
15c
16
99.14
71.27
35.57
27.78
40.46
35.46
69.76
72.34
65.51
65.02
Bn : 136.89, 128.59 (2), 128.17, 127.92 (2),
72.49; Ts: 144.99, 134.18, 129.88 (2),
128.00 (2), 21.65
97.07
72.95
Bn : 137.50, 128.43 (2), 128.04 (2), 127.86,
70.88
a
Th e assign m en t of sign als m ay be m utually in terch an ged.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

Synthesis of Epimino Derivatives
811
colum n ch rom atograph y was carried out on Kieselgel 60 (Merck, 60–230 m esh ). Th in layer
ch rom atograph y was carried out on TLC alum in ium sh eets (Merck) with Kieselgel 60 F254
an d layer th ickn ess 0.2 m m . Detection was perform ed by sprayin g with 50% sulfuric acid
an d h eatin g. UV detection was also em ployed wh en appropriate. Preparative th in -layer ch ro-
m atograph y was perform ed on plates 20 × 20 cm with Kieselgel GF254 (Merck). Solven t sys-
tem s used for ch rom atograph y were ben zen e–aceton e 10 : 1 (S1), ch loroform –m eth an ol 10 :
1 (S2), cycloh exan e–aceton e 1 : 1 (S3), un less stated oth erwise. Solution s were dried with an -
h ydrous Na2SO4 an d con cen trated un der reduced pressure an d tem peratures below 50 °C if
n ot stated oth erwise. Th e term “stan dard workup” refers to extractin g with dich loro-
m eth an e, wash in g th e dich lorom eth an e solution with water, dryin g an d con cen tratin g.
Tetrah ydrofuran was dried with LiAlH4. Sodium h ydride dispersion (60% in m in eral oil) an d
98% ben zyl brom ide, both purch ased from Sigm a–Aldrich , Czech Republic, were used for
ben zylation . If n ot stated oth erwise, ice-NaCl was used as an extern al coolin g m ixture
(ca –15 °C). Startin g dian h ydro derivatives 1a (ref.4), 1b (ref.4), 2a (ref.5), 2b (ref.5), 2c
(ref.3b), 2d (ref.6), 3a (ref.7), 4a (ref.8) an d 5a (ref.9) were prepared usin g procedures de-
scribed in literature.
Gen eral Procedure for Tosylation
A solution of startin g com poun d an d tosyl ch loride in pyridin e was allowed to stan d for a
given tim e at room tem perature un less stated oth erwise. Th e reaction m ixture was th en di-
luted with water. Th e am oun ts of reactan ts, th e volum e of pyridin e an d furth er workup are
given for th e in dividual com poun ds.
Gen eral Procedure for Ben zylation
Sodium h ydride dispersion (60% in m in eral oil) was added un der coolin g an d stirrin g to a
solution of startin g com poun d in tetrah ydrofuran –N,N-dim eth ylform am ide an d th e m ixture
was cooled an d stirred for 1–2 h . Tetrabutylam m on ium iodide (except syn th esis of com -
poun d 10b an d 14b) an d ben zyl brom ide was th en added. After addition al stirrin g an d cool-
in g for 1.5–2 h , th e coolin g bath was rem oved an d stirrin g con tin ued overn igh t at room
tem perature. Am oun ts of reactan ts, volum es of solven ts an d furth er workup are given for
in dividual com poun ds.
1,6:2,3-Dian h ydro-4-O-ben zyl-β-D-gulopyran ose (3b)
Sodium h ydride dispersion (2.54 g, 64 m m ol), dian h ydro derivative7 3a (4.61 g, 32 m m ol),
tetrah ydrofuran (80 m l), N,N-dim eth ylform am ide (30 m l), tetrabutylam m on ium iodide (20 m g,
0.05 m m ol), ben zyl brom ide (5.10 m l, 42 m m ol). Accordin g to TLC (S1) two com poun ds
h avin g RF 0.49 (m ajor product 3b) an d RF 0.34 (by-product 5a) were presen t. Th e reaction
m ixture was diluted with water an d n eutralised with 5% HCl. Stan dard workup yielded 3b
(4.70 g; 63%), m .p. 64–65 °C (eth er–petroleum eth er), [α]D –10 (c 0.4, CHCl3). 1H NMR:
7.30–7.39 m (5 H, C6H5); 5.57 bs (1 H, H-1); 4.73 d an d 4.58 d (2 H, CH2 (Bn ), J(gem ) =
11.9); 4.37 m (1 H, H-5, J(5,3) = 2.1, J(5,4) = 5.1, J(5,6en ) = 2.1, J(5,6ex) = 6.2); 4.17 ddd
(1 H, H-6en , J(6en ,1) = 0.5, J(6en ,5) = 2.1, J(6en ,6ex) = 8.1); 3.97 dt (1 H, H-4, J(4,2) = 1.0,
J(4,3) ≈ 0, J(4,5) = 5.1, J(4,6ex) = 0.8); 3.75 ddd (1 H, H-6ex, J(6ex,4) = 0.8, J(6ex,5) = 6.2,
J(6ex,6en ) = 8.1); 3.12 ddd (1 H, H-3, J(3,1) = 0.6, J(3,2) = 3.9, J(3,4) ≈ 0, J(3,5) = 2.1); 3.02 dt
(1 H, H-2, J(2,1) = 1.2, J(2,3) = 3.9, J(2,4) = 1.0). 13C NMR: 137.24, 128.62 (2), 128.20, 127.72
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(2) (C6H5); 97.06 (C-1); 71.98 (C-5); 71.94 (CH2 (Bn )); 70.46 (C-4); 63.52 (C-6); 50.98 (C-3);
48.50 (C-2). For C13H14O4 (234.3) calculated: 66.65% C, 6.02% H; foun d: 66.63% C, 6.12% H.
In prelim in ary experim en ts th e reaction was carried out with 280 m g of th e startin g
dian h ydro derivative 3a . Preparative TLC of th e m oth er liquor on silica gel (15 g) in
ben zen e–cycloh exan e–aceton e (10 : 9 : 1) gave 37 m g (8%) of 1,6:3,4-dian h ydro-4-O-ben zyl-
β-D-galactopyran ose (5a) iden tical with th e auth en tic sam ple9 accordin g to TLC, IR an d m .p.
47–49 °C (auth en tic sam ple m .p. 48–49 °C).
1,6:3,4-Dian h ydro-2-O-ben zyl-β-D-altropyran ose (4b)
Sodium h ydride dispersion (1.03 g, 26 m m ol), dian h ydro derivative8 4a (3.50 g, 24 m m ol),
tetrah ydrofuran (47 m l), N,N-dim eth ylform am ide (35 m l), tetrabutylam m on ium iodide (14 m g,
0.04 m m ol), ben zyl brom ide (3.10 m l, 25.5 m m ol). Th e reaction m ixture was diluted with
water an d n eutralised with 5% HCl. Stan dard workup gave oil residue, wh ich was twice
codistilled with toluen e to yield 4b (3.81 g; 67%), m .p. 80–82 °C (eth er), [α]D –66 (c 0.6,
CHCl3) in agreem en t with th e auth en tic sam ple22 (m .p. 80–81 °C, [α]D –68 (c 1.5, CHCl3)).
1H NMR: 7.29–7.38 m (5 H, C6H5); 5.32 t (1 H, H-1, J(1,2) = 2.8, J(1,3) = 2.4); 4.74 d an d
4.66 d (2 H, CH2 (Bn ), J(gem ) = 12.1); 4.69 m (1 H, H-5, J(5,3) = 0.6, J(5,4) = 1.5, J(5,6en ) =
0.6, J(5,6ex) = 4.3); 4.13 bd (1 H, H-6en , J(6en ,5) = 0.6, J(6en ,6ex) = 7.5); 3.87 dd (1 H,
H-6ex, J(6ex,5) = 4.3, J(6ex,6en ) = 7.5); 3.64 dd (1 H, H-2, J(2,1) = 2.8, J(2,3) ≈ 0, J(2,4) =
1.0); 3.13 dt (1 H, H-4, J(4,2) = 1.0, J(4,3) = 4.0, J(4,5) = 1.5); 3.06 ddd (1 H, H-3, J(3,1) = 2.4,
J(3,2) ≈ 0, J(3,4) = 4.0, J(3,5) = 0.6). 13C NMR: 137.14, 128.59 (2), 128.17, 128.08 (2) (C6H5);
98.21 (C-1); 72.13 (C-2); 72.02 (CH2 (Bn )); 69.97 (C-5); 67.38 (C-6); 50.16 (C-4); 49.66 (C-3).
1,6:3,4-Dian h ydro-2-azido-2-deoxy-β-D-galactopyran ose (5c)
To a solution of azide 6k (1.292 g, 3.79 m m ol) in ch loroform (30 m l) a solution of sodium
(0.27 g, 12 m m ol) in m eth an ol (9 m l) was added dropwise un der coolin g. After 40 m in th e
coolin g bath was rem oved an d th e reaction m ixture was allowed to stan d at room tem pera-
ture for 24 h . Th e reaction m ixture was th en diluted with water. Stan dard workup gave 5c
(388 m g; 61%), m .p. 79–81 °C (eth er–petroleum eth er), [α]D –87 (c 0.4, CHCl3), iden tical
with th e auth en tic com poun d 5c prepared accordin g to literature17a (ref.17a gives m .p.
76.5–78 °C, [α]D –93 (c 2, CHCl3)).
Gen eral Procedure for Preparation of Azido Derivatives 6a–6d , 7a an d 8a
Dian h ydro derivatives 1a, 1b, 2a, 3b, 4b an d 5a, sodium azide an d am m on ium ch loride
were h eated in a m ixture of 2-m eth oxyeth an ol an d water at 110–120 °C for a given tim e.
Th e reaction was m on itored by TLC (S1). After coolin g to room tem perature th e reaction
m ixture was con cen trated alm ost to dryn ess. Th e residue was diluted with water, extracted
with dich lorom eth an e, th e extract was wash ed with water, dried, decolorised with ch arcoal
an d con cen trated. Furth er workup is described for in dividual com poun ds. For th e workup of
6a see ref.11. For NMR data of azido derivatives see Tables I–III.
1,6-An h ydro-3-azido-4-O-ben zyl-3-deoxy-β-D-glucopyran ose (6a)
Preparation of th e title com poun d from 1a is described in ref.11, m .p. 74–76 °C (eth an ol–
water), [α]D –15 (c 0.6, CHCl3); ref.11 gives m .p. 74–76.5 °C, [α]D –13 (c 2.6, CHCl3).
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Synthesis of Epimino Derivatives
813
1,6-An h ydro-3-azido-3-deoxy-4-O-tosyl-β-D-glucopyran ose (6b)
Dian h ydro derivative4 1b (5.60 g, 18.8 m m ol), sodium azide (5.0 g, 77 m m ol), am m on ium
ch loride (6.0 g, 112 m m ol), 2-m eth oxyeth an ol (80 m l) an d water (20 m l) were h eated at
110–120 °C for 30 h . Th e reaction m ixture was worked up as described in Gen eral procedure
to give 6b (3.96 g; 62%), m .p. 85–91 °C (eth an ol–water) with traces of a polar com poun d ac-
cordin g to TLC (S1), but pure en ough to be used for furth er reaction s. Preparative TLC of
70 m g of th e product 6b on silica gel (10 g) in S1 afforded 46 m g of pure 6b, m .p. 93–95 °C
(eth an ol–water), [α]D –27 (c 0.7, CHCl3). IR: 3 562 (OH); 2 111 (N3); 1 375, 1 177 (SO2). For
C
13H15N3O6S (341.3) calculated: 45.74% C, 4.43% H, 12.31% N, 9.39% S; foun d: 46.08% C,
4.45% H, 12.63% N, 9.69% S.
1,6-An h ydro-2-azido-4-O-ben zyl-2-deoxy-β-D-glucopyran ose (6c)
Dian h ydro derivative5 2a (4.000 g, 17.1 m m ol), sodium azide (4.0 g, 61.5 m m ol), am m o-
n ium ch loride (4.0 g, 75 m m ol), 2-m eth oxyeth an ol (40 m l) an d water (20 m l) were h eated
at 110–120 °C for 30 h . Th e reaction m ixture was worked up as described in Gen eral proce-
dure to give 6c (3.361 g; 71%), m .p. 102–105 °C (m eth an ol–water), [α]D –7 (c 0.4, CHCl3);
ref.12 gives m .p. 101–103 °C, [α]D –7 (EtOH).
1,6-An h ydro-4-azido-2-O-ben zyl-4-deoxy-β-D-glucopyran ose (6d )
Dian h ydro derivative9 5a (790 m g, 3.37 m m ol), sodium azide (0.8 g, 12.3 m m ol), am m o-
n ium ch loride (1.4 g, 26 m m ol), 2-m eth oxyeth an ol (15 m l) an d water (5 m l) were h eated at
110–120 °C for 25 h . Th e reaction m ixture was worked up as described in Gen eral procedure
to give 6d (676 m g; 72%), m .p. 76–78 °C (eth er–petroleum eth er), [α]D –82 (c 0.4, CHCl3);
ref.13 gives [α]D –71 (c 1.0, CHCl3), m .p. n ot given .
1,6-An h ydro-3-azido-4-O-ben zyl-3-deoxy-β-D-galactopyran ose (7a)
Dian h ydro derivative 3b (3.800 g, 16.2 m m ol), sodium azide (3.8 g, 58.4 m m ol), am m on ium
ch loride (4.8 g, 90 m m ol), 2-m eth oxyeth an ol (105 m l) an d water (30 m l) were h eated at
110–120 °C. Every 25 h , am m on ium ch loride (0.5 g, 9 m m ol) an d sodium azide (0.5 g,
8 m m ol) were added in to th e reaction m ixture. After 210 h th e reaction was stopped. Th e
reaction m ixture was worked up as described in Gen eral procedure. Ch rom atograph y of oil
residue (4.4 g) on silica gel (200 g) in toluen e–aceton e (50 : 1) gave un reacted 3b (774 m g;
20%). Elution with toluen e–aceton e (5 : 1) gave syrupy 7a (3.392 g; 75%), [α]D –22 (c 0.5,
CHCl3). IR: 3 569 (OH); 2 111 (N3).
1,6-An h ydro-3-azido-2-O-ben zyl-3-deoxy-β-D-m an n opyran ose (8a)
Dian h ydro derivative 4b (3.015 g, 12.9 m m ol), sodium azide (4.0 g, 61.5 m m ol), am m on ium
ch loride (9.0 g, 168 m m ol), 2-m eth oxyeth an ol (65 m l) an d water (35 m l) were h eated at
110–120 °C. Every 25 h , am m on ium ch loride (0.5 g, 9 m m ol) an d sodium azide (0.5 g,
8 m m ol) were added in to th e reaction m ixture. After 150 h th e startin g com poun d 4a h ad
disappeared (TLC). Th e reaction m ixture was worked up as described in Gen eral procedure
to give syrupy 8a (3.076 g; 86%), [α]D –62 (c 0.6, CHCl3). IR: 3 571 (OH); 2 113 (N3).
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814
Karban, Buděšínský, Černý, Trnka:
1,6-An h ydro-2-azido-4-O-ben zyl-2-deoxy-3-O-tosyl-β-D-glucopyran ose (6f)
Azido derivative 6c (1.000 g, 3.6 m m ol), tosyl ch loride (3.5 g, 18.4 m m ol) an d pyridin e
(12 m l) were h eated at 80 °C. Com poun d 6c disappeared after 10 h accordin g to TLC (S1).
Th e reaction m ixture was poured in to water, th e separated product was filtered off an d dis-
solved in aceton e. Th e aceton e solution was decolorised with ch arcoal an d con cen trated to
yield 6f (1.35 g; 87%), m .p. 101–102.5 °C (m eth an ol), [α]D +121 (c 0.5, CHCl3). IR: 2 108
(N3); 1 374, 1 178 (SO2). For C20H21N3O6S (431.5) calculated: 55.67% C, 4.91% H, 9.74% N,
7.43% S; foun d: 55.67% C, 4.82% H, 9.35% N, 7.31% S.
1,6-An h ydro-4-azido-2-O-ben zyl-4-deoxy-3-O-tosyl-β-D-glucopyran ose (6g)
Azido derivative 6d (637 m g, 2.3 m m ol), tosyl ch loride (3.2 g, 16.8 m m ol) an d pyridin e
(12 m l) were h eated at 100 °C. Startin g 6d h ad disappeared after 6 h accordin g to TLC (S1).
Stan dard workup (th e dich lorom eth an e solution was decolorised with ch arcoal) gave 6g
(844 m g; 85%), m .p. 85.5–87 °C (m eth an ol–water), [α]D –117 (c 0.5, CHCl3). IR: 2 106 (N3);
1 374, 1 177 (SO2). For C20H21N3O6S (431.5) calculated: 55.67% C, 4.91% H, 9.74% N,
7.43% S; foun d 55.78% C, 4.89% H, 9.32% N, 7.41% S.
1,6-An h ydro-3-azido-2-O-ben zyl-3-deoxy-4-O-tosyl-β-D-glucopyran ose (6h )
Sodium h ydride dispersion (130 m g, 3.25 m m ol), azido tosylate 6b (500 m g, 1.46 m m ol),
tetrah ydrofuran (11 m l), tetrabutylam m on ium iodide (10 m g, 0.03 m m ol), ben zyl brom ide
(300 µl, 2.52 m m ol). Th e un reacted sodium h ydride was decom posed by addition of eth a-
n ol. Th e reaction m ixture was diluted with water. Stan dard workup gave 6h (438 m g; 69%),
m .p. 73–75 °C (eth er–petroleum eth er), [α]D –117 (c 0.6, CHCl3). IR: 2 113 (N3); 1 370, 1 177
(SO2). For C20H21N3O6S (431.5) calculated: 55.67% C, 4.91% H, 9.74% N, 7.43% S; foun d:
55.74% C, 4.84% H, 9.86% N, 7.39% S.
1,6-An h ydro-2-azido-2-deoxy-4-O-tosyl-β-D-glucopyran ose (6k)
an d 1,6-An h ydro-2-azido-2-deoxy-3,4-di-O-tosyl-β-D-glucopyran ose (6l)
Azide16 6j (963 m g, 5.14 m m ol), tosyl ch loride (1.0 g, 5.24 m m ol) an d pyridin e (15 m l) were
allowed to stan d for 5 days. Accordin g to TLC (S1) th e reaction m ixture con tain ed sm all
am oun t of startin g 6j an d two products: RF 0.35 (m ajor product 6k) an d RF 0.72 (by-product
6l). Stan dard workup followed by ch rom atograph y on silica gel (30 g) in ben zen e–aceton e
(20 : 1) gave th e followin g products (in order).
1,6-Anhydro-2-azido-2-deoxy-3,4-di-O-tosyl-β-D-glucopyranose (6l) (231 m g; 9%), m .p.
148–150 °C (eth an ol–aceton e), [α]D +43 (c 0.6, CHCl3). IR: 2 107 (N3); 1 376, 1 177 (SO2).
For C20H21N3O8S2 (495.5) calculated: 48.47% C, 4.27% H, 8.48% N, 12.94% S; foun d:
48.58% C, 4.34% H, 7.94% N, 12.61% S.
1,6-Anhydro-2-azido-2-deoxy-4-O-tosyl-β-D-glucopyranose17 (6k) (1.389 g; 79%), syrup, [α]D
–22 (c 0.8, CHCl3). IR: 3 605 (OH); 2 109 (N3); 1 371, 1 177 (SO2).
1,6-An h ydro-3-azido-4-O-ben zyl-3-deoxy-2-O-tosyl-β-D-galactopyran ose (7b)
Azide 7a (3.33 g, 12.0 m m ol), tosyl ch loride (4.50 g, 23.6 m m ol) an d pyridin e (58 m l) were
allowed to stan d for 42 h . Stan dard workup yielded 7b (4.42 g; 85%), m .p. 77–82 °C
(eth er–petroleum eth er), [α]D –79 (c 0.5, CHCl3). IR: 2 113 (N3); 1 373, 1 178 (SO2). For
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Synthesis of Epimino Derivatives
815
C20H21N3O6S (431.5) calculated: 55.67% C, 4.91% H, 9.74% N, 7.43% S; foun d: 55.70% C,
5.14% H, 9.55% N, 7.15% S.
1,6-An h ydro-3-azido-2-O-ben zyl-3-deoxy-4-O-tosyl-β-D-m an n opyran ose (8b)
Azide 8a (500 m g, 1.80 m m ol), tosyl ch loride (1.9 g, 10.0 m m ol) an d pyridin e (9 m l) were
allowed to stan d for 18 h . Stan dard workup yielded 8b (619 m g; 80%), m .p. 79–81 °C
(eth er–petroleum eth er), [α]D –13 (c 0.5, CHCl3). IR: 2 121 (N3); 1 371, 1 177 (SO2). For
C
20H21N3O6S (431.5) calculated: 55.67% C, 4.91% H, 9.74% N, 7.43% S; foun d: 55.63% C,
4.94% H, 9.62% N, 7.29% S.
Gen eral Procedure for Preparation of Epim in o Derivatives 9a, 10a, 11, 12a, 13, 14a, 15a,
15b an d 16
A solution of startin g azido tosylate or azido epoxide in tetrah ydrofuran was added dropwise
to a suspen sion of lith ium alum in um h ydride in tetrah ydrofuran un der coolin g an d stirrin g.
Th e coolin g bath was rem oved after given tim e an d th e reaction m ixture was allowed to
stan d at room tem perature overn igh t un til stated oth erwise. Th e am oun t of startin g com -
poun d, lith ium alum in um h ydride, th e volum e of tetrah ydrofuran an d th e tim e of coolin g
are given for th e in dividual com poun ds. Th e reaction was m on itored by TLC in S1 an d S3.
Un reacted lith ium alum in um h ydride was decom posed by dropwise addition of m oist eth er;
0.5–2 m l of eth an ol was added to com plete th e decom position . Th e precipitate was rem oved
eith er by filtration th rough a sh ort colum n of silica gel (3 g), by cen trifugation or by
decan tation . Com bin ed filtrates or supern atan ts were con cen trated. Details of th e workup
are given for th e in dividual com poun ds.
1,6-An h ydro-4-O-ben zyl-2,3-dideoxy-2,3-epim in o-β-D-allopyran ose (9a)
Azido tosylate 6f (700 m g, 1.62 m m ol) in tetrah ydrofuran (3 m l); lith ium alum in um h ydride
(246 m g, 6.48 m m ol) in tetrah ydrofuran (29 m l). Th e coolin g bath was rem oved after 2 h .
After decom position of th e un reacted lith ium alum in um h ydride, th e reaction m ixture was
filtered th rough a sh ort colum n of silica gel an d th e colum n was wash ed with eth er an d
eth yl acetate. Ch rom atograph y on silica gel (30 g) in toluen e–propan -2-ol (10 : 1) gave 330 m g
of 9a with traces of im purities accordin g to TLC. Th e product was dissolved in eth an ol an d
th e solution was decolorised with ch arcoal an d con cen trated. Ch rom atograph y on silica gel
(30 g) in eth yl acetate gave 9a (224 m g; 59%), m .p. 50–56 °C (eth er), [α]D +139 (c 0.6,
CHCl3). IR: 3 301, 3 285 (NH).
1,6-An h ydro-2,3-dideoxy-2,3-epim in o-β-D-gulopyran ose (10a)
Azido epoxide 5c (531 m g, 3.14 m m ol) in tetrah ydrofuran (2 m l); lith ium alum in um h y-
dride (265 m g, 6.98 m m ol) in tetrah ydrofuran (30 m l). Th e coolin g bath (ice-water) was re-
m oved after 20 m in . After decom position of un reacted lith ium alum in um h ydride th e
precipitate was separated by decan tation , wash ed twice with tetrah ydrofuran an d th en ap-
plied on a sh ort colum n of silica gel an d wash ed with eth yl acetate–eth an ol (10 : 1). Ch ro-
m atograph y on silica gel (50 g) in aceton e gave 10a (305 m g; 68%), m .p. 146–148 °C
(m eth an ol–eth er, at 90–100 °C crystals ch an ged sh ape an d tran sparen cy), [α]D +23 (c 0.5,
H2O); ref.15 gives m .p. 143–145 °C, [α]D +27 (c 0.45, H2O). IR: 3 636 (OH); 3 321, 3 293 (NH).
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Karban, Buděšínský, Černý, Trnka:
1,6-An h ydro-4-O-ben zyl-2,3-dideoxy-2,3-epim in o-β-D-m an n opyran ose (11)
Azido tosylate11 6e (700 m g, 1.62 m m ol) in tetrah ydrofuran (3 m l); lith ium alum in um h y-
dride (246 m g, 6.48 m m ol) in tetrah ydrofuran (29 m l). Th e coolin g bath was rem oved after
2 h . After decom position of un reacted lith ium alum in um h ydride th e reaction m ixture was
filtered th rough a sh ort colum n of silica gel an d th e colum n was wash ed with dich loro-
m eth an e. Con cen tration gave 11 (227 m g; 60%), m .p. 99–100.5 °C (aceton e–eth er), [α]D –45
(c 0.5, CHCl3). Th e product was iden tical with th e auth en tic sam ple11 (m .p. 98–99 °C, [α]D –45
(c 0.8, CHCl3)).
1,6-An h ydro-4-O-ben zyl-2,3-dideoxy-2,3-epim in o-β-D-talopyran ose (12a)
Azido tosylate 7b (700 m g, 1.62 m m ol) in tetrah ydrofuran (3 m l); lith ium alum in um h y-
dride (246 m g, 6.48 m m ol) in tetrah ydrofuran (29 m l). Th e coolin g bath was rem oved after
2 h . After decom position of un reacted lith ium alum in um h ydride th e reaction m ixture was
filtered th rough a sh ort colum n of silica gel, th e colum n was wash ed with eth er an d eth yl
acetate. Ch rom atograph y on silica gel (30 g) in toluen e–aceton e (2 : 1) gave 12a (235 m g;
62%), m .p. 45–50 °C (eth er), [α]D –138 (c 0.5, CHCl3). IR: 3 322, 3 309 (NH).
1,6-An h ydro-2-O-ben zyl-3,4-dideoxy-3,4-epim in o-β-D-allopyran ose (13)
Azido tosylate 6g (600 m g, 1.39 m m ol) in tetrah ydrofuran (3 m l); lith ium alum in um h y-
dride (120 m g, 3.16 m m ol) in tetrah ydrofuran (18 m l). Th e coolin g bath was rem oved after
3 h an d th e reaction m ixture was allowed to stan d at room tem perature overn igh t. Accord-
in g to TLC (S3) th e reaction m ixture con tain ed in addition to product 13 (RF 0.20) an oth er
com poun d (RF 0.32). Th erefore, lith ium alum in um h ydride (18 m g, 0.47 m m ol) was added
an d th e reaction m ixture was h eated at 45–50 °C for 3 h an d th en allowed to stan d at room
tem perature for 3 days. On ly epim in e 13 was presen t (TLC). After decom position of
un reacted lith ium alum in um h ydride th e precipitate was separated by cen trifugation an d
wash ed with tetrah ydrofuran an d eth er–aceton e (4 : 1). Com bin ed supern atan ts were filtered
th rough celite, con cen trated to 2 m l an d diluted with dich lorom eth an e. Dich lorom eth an e
solu tion was wash ed with water, d ried , d ecolorised with ch arcoal an d con cen trated .
Ch rom atograph y on silica gel (35 g) in S3 gave 13 (208 m g; 64%), m .p. 63–65 °C (eth er–
petroleum eth er), [α]D –178 (c 0.6, CHCl3). IR: 3 302, 3 288 (NH). For C13H15NO3 (233.3)
calculated: 66.93% C, 6.48% H, 6.01% N; foun d: 67.22% C, 6.65% H, 6.15% N.
1,6-An h ydro-3,4-dideoxy-3,4-epim in o-β-D-altropyran ose (14a)
Azido tosylate3b 2c (700 m g, 4.14 m m ol) in tetrah ydrofuran (3 m l); lith ium alum in um
h ydride 350 m g (9.22 m m ol) in tetrah ydrofuran (36 m l). Th e coolin g bath was rem oved af-
ter 1 h . After decom position of un reacted lith ium alum in um h ydride th e precipitate was
separated by decan tation , wash ed twice with tetrah ydrofuran an d com bin ed supern atan ts
were filtered th rough celite an d con cen trated to yield 14a (222 m g; 38%), m .p. 146–148 °C
(m eth an ol–eth er), [α]D –119 (c 0.6, H2O), iden tical with th e auth en tic sam ple18 (m .p.
147–148 °C, [α]D –119 (c 0.6, H2O)). IR: 3 568 (OH); 3 326, 3 295 (NH).
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Synthesis of Epimino Derivatives
817
1,6-An h ydro-3,4-dideoxy-3,4-epim in o-β-D-galactopyran ose (15a)
Azido tosylate 6b (600 m g, 1.76 m m ol) in tetrah ydrofuran (3 m l); lith ium alum in um h y-
dride (240 m g, 6.32 m m ol) in tetrah ydrofuran (20 m l). Th e coolin g bath was rem oved after
2 h . After decom position of un reacted lith ium alum in um h ydride th e precipitate was sepa-
rated by cen trifugation an d wash ed with tetrah ydrofuran –aceton (1 : 1), eth er–aceton (1 : 1)
an d aceton . Com bin ed supern atan ts were filtered th rough celite. Ch rom atograph y on silica
gel (50 g) in eth yl acetate–aceton e (2 : 1) gave 15a (140 m g; 56%), m .p. 115–118 °C (eth a-
n ol–eth er), [α]D –67 (c 0.5, H2O). IR: 3 629, 3 585 (OH); 3 327 (NH). For C6H9NO3 (143.1)
calculated: 50.34% C, 6.34% H, 9.79% N; foun d: 50.07% C, 6.27% H, 9.81% N.
1,6-An h ydro-2-O-ben zyl-3,4-dideoxy-3,4-epim in o-β-D-galactopyran ose (15b)
Azido tosylate 6h (230 m g, 0.53 m m ol) in tetrah ydrofuran (2 m l); lith ium alum in um
h ydride (80 m g, 2.11 m m ol) in tetrah ydrofuran (8 m l). Th e coolin g bath was rem oved af-
ter 2.5 h an d th e reaction m ixture was allowed to stan d at room tem perature for 4 h an d
th en at 4 °C for 18 h . Un reacted lith ium alum in um h ydride was decom posed un der coolin g
(ice-water). Th e precipitate was separated by cen trifugation an d wash ed twice with
tetrah ydrofuran . Com bin ed supern atan ts were con cen trated at room tem perature to 20 m l
an d diluted with excess of dich lorom eth an e. Dich lorom eth an e solution was wash ed with
water, dried, decolorised with ch arcoal an d con cen trated at room tem perature. Preparative
TLC on silica gel (20 g) in eth yl acetate–aceton e (5 : 1) gave syrupy 15b (72 m g; 58%), on ly
on e product was presen t accordin g to TLC (S3 an d eth yl acetate–aceton e (4 : 1)). After a few
weeks of storin g at –20 °C at least five products of decom position were detected by TLC (S3)
in addition to epim in e 15b. IR: 3 325 (NH). EI MS, m/z (rel.%): 233 (0.05, M• +), 204 (11.38,
C
12H14NO2), 190 (0.84), 158 (8.29, C11H12N), 142 (19.87, C6H8NO3), 96 (59.70, C5H6NO),
91 (100.00, C7H7).
1,6-An h ydro-2-O-ben zyl-3,4-dideoxy-3,4-epim in o-β-D-talopyran ose (16)
Azido tosylate 8b (700 m g, 1.62 m m ol) in tetrah ydrofuran (3 m l); lith ium alum in um h y-
dride (246 m g, 6.48 m m ol) in tetrah ydrofuran (29 m l). Th e coolin g bath was rem oved after
2 h . After decom position of un reacted lith ium alum in um h ydride th e reaction m ixture was
filtered th rough a sh ort colum n of silica gel, th e colum n was wash ed with eth er an d eth yl
acetate an d com bin ed filtrates con cen trated to yield 16 (306 m g; 81%); m .p. 164–166 °C
(eth er, 150 °C sublim ation ), [α]D +15 (c 0.5, CHCl3). IR: 3 322, 3 309 (NH). For C13H15NO3
(233.3) calculated: 66.93% C, 6.48% H, 6.01% N; foun d: 66.87% C, 6.47% H, 5.86% N.
1,6-An h ydro-4-O-ben zyl-2,3-dideoxy-2,3-(tosylepim in o)-β-D-allopyran ose (9b)
Epim in e 9a (40 m g, 0.17 m m ol), tosyl ch loride (77 m g, 0.40 m m ol) an d pyridin e (0.4 m l)
were allowed to stan d overn igh t. Th e precipitated 9b was filtered off to give 44 m g (67%),
m .p. 204–206 °C (aceton e–eth er), [α]D +130 (c 0.4, CHCl3). IR: 1 332, 1 162 (SO2). For
C
20H21NO5S (387.5) calculated: 62.00% C, 5.46% H, 3.62% N; foun d: 61.92% C, 5.44% H,
3.52% N.
Collect. Czech. Chem. Commun. (Vol. 66) (2001)

818
Karban, Buděšínský, Černý, Trnka:
1,6-An h ydro-4-O-ben zyl-2,3-dideoxy-2,3-epim in o-β-D-gulopyran ose (10b)
Sodium h ydride dispersion (36 m g, 0.90 m m ol), epim in e 10a (120 m g, 0.84 m m ol), tetra-
h ydrofuran (2 m l), N,N-dim eth ylform am ide (1.2 m l), ben zyl brom ide (100 µl, 0.82 mmol). Th e
reaction m ixture con tain ed accordin g to TLC (S3) com poun d with RF 0.28 (m ain product)
an d traces of two com poun ds with RF 0.39 an d 0.61. Th e reaction m ixture was diluted with
water. Stan dard workup followed by ch rom atograph y on silica gel (30 g) in eth yl acetate–
aceton e (4 : 1) gave 10b (65 m g; 33%), m .p. 81–83 °C (eth er–petroleum eth er), [α]D –5 (c 0.5,
CHCl3). IR: 3 323, 3 289 (NH). For C13H15NO3 (233.3) calculated: 66.93% C, 6.48% H, 6.01%
N; foun d: 66.74% C, 6.42% H, 5.92% N.
1,6-An h ydro-4-O-ben zyl-2,3-dideoxy-2,3-(tosylepim in o)-β-D-talopyran ose (12b)
Epim in e 12a (40 m g, 0.17 m m ol), tosyl ch loride (120 m g, 0.63 m m ol) an d pyridin e (1 m l)
were left to stan d overn igh t. Th e precipitated product was filtered off, dissolved in
dich lorom eth an e, decolorised with ch arcoal an d con cen trated. Preparative TLC on silica
gel (10 g) in toluene–acetone (15 : 1) gave 12b (39 m g; 59%), m .p. 192–193.5 °C (acetone–eth er),
[α]D –132 (c 0.5, CHCl3). IR: 1 329, 1 161 (SO2). For C20H21NO5S (387.5) calculated: 62.00% C,
5.46% H, 3.62% N, 8.28% S; foun d: 61.90% C, 5.50% H, 3.48% N, 8.09% S.
1,6-An h ydro-2-O-ben zyl-3,4-dideoxy-3,4-epim in o-β-D-altropyran ose (14b)
Sodium h ydride dispersion (60 m g, 1.50 m m ol), epim in e 14a (200 m g, 1.40 m m ol),
tetrah ydrofuran (2.5 m l), N,N-dim eth ylform am ide (3.5 m l), ben zyl brom ide (173 µl,
1.43 m m ol). Th e reaction m ixture was diluted with eth an ol, con cen trated an d th e residue
was codistilled twice with toluen e. Stan dard workup followed by ch rom atograph y on silica
gel (40 g) in eth yl acetate–aceton e (2 : 1) gave th e followin g com poun ds (in order).
A) Syrupy N,O-diben zyl derivative 14c (48 m g; 11%);
B) Syrupy epim in o derivative 14b (160 m g; 49%). IR: 3 326, 3 294 (NH).
1,6-An h ydro-2-O-ben zyl-3,4-dideoxy-3,4-[(4-n itroben zen esulfon yl)epim in o]-
β-D-altropyran ose (14d )
Epim in e 14b (50 m g, 0.21 m m ol) an d 4-n itroben zen esulfon yl ch loride (100 m g, 0.45 m m ol)
in pyridin e (2 m l) were allowed to stan d overn igh t. Th e reaction m ixture was th en diluted
with water, th e precipitated product was separated an d dissolved in aceton e. Th e aceton e so-
lution was decolorised with ch arcoal, filtered th rough a sh ort colum n of celite an d con cen -
trated to give 14d (59 m g; 66%), m .p. 139–141 °C (eth er), [α]D –51 (c 0.6, CHCl3). IR: 1 537
(NO2); 1 167 (SO2). For C19H18N2O7S (418.4) calculated: 54.54% C, 4.34% H, 6.67% N,
7.66% S; foun d: 54.59% C, 4.27% H, 6.65% N, 7.70% S.
1,6-An h ydro-2-O-ben zyl-3,4-dideoxy-3,4-(tosylepim in o)-β-D-galactopyran ose (15c)
Epim in e 15b (56 m g, 0.24 m m ol), tosyl ch loride (150 m g, 0.79 m m ol) an d pyridin e (1.5 m l)
were left to stan d overn igh t. Th e reaction m ixture was worked up as described for 14d to
give 15c (55 m g; 59%), m .p. 152–152.5 °C (eth er–petroleum eth er), [α]D –6 (c 0.6, CHCl3).
IR: 1 332, 1 163 (SO2). For C20H21NO5S (387.5) calculated: 62.00% C, 5.46% H, 3.62% N,
8.28% S; foun d: 61.78% C, 5.47% H, 3.70% N, 8.04% S.
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Synthesis of Epimino Derivatives
819
This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic
(grant No. VS96140).
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