Synthesis of some 1,4-oxazepanes fused with 1,6-anhydro-β-D- hexopyranoses. 3,11,43-Trioxa-7-azatricyclo[8.2.1.02,8]-tridecane derivatives

Article abstract of DOI:10.1135/cccc20041818

Some 1,4-oxazepanes based on 1,6-anhydro-β-D-hexopyranoses were prepared from 1,6:3,4-dianhydro-2-O-tosyl-β-D-galactopyranose (1). Cleavage of its oxirane ring with 3-chloropropanol gave 1,6-anhydro-4-O-(3-chloropropyl) -2-O-tosyl-β-D-glucopyranose (2), w

Full text of DOI:10.1135/cccc20041818

1818
Trtek, Černý, Trnka, Buděšínský, Císařová:
SYNTHESIS OF SOME 1,4-OXAZEPANES FUSED WITH 1,6-ANHYDRO-
β-D-HEXOPYRANOSES. 3,11,13-TRIOXA-7-AZATRICYCLO[8.2.1.02,8]-
TRIDECANE DERIVATIVES
b,
Tomáš TRTEK1a, Miloslav ČERNÝ2a, Tomáš TRNKA3a, Miloš BUDĚŠÍNSKÝ * and
c
Ivana CÍSAŘOVÁ
a
Department of Organic Chemistry, Charles University, Hlavova 2030, 128 40 Prague 2,
1
2
3
Czech Republic; e-mail: tomastrtek@email.cz, mila@natur.cuni.cz, trnka@natur.cuni.cz
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
Flemingovo nám. 2, 166 10 Prague 6, Czech Republic; e-mail: budesinsky@uochb.cas.cz
Department of Inorganic Chemistry, Charles University, Hlavova 2030, 128 40 Prague 2,
Czech Republic; e-mail: cisarova@natur.cuni.cz
b
c
Received May 3, 2004
Accepted Jun e 12, 2004
The other authors (T. T., T. T., M. B. and I. C.) wish to dedicate this paper to Professor Miloslav
Černý on the occasion of his 75th birthday.
Som e 1,4-oxazepan es based on 1,6-an h ydro-β-D-h exopyran oses were prepared from 1,6:3,4-
dian h ydro-2-O-tosyl-β-D-galactopyran ose (1). Cleavage of its oxiran e rin g with 3-ch loro-
propan ol gave 1,6-an h ydro-4-O-(3-ch loropropyl)-2-O-tosyl-β-D-glucopyran ose (2), wh ich was
con verted in th ree steps in to 4-O-(3-am in opropyl)-1,6:2,3-dian h ydro-β-D-m an n opyran ose (5).
Th e latter com poun d un derwen t in tram olecular cyclization to afford 3-am in o-1,6-an h ydro-
3-deoxy-3-N,4-O-(propan e-1,3-diyl)-β-D-altropyran ose (6) th at gave th e correspon din g qua-
tern ary am m on ium salt 10 by N-m eth ylation . Acid cleavage of th e 1,6-an h ydro bon d in 7
gave th e D-altrose derivative 3-acetam ido-3-deoxy-3-N,4-O-(propan e-1,3-diyl)-β-D-altro-
pyran ose (11).
Keyw ord s: Carboh ydrates; Heterocycles; 1,6-An h ydrosugars; 1,4-Oxazepan es; Am in o sugars;
Oxiran es; Epoxides; Cyclization s; X-ray diffraction ; NMR spectroscopy.
Nitrogen -con tain in g h eterocyclic com poun ds fused with th e pyran rin g of
carboh ydrates in n on -an om eric position h ave been studied to a lim ited ex-
ten t, irrespective of th eir poten tial biological activity1,2. In con n ection with
our previous paper on 1,6-an h ydro-β-D-h exopyran oses fused with m orph o-
lin e3, we focused h erein on th e syn th esis of an alogous h eterocycles based
on 1,4-oxazepan e rin g.
1,6:3,4-Dian h ydro-2-O-tosyl-β-D-galactopyran ose4 (1), wh ich is readily ac-
cessible from 1,6-an h ydro-β-D-glucopyran ose in two sim ple steps, was
Collect. Czech. Chem. Commun. (Vol. 69) (2004)
doi:10.1135/cccc20041818

3,11,13-Trioxa-7-azatricyclo[8.2.1.02,8]tridecane Derivatives
1819
a suitable startin g com poun d in th e syn th esis of com poun d 6 (Sch em e 1).
Th e oxiran e rin g of 1 was cleaved with 3-ch loropropan ol un der catalysis
with boron trifluoride in refluxin g dich lorom eth an e to give 3-ch loropropyl
derivative 2 in 92% yield. Th is reaction proceeds with h igh regioselectivity
un der sim ilar con dition s as with oth er n ucleoph iles5,6. After acetylation of
2 an d subsequen t treatm en t of th e resultin g acetate 3 with sodium azide in
N,N-dim eth ylform am ide, 3-azidopropyl derivative 4 was form ed. Th e latter
was reduced with h ydrogen over palladium catalyst an d th e am in o deriva-
tive th us obtain ed was con verted in to epoxide 5 by th e action of m eth an -
olic sodium m eth oxide at room tem perature. Base-catalyzed (DBU) in tra-
m olecular open in g of th e epoxide rin g in 5 by th e am in o group resulted in
th e form ation of 3-am in o-1,6-an h ydro-3-deoxy-3-N,4-O-(propan e-1,3-diyl)-
β-D-altropyran ose (6) in 72% yield. In spite of th e fact th at th is five-step
syn th esis of 6 was n ot optim ized it was effected in overall 48% yield.
O
O
OR
O
(i)
O
O
X
O
OTs
OTs
1
2, R = H, X = Cl
3, R = Ac, X = Cl
4, R = Ac, X = N3
(ii)
(iii)
(iv)
O
O
O
(v)
O
O
OH
NH
O
H2N
O
5
6
(i) Cl(CH2)3OH, BF3·Et2O, CH2Cl2, 40 oC; (ii) Ac2O, pyridine, r.t.; (iii) NaN3, DMF, 90 oC;
(iv) H2, Pd/C, EtOH, r.t., then MeONa, MeOH, r.t.; (v) DBU, BuOH, 120 oC
SCHEME 1
Acid h ydrolysis of th e 1,6-an h ydride bon d in com poun d 6 with aqueous
h ydroch loric acid failed because th e ch em ical equilibrium between th e
com poun d 6 an d th e correspon din g reducin g sugar is com pletely sh ifted to
6. Such a ten den cy to form th e 1,6-an h ydride bon d is typical of h exoses of
altro, gulo, an d ido con figuration 7. Neverth eless, acetolysis of 7 in a m ixture
of trifluoroacetic acid an d acetic an h ydride at room tem perature an d subse-
quen t Zem plén deacetylation gave th e expected N-acetylated reducin g
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1820
Trtek, Černý, Trnka, Buděšínský, Císařová:
sugar 11 (Sch em e 2) as a m ixture of four com poun ds, n am ely (Z)- an d (E)-
isom ers, an d α an d β an om ers iden tified by NMR data (Tables I–III).
Quatern ary am m on ium salt 10 was prepared by a two-step procedure in -
volvin g th e Esch weiler–Clarke m eth ylation followed by N-m eth ylation of
th e in term ediate 9 with m eth yl iodide in tetrah ydrofuran at room tem pera-
ture. Th e resultin g am m on ium salt 10 did n ot sh ow an y activity at
m uscarin ic M3 receptors.
O
O
O
(iv)
OR2
O
O
O
OH
OH
+N
CH3
CH3
NR1
N
O
CH3
O
O
(iii)
9
10
CH2OH
OH
OH
6, R1 = R2 = H
7, R1 = R2 = Ac
8, R1 = Ac, R2 = H
(i)
(v), (ii)
O
(ii)
NAc
O
11
(i) Ac2O, py, r.t.; (ii) MeONa, MeOH, r.t.; (iii) CH2O, HCOOH, 80 oC;
(iv) MeI, THF, r.t.; (v) CF3COOH, Ac2O, r.t.
SCHEME 2
NMR DISCUSSION
Th e structure of com poun ds 2–11 was determ in ed by 1H an d 13C NMR
spectroscopy. Structural assign m en t of proton s an d carbon atom s was
ach ieved usin g correlated h om on uclear 2D-COSY an d h eteron uclear 1H,
13C-2D-HMQC spectra. Th e lon g-ran ge couplin gs, typical of com poun ds
2–4 with D-gluco con figuration , were iden tified with selective decouplin g
experim en ts in 1D 1H NMR spectra. In com poun d 2 th e h igh er observed
values of couplin g con stan ts J(2,3) = 3.3 an d J(3,4) = 3.5 Hz (com pared with
typical lower values J(2,3) ≈ 1.8, J(3,4) ≈ 1.8 Hz foun d in 3 an d 4) can be ex-
plain ed eith er by flatten in g of th e pyran oid rin g, an d/or a certain am oun t
of a B3,O boat form in a ch air-boat equilibrium of com poun d 2.
Th e presen ce of oxiran e rin g in D-manno-derivative 5 is m an ifested by up-
field sh ifts of proton s an d carbon atom s in position s 2 an d 3 (δ(H) 3.42 an d
3.14; δ(C) 54.31 an d 47.55) an d ch aracteristic J-value of cis-oxiran e proton s
(J(2,3) = 3.8 Hz). Also oth er proton couplin g con stan ts (J(1,2) = 3.2; J(3,4) ≈
J(4,5) = 1.5 Hz) are in agreem en t with th e D-manno con figuration .
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

3,11,13-Trioxa-7-azatricyclo[8.2.1.02,8]tridecane Derivatives
1821
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1822
Trtek, Černý, Trnka, Buděšínský, Císařová:
TABLE II
1H NMR couplin g con stan ts of com poun ds 2–9, 11 in CDCl3 an d 10 in D2O
O-CH H -CH H -CH H -X
a
b
c
d
e
f
Com p.
J(1,2)
J(2,3)
J(3,4)
J(4,5)
J(5,6n ) J(5,6x) J(6n ,6x)
J(a,b)
J(c,d)
J(e,f)
J(a,c)
J(a,d)
J(b,c)
J(b,d)
J(c,e)
J(c,f)
J(d,e)
J(d,f)
a
e
e
e
e
e
e
e
e
e
e
2
1.3
1.7
2.0
3.3
1.8
1.5
3.5
1.8
1.8
1.5
1.8
1.8
1.0
1.1
1.1
5.4
5.7
5.7
7.5
7.6
7.6
b
3
c
4
9.4
5.9
5.9
5.8
5.8
6.7
6.7
6.1
6.1
e
12.3
d
e
e
e
e
e
5
3.2
2.0
3.8
9.0
1.5
4.8
1.5
2.3
2.2
1.1
6.4
5.7
7.2
7.8
6
12.6
14.6
14.4
6.7
2.8
10.5
4.8
3.6
9.0
6.2
3.1
(Z)-7
76%
1.9
1.9
2.0
2.0
1.8
2.1
10.2
9.8
4.2
4.4
2.2
2.2
2.3
2.2
2.5
2.6
1.1
1.1
1.0
1.0
1.0
1.1
5.6
5.4
5.6
5.5
5.5
5.6
8.0
8.2
8.1
8.2
7.8
8.7
12.8
13.9
15.9
8.4
2.0
10.4
6.5
5.5
1.9
11.7
6.5
(E)-7
24%
12.6
8.6
1.9
9.4
7.2
5.8
2.2
11.5
5.1
e
14.1
(Z)-8
77%
10.0
9.2
4.2
12.7
14.0
15.6
8.3
2.8
9.6
6.5
2.3
5.3
6.2
11.4
e
(E)-8
23%
12.7
8.6
2.6
9.8
6.9
2.0
5.8
5.1
11.4
e
13.7
9
9.7
3.6
4.7
12.6
14.6
14.7
4.4
8.7
7.3
7.8
11.3
4.7
4.1
3.5
10
10.2
12.6
16.6
14.5
6.9
1.1
7.8
4.2
13.2
2.0
4.0
3.0
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
e
β-(Z)-11 3.8
41%
11.2
11.5
2.8
4.3
α-(Z)-11 6.1
32%
β-(E)-11 3.8
15%
10.3
2.7
e
e
α-(E)-11 5.5
12%
a
Addition al couplin g con stan ts: J(1,3) = 1.1, J(1,4) = 0.4, J(1,6x) ≤ 0.3, J(2,4) = 0.7, J(3,OH) =
b
5.4, J(3,5) = 1.1. J(1,3) = 1.4, J(1,4) = 0.7, J(1,6x) = 0.4, J(2,4) = 1.0, J(2,5) = 0.5, J(3,5) = 1.8.
c
d
J(1,3) = 1.4, J(1,4) = 0.6, J(1,6x) = 0.4, J(2,4) = 1.1, J(2,5) = 0.6, J(3,5) = 1.9. J(1,3) = 0.6,
e
J(2,4) = 0.8. Th e J-value could n ot be determ in ed.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

3,11,13-Trioxa-7-azatricyclo[8.2.1.02,8]tridecane Derivatives
1823
Th e D-altro con figuration of tricyclic com poun ds 6–10, wh ich is in agree-
m en t with h igh n egative values of th eir optical rotation s3,5a was proved by
a h igh value of J(2,3) = 9.0–10.2 Hz (in dicatin g a trans-diaxial arran gem en t
of H-2, H-3) an d a low value of J(3,4) = 3.6-4.8 Hz of gauche-orien ted H-3
an d H-4. Th e presen ce of n itrogen substituen t in stead of oxygen in position
3 (eviden ced by upfield sh ifts of carbon C-3 to δ 50–64 in com poun ds 6–9)
also leads to an in crease in both of th e above m en tion ed vicin al couplin gs
of proton H-3. Th e seven -m em bered 1,4-oxazepan e rin g fused in position s
TABLE III
13C NMR ch em ical sh ifts of com poun ds 2–9, 11 in CDCl3 an d 10 in D2O
Com poun d
C-1
C-2
C-3
C-4
C-5
C-6
Oth er carbon s
2
3
99.83 78.86
99.20 74.40
70.06
68.91
79.60
76.25
74.97
74.39
66.34
65.40
O-CH -CH -CH -Cl: 66.08, 32.52, 41.70
2 2 2
OTs: 145.38, 133.01, 130.01(2), 127.98(2), 21.68
O-CH -CH -CH -Cl: 66.08, 32.54, 41.59
2
2
2
OAc: 168.98, 20.82
OTs: 145.27, 133.35, 129.92(2), 128.00(2), 21.64
4
99.06 74.21
68.74
76.00
74.19
65.32
O-CH -CH -CH -N: 66.30, 29.10, 48.09
2 2 2
OAc: 169.03, 20.85
OTs: 145.33, 133.26, 129.94(2), 127.97(2), 21.66
5
97.56 54.31
101.80 71.70
99.90 68.83
47.55
58.88
50.88
74.90
81.54
82.81
71.30
77.17
76.84
65.75
66.19
66.21
O-CH -CH -CH -N: 67.56, 29.51, 37.77
2 2 2
6
O-CH -CH -CH -N: 72.03, 34.33, 41.93
2 2 2
(Z)-7 76%
O-CH -CH -CH -N: 68.91, 28.80, 40.69
2 2 2
NAc: 171.44, 21.27
OAc: 170.63, 20.87
(E)-7 24%
99.64 69.20
56.09
83.72
76.84
66.45
O-CH -CH -CH -N: 69.76, 27.61, 37.61
2 2 2
NAc: 171.44, 21.27
OAc: 170.63, 20.87
(Z)-8 77%
(E)-8 23%
9
102.23 68.50
102.00 67.99
101.72 68.72
104.26 70.76
93.22 64.83
96.67 67.77
92.50 64.46
97.29 67.70
53.87
59.60
64.31
75.82
51.67
54.39
56.70
59.65
82.15
83.59
79.64
80.53
80.19
79.57
81.14
80.31
76.72
76.78
77.66
79.69
79.23
75.17
79.50
74.58
66.10
66.30
66.33
68.37
68.56
67.82
69.18
68.44
O-CH -CH -CH -N: 68.51, 28.99, 40.43
2 2 2
NAc: , 21.40
a
O-CH -CH -CH -N: 69.57, 27.60, 37.32
2
2
2
a
NAc: , 21.95
O-CH -CH -CH -N: 69.18, 26.65, 45.31
2
2
2
NMe: 42.07
10
O-CH -CH -CH -N: 73.83, 28.93, 68.19
2
2
2
NMe : 63.63, 51.32
2
β-(Z)-11 41%
α-(Z)-11 32%
β-(E)-11 15%
α-(E)-11 12%
O-CH -CH -CH -N: 66.46, 29.01, 40.83
2 2 2
NAc: 173.44, 21.68
O-CH -CH -CH -N: 63.66, 28.81, 40.40
2
2
2
NAc: 173.42, 21.18
O-CH -CH -CH -N: 61.74, 28.19, 36.76
2
2
2
NAc: 173.16, 21.71
O-CH -CH -CH -N: 64.25, 27.73, 37.21
2
2
2
OAc: 173.20, 21.89
a
Th e position of sign als could n ot be accurately determ in ed.
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1824
Trtek, Černý, Trnka, Buděšínský, Císařová:
7
C-3–C-4 adopts a ch air C3,4-type con form ation (sligh tly in fluen ced by sub-
stitution at n itrogen atom ) as it is in dicated by vicin al couplin gs in th e
O–CH2–CH2–CH2–N fragm en t (Table II).
Th e partial double-bon d ch aracter of tertiary am ide bon d in N-acetyl de-
rivatives 7 an d 8 leads to th e existen ce of two isom ers observed in th eir
NMR spectra. Th ese isom ers could be iden tified as (Z)- an d (E)-isom ers on
th e basis of th e observed NOE con tacts between m eth yl proton s of N-acetyl
group an d th e equatorial h ydrogen of N–CH2 group (in (Z)-isom er) an d/or
H-3 proton (in (E)-isom er), in accordan ce with a sh ort distan ce (ca. 2.5 Å)
between th e correspon din g proton s in calculated en ergy-m in im ized struc-
tures. In all cases, th e population of th e (Z)-isom er sign ifican tly prevails
(76% in 7 an d 77% in 8; determ in ed from th e in ten sities of H-1 sign als).
Cleavage of th e 1,6-an h ydride bon d in 7 leads to th e observation of an
equilibrium m ixture of four sh apes of 11 due to th e presen ce of α an d β
an om ers, each as (Z)- an d (E)-isom ers at th e tertiary am ide bon d. Isom ers
are presen t in th e ratio β-(Z):α-(Z):β-(E):α-(E) = 41:32:15:12 (determ in ed
from th e h eigh ts of doublet lin es of H-1 on ly, sin ce partial overlap of two
H-1 doublets at 5.08 an d 5.09 did n ot allow th eir separate in tegration ). Th e
detailed NMR an alysis com bin in g h om on uclear an d h eteron uclear corre-
lated 2D-NMR spectra resulted in a n early com plete structure assign m en t of
sign als in all th e four isom ers (Tables I an d III). Th e differen t J(1,2) cou-
plin gs were used to distin guish α an om ers (J(1,2) ≈ 6 Hz) an d β an om ers
(J(1,2) = 3.8 Hz) wh ile (E)/(Z)-isom ers were distin guish ed in 2D-ROESY spec-
tra sim ilarly as described above for com poun ds 7 an d 8. It is in terestin g
th at th e pyran rin g in all th e four isom ers of bicyclic com poun d 11 adopts
1
th e C4 con form ation (th e observed J(2,3) = 10–11.5 Hz in dicate diaxial ori-
en tation of H-2 an d H-3 proton s) sim ilarly to th ose in th e tricyclic com -
poun ds 6–10.
Th e presen ce of N-m eth yl sign als (1H: δ 2.61 s (3 H) an d 13C: δ 42.07 in
1
N-m eth yl derivative 9; H: δ 3.48 s (3 H), δ 3.81 s (3 H) an d 13C: δ 51.32,
63.63 in N,N-dim eth ylam m on ium derivative 10) an d dram atic down field
sh ifts of carbon sign als C-3 an d N–CH2 in 10 con firm th e structure of com -
poun ds 9 an d 10.
EXPERIMENTAL
Th e m eltin g poin ts were determ in ed with a Boëtius m icro m eltin g-poin t apparatus an d are
un corrected. Optical rotation s were m easured with a polarim eter Autopol III (Rudolph
Research , Flan ders (NJ)) at 23–25 °C, [α]D values are given in 10–1 deg cm 2 g–1. NMR spectra
were m easured on Varian UNITY-500 apparatus (1H at 500 MHz, 13C at 125.7 MHz) in
CDCl3 or D2O. Ch em ical sh ifts (in ppm , δ-scale) were referen ced to tetram eth ylsilan e as in -
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

3,11,13-Trioxa-7-azatricyclo[8.2.1.02,8]tridecane Derivatives
1825
tern al stan dard; couplin g con stan ts (J) are given in Hz. ESI MS were m easured on Esquire
3000 (Bruker) in strum en t. Th in -layer ch rom atograph y (TLC) was perform ed on DC Alufolien
plates (Merck, type 5554) coated with Kieselgel 60 F254; detection was perform ed with 3%
eth an olic solution of an isaldeh yde acidified with con cen trated sulfuric acid, an d h eatin g.
For preparative colum n ch rom atograph y, silica gel Kieselgel 60 (Merck) was used. Solution s
were dried with an h ydrous calcium ch loride an d th en evaporated un der reduced pressure at
tem peratures below 40 °C. An alytical sam ples were dried over ph osph orus pen toxide at
room tem perature un der reduced pressure. For 1H an d 13C NMR data, see Tables I–III.
1,6-An h ydro-4-O-(3-ch loropropyl)-2-O-tosyl-β-D-glucopyran ose (2)
To a solution of tosyl epoxide4 1 (2.0 g, 6.7 m m ol) in an h ydrous dich lorom eth an e (20 m l)
boron trifluoride eth erate (1.0 m l, 7.9 m m ol) an d 3-ch loropropan ol (2.8 m l, 34.5 m m ol)
were added. Th e m ixture was refluxed for 4 h . Th e reaction course was m on itored by TLC
(eth yl acetate–toluen e 1:2). Th e solution was wash ed with a saturated solution of sodium
h ydrogen carbon ate (2 × 20 m l) an d with water (20 m l). Com bin ed organ ic extracts were
dried, dich lorom eth an e an d 3-ch loropropan ol were evaporated to obtain 2.4 g (92%) of 2,
m .p. 74–76 °C (eth er–ligh t petroleum ), [α]D –35 (c 0.19, CHCl3). For C16H21ClO7S (392.8)
calculated: 48.92% C, 5.39% H, 9.02% Cl, 8.16% S; foun d: 49.00% C, 5.47% H, 9.01% Cl,
8.05% S.
3-O-Acetyl-1,6-an h ydro-4-O-(3-ch loropropyl)-2-O-tosyl-β-D-glucopyran ose (3)
To a solution of ch loropropyl derivative 2 (1.9 g, 4.8 m m ol) in an h ydrous pyridin e (4.0 m l),
acetic an h ydride (1.4 m l, 11.0 m m ol) was added dropwise at 0 °C. Th e solution was stirred
at room tem perature overn igh t an d th en poured in to ice-water (30 m l) wh ile stirrin g. Th e
resultin g precipitate was filtered off after 20 m in , wash ed with water (30 m l) an d dried to
give 2.0 g (96%) of 3, m .p. 64–66 °C (eth er–ligh t petroleum ), [α]D –29 (c 0.17, CHCl3). For
C
18H23ClO8S (434.8) calculated: 49.71% C, 5.33% H, 8.15% Cl, 7.37% S; foun d: 49.59% C,
5.46% H, 8.02% Cl, 7.43% S.
3-O-Acetyl-1,6-an h ydro-4-O-(3-azidopropyl)-2-O-tosyl-β-D-glucopyran ose (4)
Com poun d 3 (2.0 g, 4.6 m m ol) an d sodium azide (600 m g, 9.2 m m ol) were dissolved in an -
h ydrous N,N-dim eth ylform am ide (7.0 m l) an d th e m ixture was h eated to 90 °C for 3 h un -
der argon atm osph ere, wh ile stirrin g. After evaporation of N,N-dim eth ylform am ide, water
(40 m l) was added to th e residue. Th e in soluble product was filtered off an d crystallized
from eth er–ligh t petroleum to afford 1.8 g (86%) of 4, m .p. 69–70 °C (eth er–ligh t petro-
leum ), [α]D –31 (c 0.19, CHCl3). For C18H23N3O8S (455.4) calculated: 48.97% C, 5.25% H,
9.52% N, 7.26% S; foun d: 48.93% C, 5.18% H, 9.26% N, 7.15% S.
4-O-(3-Am in opropyl)-1,6:2,3-dian h ydro-β-D-m an n opyran ose (5)
Azide derivative 4 (1.8 g, 4.0 m m ol) was h ydrogen ated in eth an ol (60 m l) over Pd/C (90 m g,
5%) at atm osph eric pressure for 24 h . Th e catalyst was rem oved by filtration , wash ed with
eth an ol an d th e com bin ed filtrates were evaporated. Th e residue was dissolved in water
(15 m l), an d n eutralized with 10% h ydroch loric acid to pH ≈ 6. Th e aqueous solution was
extracted with dich lorom eth an e (2 × 10 m l) an d organ ic extracts were wash ed with water
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1826
Trtek, Černý, Trnka, Buděšínský, Císařová:
(5 m l) again . Com bin ed aqueous ph ases were evaporated an d codistilled with toluen e (3 ×
10 m l). Th e residue was dissolved, wh ile stirrin g, in 0.5 M m eth an olic sodium m eth oxide
(20 m l) an d th e solution was set aside at room tem perature overn igh t. Th en th e m ixture was
n eutralized with acetic acid (0.34 m l, 6.0 m m ol) to pH ≈ 8. After evaporation of th e solven t,
dich lorom eth an e (10 m l) was added. In soluble salts were filtered off an d wash ed with di-
ch lorom eth an e (2 m l). Th e filtrate was con cen trated an d purified on a sh ort silica gel col-
um n (15 g) in eth yl acetate–m eth an ol–am m on ia (40:10:1) to obtain 680 m g (84%) of syrupy
5, [α]D –33 (c 0.22, CHCl3).
3-Am in o-1,6-an h ydro-3-deoxy-3-N,4-O-(propan e-1,3-diyl)-β-D-altropyran ose (6)
A solution of am in oepoxide 5 (680 m g, 3.4 m m ol) an d 1,8-diazabicyclo[5.4.0]un dec-7-en e
(0.6 m l, 4.0 m m ol) in butan -1-ol (20 m l) was refluxed for 8 h . Th e solven t was evaporated
an d th e residue ch rom atograph ed on a silica gel colum n (30 g) in eth yl acetate–m eth an ol–
am m on ia (50:10:1) to give 490 m g (72%) of com poun d 6, m .p. 175–177 °C (eth an ol–eth er),
[α]D –139 (c 0.18, MeOH). For C9H15NO4 (201.2) calculated: 53.72% C, 7.51% H, 6.96% N;
foun d: 53.57% C, 7.51% H, 6.58% N.
Crystal Structure An alysis of Com poun d 6
C9H15NO4, M = 201.22, orth orh om bic, P212121 (No. 19), a = 5.2480(1) Å, b = 10.8820(2) Å,
c = 15.6700(5) Å, V = 894.89(4) Å3, Z = 4, Dx = 1.494 Mg m –3. A colorless crystal of dim en -
sion s 0.5 × 0.3 × 0.25 m m was m oun ted on glass capillary with epoxy glue an d m easured at
Non ius KappaCCD diffractom eter by m on och rom atized MoKα radiation (λ = 0.71073 Å) at
150(2) K. An absorption was n eglected (µ = 0.117 m m –1); a total of 10 129 m easured reflec-
tion s in th e ran ge h = –6 to 6, k = –14 to 13, l = –20 to 20 (θm ax = 27.5°), from wh ich 2044
were un ique (Rin t = 0.024) an d 1979 observed accordin g to th e I > 2σ(I) criterion . Cell pa-
ram eters from 5994 reflection s (θ = 1–27.5°). Th e structure was solved by direct m eth ods
(SIR92 9, Altom are, 1994) an d refin ed by full-m atrix least squares based on F2 (SHELXL97 10).
Th e h ydrogen atom s were foun d on differen ce Fourier m ap an d refin ed isotropically. Th e re-
fin em en t con verged (∆/σm ax = 0.000) to R = 0.026 for observed reflection s an d wR = 0.067,
GOF = 1.065 for 187 param eters an d all 2044 reflection s. Th e fin al differen ce m ap displayed
n o peaks of ch em ical sign ifican ce (∆ρm ax = 0.219, ∆ρm in –0.168 e Å–3). Th e absolute structure
was assign ed by referen ce to th e kn own ch iral cen tre. (Flack param eter = –0.2(8) (Fig. 1).)
CCDC 237036 con tain s th e supplem en tary crystallograph ic data for th is paper. Th ese data
can be obtain ed free of ch arge via www.ccdc.cam .ac.uk/con ts/retrievin g.h tm l (or from th e
Cam bridge Crystallograph ic Data Cen tre, 12, Un ion Road, Cam bridge, CB2 1EZ, UK; fax:
+44 1223 336033; or deposit@ccdc.cam .ac.uk).
3-Acetam ido-2-O-acetyl-1,6-anhydro-3-deoxy-3-N,4-O-(propane-1,3-diyl)-β-D-altropyranose (7)
an d 3-Acetam ido-1,6-an h ydro-3-deoxy-3-N,4-O-(propan e-1,3-diyl)-β-D-altropyran ose (8)
Am in o derivative 6 (140 m g, 0.70 m m ol) was dissolved in an h ydrous pyridin e (1 m l) an d
acetic an h ydride (0.25 m l, 2.6 m m ol) was added dropwise. Th e solution was stirred at room
tem perature overn igh t an d th en poured in to ice-water (5 m l) wh ile stirrin g. After decom po-
sition of acetic an h ydride, th e m ixture was extracted with ch loroform (3 × 5 m l). Com bin ed
organ ic layers were dried, evaporated an d codistilled with toluen e (3 × 5 m l) to give syrupy
7 (180 m g, 91%), wh ich was dissolved in 0.1 M sodium m eth an olate (3 m l). Th e solution
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

3,11,13-Trioxa-7-azatricyclo[8.2.1.02,8]tridecane Derivatives
1827
was stirred at room tem perature for 1 h . Th e m ixture was th en n eutralized with Dowex 50
(H+), th e resin was filtered off, wash ed with m eth an ol an d th e com bin ed filtrates were evap-
orated to give 135 m g (80%) of th e crystallin e com poun d 8, m .p. 194–196 °C (aceton e–
eth er–ligh t petroleum ), [α]D –103 (c 0.26, CHCl3). For C11H17NO5 calculated: 243.1. ESI MS,
m/z: 244.0 [M + H]+, 266.0 [M + Na]+, 282.2 [M + K]+, 304.3.
1,6-An h ydro-3-deoxy-3-(m eth ylam in o)-3-N,4-O-(propan e-1,3-diyl)-β-D-altropyran ose (9)
Com poun d 6 (400 m g, 2.0 m m ol) was dissolved in 85% form ic acid (0.15 m l, 3.3 m m ol)
an d a solution of 35% aqueous form aldeh yde (0.23 m l, 3.1 m m ol) was added. Th e m ixture
was h eated to 80 °C overn igh t. After coolin g to room tem perature, th e solution was acidified
with 6 M h ydroch loric acid (0.5 m l) an d extracted with ch loroform (2 × 1 m l). Evaporation
of com bin ed organ ic layers afforded 8 m g of a syrup. Aqueous layer was alkalin ized with a
20% water solution of NaOH an d set aside at room tem perature for 30 m in . Th e reaction
m ixture was th en extracted with ch loroform (6 × 1 m l). Th e com bin ed ch loroform extracts
were dried an d evaporated to give 350 m g (82%) of syrupy 9, [α]D –136 (c 0.27, CHCl3). For
C
10H17NO4 calculated: 215.1. EI MS, m/z (rel.%): 215 (45) [M+], 184 (15), 113 (20), 84 (100),
42 (35). ESI MS, m/z: 216.1 [M + H]+, 238.1 [M + Na]+.
1,6-An h ydro-3-deoxy-3-(dim eth ylam m on io)-3-N,4-O-(propan e-1,3-diyl)- β-D-altropyran ose
Iodide (10)
Th e crude product 9 (350 m g, 1.6 m m ol) was dissolved in tetrah ydrofuran (3 m l), m eth yl io-
dide (350 µl, 5.6 m m ol) was added an d th e m ixture was kept at room tem perature for 24 h .
Th e precipitated product was filtered off an d wash ed with tetrah ydrofuran (2 m l) to give
510 m g (88%) of 10, m .p. 277–279 °C (decom p., eth an ol), [α]D –113 (c 0.23, MeOH). For
C
11H20INO4 (355.2) calculated: 36.99% C, 5.64% H, 35.53% I, 3.92% N; foun d: 37.00% C,
5.86% H, 35.58% I, 3.65% N.
O2
C1
C6
C5
O1
C2
C3
O3
C4
O4
N1
C7
C9
C8
FIG. 1
8
View of com poun d 6. Th erm al ellipsoids are drawn on th e 50% probability level (PLATON
)
Collect. Czech. Chem. Commun. (Vol. 69) (2004)

1828
Trtek, Černý, Trnka, Buděšínský, Císařová:
3-Acetam ido-3-deoxy-3-N,4-O-(propan e-1,3-diyl)-β-D-altropyran ose (11)
Th e com poun d 7 (800 m g, 2.8 m m ol) was dissolved in acetic an h ydride (5.0 m l) wh ile cool-
in g to 0 °C, an d trifluoroacetic acid (0.5 m l, 6.5 m m ol) was added. Th e m ixture was stirred
for 2 days. Solven ts were evaporated an d th e residue was separated between a saturated solu-
tion of sodium h ydrogen carbon ate (10 m l) an d ch loroform (10 m l). Th e aqueous layer was
th en extracted with ch loroform (2 × 10 m l). Th e com bin ed organ ic layers were dried an d
evaporated. Th e crude product th us obtain ed was deacetylated in a solution of 0.1
M
m eth an olic sodium m eth an olate (10 m l) at room tem perature for 2 h . Th e m ixture was th en
n eutralized with Dowex 50 (H+), th e resin was filtered off, wash ed with m eth an ol an d th e
com bin ed filtrates were evaporated. Th e residue was ch rom atograph ed on a silica gel col-
um n (20 g) in eth yl acetate–m eth an ol (6:1) to give 410 m g (56%) of th e syrupy 11, [α]D +27
(c 0.29, MeOH). For C11H19NO6 calculated 261.1. ESI MS, m/z: 284.1 [M + Na]+.
We thank Dr M. Štícha for the measurement of mass spectra, Mgr B. Šperlichová for the measure-
ment of optical rotations, and the Analytical Department of the Institute of Organic Chemistry and
Biochemistry of the Academy of Sciences of the Czech Republic, Prague for elementary analyses. This
project was supported by the Ministry of Education, Youth and Sports of the Czech Republic (grant
MSM 1131 00001).
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