New heterocyclic derivatives of 2-amino-1,6-anhydro-2-deoxy-β-D- glucopyranose containing 1,4-oxazepane or azepane ring

Article abstract of DOI:10.1135/cccc20050466

Two heterocyclic derivatives of D-glucosamine, 2-amino-1,6-anhydro-2-deoxy- 2-N,4-O-(ethane-1.2-diyl)-β-D-glucopyranose (13) and 2-amino-1,6-anhydro-2, 4-dideoxy-2-N,4-(propane-1.3-diyl)-β-D-glucopyranose (14) were prepared from 1,6-anhydro-β-D-glucopyran

Full text of DOI:10.1135/cccc20050466

466
Trtek, Černý, Buděšínský, Trnka, Císařová:
NEW HETEROCYCLIC DERIVATIVES OF
2-AMINO-1,6-ANHYDRO-2-DEOXY-β-D-GLUCOPYRANOSE
CONTAINING 1,4-OXAZEPANE OR AZEPANE RING
b,
a3
Tomáš TRTEKa1, Miloslav ČERNÝa2, Miloš BUDĚŠÍNSKÝ *, Tomáš TRNKA 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 Decem ber 15, 2004
Accepted Jan uary 7, 2005
Two h eterocyclic derivatives of D-glucosam in e, 2-am in o-1,6-an h ydro-2-deoxy-2-N,4-O-(eth an e-
1,2-diyl)-β-D-glucopyran ose (13) an d 2-am in o-1,6-an h ydro-2,4-dideoxy-2-N,4-(propan e-
1,3-diyl)-β-D-glucopyran ose (14) were prepared from 1,6-an h ydro-β-D-glucopyran ose
(levoglucosan ) in ten steps via O-4 or C-4 substituted 1,6:2,3-dian h ydro-β-D-m an n opyran ose
derivatives 2 an d 4. Selective oxiran e-rin g cleavage with sodium azide at C-2 followed by
tosylation afforded 2-azido-2-deoxy derivatives 7 an d 8 of D-gluco con figuration . Th ese were
reduced to am in es an d, after tosylation , azepan e an d oxazepan e N-tosyl derivatives 11 an d
12 were form ed by in tram olecular substitution . Th eir detosylation afforded th e target
D-glucosam in e derivatives 13 an d 14.
Keyw ord s: Carboh ydrates; Am in osugars; Oxazepan es; Azepan es; Heterocycles; 1,6-An h ydro-
sugars; 2-Am in o-2-deoxy-D-glucose; Oxiran es; Epoxides; Cyclization s; X-ray diffraction ; NMR
spectroscopy; Con form ation an alysis.
Man y glycocon jugates of biological im portan ce an d som e n aturally occur-
rin g am in oglycoside an tibiotics con tain 2-am in o-2-deoxy-D-glucose. A
n um ber of its derivatives were syn th esized in recen t decades1. Th ese com -
poun ds are effective as poten tial in h ibitors of carboh ydrate-processin g en -
zym es or can in terfere with biosyn th esis of glycocon jugates. Lately, it was
sh own th at glycosylated glucosam in e derivatives could in teract with ribo-
som al RNA of bacteria in an alogy to am in oglycoside an tibiotics2. In con -
n ection with our previous papers3, we report h erein a syn th esis of two de-
rivatives of 2-am in o-1,6-an h ydro-2-deoxy-β-D-glucopyran ose 13 an d 14
Collect. Czech. Chem. Commun. (Vol. 70) (2005)
doi:10.1135/cccc20050466

Derivatives of 2-Amino-1,6-anhydro-2-deoxy-β-D-glucopyranose
467
wh ich in volve 1,4-oxazepan e an d azepan e rin g, respectively, an n elated at
C-2 an d C-4 position of th e pyran ose rin g.
As startin g com poun ds in th e parallel syn th esis of target com poun ds 13
4
an d 14 we used a pair of epoxides 2 an d 4 (Sch em e 1), accessible from
1,6-an h ydro-β-D-glucopyran ose5 via 1,6:3,4-dian h ydro-2-O-tosyl-β-D-galacto-
pyran ose6 (1) in four steps. Acid-catalyzed reaction of th e tosyl epoxide 1
with eth an e-1,2-diol an d subsequen t alkalization of th e reaction m ixture
gave th e epoxide 2 in 73% yield. Treatm en t of 1 with allylm agn esium ch lo-
ride gave th e kn own allyl derivative7 3. Hydroboration of th e term in al dou-
O
O
(i)
O
O
O
O
O
OTs
HO
1
2
(ii)
O
O
OH
(iii)
O
O
O
OTs
HO
4
3
O
O
OH
O
OH
O
(vii)
(iv)
2 or 4
NR
X
R1
X
R2O
5, X = O, R1 = N3, R2 = H
11, X = O, R = Ts
13, X = O, R = H
15, X = O, R = Ac
12, X = CH2, R = Ts
14, X = CH2, R = H
(v)
(viii)
(ix)
7, X = O, R1 = N3, R2 = Ts
9, X = O, R1 = NHTs, R2 = Ts
6, X = CH2, R1 = N3, R2 = H
8, X = CH2, R1 = N3, R2 = Ts
10, X = CH2, R1 = NHTs, R2 = Ts
(vi), (v)
(viii)
(v)
(vi), (v)
(i) ethylene glycol, BF3·Et2O, DME, 100 oC; then NaOMe, MeOH, CHCl3, r.t.;
(ii) CH2=CHCH2MgCl, CuI, THF, r.t.; (iii) BH3·THF, then NaOH, H2O2; (iv) NaN3, NH4Cl,
CH3OCH2CH2OH, H2O, 115 oC; (v) TsCl, pyridine, r.t.; (vi) H2, Pd/C, EtOH, AcOH, r.t.;
(vii) K2CO3, DMF, 60 oC; (viii) sodium naphthalenide, DME, –10 oC; (ix) TFA, Ac2O, r.t
SCHEME 1
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Trtek, Černý, Buděšínský, Trnka, Císařová:
ble bon d in 3 with gaseous diboran e followed by con ven tion al work-up of
th e reaction m ixture with H2O2 an d NaOH, resulted in form ation of
epoxide 4 in 87% yield. Cleavage of th e oxiran e rin g in epoxides 3 an d 4
with sodium azide afforded azido derivatives 5 an d 6 in 73 an d 68% yield,
respectively. Th e prim ary h ydroxy group in both azido derivatives was se-
lectively tosylated to obtain tosylates 7 an d 8. Th e azido group in 7 an d 8
was reduced with h ydrogen in th e presen ce of 10% Pd on activated carbon .
Th e correspon din g am in es th us obtain ed proved to be in stable after stan d-
in g at room tem perature for several h ours. Con sequen tly, th ey were directly
tosylated with out purification to give tosyl am ides 9 an d 10. Form ation of
th e seven -m em bered rin g in 11 an d 12 was effected by th e m odified
Rich m an –Atkin s procedure8 in 85 an d 82% yields on h eatin g tosyl deriva-
tives 9 an d 10 with a m ixture of potassium carbon ate in dim eth ylform -
am ide at 60 °C. Th e target com poun ds 13 an d 14 were obtain ed in 69 an d
73% yield by detosylation with sodium n aph th alen ide in 1,2-dim eth oxy-
eth an e. Attem pted acid h ydrolysis as well as acetolysis of th e 1,6-an h ydride
bon d in 13 failed an d N-acetyl derivative 15 was isolated as a sole product.
Th is m ay be accoun ted for by th e fact th at th e pyran oid rin g in 13 adopts a
less com m on 1C4 con form ation an d sh ould also adopt th is con form ation ,
due to lim ited flexibility of th e bicyclic pyran oid–oxazepan e skeleton , if th e
1,6-an h ydride bon d is in terrupted. As a result, a stron g ten den cy to regen -
erate th e 1,6-an h ydride bon d in th e equilibrium m ixture m ay be expected.
An an alogy of th is situation was described for acid equilibration of som e
1
free h exoses partially adoptin g C4 con form ation 9.
NMR AND X-RAY DISCUSSION
Th e structure of com poun ds 2, 4–15 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-HSQC spectra. Th e lon g-ran ge couplin gs, typical of com poun ds
with D-gluco con figuration , were iden tified by selective decouplin g experi-
1
m en ts in 1D H NMR spectra. Th e 2,3-epoxy group in com poun ds 2 an d 4
m an ifests itself by upfield sh ifts of carbon atom s C-2 an d C-3 (δ 50–54) an d
ch aracteristic vicin al couplin g J(2,3) ≈ 4 Hz. Th e NMR data of com poun ds
5–15 are sum m arized in Tables I–III. Th e gluco con figuration of com poun ds
1
5–15 an d preferred C4 con form ation of th eir pyran ose rin g is docum en ted
by low values of vicin al couplin gs J(2,3) an d J(3,4). Sligh tly h igh er values of
J(2,3) an d J(3,4) in 6, 8, 10 (see Table II) in dicate a certain am oun t of B3,O
boat form in a ch air–boat equilibrium due to th e steric in teraction s be-
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Derivatives of 2-Amino-1,6-anhydro-2-deoxy-β-D-glucopyranose
469
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

470
Trtek, Černý, Buděšínský, Trnka, Císařová:
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Derivatives of 2-Amino-1,6-anhydro-2-deoxy-β-D-glucopyranose
471
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

472
Trtek, Černý, Buděšínský, Trnka, Císařová:
tween th e substituen t at C-2 an d alkyl ch ain at C-4 (for detailed discussion
of th is ph en om en on , see lit.10). Th e presen ce of all substituen ts as well as
an addition al seven -m em bered rin g in 11–15 is clearly proved by corre-
spon din g sign als in 1H an d 13C NMR spectra. Th e partial double-bon d ch ar-
acter of tertiary am ide bon d in N-acetyl derivatives 15 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 be-
tween m eth yl proton s of N-acetyl group an d th e proton s of N-CH2 group
(in Z-isom er; 82%) an d/or H-2 proton (in E-isom er; 18%).
Th e crystal structure of com poun d 11 is sh own in Fig. 1. Th e five-
m em bered rin g adopts en velope form EO2, th e six-m em bered rin g a flat-
C3
ten ed ch air form
C
an d th e seven -m em bered rin g exists in a sligh tly
O2
C4,O4
distorted ch air con form ation
C
. Th e arom atic rin g of tosyl group is
N1
folded over bottom face of th e seven -m em bered rin g. Th e selected torsion
an gles are given in Table IV.
Th e con form ation of com poun d 11 in solution is very close to th at foun d
in crystal as it is eviden ced by vicin al in terproton couplin g con stan ts wh en
com pared with torsion an gles of correspon din g h ydrogen atom s in crystal
(see Table IV).
C6
O1
C1
C2
O2
C5
O3
C3
C4
O4
N1
S1
C7
C8
O5
C14
O6
C13
C9
C10
C12
C11
C15
FIG. 1
View of th e m olecule of 11 with atom n um berin g sch em e. Th e displacem en t ellipsoids are
drawn on 50% probability level (PLATON)13
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Derivatives of 2-Amino-1,6-anhydro-2-deoxy-β-D-glucopyranose
473
TABLE IV
Selected torsion an gles (in °) foun d in crystal structure of com poun d 11 an d vicin al couplin g
con stan ts of correspon din g h ydrogen atom s in solution (in paren th eses)
Five-m em bered rin g
Six-m em bered rin g
Seven -m em bered rin g
O1–C1–O2–C5
C1–O2–C5–C6
O2–C5–C6–O1
C5–C6–O1–C1
C6–O1–C1–O2
–46
C1–C2–C3–C4
39
C2–N1–C8–C7
N1–C8–C7–O4
C8–C7–O4–C4
C7–O4–C4–C3
O4–C4–C3–C2
C4–C3–C2–N1
C3–C2–N1–C8
–52
78
44
–28
1
C2–C3–C4–C5
C3–C4–C5–O2
C4–C5–O2–C1
C5–O2–C1–C2
O2–C1–C2–C3
–41
62
–61
–12
81
–76
74
27
–58
–84
53
H5–C5–C6–H6en
95 (0.8) H1–C1–C2–H2
62 (2.3)
H3–C3–C4–H4
80 (1.5)
H5–C5–C6–H6ex –26 (5.2) H2–C2–C3–H3
H3–C3–C4–H4
–82 (1.7)
80 (1.5)
–59 (2.1)
H4–C4–C5–H5
–59 (2.1)
78 (1.2)
–38 (6.4)
H7A–C7–C8–H8A
H7A–C7–C8–H8B
H4–C4–C5–H5
H7B–C7–C8–H8A
H7B–C7–C8–H8B
–166 (8.9)
78 (1.2)
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 Re-
search , 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 a Varian UNITY-500 an d/or a Bruker Avan ce-500 apparatus (1H at 500 MHz,
13C at 125.7 MHz). Ch em ical sh ifts (in ppm , δ-scale) were referen ced to tetram eth ylsilan e
(in 1H NMR spectra) an d/or to th e sign al of solven t (δ(CDCl3) 77.0 in 13C NMR spectra);
couplin g con stan ts (J) are given in Hz. For 1H an d 13C NMR data see Tables I–III. ESI MS
were m easured on an Esquire 3000 apparatus (Bruker). Th in -layer ch rom atograph y (TLC)
was perform ed on DC Alufolien plates (Merck, type 5554) coated with Kieselgel 60 F254; de-
tection 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 were evapo-
rated 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.
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Trtek, Černý, Buděšínský, Trnka, Císařová:
1,6:2,3-Dian h ydro-4-O-(2-h ydroxyeth yl)-β-D-m an n opyran ose (2)
Modified procedure4 for preparation of 2: A m ixture of 1,6:3,4-dian h ydro-2-O-tosyl-
β-D-galactopyran ose (1; 10.0 g, 33.6 m m ol), dry 1,2-dim eth oxyeth an e (25 m l), eth ylen e
glycol (25 ml) and BF3·Et2O (1.0 ml) was heated to 100 °C under argon atmosphere. TLC (toluene–
eth yl acetate, 4:1) sh owed com plete con version after 1 h . 1,2-Dim eth oxyeth an e was evapo-
rated an d water (25 m l) was added. Th e m ixture was set aside at 0 °C overn igh t. Precipitated
crystals were filtered off, wash ed with water an d dried; yield 11.0 g (91%) of crude
1,6-an h ydro-4-O-(2-h ydroxyeth yl)-2-O-tosyl-β-D-glucopyran ose4. Th is was dissolved in a m ix-
ture of ch loroform –m eth an ol (1:1, 50 m l) an d cooled to 0 °C. A solution of NaOMe in
MeOH (1 m ol l–1, 35 m l, 35 m m ol) was added, resultin g m ixture was stirred for 1 h an d
th en n eutralized with acetic acid. Solven ts were evaporated to dryn ess an d th e residue was
extracted with dich lorom eth an e (50 m l). Salts were filtered off an d wash ed with dich loro-
m eth an e. Th e dich lorom eth an e solution was evaporated an d th e residue was crystallized
from eth an ol–eth er–ligh t petroleum . Yield 4.6 g (73% overall) of 2, m .p. 92–95 °C; lit.4 gives
m .p. 93–95 °C. 1H NMR (CDCl3): 5.72 d, 1 H, J(1,2) = 3.1 (H-1); 4.54 ddd, 1 H, J(5,4) = 1.1,
J(5,6en ) = 2.1, J(5,6ex) = 6.6 (H-5); 3.80 m , 4 H (O-CH2-CH2-O); 3.75 dd, 1 H, J(6ex,6en ) =
7.3, J(6ex,5) = 6.6 (H-6ex); 3.72 dd, 1 H, J(6en ,6ex) = 7.3, J(6en ,5) = 2.1 (H-6en ); 3.65 dd, 1 H,
J(4,3) = 0.7, J(4,5) = 1.1 (H-4); 3.47 dd, 1 H, J(2,1) = 3.1, J(2,3) = 3.8 (H-2); 3.20 dd, 1 H, J(3,2) =
3.8, J(3,4) = 0.7 (H-3).
1,6:2,3-Dian h ydro-4-deoxy-4-(3-h ydroxypropyl)-β-D-m an n opyran ose (4)
A m ixture of BF3·Et2O (10 m l) an d bis(2-m eth oxyeth yl) eth er (10 m l) was added dropwise
un der n itrogen to a stirred suspen sion of sodium boroh ydride (4 g) in bis(2-m eth oxyeth yl)
eth er (20 m l), an d th e resultin g stream of diboran e was passed th rough a stirred solution
7
of 3 (6.3 g, 18 m m ol) in dry THF (20 m l) at room tem perature. After 1 h , th e reaction was
quen ch ed cautiously with aqueous 3 M NaOH (20 m l) an d subsequen tly 30% H2O2 (20 m l)
was added. Th e m ixture was stirred at room tem perature overn igh t. Th e water layer was sat-
urated with Na2SO4 an d th e organ ic ph ase was separated. Th e aqueous layer was extracted
twice m ore with CHCl3 (2 × 30 m l). Com bin ed organ ic ph ases were wash ed with a saturated
solution of Na2SO3 (30 m l), dried an d evaporated givin g 3.0 g (87%) of syrupy com poun d 4;
[α]D –19 (c 0.75, CHCl3). ESI MS, m/z (%): for C9H14O4 calculated 186.1; foun d 209.0 (100)
[M + Na]+. 1H NMR (CDCl3 + C6D6, 3:1): 5.60 dm , 1 H, J(1,2) = 3.1, J(1,4) = 1.0, J(1,6en ) =
0.5, J(1,6ex) = 0.5 (H-1); 4.12 m , 1 H, J(5,3) = 0.8, J(5,4) = 1.2, J(5,6en ) = 2.2, J(5,6ex) = 6.0
(H-5); 3.68 ddd, 1 H, J(6en ,6ex) = 6.8, J(6en ,5) = 2.2, J(6en ,1) = 0.5 (H-6en ); 3.66 ddd, 1 H,
J(6ex,6en ) = 6.8, J(6ex,5) = 6.0, J(6ex,1) = 0.5 (H-6ex); 3.58 t, 2 H, 3J = 6.2 (CH2-OH); 3.25
ddd, 1 H, J(2,1) = 3.1, J(2,3) = 4.0, J(2,4) = 0.7 (H-2); 2.85 ddd, 1 H, J(3,2) = 4.0, J(3,4) = 0.3,
J(3,5) = 0.8 (H-3); 1.83 m , 1 H, J(4,1) = 1.0, J(4,2) = 0.7, J(4,3) = 0.3, J(4,5) = 1.2, J(4,CH2) =
7.0 (H-4); 1.50–1.70 m , 4 H (CH2-CH2). 13C NMR (CDCl3): 98.02 (C-1); 71.63 (C-5); 68.62
(C-6); 62.59 (CH2OH); 53.86 (C-2); 50.71 (C-3); 39.36 (C-4); 30.19 an d 27.18 (CH2-CH2).
Gen eral Procedure for Preparation of Com poun ds 5 an d 6
A m ixture of 1,6:2,3-dian h ydro-4-O-(2-h ydroxyeth yl)-β-D-m an n opyran ose (2; 1.9 g, 10 m m ol)
or 1,6:2,3-dian h ydro-4-deoxy-4-(3-h ydroxypropyl)-β-D-m an n opyran ose (4; 1.9 g, 10 m m ol),
sodium azide (3.3 g, 50 m m ol), am m on ium ch loride (4.0 g, 74 m m ol), 2-m eth oxyeth an ol
(50 m l) an d water (15 m l) was h eated to 115 °C for 28 h . Th e reaction course was m on itored
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

Derivatives of 2-Amino-1,6-anhydro-2-deoxy-β-D-glucopyranose
475
by TLC in ch loroform –m eth an ol (10:1). After coolin g, th e reaction m ixture was evaporated
to dryn ess an d th e solid residue was extracted with ch loroform (20 m l). Th e in soluble salts
were filtered off an d wash ed with ch loroform (10 m l). Com bin ed ch loroform solution s were
evaporated an d th e residue was ch rom atograph ed on a silica gel colum n (80 g) in ch loroform –
m eth an ol (10:1) to give th e syrupy product.
1,6-Anhydro-2-azido-2-deoxy-4-O-(2-hydroxyethyl)-β-D-glucopyranose (5). Yield 1.7 g (73%),
[α]D –10 (c 0.60, CHCl3). ESI MS, m/z (%): for C8H13N3O5 calculated 231.1; foun d 254.0
(100) [M + Na]+, 318.3 (23).
1,6-Anhydro-2-azido-2,4-dideoxy-4-(3-hydroxypropyl)-β-D-glucopyranose (6). Yield 1.6 g (68%),
[α]D –18 (c 0.42, CHCl3). ESI MS, m/z (%): for C9H15N3O4 calculated 229.1; foun d 252.2
(100) [M + Na]+.
Gen eral Procedure for Preparation of Com poun ds 7 an d 8
A solution of com poun d 5 or 6 (1.5 g, 6.5 m m ol) in dry pyridin e (10 m l) was cooled to 0 °C
an d tosyl ch loride (1.8 g, 9.4 m m ol) in pyridin e (10 m l) was added. Th e m ixture was stirred
at room tem perature for 2 h an d th en was poured in to ice–water (50 m l). Th e solution was
extracted with ch loroform (3 × 20 m l). Com bin ed organ ic ph ases were dried an d evaporated.
Th e syrupy residue was purified on a silica gel colum n (100 g) with toluen e–aceton e (10:1).
1,6-Anhydro-2-azido-2-deoxy-4-O-[2-(tosyloxy)ethyl]-β-D-glucopyranose (7). Yield 2.0 g (80%)
of slowly crystallizin g syrup, m .p. 50–52 °C (eth er–ligh t petroleum ), [α]D –9 (c 0.66, CHCl3).
For C15H19N3O7S (385.4) calculated: 46.75% C, 4.97% H, 10.90% N, 8.32% S; foun d: 46.86% C,
4.90% H, 10.64% N, 8.25% S.
1,6-Anhydro-2-azido-2,4-dideoxy-4-[3-(tosyloxy)propyl]-β-D-glucopyranose (8). Yield 2.0
g
(80%) of a syrup wh ich con tain ed a sm all am oun t of ditosylate as in dicated by NMR spec-
trum , [α]D –16 (c 0.34, CHCl3). ESI MS, m/z (%): for C16H21N3O6S calculated 383.1; foun d
301.2 (74), 406.1 (100) [M + Na]+. Th is product was used with out furth er purification .
Gen eral Procedure for Preparation of Com poun ds 9 an d 10
Azido com poun d 7 or 8 (1.8 g, 4.7 m m ol) was h ydrogen ated in a m ixture of eth an ol (45 m l)
an d acetic acid (1 m l) over palladium on activated carbon (200 m g, 5%) for 24 h . Th e cata-
lyst was filtered off an d solven ts were evaporated. Th e crude product was purified on a silica
gel colum n (30 g). Non polar im purities were eluted with eth yl acetate an d th e product with
a m ixture of eth yl acetate–m eth an ol–20% am m on ia in m eth an ol (30:2:1). Fraction s con tain -
in g th e correspon din g am in e were evaporated, several tim es codistilled with toluen e (20 m l)
an d tosylated in th e m ixtu re of pyridin e (10 m l) an d tosyl ch loride (0.8 g, 4.6 m m ol) at
0 °C. After 1 h th e reaction m ixture was poured in to ice–water (50 m l) an d extracted with
ch loroform (3 × 20 m l). Com bin ed ch loroform extracts were dried, evaporated an d th e resi-
due was ch rom atograph ed on a silica gel colum n (40 g) in toluen e–aceton e (10:1).
1,6-Anhydro-2-deoxy-2-(tosylamino)-4-O-[2-(tosyloxy)ethyl]-β-D-glucopyranose (9). Yield 1.2 g
(50%), m .p. 139–140 °C (eth an ol), [α]D –32 (c 0.63, CHCl3). For C22H27NO9S2 (513.6)
calculated: 51.45% C, 5.30% H, 2.73% N, 12.49% S; foun d: 51.13% C, 5.23% H, 2.56% N,
12.24% S.
1,6-Anhydro-2,4-dideoxy-2-(tosylamino)-4-[3-(tosyloxy)propyl]-β-D-glucopyranose (10). Yield 1.0
(42%) of syrup, [α]D –44 (c 0.67, CHCl3). ESI MS, m/z (%): for C23H29NO8S2 calculated 511.1;
foun d 534.1 (100) [M + Na]+, 550.1 (95) [M + K]+.
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Gen eral Procedure for Preparation of Com poun ds 11 an d 12
A m ixture of ditosyl derivative 9 or 10 (900 m g, 1.8 m m ol) an d K2CO3 (750 m g, 5.4 m m ol)
in DMF (22 m l) was h eated at 60 °C for 3 h . DMF was evaporated at 40 °C an d th e residue
was p artition ed between ch loroform (10 m l) an d water (10 m l). Th e water p h ase was
extracted with ch loroform again (2 × 5 m l). Com bin ed ch loroform extracts were dried an d
evaporated. Th e crude product was crystallized from eth an ol–eth er–ligh t petroleum (com -
poun d 11) or toluen e (com poun d 12). Th e m oth er liquor was evaporated an d th e residue
was ch rom atograph ed on a silica gel colum n in toluen e–aceton e (10:1).
1,6-Anhydro-2-deoxy-2-N,4-O-(ethane-1,2-diyl)-2-(tosylamino)-β-D-glucopyranose (11). Yield
490 m g (82%), m .p. 159–161 °C (eth an ol–eth er–ligh t petroleum ), [α]D +34 (c 0.70, CHCl3).
For C15H19NO6S (341.4) calculated: 52.77% C, 5.61% H, 4.10% N, 9.39% S; foun d: 52.52% C,
5.65% H, 4.10% N, 9.06% S.
1,6-Anhydro-2,4-dideoxy-2-N,4-(propane-1,3-diyl)-2-(tosylamino)-β-D-glucopyranose (12). Yield
510 m g (85%), m .p. 108–109 °C (toluen e), [α]D +29 (c 0.63, CHCl3). For C16H21NO5S (339.4)
calculated: 56.62% C, 6.24% H, 4.13% N, 9.45% S; foun d: 56.71% C, 6.33% H, 3.90% N,
9.43% S.
Gen eral Procedure for Preparation of Com poun ds 13 an d 14
A m ixture of sodium (230 m g, 10 m m ol) an d n aph th alen e (650 m g, 5.0 m m ol) in
dim eth oxyeth an e (10 m l) was stirred un der argon atm osph ere at room tem perature for 2 h .
Th us prepared solution of sodium n aph th alen ide was added dropwise at –10 °C to a stirred
solution of tosylam ide 11 or 12 (400 m g, 1.2 m m ol) in 1,2-dim eth oxyeth an e (4 m l) un til it
becam e dark. After 10 m in , th e reaction was quen ch ed with water (0.1 m l) an d evaporated
to dryn ess. Naph th alen e was rem oved by dissolution in ligh t petroleum (10 m l) an d th e
product was extracted from th e residue with h ot eth an ol (10 m l). Salts were filtered off an d
th e filtrate was evaporated. Th e residue was purified on a silica gel colum n (10 g) in eth yl
acetate–m eth an ol–20% am m on ia in m eth an ol (15:3:1).
2-Amino-1,6-anhydro-2-deoxy-2-N,4-O-(ethane-1,2-diyl)-β-D-glucopyranose (13). Yield 160 m g
(73%), m .p. 210–213 °C (eth an ol–eth er, decom p.), [α]D –72 (c 0.50, MeOH). For C8H13NO4
(187.2) calculated: 51.33% C, 7.00% H, 7.48% N; foun d: 51.09% C, 7.03% H, 7.56% N.
2-Amino-1,6-anhydro-2,4-dideoxy-2-N,4-(propane-1,3-diyl)-β-D-glucopyranose (14). Yield 150 m g
(69%), m .p. 196–197 °C (eth an ol), [α]D –60 (c 0.66, MeOH). For C9H15NO3 (185.2) calcu-
lated: 58.36% C, 8.16% H, 7.56% N; foun d: 58.11% C, 8.15% H, 7.29% N.
Attem pted Acid Hydrolysis of th e 1,6-An h ydride Bon d in Com poun d 13
Com poun d 13 (15 m g) was h eated to 100 °C in aqueous h ydroch loric acid (6 m ol l–1, 0.3 m l)
in a sealed tube for 3 h . 1H NMR spectrum as well as TLC (butan ol–pyridin e–water, 3:2:1) of
th e evaporated reaction m ixture sh owed on ly th e presen ce of th e startin g com poun d.
Attem pted Acetolysis of th e 1,6-An h ydride Bon d in Com poun d 13
2-Acetamido-1,6-anhydro-2-deoxy-2-N,4-O-(ethane-1,2-diyl)-β-D-glucopyranose (15). Com poun d
13 (50 m g, 0.27 m m ol) was dissolved in acetic an h ydride (0.5 m l) wh ile coolin g to 0 °C, an d
trifluoroacetic acid (50 µl, 0.7 m m ol) was added. Th e m ixture was kept at room tem perature
un der stirrin g for 2 days. Solven ts were evaporated at 30 °C. Th e syrupy m aterial th us ob-
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Derivatives of 2-Amino-1,6-anhydro-2-deoxy-β-D-glucopyranose
477
tain ed was deacetylated with 0.1 M m eth an olic sodium m eth an olate (2 m l) at room tem pera-
ture for 1 h . TLC (ch loroform –m eth an ol, 5:1) sh owed th e presen ce of sin gle product. 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 colum n (2 g). Com poun d 15 was eluted with eth yl acetate. Addition of m eth an ol
to th e eluen t did n ot afford an y m ore polar com poun ds. Yield 45 m g (74%) of acetate 15,
m .p. 223–225 °C (eth an ol–eth er). ESI MS, m/z (%): for C10H15NO5 calculated 229.1; foun d
230.0 (13) [M + H]+, 252.0 (100) [M + Na]+, 276.2 (16), 481.1 (100) [2 M + Na]+.
Crystal Structure An alysis of Com poun d 11
C15H19NO6S, M = 341.37, orth orh om bic, P212121 (No. 19), a = 6.2580(2) Å, b = 11.9860(3) Å,
c = 20.1180(5) Å, V = 1509.02(7) Å3, Z = 4, Dx = 1.503 Mg m –3. A colorless crystal of dim en -
sion s 0.5 × 0.18 × 0.17 m m was m oun ted on glass capillary with epoxy glue an d m easured
with a Non ius KappaCCD diffractom eter usin g m on och rom atized MoKα radiation (λ =
0.71073 Å) at 150(2) K. Absorption was n eglected (µ = 0.247 m m –1); a total of 10 002 m ea-
sured reflection s in th e ran ge h = –8 to 8, k = –15 to 15, l = –25 to 25 (θm ax= 27.5°), from
wh ich 3456 were un ique (Rin t = 0.030) an d 3201 observed accordin g to th e I > 2σ(I) crite-
rion . Cell param eters from 1968 reflection s (θ = 1–27.5°). Th e structure was solved by direct
m eth ods (SIR92, Altom are, 1994)11 an d refin ed by full-m atrix least squares based on F2
(SHELXL97)12. Th e h ydrogen atom s on carbon s were foun d on differen ce Fourier m ap, recal-
culated in to idealized position s an d fixed durin g refin em en t (ridin g m odel) with assign ed
tem perature factors Hiso(H) = 1.2 Ueq (pivot atom ) or Hiso(H) = 1.5 Ueq (pivot atom ) for m eth yl
group. Th e h ydrogen atom of h ydroxy group was foun d on differen ce Fourier m ap an d re-
fin ed isotropically. Th e refin em en t con verged (∆/σm ax = 0.000) to R = 0.034 for observed re-
flection s an d wR = 0.082, GOF = 1.074 for 213 param eters an d all 3456 reflection s. Th e fin al
difference m ap displayed no peaks of chem ical significance (∆ρm ax = 0.191, ∆ρm in = –0.347 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 =
–0.04(7)). CCDC 256863 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).
We thank Mgr M. Valášek for the measurement of mass spectra, Mgr B. Šperlichová for the mea-
surement 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 a part of a research project Z4 055 0506 and was supported by grant MSM 1131 00001.
REFERENCES
1. Sharma M., Korytnyk W.: Carbohydr. Res. 1980, 79, 39.
2. Rosenbohm C., Berghe D. V., Vlietinck A., Wengel J.: Tetrahedron 2001, 57, 6277.
3. a) Trtek T., Černý M., Trnka T., Buděšínský M., Císařová I.: Collect. Czech. Chem.
Commun. 2003, 68, 1295; b) Trtek T., Černý M., Trnka T., Buděšínský M., Císařová I.:
Collect. Czech. Chem. Commun. 2004, 69, 1818.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)

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Trtek, Černý, Buděšínský, Trnka, Císařová:
4. Jindřich J., Černý M., Trnka T., Buděšínský M.: Collect. Czech. Chem. Commun. 1991, 56,
2950.
5. Černý M., Trnka T., Redlich H.: Carbohydr. Res. 1988, 174, 349.
6. Černý M., Gut V., Pacák J.: Collect. Czech. Chem. Commun. 1961, 26, 2542.
7. a) Kelly A. G., Roberts J. S.: J. Chem. Soc., Chem. Commun. 1980, 228; b) Kalè V. N., Clive
D. L. J.: J. Org. Chem. 1984, 49, 1554.
8. Richman J. E., Atkins T. J.: J. Am. Chem. Soc. 1974, 96, 2268.
9. a) Angyal S. J., Dawes K.: Aust. J. Chem. 1968, 21, 2747; b) Černý M., Staněk J., Jr.: Adv.
Carbohydr. Chem. Biochem. 1977, 34, 23.
10. Grindley T. B., Cude A., Kralovic J., Thangarasa R. in: Levoglucosenone and Levoglucosans,
Frontiers in Biomedicine and Biotechnology (Z. J. Witzak, Ed.), Vol. 2, p. 147. ATL Press,
Mount Prospect (IL) 1994.
11. Altomare A., Cascarano G., Giacovazzo C., Guagliardi A., Burla M. C., Polidori G.,
Camalli M.: J. Appl. Crystallogr. 1994, 27, 435.
12. Sheldrick G. M.: SHELXL97, Program for Structure Determination. University of Göttingen,
Göttingen 1997.
13. Spek A. L.: PLATON, A Multipurpose Crystallographic Tool. Utrecht University, Utrecht
2001.
Collect. Czech. Chem. Commun. (Vol. 70) (2005)