Synthesis and conformation of 6-amino-3,6-dideoxyhexono-1,6-lactams

Article abstract of DOI:10.1135/cccc20020622

Three isomeric 6-amino-3,6-dideoxyhexono-1,6-lactams of D-ribo (1a), L-lyxo (2a) and L-arabino (3a) configuration were synthesized via the corresponding 6-azido-3,6-dideoxyhexoses starting from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose. Conformation o

Full text of DOI:10.1135/cccc20020622

622
Hamerníková et al.:
SYNTHESIS AND CONFORMATION
OF 6-AMINO-3,6-DIDEOXYHEXONO-1,6-LACTAMS
b
c
Michaela HAMERNÍKOVÁa1,*,+, Jaroslav HAVLÍČEK , †Hana VOTAVOVÁ
a2
and Karel KEFURT
a
Department of Chemistry of Natural Compounds, Institute of Chemical Technology, Prague,
166 28 Prague 6, Czech Republic; e-mail: 1hamernikova@faf.cuni.cz, karel.kefurt@vscht.cz
2
b
Department of Analytical Chemistry, Institute of Chemical Technology, Prague,
166 28 Prague 6, Czech Republic; e-mail: jaroslav.havlicek@vscht.cz
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
c
166 10 Prague 6, Czech Republic
Received Jan uary 17, 2002
Accepted April 17, 2002
Th ree isom eric 6-am in o-3,6-dideoxyh exon o-1,6-lactam s of D-ribo (1a ), L-lyxo (2a ) an d
L-arabino (3a) con figuration were syn th esized via th e correspon din g 6-azido-3,6-dideoxy-
h exoses startin g from 1,2:5,6-di-O-isopropyliden e-α-D-glucofuran ose. Con form ation of lac-
tam s 1a, 2a an d 3a an d th eir tri-O-acetyl derivatives 1b, 2b an d 3b was studied usin g NMR
spectroscopy. CD spectra of th e lactam s 1a–3a, togeth er with th e D-xylo diastereoisom er 4a,
were m easured an d in terpreted accordin g to sem iem pirical rules. NMR an d CD m easure-
m en ts con firm ed th e ch air con form ation with an equatorial substituen t on C-2 as prevailin g
for th e all m easured lactam s.
Keywords: Carboh ydrates; Lactam s; Am in o sugars; Con form ation an alysis; NMR spectroscopy;
Circular dich roism .
Con form ation of am in odeoxyh exon olactam s h as been studied in our labo-
ratory for a lon g period. In vestigation s h ave so far con cen trated on
6-am in o-6-deoxyh exon o-1,6-lactam s1–9 an d 5-am in o-5-deoxypen ton o-1,5-
lactam s10,11. Th e con form ation al study of six- an d seven -m em bered lactam
rin gs perform ed by NMR, IR, CD spectroscopy4,5,9,11 an d X-ray m easure-
m en ts6–8 open ed discussion on th e relation sh ip between lactam con figura-
tion an d con form ation of th e lactam rin g especially with regard to
in terpretation of CD spectra4. In addition to th e stereoch em ical aspects,
+ Presen t address: Departm en t of Bioph ysics an d Ph ysical Ch em istry, Faculty of Ph arm acy,
Ch arles Un iversity, Heyrovskéh o 1203, 500 05 Hradec Králové, Czech Republic.
Collect. Czech. Chem. Commun. (Vol. 67) (2002)
doi:10.1135/cccc20020622

6-Amino-3,6-dideoxyhexono-1,6-lactams
623
an y kn owledge of stereoch em istry of lactam rin gs is sign ifican t also in con -
n ection with biological effects of th ese an d related com poun ds, n am ely,
with th eir poten tial action as in h ibitors of glycosidases (see refs12–14).
Followin g our previous paper9, we presen t h ere syn th eses an d con -
form ation al NMR studies of 6-am in o-3,6-dideoxy-D-ribo-h exon o-1,6-lactam
(1a), 6-am in o-3,6-dideoxy-L-lyxo-h exon o-1,6-lactam (2a) an d 6-am in o-3,6-
dideoxy-L-arabino-h exon o-1,6-lactam (3a), an d th eir 2,4,5-tri-O-acetyl de-
rivatives 1b, 2b an d 3b, respectively. Con clusion s from NMR are com pared
with CD m easurem en t of th e lactam s 1a–3a an d of th e previously de-
scribed9 6-am in o-3,6-dideoxy-D-xylo-h exon o-1,6-lactam (4a).
R1
OH
OAc
OH
OAc
H
H
H
H
R2
H
H
H
H
OH
OAc
OH
OAc
R3
OH
OAc
H
H
H
H
OH
OAc
R4
H
H
OH
OAc
OH
OAc
H
R4
R3
1a
1b
2a
2b
3a
3b
4a
4b
R2
R1
NH
C O
OH
H
RESULTS AND DISCUSSION
Synthesis
Th ree n ew studied lactam s 1a–3a were prepared via correspon din g 6-azido-
3,6-dideoxyh exoses. 1,2:5,6-Di-O-isopropyliden e-α-D-glucofuran ose (5) was
used as startin g com poun d for syn th esis of lactam 1a (Sch em e 1). Th e
h ydroxy group in position 3 of was displaced by iodin e with th e in version
of con figuration usin g iodin e, triph en ylph osph in e an d im idazole in tolu-
en e15. 3-Deoxy-3-iodo-1,2:5,6-di-O-isopropyliden e-α-D-allofuran ose (6) was
reduced with h ydrogen on 5% Pd/C in th e presen ce of trieth ylam in e to
3-deoxy-1,2:5,6-di-O-isopropyliden e-α-D-ribo-h exofuran ose (7). Partial h y-
drolysis of th is com poun d with dilute acetic acid led to 3-deoxy-1,2-O-iso-
propyliden e-α-D-ribo-h exofuran ose (8) with th e ph ysical con stan ts iden tical
with th ose in literature15
.
We m odified th e two-step process from 6 to 8 to an “on e-pot” syn th esis
usin g acidity of h ydrogen iodide form in g durin g th e reduction to produce
directly th e partially h ydrolysed product 8. Reduction of startin g iodo de-
rivative 6 in m eth an ol with out trieth ylam in e resulted in a sm all am oun t of
deoxy derivative 7. Th e presen ce of h ydrogen iodide in th is step deceler-
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

624
Hamerníková et al.:
ated th e reduction an d caused th e partial h ydrolysis of 6 to 3-deoxy-
3-iodo-1,2-O-isopropyliden e-α-D-allofuran ose (9) wh ich was com plete in
several h ours. Th en , trieth ylam in e an d th e fresh 5% Pd/C were added to
th e reaction m ixture. Hydrogen olysis gave a sin gle product 8. Selective
tosylation of com poun d
8
afforded16 3-deoxy-1,2-O-isopropyliden e-
O
O
I2, PPh3,
imidazole,
toluene
O
O
O
O
OH
O
O
I
O
O
5
6
H2/Pd
Et3N
H2/Pd
MeOH
HO
HO
O
O
O
O
O
O
O
I
O
H2/Pd
Et3N
9
7
H+
R
N3
HO
HO
O
O
H+
OH
O
OH
O
12
8, R = OH
10, R = OTs
11, R = N3
TsCl, py
Br2, H2O
BaCO3
NaN3, DMF
N3
RO
O
H2/Pd
MeOH
O
Ac2O, py
1b
1a
OH
13, R = H
14, R = Ac
A2O, py
SCHEME 1
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6-Amino-3,6-dideoxyhexono-1,6-lactams
625
6-O-tosyl-α-D-ribo-h exofuran ose (10). Treatm en t of 10 with sodium azide in
dim eth ylform am ide yielded 6-azido-3,6-dideoxy-1,2-O-isopropyliden e-
1
α-D-ribo-h exofuran ose (11). H NMR spectrum of th is com poun d was in ac-
cord with th e described on e17. Acid h ydrolysis of azido derivative 11 gave17
th e syrupy 6-azido-3,6-dideoxy-D-ribo-h exose (12). Oxidation of 12 by
m ean s of brom in e in water in th e presen ce of barium carbon ate led to
6-azido-3,6-dideoxy-D-ribo-h exon o-1,4-lacton e (13). Th e stretch in g absorp-
tion on 1 744 cm –1 would give eviden ce rath er for th e six-m em bered
1
lacton e rin g, but th e H NMR spectrum con firm ed th e five-m em bered rin g,
especially because of th e ch em ical sh ift of H-4 (≈4.7 ppm ) an d th e great
1
couplin g con stan ts between H-2, H-3′, H-3, H-4. In th e H NMR spectrum
of 2,5-di-O-acetyl-6-azido-3,6-dideoxy-D-ribo-h exon o-1,4-lacton e (14), th e
sign als of H-2 an d H-5 were desh ielded, wh ich m ade th e spectrum easily
“readable” an d con firm ed also th e five-m em bered lacton e rin g. Lacton e 13
was reduced by m ean s of h ydrogen on 5% Pd/C in m eth an ol to 6-am in o-
3,6-dideoxy-D-ribo-h exon o-1,6-lactam (1a), wh ich was recrystallized from
h ot m eth an ol. Con ven tion al acetylation of lactam 1a with acetic an h y-
dride in pyridin e gave tri-O-acetyl derivative 1b.
For th e preparation of 6-am in o-6-deoxy-L-lyxo-h exon o-1,6-lactam (2a)
(Sch em e 2), we used th e in version of con figuration on C-5 of com poun d 8
via 5,6-an h ydro-3-deoxy-1,2-O-isopropyliden e-β-L-lyxo-h exofuran ose (17).
Accordin g to th e described18 procedure, 17 was prepared by alkalin e
cyclization of 6-O-ben zoyl-3-deoxy-1,2-O-isopropyliden e-5-O-tosyl-α-D-
ribo-h exofuran ose (16) obtain ed from 6-O-ben zoyl-3-deoxy-1,2-O-iso-
propyliden e-α-D-ribo-h exofuran ose (15). We were successful in th e prepara-
tion of 16 also by regioselective displacem en t of a tosyloxy group in
3-deoxy-1,2-O-isopropyliden e-5,6-di-O-tosyl-α-D-ribo-h exofuran ose (18)
with ben zoyloxy group usin g sodium ben zoate in dim eth ylform am ide. Th e
form ation of an h ydro com poun d 17 in cluded two steps: deben zoylation
followed by n ucleoph ilic cyclization of 3-deoxy-1,2-O-isopropyliden e-5-O-
tosyl-α-D-ribo-h exofuran ose (19). Provided th at th e reaction was perform ed
at room tem perature, we were able to isolate in term ediate 19. Treatm en t of
com poun d 17 with sodium azide in dim eth ylform am ide caused th e
n ucleoph ilic open in g of th e an h ydro rin g to produce 6-azido-3,6-dideoxy-
1,2-O-isopropyliden e-β-L-lyxo-h exofuran ose (20). Acid h ydrolysis of 20 led
to 6-azido-3,6-dideoxy-L-lyxo-h exose (21). In oxidation of 21 with brom in e
in water, th e correspon din g lacton e was form ed (accordin g to TLC), but it
was rapidly h ydrolyzed so th at on ly 6-azido-3,6-dideoxy-L-lyxo-h exon ic
acid (22) was isolated. Structure of 22 was con firm ed by IR spectra exh ibit-
in g ban ds of associated OH groups (3 438, 3 340, 3 295 cm –1), a ch aracteris-
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

626
Hamerníková et al.:
BzO
HO
HO
HO
TsO
TsO
O
O
O
BzCl, py
TsCl, py
O
O
O
O
8
18
15
O
O
TsCl, py
NaOBz, DMF
BzO
TsO
HO
TsO
O
O
NaOMe, MeOH
O
O
O
O
16
19
N3
NaOMe, MeOH, ∆
OH
O
NaN3,
2-methoxyethanol
O
O
O
O
20
O
O
17
H+
COOR1
OH
N3
OH
O
Br2, H2O, BaCO3
CH2
OH
OH
HO
OH
R2
21
22, R1 = H, R2 = N3
23, R1 = H, R2 = NH2
24, R1 = CH3, R2 = NH2·HCl
H2/Pd
HCl, MeOH
NaOMe, MeOH
2a, R = H
Ac2O, py
2b, R = Ac
SCHEME 2
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6-Amino-3,6-dideoxyhexono-1,6-lactams
627
tic series of absorption s at 2 930–2 500 cm –1 an d carboxylate ban ds at
1 730–1 636 an d 1 404 cm –1. 6-Am in o-3,6-dideoxy-L-lyxo-h exon ic acid (23)
was prepared by catalytic reduction of 22. IR spectrum exh ibited an expres-
sive ban d of associated am in o an d h ydroxy groups at 3 600–2 500 cm –1
,
an d a carboxylate ban d (1 765–1 615, 1 405 cm –1). Am in o acid 23 was
treated with h ydrogen ch loride in m eth an ol to form m eth yl ester h ydro-
ch loride 24 wh ich was tran sform ed with out isolation to 2,4,5-tri-O-acetyl-
6-am ino-3,6-dideoxy-L-lyxo-hexono-1,6-lactam (2b) with sodium m ethanolate
in m eth an ol an d acetylated. Acetate 2b after ch rom atograph ic purification
was treated with sodium m eth an olate in m eth an ol an d th e resultin g solu-
tion n eutralized with ion exch an ger in H+ gen eration . Structure of syrupy
6-am in o-3,6-dideoxy-L-lyxo-h exon o-1,6-lactam (2a) was con firm ed by
NMR, IR an d elem en tal an alysis.
In th e preparation of 6-am in o-6-deoxy-L-arabino-h exon o-1,6-lactam (3a),
5,6-an h ydro-3-deoxy-1,2-O-isopropyliden e-β-L-arabino-h exofuran ose (25)
was th e key in term ediate (Sch em e 3). 3-Deoxy-1,2-O-isopropyliden e-α-D-
xylo-h exofuran ose19,20 (26) was con verted to 6-O-ben zoyl-3-deoxy-1,2-O-
isopropyliden e-5-O-tosyl-α-D-xylo-h exofuran ose (27). We suggested two
path ways for th is preparation . Th e first procedure in cluded partial ben zoyla-
tion of 26 yieldin g m ain ly 6-O-ben zoyl-3-deoxy-1,2-O-isopropyliden e-
α-D-xylo-h exofuran ose (28) as expected, but also 8% of 5-O-ben zoyl-
3-deoxy-1,2-O-isopropyliden e-α-D-xylo-h exofuran ose (29), 4% of 5,6-di-O-
ben zoyl-3-deoxy-1,2-O-isopropyliden e-α-D-xylo-h exofuran ose (30) an d th e
un reacted startin g m aterial. Tosylation of 6-ben zoate 28 led to 5-O-tosyl de-
rivative 27. Structures of com poun ds 27, 28, 29 an d 30 were con firm ed by
NMR. Th e n um ber of arom atic proton s could be observed in th e region 7–9
ppm , th e position s of ben zoyloxy groups resulted on th e desh ieldin gs of
sign als H-5 an d H-6. A better route to th e preparation of com poun d 27
started from 3-deoxy-1,2-O-isopropyliden e-5,6-di-O-tosyl-α-D-xylo-h exo-
furan ose (31). Treatm en t of 31 with sodium ben zoate in dim eth yl-
form am ide yielded 90% of com poun d 27 wh ich after alkalin e
deben zoylation afforded 74% of 5,6-an h ydro derivative 25 an d 10% of
3-deoxy-1,2-O-isopropyliden e-5-O-tosyl-α-D-xylo-h exofuran ose (32) at room
tem perature or 80% of 25 at 50 °C. Th e form ation of th e an h ydro rin g in
position s 5 an d 6 was in 1H NMR accom pan ied by th e upfield sh ift of sig-
n als H-6 an d H-6′ by 2 ppm an d by th e reduction of th e gem in al spin –spin
couplin g con stan ts between proton s H-6 an d H-6′ in α-position to th e
2
oxiran e oxygen to th e value J6,6´ ≈ 5 Hz. Nucleoph ilic open in g of th e
oxiran e rin g by an azide an ion led to 6-azido-3,6-dideoxy-1,2-O-isopropyl-
iden e-β-L-arabino-h exofuran ose (33). Th is com poun d exh ibited IR absorp-
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

628
Hamerníková et al.:
tion s at 2 107 cm –1 (azide), 3 466 cm –1 (h ydroxyl) an d a ben din g doublet
on 1 377 an d 1 374 cm –1 (isopropyliden e). Th e structure was con firm ed by
NMR an d by com parison of th e data with th ose described17 for D-en an tio-
m er. Com poun d 33 was quan titatively h ydrolyzed un der acid con dition s to
produce 6-azido-3,6-dideoxy-L-arabino-h exose (34). It was oxidized sim ilarly
– as m en tion ed above – to 6-azido-3,6-dideoxy-L-arabino-h exon o-1,4-lacton e
(35). Th e five-m em bered lacton e was ch aracterized in IR spectrum by th e
elevated waven um ber of a carbon yl ban d (1 776 cm –1). In 1H NMR spec-
trum th is fact is eviden t from th e in creased ch em ical sh ift of H-4. Th e great
spin –spin in teraction s between proton s H-2, H-3 an d H-3, H-4 give evi-
den ce of th e prevailin g E3 con form ation of th e lacton e rin g. Azidolacton e
O
O
O
TsCl, py
BzCl, py
O
O
O
O
OH
O
O
OR1
OR2
OR1
OR2
OH
26
28, R1 = H, R2 =Bz
29, R1 = Bz, R2 = H
30, R1 = R2 = Bz
31, R1 = R2 = Ts
27, R1 = Ts, R2 = Bz
TsCl, py
NaOBz, DMF
NaOMe, MeOH
O
O
NaN3,
2-methoxyethanol
O
NaOMe, MeOH
O
O
O
∆
O
O
HO
O
O
OTs
N3
25
OH
32
33
H+
O
O
Br2, H2O, BaCO3
O
OH
H2/Pd, MeOH
HO
HO
OH
OH
N3
N3
34
SCHEME 3
3a
3b
Ac2O, py
35
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6-Amino-3,6-dideoxyhexono-1,6-lactams
629
35 was reduced with h ydrogen on 5% Pd/C in m eth an ol to give 6-am in o-
3,6-dideoxy-L-arabino-h exon o-1,6-lactam (3a). Con ven tion al acetylation af-
forded th e correspon din g tri-O-acetyl derivative 3b.
Conformational Analysis
Because of th e approxim ately plan ar arran gem en t of th e am ide segm en t, a
4
seven -m em bered lactam rin g is able to exist as a C1,N or 1,NC4 ch air an d
BN,1,4 or 4,1,NB boat con form ers (Fig. 1).
NMR Measurem en ts
Th e con form ation al study of cyclic com poun ds is based on m odified
Karplus’s equation 21. For each substituted HaR1R2C-CR3R4Hb segm en t in a
lactam m olecule it is possible, accordin g to m odified Karplus’s equation 21
,
to calculate th e couplin g con stan ts for an arbitrary torsion an gle
HaR1R2C-CR3R4Hb. A com parison of th e couplin g con stan ts, foun d in th e
4
1H NMR spectra, with th e values calculated for C1,N an d 1,NC4 con form ers
m akes it possible to determ in e th e prevailin g con form er. Eigh t con figura-
tion isom ers of 6-am in o-6-deoxyh exon olactam s4 an d four isom ers of
5-am in o-5-deoxypen ton olactam s11 h ave been studied previously. 1H NMR
con form ation al an alysis revealed th e predom in an ce of th e con form er with
H
N
NH
C
O
C
O
4,1,NB
BN,1,4
H
N
C
O
NH
C
O
4C1,N
1,NC4
FIG. 1
Possible con form ation of seven -m em bered lactam rin g
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

630
Hamerníková et al.:
equatorial h ydroxy or acetoxy group on C-2, even in th e case of 6-am in o-
6-deoxy-L-gulon olactam with th ree rem ain in g axial groups. Sim ilar situa-
tion was observed studyin g 5-am in o-5-deoxypen ton olactam s11. Th is fact
was discovered previously22,23 an d h as been explain ed by th e in teraction of
π-electron s of a carbon yl group with th e lon e electron pair of th e h etero-
atom of th e n eigh bourin g substituen t. A plan e arran gem en t desirable for
in teractin g atom s is available rath er for equatorial th an for axial substituen t
on C-2. In order to study th e solution con form er equilibrium in our set of
lactam s, we perform ed low-tem perature NMR spectroscopy. Geom etries of
4C1,N an d 1,NC4 con form ers were optim ized usin g m olecular m ech an ics
(MM+) in vacuum 24 to obtain th e th eoretical values of torsion an gles be-
tween vicin al proton s. Con form ation of 6-am in o-3,6-dideoxy-D-xylo-
h exon o-1,6-lactam (4a) an d its tri-O-acetyl derivative 4b h as been studied
4
recen tly9 an d th e C1,N (D) con form er was foun d both in solution s of lac-
tam s 2a, 2b or in th e solid 2a. Th e decisive effect of th e equatorial h ydroxy
group on C-2 caused in th is case th e axial position s of th e rem ain in g OH
groups.
1H NMR spectrum of 6-am in o-3,6-dideoxy-D-ribo-h exon o-1,6-lactam (1a)
4
at 300 an d 340 K revealed th e prevailin g C1,N con form er in solution
(Tables I–III). Low-tem perature NMR experim en ts did n ot record an y
ch an ges eith er in ch em ical sh ifts or in th e values of couplin g con stan ts.
Th e n uclear Overh auser effect between H-2 an d H-6′, H-4, H-3´ (Fig. 2) con -
4
firm ed th e C1,N con form er with two equatorial an d on e axial h ydroxy
groups. NOE between H-3′ an d H-5 supportin g th e less advan tageous 1,NC4
con form er was n ot observed.
1H NMR spectrum of 6-am in o-3,6-dideoxy-L-lyxo-h exon o-1,6-lactam (2a)
recorded in deuterium oxide at 300 K exh ibited a quartet of H-3 at 1.82 ppm
split with th ree couplin g con stan ts J ≈ 11 Hz wh ich correlates with geom e-
4
try of th e C1,N con form er (Tables I an d III) with th ree equatorial OH
groups. Th e low-tem perature 1H NMR spectrum of correspon din g tri-O-
acetyl derivative 2b is sim ilar to th e spectrum recorded at n orm al tem pera-
FIG. 2
NOE in 6-am in o-3,6-dideoxy-D-ribo-h exon o-1,6-lactam (1a)
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

6-Amino-3,6-dideoxyhexono-1,6-lactams
631
TABLE I
1H NMR (500 MHz) of lactam s 1a, 2a, 3a in CD3SOCD3 (A), CD3OD (B), D2O (C), an d th eir
tri-O-acetyl derivatives 1b, 2b, 3b in CDCl3 (D)
1a
1b
2a
2b
3a
3b
Param eter
a
b
c
d
e
f
A
B
B
D
C
D
D
A
B
B
D
300 K 200 K 300 K
300 K
300 K
300 K 210 K
300 K 300 K 190 K
300 K
Ch em ical sh ifts (δ-scale, ppm )
H-2
4.00
(d)
4.29
(d)
4.19
(dd)
5.20
(dd)
4.51
(dd)
5.30
(dd)
5.20
(d)
4.40
(d)
4.69
(dd)
4.74
(d)
5.59
(dd)
1.68
(ddd) (q)
2.00
1.98
(ddd)
2.33
(q)
1.82
(q)
2.15
(q)
2.17
(m )
1.64
1.89
2.01
2.28
(ddd)
H-3
H-3′
H-4
H-5
H-6
H-6′
NH
g
g
(ddd) (ddd) (m )
1.65
(dd)
1.85
(d)
1.83
(d)
2.05
2.16
(dd)
2.36
(ddd) (d)
2.36
1.85
2.12
2.01
2.22
(ddd)
g
g
(m )
(ddd) (ddd) (m )
3.59
(ddd) (d)
3.81
3.79
(ddd)
5.10
(ddd)
3.75
(ddd)
5.26
(ddd) (bs)
5.09
3.83
(bs)
4.07
(d)
4.07
(bs)
5.49
(bs)
3.63
(dd)
3.84
(s)
3.84
(s)
5.18
(dd)
3.38
(ddd)
4.81
(ddd) (bs)
4.84
3.28
(d)
3.52
(d)
3.51
(d)
4.83
(d)
3.03
(ddd) (dd)
3.24
3.25
(dd)
3.56
(ddd)
3.18
(dd)
3.43
(dd)
3.55
2.63
(dd)
2.89
(d)
2.79
(d)
3.11
(dd)
g
(m )
3.10
(dd)
3.31
(d)
3.30
(d)
3.47
(dd)
3.24
(dd)
3.33
(ddd) (m )
3.55
3.43
(ddd) (dd)
3.67
3.70
(dd)
3.88
(ddd)
g
7.62
(s)
6.05
(t)
3.93
(bs)
7.28
(s)
7.85
–
6.22
(bs)
–
–
–
–
(bs)
3
Couplin g con stan ts J(H,H) in Hz
J(2,3)
10.3
<0.5
10.4
4.2
11.6
<0.5
11.6
<0.5
10.7
3.0
11.6
4.0
12.9
3.0
6.6
<0.5
15.6
–
12.3
1.5
11.8
1.7
11.7
4.7
11.7
9.0
3.4
9.4
15.0
–
11.9
1.5
12.1
11.2
1.9
11.5
2.2
9.3
10.9
2.5
J(2,3′)
J(3,4)
<0.5
<0.5
g
g
12.3
4.0
11.3
4.8
1.8
2.1
2.4
g
g
g
J(3′,4)
J(3,3′)
J(4,5)
5.4
5.5
5.6
12.2
2.5
11.6
12.3
2.7
13.4
9.5
10.6
14.0
<0.5
<0.5
10.2
14.0
6.3
14.3
<0.5
<0.5
10.5
14.3
–
14.9
<0.5
<0.5
10.1
13.0
7.0
g
g
<0.5
<0.5
9.3
11.1
–
g
g
g
g
g
J(5,6)
5.6
4.2
<0.5
11.5
–
6.2
3.0
J(5,6′)
J(6,6)
<0.5
15.1
7.3
<0.5
16.0
7.6
10.0
15.5
10.3
2.9
J(6,NH)
J(6′,NH)
4.7
–
–
5.4
–
4.9
–
–
5.4
a
b
c
Oth er sign als: 4.70, 4.50, 4.27 (3 s, 3 H, 3 OH); 2.16, 2.11, 2.03 (3 s, 9 H, 3 OAc); 2.20,
d
e
2.09, 2.08 (3 s, 9 H, 3 OAc); 2.17 (1 s, 9 H, 3 OAc); 4.80, 4.73, 4.20 (3 s, 3 H, 3 OH);
2.06, 2.18, 2.19 (3 s, 9 H, 3 OAc); overlappin g sign als.
f
g
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

632
Hamerníková et al.:
TABLE II
13C NMR (75 MHz) ch em ical sh ifts (δ-scale, ppm ) of lactam s 1a, 2a in D2O (A) an d 3a in
CD3SOCD3 (B), an d th eir acetyl derivatives 1b, 2b an d 3b in CDCl3 (C)
Param eter
1a (A)
1b (C)
2a (A)
2b (C)
3a (B)
3b (C)
C-1
C-2
C-3
C-4
C-5
C-6
176.1
65.2
35.8
71.6
67.9
41.4
–
171.9
68.2
29.7
72.1
68.4
40.4
177.8
64.9
38.7
52.6
55.0
42.3
–
172.2
67.3
33.5
72.7
73.3
41.5
177.8
61.9
35.5
66.7
68.7
37.8
–
173.0
68.6
30.4
68.5
72.1
39.7
170.8
170.7
170.5
170.7
170.6
170.6
170.7
170.5
170.3
COCH3
COCH3
–
21.3
21.3
21.1
–
21.4
21.3
21.2
–
21.7
21.4
21.4
TABLE III
4
Calculated values of vicin al couplin g con stan ts 3J(H,H) (in Hz) in th e C1,N an d 1,NC4 con -
form ers of 6-am in o-3,6-dideoxyh exon o-1,6-lactam s 1a, 2a, an d 3a
Lactam
1a
2a
3a
4
J(2,3) C1,N
11.5
6.3
2.1
1.1
11.3
4.5
4.3
2.2
2.1
2.2
5.9
10.8
0.9
2.8
11.6
6.7
1.9
1.2
11.3
4.3
4.3
2.2
8.9
2.7
2.9
0.9
10.9
5.9
11.6
6.9
2.1
1.1
1.8
4.4
4.8
11.2
2.3
2.2
2.8
0.9
10.9
5.9
J(2,3) 1,NC4
4
J(2,3′) C1,N
J(2,3′) 1,NC4
4
J(3,4) C1,N
J(3,4) 1,NC4
4
J(3′,4) C1,N
J(3′,4) 1,NC4
4
J(4,5) C1,N
J(4,5) 1,NC4
4
J(5,6) C1,N
J(5,6) 1,NC4
4
J(5,6′) C1,N
J(5,6′) 1,NC4
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

6-Amino-3,6-dideoxyhexono-1,6-lactams
633
ture. NOE observed between H-2, H-6′ an d H-4 con firm s th eir axial posi-
4
tion s (Fig. 3) an d supports th e prevailin g C1,N con form er. Th e directive
in fluen ce of th e equatorial h ydroxy groups on C-2 is in th is case in accor-
dan ce with th e in fluen ce of h ydroxy groups on C-4 an d C-5, so th at th e oc-
curren ce of th e 1,NC4 con form er is practically im possible.
4
Prevailin g C1,N (L) con form ation of 6-am in o-3,6-dideoxy-L-arabino-
h exon o-1,6-lactam (3a) an d of th e correspon din g tri-O-acetyl derivative 3b
1
is eviden t from com parison of H NMR spectra (Table I) with th e calculated
values of th e couplin g con stan ts (Table III). Th e expected m ore advan ta-
4
geous C1,N con form er was con firm ed also by low-tem perature 1H NMR
with out im portan t ch an ges in ch em ical sh ifts an d couplin g con stan ts an d
by NOE between H-3 an d H-5, H-2 an d H-6 (Fig. 4).
CD Measurem en t
Th e lactam rule25–27, applicable to four- to seven -m em bered rin gs, describes
th e relation sh ip between th e con form ation of a lactam rin g an d th e sign of
th e Cotton effect. Th e quadran t (am ide) rule28–30 projects th e m olecule in
quadran ts. Th e sign of th e Cotton effect is given as th e sum of con tribu-
tion s of particular atom s in cludin g substituen ts. Japan ese auth ors22,23 stud-
FIG. 3
NOE in 2,4,6-tri-O-acetyl-6-am in o-3,6-dideoxy-L-lyxo-h exon o-1,6-lactam (2b)
FIG. 4
NOE in 6-am in o-3,6-dideoxy-L-arabino-h exon o-1,6-lactam (3a)
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

634
Hamerníková et al.:
ied circular dich roism of five- an d six-m em bered lactam s substituted in
α-position to carbon yl by groups with a h eteroatom s with lon e electron
pairs (OR, NR2, SR). Th ey revealed a crucial effect of th e con figuration on
th e atom n eigh borin g to carbon yl on th e sign of th e Cotton effect. Th e ex-
isten ce of an in h eren tly ch iral ch rom oph ore arisin g by th e in teraction be-
tween π-electron s of th e carbon yl an d th e lon e electron pair of th e
substituen t was suggested. Th ese in vestigation s lead to th e followin g rule:
com poun ds with R con figuration on C-2 sh ow a n egative Cotton effect,
wh ereas S con figuration on C-2 gives rise to positive Cotton effect.
Th e study of ch iroptic properties of bi- an d tricyclic lactam s31,32 led to
th e form ulation of th e spiral rule for n on -plan ar am ides. Am ides with a
positive torsion an gle O=C1–N–C6 exh ibite a n egative Cotton effect an d
vice versa. Th is m ean s th at a n egative Cotton effect correspon ds to a n ega-
tive torsion an gle33 C2–C1–N–C6 (Fig. 5).
Circular dich roism was studied on ly in th e case of free lactam s 4a, 1a, 2a
an d 3a with a sin gle ch rom oph or -CONH. In all spectra, ban ds with a n ega-
tive Cotton effect at 195 n m belon gin g to th e π→π* tran sition were foun d
but th ey are n ot con ven ien t for stereoch em ical con clusion s. Ban ds lyin g
above 200 n m belon gin g to th e n →π* tran sition were an alyzed in th is
study. For con form ation al study of lactam s of D- an d L-con figuration , we
form ally con verted th e obtain ed data to a sin gle con figuration al series by
m ultiplication of m easured values ∆ε of lactam s 2a an d 3a by –1. Table IV
sh ows CD ban ds recorded in CD spectra of four studied lactam s.
Th e sign s of extrem es foun d in th e ran ge 208–215 n m correspon d
4
accordin g to lactam 25–27 an d am ide28–30 rules with th e observed C1,N (D) or
1,NC4 (D) con form ation (Table V). Th e rem ain in g rule22,23 predicts th e oppo-
site sign of Cotton effect to th e observed con form ation s. Accordin g to
X-ray an alysis9, th e am ide segm en t in th e crystallin e lactam 4a is n ot quite
plan ar, with a torsion an gle C6–N–C1–C2 Φ = +5°. On con dition th e un ity
of lactam con form ation s in solid state an d in th e solution th is fact supports
th e validity of spiral rule31,32, accordin g to wh ich th e positive Cotton effect
correspon ds with th e positive torsion an gle of am ide n on -plan arity.
H
C2
C1
O
C6
FIG. 5
Torsion an gles in n on -plan ar am ide
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

6-Amino-3,6-dideoxyhexono-1,6-lactams
635
TABLE IV
Circular dich roism of lactam s 1a, 2a, 3a, an d 4a
Con form ation in
Con figuration on
CD ban ds λ, n m ;
∆ε, cm 2 m m ol–1
Sign of Cotton
Lactam
solution
C-2
effect
(from 1H NMR)
a
1a
R
S
4C1,N (D)
1,NC4 (D)
215, –0.15;
236, –0.2
+
–
2a (D)b
215, –0.07;
227, +0.13
–
+
3a (D)b
R
S
1,NC4 (D)
4C1,N (D)
208, –2.4
212, +1.8
–
4a
+
a
b
Negative m in im um correspon din g to positive ban d. Th e actually m easured com poun d
was of th e L-con figuration an d its ∆ε ban d h ad th e opposite sign th an given in Table IV.
TABLE V
Th eoretical sen se of CD ban ds accordin g to sem iem pirical rules
Sign of Cotton effect
Lactam
lactam rule (refs25–27
)
am ide rule (refs28–30
)
m eguro (refs22,23
)
4a
+
+
–
–
+
+
–
–
–
–
+
+
1a
2a (D)a
3a (D)a
a
Th e actually m easured com poun d was of th e L-con figuration an d its ∆ε ban d h ad th e op-
posite sign th an given in Table V.
EXPERIMENTAL
Meltin g poin ts were determ in ed on a Kofler block an d are un corrected. Optical rotation s
were m easured with an Opton ph otoelectric polarim eter at 20 °C, [α]D values are given in
10–1 deg cm 2 g–1. NMR spectra in CDCl3, CD3OD, CD3SOCD3 an d D2O were recorded with
Bruker AM 400 in strum en t (1H at 400 MHz, 13C at 100 MHz), 300HC Varian Gem in i 2000
(1H at 300 MHz, 13C at 75 MHz) an d Bruker AVANCE DRX 500 (1H at 500 MHz, 13C at
125 MHz) in strum en ts. Ch em ical sh ifts are given in ppm (δ-scale), couplin g con stan ts (J)
in Hz. Most of m easurem en ts were recorded at 300 K, low-tem perature experim en ts at
190–210 K. Assign m en ts of sign als were proved by 2D h om on uclear an d h eteron uclear cor-
related spectra (1H-1H COSY, 1H-13C HETCOR) or spectra based on APT experim en ts. NOE
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

636
Hamerníková et al.:
experim en ts were m ade usin g th e DPFGSE-NOE m eth od34. IR spectra (waven um bers in cm –1
)
were m easured with a Nicolet 750 FT IR in strum en t in ch loroform solution s, KBr pellets
or film s. UV spectra were m easured with an M 40 Carl Zeiss Jen a in strum en t in water.
CD spectra of lactam s m easured in th e ran ge 190–260 n m in water (con cen tration s
ca 1 · 10–3 m ol l–1) were obtain ed usin g a Jobin –Yvon dich rograph Mark V. Th e data are
given as differen ces of m olar absorption coefficien ts for th e left an d righ t polarized ligh t,
∆ε = εΛ – εR (cm 2 m m ol–1).
Th e geom etry of lactam s was optim ized usin g MM+ m olecular m ech an ics24. Colum n
ch rom atograph y was carried out on silica gel (Lach em a Brn o, 100–200 µm ). Reaction s were
m on itored by TLC on silica gel G (Merck, 10–40 µm ) in petroleum eth er–eth yl acetate 2 : 1
(A), toluen e–aceton e 9 : 1 (B), toluen e–aceton e 7 : 3 (C), petroleum eth er–dieth yl eth er 3 : 1
(D) or petroleum eth er–dieth yl eth er–eth yl acetate 6 : 1 : 1 (E) m ixtures, an d 1% solution of
cerium (IV) sulfate in 10% sulfuric acid was used for detection . Solution s were evaporated on
a rotatory vacuum evaporator at 40–50 °C.
3-Deoxy-1,2-O-isopropyliden e-α-D-ribo-h exofuran ose (8)
a) 3-Deoxy-3-iodo-1,2-O-isopropyliden e-α-D-allofuran ose (9; 2.4 g, 7.2 m m ol) was reduced
by 2 h h ydrogen ation in m eth an ol (70 m l) with trieth ylam in e (5 m l). After rem ovin g th e
catalyst, evaporation of th e solven t an d colum n ch rom atograph y of th e crude product
(system C) com poun d 8 (1.48 g, 100%) was isolated.
b) 3-Deoxy-3-iodo-1,2:5,6-di-O-isopropyliden e-α-D-allofuran ose (6; 4.0 g, 10.8 m m ol) was
dissolved in m eth an ol (70 m l) an d reduced with h ydrogen in th e presen ce of 5% Pd/C (1 g).
After 12 h accordin g to TLC (system C), th e h ydrolysis of an isopropyliden e group in posi-
tion 5,6 occurred to give 3-deoxy-3-iodo-1,2-O-isopropyliden e-α-D-allofuran ose (9). After ad-
dition of trieth ylam in e (10 m l), reduction by m ean s of h ydrogen was con tin ued an d after
1 h TLC (C) sh owed quan titative tran sform ation of th e in term ediate to th e desired product
8, wh ich was isolated by th e procedure iden tical to th e procedure a) described above. Col-
um n ch rom atograph y in system C afforded th e syrupy product 8 (1.5 g, 68%). 1H NMR (400
MHz, CDCl3): 5.81 d, 1 H, J(1,2) ≈ 3.6 (H-1); 4.76 t, 1 H, J(2,3) < 0.5, J(2,3′) ≈ 4.1 (H-2); 4.23
dt, 1 H, J(4,3) ≈ J(4,5) ≈ 4.4, J(4,3′) ≈ 10.8 (H-4); 3.94 ddd, 1 H, J(5,6) ≈ 4.0, J(5,6′) ≈ 7.6
(H-5); 3.73 dd, 1 H, J(6,6′) ≈ 11.4 (H-6); 3.60 dd, 1 H (H-6′); 2.13 bs, 2 H (OH); 2.06 dd, 1 H,
J(3,3′) ≈ 13.5 (H-3); 1.85 ddd, 1 H (H-3′); 1.5 s, 3 H (CH3); 1.32 s, 3 H (CH3). Th ese data are
com parable with th ose obtain ed17 at 500 MHz in MeOH-d4.
3-Deoxy-3-iodo-1,2-O-isopropyliden e-α-D-allofuran ose (9)
A solution con tain in g 3-deoxy-3-iodo-1,2:5,6-di-O-isopropyliden e-α-D-allofuran ose (6; 8.0 g,
21.6 m m ol) in m eth an ol (150 m l) was reduced by m ean s of h ydrogen in th e presen ce of 5%
Pd/C (0.68 g). After 12 h , th e reaction m ixture was n eutralized with trieth ylam in e (8 m l),
th en th e catalyst was filtered off an d m eth an ol evaporated. After colum n ch rom atograph y
of th e crude product in system C, th e followin g products were isolated: th e wh ite crystallin e
com poun d 9 (2.4 g, 34%; RF 0.38), m .p. 103–105 °C (ref.35 gives 103–105 °C), startin g m aterial
6 (5 g; RF 0.92), 3-deoxy-1,2-O-isopropylidene-α-D-ribo-hexofuranose (8; 0.13 g, 3.2%; RF 0.15).
1H NMR (400 MHz, CDCl3) of com poun d 9 was in accordan ce with ref.36
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

6-Amino-3,6-dideoxyhexono-1,6-lactams
637
6-Azido-3,6-dideoxy-1,2-O-isopropyliden e-α-D-ribo-h exofuran ose (11)
Accordin g to gen eral procedure17 th e syrupy azido derivative 11 (0.86 g, 87%) was obtain ed
from 3-deoxy-1,2-O-isopropyliden e-6-O-tosyl-α-D-ribo-h exofuran ose (10; 1.56 g, 4.35 m m ol),
[α ]2D0 –15 (c 0.6, ch loroform ). IR (ch loroform ): 3 588, 3 480 (OH); 2 107 (N3); 1 375
(C(CH3)2). 1H an d 13C NMR are in accordan ce with ref.17
6-Azido-3,6-dideoxy-D-ribo-h exon o-1,4-lacton e (13)
Azidoh exose 12 (0.6 g, 3.17 m m ol) dissolved in water (30 m l) was oxidized at 0 °C with bro-
m in e (0.6 m l ) in th e presen ce of barium carbon ate (3.4 g) added to th e solution . Wh en TLC
sh owed com pletion of th e reaction , excess of brom in e was rem oved with a stream of air an d
barium carbon ate was filtered off. Th e solution was stirred at room tem perature for 2 h with
th e fresh ly prepared silver carbon ate (2 g) to rem ove brom ide an ion s. After rem ovin g th e
salts an d th orough wash in g with water, th e solution was poured th rough a colum n of
Dowex 50WX4 in H+ cycle an d water was evaporated. Th e yield of syrupy lacton e 13 was
0.59 g (99%), [α ]D20 +14.8 (c 0.19, water), RF 0.62 (EtOAc). IR (n eat): 3 370, 3 207 (OH); 2 112
1
(N3); 1 743 (CO). H NMR (400 MHz, D2O): 4.70 m , 2 H (H-2, H-4); 2.26 ddd, 1 H, J(3,2) ≈
2.6, J(3,3′) ≈ 13.6, J(3,4) ≈ 8.9 (H-3); 2.63 ddd, 1 H, J(3′, 2) ≈ 8.7, J(3′,4) ≈ 2.6 (H-3′); 4.02
ddd, 1 H, J(5,4) ≈ 8.11, J(5,6) ≈ 3.9, J(5,6′) ≈ 4.1 (H-5); 3.45 dd, 1 H, J(6,6′) ≈ 13.1 (H-6); 3.39
dd (H-6′). 13C NMR (100 MHz, D2O): 180.43 (C-1); 79.94, 74.40 (C-2, C-4, in terch an geable);
31.63 (C-3); 67.79 (C-5); 53.35 (C-6). For C6H9N3O4 (187.2) calculated: 38.50% C, 4.81% H;
foun d: 38.14% C, 4.86% H.
2,5-Di-O-acetyl-6-azido-3,6-dideoxy-D-ribo-h exon o-1,4-lacton e (14)
Lacton e 13 (0.1 g, 0.53 m m ol) was treated with acetic an h ydride (1 m l) in pyridin e (14 m l).
Th e reaction m ixture was worked up by a usual procedure an d acetate 14 (0.14 g, 98%) was
obtain ed as a colorless syrup, [α ]D20 +24 (c 1.0, ch loroform ). 1H NMR (400 MHz, CDCl3):
5.41 dd, 1 H, J(2,3) ≈ 8.9, J(2,3′) ≈ 7.4 (H-2); 2.36 ddd, 1 H, J(3,3′) ≈ 13.0, J(3,4) ≈ 8.3 (H-3);
2.67 ddd, 1 H, J(3′,4) ≈ 3.9 (H-3′); 4.81 ddd, 1 H, J(4,5) ≈ 5.4 (H-4); 5.11 q, 1 H, J(5,6) ≈ 5.0,
J(5,6′) ≈ 5.0 (H-5); 3.59 dd, 1 H, J(6,6′) ≈ 13.3 (H-6); 3.54 dd (H-6′); 2.13 s, 3 H (COCH3);
2.15 s, 3 H (COCH3). 13C NMR (100 MHz, CDCl3): 172.36 (C-1); 76.13, 72.68, 67.99 (C-2,
C-4, C-5, in terch an geable); 30.55 (C-3); 50.82 (C-6); 170.34, 170.26 (COCH3); 21.43, 21.20
(COCH3). For C10H13N3O6 (271.1) calculated: 44.30% C, 4.79% H, 15.49% N; foun d: 44.36%
C, 4.92% H, 15.49% N.
6-Am in o-3,6-dideoxy-D-ribo-h exon olactam (1a)
Azidolacton e 13 (0.5 g, 2.67 m m ol) was reduced in m eth an ol (25 m l) by m ean s of h ydrogen
usin g 5% Pd/C (50 m g) for 5 h . Th e catalyst was rem oved, m eth an ol was evaporated, an d
th e lactam was obtain ed as a syrup, [α ]2D0 –28 (c 0.5, water). IR (KBr): 3 342 (OH, NH); 1 640
(CONH). UV: λm ax 194 n m . For NMR, see Tables I an d II. For C6H11NO4 (161.1) calculated:
44.74% C, 6.83% H, 8.69% N; foun d: 44.86% C, 6.57% H, 8.41% N.
2,4,5-Tri-O-acetyl-6-am in o-3,6-dideoxy-D-ribo-h exon olactam (1b)
Lactam 1a (0.1 g, 0.62 m m ol) was treated with acetic an h ydride (2 m l) in pyridin e (3 m l) for
24 h . Th e reaction m ixture was poured in to water with ice an d th e product was extracted
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Hamerníková et al.:
with ch loroform . Com bin ed organ ic layers were dried an d th icken ed. Th e syrupy product 1b
was purified by colum n ch rom atograph y in system C (0.13 g, 69%) to give a wh ite crystal-
lin e m aterial, m .p. 155–165 °C (eth an ol), [α ]2D0 –83 (c 0.7, ch loroform ). For NMR, see Tables I
an d II. For C12H17NO7 (287.1) calculated: 50.21% C, 5.92% H, 4.88% N; foun d: 49.96% C,
6.01% H, 4.62% N.
5,6-An h ydro-3-deoxy-1,2-O-isopropyliden e-β-L-lyxo-h exofuran ose (17)
an d 3-Deoxy-1,2-O-isopropyliden e-5-O-tosyl-α-D-ribo-h exofuran ose (19)
6-O-Ben zoyl-3-deoxy-1,2-O-isopropyliden e-5-O-tosyl-α-D-ribo-h exofuran ose (16; 2.2 g, 4.7 m m ol)
dissolved in ch loroform (100 m l) was treated with a m eth an olic sodium m eth oxide (100 m l,
0.055 M solution ). After 12 h , th e reaction m ixture con tain ed an h ydro derivative 17 (TLC B,
RF 0.5) an d tosylate 19 (RF 0.17) wh ich after h eatin g at 50 °C disappeared in 15 m in . Th e re-
action m ixture was wash ed with 20 m l of water. Th e organ ic layer con tain in g product 17
an d m eth yl ben zoate was dried over an h ydrous m agn esium sulfate. Th e solven t was evapo-
rated to give 1.5 g of th e crude product wh ich , after colum n ch rom atograph y on silica gel
(40 g, system B), yielded syrupy an h ydro derivative 17 (0.6 g, 68%), [α ]2D0 –31 (c 2, ch loro-
form ); ref.37 gives –21.9, ref.38 gives –27.6 (c 1.1, ch loroform ). 1H NMR (500 MHz, CDCl3):
5.78 d, 1 H, J(1,2) ≈ 3.5 (H-1); 4.72 t, 1 H, J(2,3) < 0.5, J(2,3′) ≈ 4.1 (H-2); 2.13 dd, 1 H,
J(3,3′) ≈ 13.3, J(3,4) ≈ 4.5 (H-3); 1.82 ddd, 1 H, J(3′,4) ≈ 10.3 (H-3′); 4.14 ddd, 1 H, J(4,5) ≈
4.5 (H-4); 3.01 ddd, 1 H, J(5,6) ≈ 3.9, J(5,6′) ≈ 3.9 (H-5); 2.78 m , 2 H (H-6, H-6′); 1.48 s, 3 H,
1.29 s, 3 H (C(CH3)2). 13C NMR (100 MHz): 106.39 (C-1); 80.98 (C-2); 36.32 (C-3); 77.68
(C-4); 53.00 (C-5); 44.98 (C-6); 27.48, 26.89 (C(CH3)2); 112.09 (C(CH3)2). In term ediate 19
(0.2 g, 12%) was also isolated, [α ]2D0 –6.3 (c 0.66, ch loroform ). IR (ch loroform ): 3 601, 3 537
(OH); 1 374 (C(CH3)2); 1 175 (OSO2). 1H NMR (500 MHz, CDCl3): 5.56 d, 1 H, J(1,2) ≈ 3.5
(H-1); 4.66 m , 2 H (H-2, H-5); 2.12 dd, 1 H, J(3,2) < 0.5, J(3,3′) ≈ 13.5, J(3,4) ≈ 4.5 (H-3); 1.71
ddd, 1 H, J(3′,2) ≈ 4.7, J(3′,4) ≈ 10.7 (H-3′); 4.29 ddd, 1 H, J(4,5) ≈ 5.0 (H-4); 3.86 dd, 1 H,
J(6,5) ≈ 3.6, J(6,6′) ≈ 12.7 (H-6); 3.76 dd, 1 H, J(6′,5) ≈ 5.3 (H-6′); 1.50 s, 3 H, 1.28 s, 3 H
(C(CH3)2); 2.45 s (ArCH3); 7.81, 2 H, 7.35, 2 H (Ar). 13C NMR (100 MHz): 106.03 (C-1);
83.57, 80.86 (C-2, C-5, in terch an geable); 35.73 (C-3); 77.23 (C-4); 63.30 (C-6); 27.48, 26.82
(C(CH3)2); 112.35 (C(CH3)2); 22.37 (ArCH3); 130.49, 128.72 (Ar).
6-O-Ben zoyl-3-deoxy-1,2-O-isopropyliden e-5-O-tosyl-α-D-ribo-h exofuran ose (16)
a) 6-O-Ben zoyl derivative7 (15; 2 g, 6.5 m m ol), dissolved in pyridin e (20 m l) was treated
with tosyl ch loride (3.7 g, 19.5 m m ol) an d th e reaction m ixture was poured in to water after
60 h , wh ereupon product 16 crystallized (3 g, 100%).
b) 3-Deoxy-1,2-O-isopropyliden e-5,6-di-O-tosyl-α-D-ribo-h exofuran ose (18; 3.57 g, 6.98 m m ol)
was dissolved in dim eth ylform am ide (30 m l) an d th e solution was stirred at 80 °C with so-
dium ben zoate (1.09 g, 7.56 m m ol). After 6 h , dim eth ylform am ide was evaporated an d th e
residue partition ed between water an d ch loroform . Th e organ ic layer was dried an d evapo-
rated, th e crystallin e m aterial 16 (2.9 g, 90%; RF 0.27 in system E) was obtain ed, m .p.
120–121 °C (eth er), [α ]2D0 +16.1 (c 2, ch loroform ); ref.18 gives 121–122 °C, [α ]2D0 +16 (c 1, ch lo-
roform ). 1H NMR (500 MHz, CDCl3): 7.96 d, 2 H, 7.56 t, 1 H, 7.42 dd, 2 H (Bz); 7.76 d, 2 H,
7.21 d, 2 H (Ts); 5.56 d, 1 H, J(1,2) ≈ 3.4 (H-1); 5.01 dt, 1 H, J(5,6) ≈ J(5,6′) ≈ 3,4, J(5,4) ≈ 7.8
(H-5); 4.69 dd, 1 H, J(2,3).5, J(2,3′) ≈ 4.0 (H-2); 4.54 dd, 1 H, J(6,6′) ≈ 12.5 (H-6); 4.39 m , 2 H
(H-6′, H-4); 2.35 s, 3 H (CH3-Ar); 2.18 dd, 1 H, J(3,3′) ≈ 13.5, J(3,4) ≈ 4.7 (H-3); 1.87 ddd, 1 H,
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6-Amino-3,6-dideoxyhexono-1,6-lactams
639
J(3′,4) ≈ 10.7 (H-3′); 1.45 s, 3 H (CH3); 1.29 s, 3 H (CH3). 13C NMR (100 MHz, CDCl3):
166.64 (CO); 133.93, 130.50, 130.37, 129.07, 128.51 (Ar); 112.41 (C(CH3)2); 106.11 (C-1);
80.92 (C-2); 80.37 (H-5); 77.14 (H-4); 64.50 (H-6); 35.50 (H-3); 27.51; 26.87 (C(CH3)2); 22.31
(CH3-Ar).
6-Azido-3,6-dideoxy-1,2-O-isopropyliden e-β-L-lyxo-h exofuran ose (20)
To a solution of an h ydro derivative 17 (0.6 g, 3.22 m m ol) in 2-m eth oxyeth an -1-ol (10 m l)
water (0.8 m l), sodium azide (0.76 g, 11.6 m m ol) an d am m on ium ch loride (0.4 g, 7.5 m m ol)
were added an d th e reaction m ixture was h eated to 140 °C. After 15 m in , th e solven ts were
evaporated an d th e brown residue was purified usin g ch rom atograph y on silica gel (17 g;
system B, RF 0.31) yieldin g azido derivative 20 (0.66 g, 90%) as a colorless syrup, [α ]2D0 –4.62
(c 0.7, ch loroform ). IR (ch loroform ): 3 560, 3 469 (OH); 2 106 (N3); 1 375 (C(CH3)2). 1H
NMR (500 MHz, CDCl3): 5.79 d, 1 H, J(1,2) ≈ 3.6 (H-1); 4.72 t, 1 H, J(2,3) < 0.5, J(2,3′) ≈ 4.7
(H-2); 2.02 dd, 1 H, J(3,3′) ≈ 13.4, J(3,4) ≈ 4.5 (H-3); 1.83 ddd, 1 H, J(3′,4) ≈ 10.8 (H-3′); 4.21
ddd, 1 H, J(4,5) ≈ 4.2 (H-4); 3.68 ddd, 1 H, J(5,6) ≈ 4.2, J(5,6′) ≈ 7.6 (H-5); 3.32 dd, 1 H,
J(6,6′) ≈ 12.8 (H-6); 3.10 dd, 1 H (H-6′); 1.48 s, 3 H, 1.29 s, 3 H (C(CH3)2); 2.60 s (OH).
13C NMR (100 MHz, CDCl3): 106.20 (C-1); 81.25 (C-2); 35.20 (C-3); 79.14 (C-4); 72.18 (C-5);
54.83 (C-6); 27.45, 26.84 (C(CH3)2); 112.28 (C(CH3)2). For C9H15N3O4 (229.2) calculated:
47.16% C, 6.60% H; foun d: 47.16% C, 6.74% H.
6-Azido-3,6-dideoxy-L-lyxo-h exose (21)
Azidoh exose 20 (0.5 g, 2.64 m m ol) dissolved in water (5 m l) was stirred with Dowex 50WX4
in H+ form (2.5 m l) at 60 °C. After 0.5 h , th e ion exch an ger was rem oved an d th e filtrate
was evaporated yieldin g th e syrupy product 21 (0.4 g, 99%), [α ]2D0 –7.9 (10 h ; c 0.7, water), RF
0.5 (EtOAc). IR (n eat): 3 371 (OH); 2 106 (N3). For C6H11N3O4 (189.2) calculated: 38.09% C,
5.86% H; foun d: 38.35% C, 5.58% H.
6-Azido-3,6-dideoxy-L-lyxo-h exon ic Acid (22)
Oxidation of azidoh exose 21 (0.6 g, 3.17 m m ol) with brom in e in water was perform ed sim i-
larly to th e oth er oxidation s of azidoh exoses described above. Accordin g to TLC (EtOAc),
h ydrolysis of th e form ed 6-azido-3,6-dideoxy-L-lyxo-h exon olacton e (RF 0.58) occurred givin g
rise to th e correspon din g azido acid. After 10 h , th e reaction m ixture con tain ed on ly com -
poun d 22 (RF 0.0). Azido acid 22 (0.4 g, 67%) was isolated as th e wh ite foam . IR (n eat):
3 438, 3 295, 3 334, 3 205 (OH); 2 106 (N3); 1 730, 1 636, 1 403 (COO–). Th e crude m aterial
was used in th e n ext step with out purification .
6-Am in o-3,6-dideoxy-L-lyxo-h exon ic Acid (23)
Azido acid 22 (0.4 g, 2.14 m m ol) was reduced by m ean s of h ydrogen in water on 5% Pd/C
(0.05 g). After 24 h , th e catalyst was rem oved an d water was evaporated. Th e syrupy am in o
acid 23 (0.38 g, 99%) was obtain ed. IR (n eat): 3 171, 3 036 (CH, OH, NH); 1 765, 1 720,
1 615, 1 405 (COO–).
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6-Am in o-3,6-dideoxy-L-lyxo-h exon o-1,6-lactam (2a)
Acid 23 (0.38 g, 2.1 m m ol) was dissolved in m eth an ol (35 m l) with addition of m eth an olic
HCl (10 m l of 5% solution ) an d th e solution was refluxed for 5 h . Meth an ol was evaporated
an d th e form ed m eth yl ester h ydroch loride 24 was alkalized with sodium m eth an olate (2.1
m m ol) in
m eth an ol with out purification . After evaporation
of m eth an ol,
6-am in o-3,6-dideoxy-L-lyxo-h exon o-1,6-lactam (2a) in a m ixture with salts was treated with
acetic an h ydride (3 m l) in pyridin e (5 m l) for 24 h . 2,4,5-Tri-O-acetyl-6-am in o-3,6-dideoxy-
L-lyxo-h exon o-1,6-lactam (2b; 0.06 g, 10%) was isolated in a usual m an n er an d purified on a
colum n of silica gel in system B. Th e product m elted at 96–98 °C (eth an ol), [α ]2D0 +4 (c 1,
ch loroform ). For NMR, see Tables I an d II. For C12H17NO7 (287.1) calculated: 50.21% C,
5.92% H, 4.88% N; foun d: 50.30% C, 6.11% H, 4.74% N.
Tran sacetylation of com poun d 2b (0.03 g, 0.18 m m ol) by th e action of sodium m eth -
oxide (0.3 m l 0.055 M solution ) in 12 h , subsequen t n eutralization usin g Dowex 50WX4 in
H+ form an d evaporation gave th e required syrupy lactam 2a (0.015 g, 89%). IR (KBr): 3 333,
3 309 (OH, NH); 1 656 (CONH). UV: λm ax 193 n m . For NMR, see Tables I an d II. For
C6H11NO4 (161.1) calculated: 44.74% C, 6.83% H, 8.69% N; foun d: 44.96% C, 6.69% H,
8.52% N.
5,6-An h ydro-3-deoxy-1,2-O-isopropyliden e-β-L-arabino-h exofuran ose (25)
To a solution of 6-O-ben zoyl-3-deoxy-1,2-O-isopropyliden e-5-O-tosyl-α-D-xylo-h exofuran ose
(27; 1.9 g, 3.9 m m ol) in ch loroform (100 m l), a m eth an olic sodium m eth oxide solution
(from 0.28 g of sodium an d 10 m l of m eth an ol) was added. After 12 h at room tem perature,
th e reaction m ixture was wash ed th ree tim es with water (20 m l) an d th e ch loroform layer
was dried with an h ydrous m agn esium sulfate. After evaporation , th e product was purified
on a colum n of silica gel in system B (RF 0.42) yieldin g an h ydro derivative 25 (0.53 g, 74%),
[α ]2D0 –32 (c 0.5, ch loroform ). 1H NMR (500 MHz, CDCl3): 5.85 d, 1 H, J(1,2) ≈ 3.6 (H-1);
4.80 dd, 1 H, J(2,3) ≈ 1.7, J(2,3′) ≈ 8.7 (H-2); 2.37 d, 1 H, J(3,3′) ≈ 14.3, J(3,4) ≈ 1.1 (H-3);
2.27 ddd, 1 H, J(3′,4) ≈ 8.2, 3.79 ddd, 1 H, J(4,5) ≈ 8.2 (H-4); 3.33 ddd, 1 H, J(5,6) ≈ 3.8,
J(5,6′) ≈ 2.2 (H-5); 2.90 dd, 1 H, J(6,6′) ≈ 5.0 (H-6); 2.69 dd, 1 H (H-6′); 1.60 s, 3 H, 1.37 s,
3 H (C(CH3)2). 13C NMR (100 MHz): 107.50 (C-1); 81.40 (C-2); 35.44 (C-3); 83.04 (C-4);
53.78 (C-5); 48.04 (C-6); 27.81, 26.55 (C(CH3)2); 113.00 (C(CH3)2). For C9H14O4 (186.2) cal-
culated: 58.05% C, 7.58% H; foun d: 57.81% C, 7.55% H.
After colum n ch rom atograph y, 3-deoxy-1,2-O-isopropyliden e-5-O-tosyl-α-D-xylo-h exo-
furan ose (32; 0.14 g, 10%; RF 0.16, system B) was isolated, [α ]2D0 –36 (c 0.8, ch loroform ). IR
(ch loroform ): 3 588, 3 524 (OH); 1 175 (OSO2); 1 375 (C(CH3)2). 1H NMR (300 MHz,
CDCl3): 5.67 d, 1 H, J(1,2) ≈ 3.8 (H-1); 4.69 ddd, 1 H, J(2,3) ≈ 1.8, J(2,3′) ≈ 7.1 (H-2); 2.15 m ,
2 H (H-3, H-3′); 4.30 ddd, 1 H, J(4,3) ≈ 4.9, J(4,3′) ≈ 8.3, J(4,5) ≈ 8.3 (H-4); 4.86 ddd, 1 H,
J(5,6) ≈ 3.8, J(5,6′) ≈ 3.8 (H-5); 3.96 dd, 1 H, J(6,6′) ≈ 12.0 (H-6); 3.80 dd, 1 H (H-6′); 1.46 s,
3 H, 1.29 s, 3 H (C(CH3)2); 2.50 s, 1 H (OH); 2.42 s, 3 H (ArCH3); 7.86, 2 H, 7.32, 2 H (Ar).
13C NMR (75 MHz, CDCl3): 106.9 (C-1); 79.04, 71.09, 84.36 (C-2, C-4, C-5, in terch an geable);
33.69 (C-3); 63.10 (C-6); 27.54, 26.84 (C(CH3)2); 112.35 (C(CH3)2); 130.58, 130.29, 128.74
(Ar).
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641
6-O-Ben zoyl-3-deoxy-1,2-di-O-isopropyliden e-5-O-tosyl-α-D-xylo-h exofuran ose (27)
a) To a solution of of 3-deoxy-1,2-O-isopropyliden e-5,6-di-O-tosyl-α-D-xylo-h exofuran ose
(31; 2.2 g, 4.3 m m ol) in DMF (20 m l), sodium ben zoate (0.72 g, 4.6 m m ol) was added. Th e
suspen sion was stirred at 80 °C. After 6 h TLC (system E, for 31 RF 0.18, for 27 RF 0.28)
sh owed th e proceedin g reaction . Dim eth ylform am ide was evaporated at 60 °C, th e residue
was diluted with water an d th e product was extracted with ch loroform . Th e organ ic layer,
after dryin g with an h ydrous m agn esium sulfate, was evaporated. Th e product after
recrystallization from eth er (1.8 g, 90%), m .p. 90–91 °C, [α ]2D0 –20 (c 0.91, ch loroform ). IR
(ch loroform ): 1 723 (CO); 1 273 (OSO2); 1 376 (C(CH3)2). 1H NMR (500 MHz, CDCl3): 5.75 d,
1 H, J(1,2) ≈ 3.8 (H-1); 4.77 ddd, 1 H, J(2,3) ≈ 1.6, J(2,3′) ≈ 5.9 (H-2); 2.21 ddd, 1 H, J(3,3′) ≈
14.5, J(3,4) ≈ 4.7 (H-3); 2.26 ddd, 1 H, J(3′,4) ≈ 8.2 (H-3′); 4.37 ddd, 1 H, J(4,5) ≈ 8.0 (H-4);
5.24 ddd, 1 H, J(5,6) ≈ 3.2, J(5,6′) ≈ 6.1 (H-5); 4.65 dd, 1 H, J(6,6′) ≈ 12.6 (H-6); 4.54 dd, 1 H
(H-6′); 1.59 s, 3 H, 1.35 s, 3 H (C(CH3)2); 2.40 s, _ H (ArCH3); 7.28, 2 H, 7.88, 2 H (Ar, Ts);
8.03, 2 H, 7.16, 2 H, 7.6, 1 H (Ar, Bz). 13C NMR (100 MHz, CDCl3): 107.05 (C-1); 81.14,
81.05 (C-2, C-5, in terch an geable); 33.78 (C-3); 78.93 (C-4); 64.47 (C-6); 27.66, 26.91
(C(CH3)2); 114.03 (C(CH3)2); 145.24 (CO); 22.36 (ArCH3); 133.98, 130.57, 130.24, 129.12,
128.80 (Ar). For C23H26O8S (462.5) calculated: 59.79% C, 5.67% H, 6.93% S; foun d: 59.77% C,
5.57% H, 6.55% S.
b) A solution of of 6-O-ben zoyl-3-deoxy-1,2-O-isopropyliden e-α-D-xylo-h exofuran ose (28;
0.34 g, 1.1 m m ol) in pyridin e (3 m l) was reacted with tosyl ch loride (0.4 g, 2.2 m m ol) at
room tem perature for 12 h (RF of product 0.69, system B). Th e reaction m ixture was poured
in to water, th e crude crystallin e product recrystallized from eth er (0.48 g, 94%). Ph ysical
con stan ts were iden tical with th ose of th e product obtain ed by th e m eth od a).
6-O-Ben zoyl-3-deoxy-1,2-O-isopropyliden e-α-D-xylo-h exofuran ose (28)
To an ice cool solution of 3-deoxy-1,2-O-isopropyliden e-α-D-xylo-h exofuran ose (26; 0.69 g,
3.3 m m ol) in pyridin e (5 m l), ben zoyl ch loride (0.34 m l, 3.6 m m ol) in ch loroform (1 m l)
was added dropwise. Th e reaction m ixture was stirred at room tem perature for 12 h . Th en
th e reaction m ixture was poured in to water with ice an d, after 1 h , extracted with ch loro-
form . Th e organ ic layer was dried over an h ydrous m agn esium sulfate an d th e solven t was
evaporated. After colum n ch rom atograph y in system C (RF 0.66), 6-O-ben zoyl derivative 28
(0.47 g, 46%) was isolated, [α ]2D0 –11 (c 2, ch loroform ). IR (ch loroform ): 3 563 (OH); 1 719
(CO); 1 383 (CH3). 1H NMR (500 MHz, CDCl3): 5.85 d, 1 H, J(1,2) ≈ 3.9 (H-1); 4.79 ddd, 1 H,
J(2,3) ≈ 1.2, J(2,3′) ≈ 5.7 (H-2); 2.19 dd, 1 H, J(3,3′) ≈ 14.3, J(3,4) ≈ 3.3 (H-3); 2.29 ddd, 1 H,
J(3′,4) ≈ 8.4 (H-3′); 4.30 ddd, 1 H, J(4,5) ≈ 8.3 (H-4); 4.16 ddd, 1 H, J(5,6) ≈ 5.3, J(5,6′) ≈ 4.3
(H-5); 4.40 dd, 1 H, J(6,6′) ≈ 11.3 (H-6); 4.43 dd, 1 H (H-6′); 1.49 s, 3 H, 1.23 s, 3 H
(C(CH3)2); 8.07, 2 H, 7.57, 1 H, 7.44, 2 H (Ar); 3.40 s, 1 H (OH). 13C NMR (100 MHz,
CDCl3): 106.97 (C-1); 81.36 (C-2); 34.21 (C-3); 81.99 (C-4); 71.68 (C-5); 66.41 (C-6); 27.70,
26.64 (C(CH3)2); 113.37 (C(CH3)2); 167.16 (CO); 133.81, 129.09, 130.42 (Ar). For C16H20O6
(308.3) calculated: 62.33% C, 6.54% H; foun d: 62.39% C, 6.54% H.
Sm all am oun ts of oth er products were isolated after colum n ch rom atograph y:
5-O-Benzoyl-3-deoxy-1,2-O-isopropylidene-α-D-xylo-hexofuranose (29; 0.08 g, 8%; RF 0.58, C).
IR (ch loroform ): 3 608, 3 494 (OH); 1 715 (CO); 1 375 (CH3). 1H NMR (500 MHz, CDCl3):
5.73 d, 1 H, J(1,2) ≈ 3.7 (H-1); 4.73 d, 1 H, J(2,3) < 0.5, J(2,3′) ≈ 7.6 (H-2); 2.17 dd, 1 H,
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Hamerníková et al.:
J(3,3′) ≈ 14.1, J(3,4) ≈ 4.5 (H-3); 2.23 ddd, 1 H, J(3′,4) ≈ 7.6 (H-3′); 4.46 ddd, 1 H, J(4,5) ≈ 7.7
(H-4); 5.36 ddd, 1 H, J(5,6) ≈ 3.6, J(5,6′) ≈ 4.3 (H-5); 3.93 dd, 1 H, J(6,6′) ≈ 12.4 (H-6);
3.84 dd, 1 H (H-6′); 1.59 s, 3 H, 1.30 s, 3 H (C(CH3)2); 2.85 s, 1 H (OH); 8.8, 2 H, 7.54, 1 H,
7.41, 2 H (Ar). 13C NMR (100 MHz, CDCl3): 106.87 (C-1); 81.26 (C-2); 33.91 (C-3); 79.17
(C-4); 76.55 (C-5); 63.27 (C-6); 27.90, 26.99 (C(CH3)2); 113.90 (C(CH3)2); 167.24 (CO);
133.81, 130.62, 129.01 (Ar).
5,6-Di-O-benzoyl-3-deoxy-1,2-O-isopropylidene-α-D-xylo-hexofuranose (30; 0.05 g, 4%; RF 0.8,
C). IR (ch loroform ): 1 721 (CO); 1 376 (C(CH3)2). 1H NMR (400 MHz, CDCl3): 5.80 d, 1 H,
J(1,2) ≈ 3.7 (H-1); 4.80 ddd, 1 H, J(2,3) ≈ 1.4, J(2,3′) ≈ 5.5 (H-2); 2.23 dd, 1 H, J(3,3′) ≈ 14.3,
J(3,4) ≈ 4.2 (H-3); 2.32 ddd, 1 H, J(3′,4) ≈ 8.1 (H-3′); 4.54 ddd, 1 H, J(4,5) ≈ 8.0 (H-4); 7.77
ddd, 1 H, J(5,6) ≈ 3.6, J(5,6′) ≈ 5.6 (H-5); 4.68 dd, 1 H, J(6,6′) ≈ 12.3 (H-6); 4.85 dd, 1 H
(H-6′); 1.32 s, 3 H, 1.06 s, 3 H (C(CH3)2); 8.10, 2 H, 8.00, 2 H, 7.55, 2 H, 7.42, 4 H (Ar);
2.57 s, 1 H (OH). 13C NMR (75 MHz, CDCl3): 107.02 (C-1); 81.19, 79.02, 73.59 (C-2, C-4,
C-5, in terch an geable); 34.14 (C-3); 64.69 (C-6); 27.83, 26.96 (C(CH3)2); 113.97 (C(CH3)2);
166.85, 166.70 (CO); 133.88, 133.77, 130.76, 130.46, 129.14, 129.02 (Ar).
6-Azido-3,6-dideoxy-1,2-O-isopropyliden e-β-L-arabino-h exofuran ose (33)
To a solution of an h ydro derivative 25 (0.9 g, 4.8 m m ol) in 2-m eth oxyeth an -1-ol (15 m l)
an d water (1.2 m l), am m on ium ch loride (0.61g, 11.5 m m ol) an d sodium azide (1 g,
15.3 m m ol) were added an d th e reaction m ixture was refluxed for 0.5 h . After coolin g an d
repeated evaporation with water, th e obtain ed brown syrup was partition ed between water
an d ch loroform . Th e organ ic layer was purified on a colum n of silica gel usin g system B
(RF 0.37) givin g 0.85 g (78%) of th e wh ite crystallin e m aterial m eltin g at 58–60 °C (ch loro-
form –eth er), [α ]2D0 –26 (c 0.23, ch loroform ). IR (ch loroform ): 3 565, 3 485 (OH); 2 108 (N3);
1 377 (C(CH3)2). 1H NMR (400 MHz, CDCl3): 5.79 d, 1 H, J(1,2) ≈ 3.8 (H-1); 4.75 ddd, 1 H,
J(2,3) ≈ 0.6, J(2,3′) ≈ 6.1 (H-2); 2.35 d, 1 H, J(3,3′) ≈ 14.5, J(3,4) < 0.5 (H-3); 4.05 m , 2 H (H-4,
H-5); 3.60 dd, 1 H, J(6,5) ≈ 2.4, J(6,6′) ≈ 12.5 (H-6); 3.42 dd, 1 H, J(6′,5) ≈ 6.2 (H-6′); 1.52 s,
3 H, 1.31 s, 3 H (C(CH3)2); 2.55 s, 1 H (OH). 13C NMR (100 MHz, CDCl3): 107.27 (C-1);
81.32 (C-2); 33.52 (C-3); 72.55, 82.02 (C-4, C-5, in terch an geable); 55.04 (C-6); 27.74, 26.46
(C(CH3)2); 113.05 (C(CH3)2). For C9H15N3O4 (229.2) calculated: 47.16% C, 6.60% H, 18.33% N;
foun d: 47.40% C, 6.47% H, 18.05% N.
6-Azido-3,6-dideoxy-β-L-arabino-h exose (34)
6-Azido-3,6-dideoxy-1,2-O-isopropyliden e-L-arabino-h exofuran ose (33; 0.8 g, 3.5 m m ol) was
h ydrolyzed at 70 °C for 10 m in with water (20 m l) in th e presen ce of Dowex 50WX4 in H+
cycle (4 m l). After rem ovin g th e ion exch an ger, water was evaporated an d th e rest dried in
vacuum . Th is procedure afforded 0.67 g (100%) of pure (TLC) syrupy azidoh exose 34, [α ]D20
–34 (c 0.66, water). IR (n eat): 3 373 (OH). For C6H11N3O4 (189.2) calculated: 38.09% C,
5.86% H, 22.21% N; foun d: 38.00% C, 5.64% H, 22.32% N.
6-Azido-3,6-dideoxy-L-arabino-h exon o-1,4-lacton e (35)
Azidoh exose 34 (0.6 g, 3.2 m m ol) dissolved in water (50 m l) was oxidized at 0 °C with bro-
m in e (0.6 m l) in th e presen ce of barium carbon ate (5 g). Wh en TLC sh owed com pletion th e
reaction (RF 0.64, eth yl acetate), excess of brom in e was rem oved with a stream of air an d
barium carbon ate was filtered off. Th e solution was stirred at room tem perature for 2 h with
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6-Amino-3,6-dideoxyhexono-1,6-lactams
643
fresh ly prepared silver carbon ate (1 g). After rem ovin g th e salts an d th orough wash in g with
water, th e solution was passed th rough a colum n of Dowex 50WX4 in H+ cycle an d water
was evaporated. Th e syrupy lacton e 35 (0.5 g, 88%) was dried at 40 °C for 12 h in vacuum ,
[α ]2D0 –17 (c 0.4, water). IR (n eat): 3 376 (OH); 2 108 (N3); 1 776 (CO). 1H NMR (400 MHz,
D2O): 4.75 dd, 1 H, J(2,3) ≈ 10.9, J(2,3′) ≈ 8.8 (H-2); 2.11 q, 1 H, J(3,3′) ≈ 10.9, J(3,4) ≈ 10.9
(H-3); 2.71 ddd, 1 H, J(3′,4) ≈ 5.6 (H-3′); 4.57 ddd, 1 H, J(4,5) ≈ 5.0 (H-4); 4.11 ddd, 1 H,
J(5,6) ≈ 3.8, J(5,6′) ≈ 7.3 (H-5); 3.40 dd, 1 H, J(6,6′) ≈ 13.2 (H-6); 3.52 dd, 1 H (H-6′).
13C NMR (100 MHz, D2O): 180.09 (C-1); 68.88 (C-2); 32.63 (C-3); 78.31 (C-4); 71.22 (C-5);
53.14 (C-6). For C6H9N3O4 (187.2) calculated: 38.50% C, 4.81% H, 22.44% N; foun d:
38.12% C, 4.90% H, 22.33% N.
6-Am in o-3,6-dideoxy-D-arabino-h exon o-1,6-lactam (3a)
Azidolacton e 35 (0.42 g, 2.2 m m ol) was reduced in m eth an ol (20 m l) by m ean s of h ydrogen
usin g 5% Pd/C (40 m g) as a catalyst for 7 h . Th e catalyst was rem oved, m eth an ol was evapo-
rated an d th e lactam 3a was obtain ed as a syrupy form , [α ]2D0 –15 (c 0.15, water). IR (KBr):
3 475 (OH); 3 241 (NH); 1 666 (CONH). UV: λm ax 195 n m . For NMR, see Tables I an d II. For
C6H11NO4 (161.1) calculated: 44.74% C, 6.83% H, 8.69% N; foun d: 45.01% C, 6.81% H,
8.50% N.
2,4,5-Tri-O-acetyl-6-am in o-3,6-dideoxy-D-arabino-h exon o-1,6-lactam (3b)
Lactam 3a (0.07 g, 0.43 m m ol) was treated with acetic an h ydride (1 m l) in pyridin e (2 m l)
for 48 h . Th e reaction m ixture was poured in to water with ice, th e product was extracted
with ch loroform . Th e com bin ed organ ic layers were dried an d th icken ed. Th e syrupy prod-
uct 3b was purified by colum n ch rom atograph y in system C (0.1 g, 80%), [α ]2D0 –18 (c 2.3,
ch loroform ). For NMR, see Tables I an d II. For C12H17NO7 (287.1) calculated: 50.20% C,
5.92% H, 4.88% N; foun d: 50.48% C, 6.08% H, 4.59% N.
The authors are indebted to colleagues from several departments of the Central laboratories, Insti-
tute of Chemical Technology, Prague for careful spectral measurements and elemental analyses. This
research was partly supported by the Grant Agency of the Czech Republic (grant No. 203/97/0621)
and also by the Ministry of Education, Youth and Sports of the Czech Republic (project No.
223300006).
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