Synthesis of 5-amino-5-deoxypentonolactams

Article abstract of DOI:10.1135/cccc19961027

5-Azido-5-deoxy-1,2-O-isopropylidene-α-D-xylofuranose (4) and 5-azido-5-deoxy-1,2-O-isopropy-lidene-β-D-arabinofuranose (10) were prepared starting from D-xylose and D-arabinose, respectively. Using the oxidation-reduction way for the C-3 epimerization, 5

Full text of DOI:10.1135/cccc19961027

5-Amino-5-deoxypentonolactams
1027
SYNTHESIS OF 5-AMINO-5-DEOXYPENTONOLACTAMS
1
Karel KEFURT , Zdenka KEFURTOVA, Vera MARKOVA and Karla SLIVOVA
Department of Natural Compounds, Prague Institute of Chemical Technology, 166 28 Prague 6,
Czech Republic; e-mail: 1 karel.kefurt@vscht.cz
Received March 8, 1996
Accepted April 23, 1996
5-Azido-5-deoxy-1,2-O-isopropylidene-α-D-xylofuranose (4) and 5-azido-5-deoxy-1,2-O-isopropy-
lidene-β-D-arabinofuranose (10) were prepared starting from D-xylose and D-arabinose, respectively.
Using the oxidation-reduction way for the C-3 epimerization, 5-azido-5-deoxy-1,2-O-isopropylidene-
α-D-ribofuranose (15) and 5-azido-5-deoxy-1,2-O-isopropylidene-β-D-lyxofuranose (17) were ob-
tained from 4 and 10, respectively. The derivatives 4, 10, 15 and 17 afforded by acid hydrolysis,
oxidation with bromine and catalytic hydrogenation successively the corresponding 5-azido-5-deoxy-
D-pentofuranoses 6, 11, 18, 19, 5-azido-5-deoxy-D-pentonolactones 7, 12, 20, 21 and 5-amino-5-
deoxy-D-pentonolactams 8, 13, 22, 23.
Key words: 5-Azido-5-deoxypentoses; 5-Amino-5-deoxypentonolactams; Synthesis.
Some time ago we prepared1–3 and assembled the complete set of eight diastereo-
isomeric 6-amino-6-deoxyhexonolactams and their tetra-O-acetyl derivatives. Later, we
studied structures of these seven-membered cyclic compounds by NMR, CD and IR
spectroscopy4,5 as well as by X-ray measurements6–8. Some non-answered questions,
namely rised from the CD spectra measurements4 demanded to perform similar studies
also on analogical six-membered cyclic compounds, i.e. on 5-amino-5-deoxypentono-
lactams. From the four possible 5-amino-5-deoxy-D-pentonolactams only D-ribo dia-
stereoisomer prepared from 5-azido-2,3-O-benzylidene-5-deoxy-β-D-ribofuranose9,10 or
1,2-O-isopropylidene-D-ribono-1,4-lactone11 is known until now (L-arabino diastereo-
isomer which was without any data mentioned in the patent12 is not here considered). A
different way, in comparison with the methods mentioned above9–11, leading to D-ribo
diastereoisomer and further three diastereoisomers, is presented in this paper.
As follows, our synthetic routes to all 5-amino-5-deoxy-D-pentonolactams employ
corresponding 5-azido-5-deoxy-1,2-O-isopropylidene-α/β-D-pentofuranoses as advan-
tageous key intermediates.
Partial tosylation of the readily accessible13 1,2-O-isopropylidene-α-D-xylofuranose
(1) gave a mixture of 1,2-O-isopropylidene-5-O-p-toluenesulfonyl-α-D-xylofuranose
(2) and 1,2-O-isopropylidene-3,5-di-O-p-toluenesulfonyl-α-D-xylofuranose (3) in a
ratio ca 7 : 1. This mixture was converted without separation to the corresponding 5-azido-
derivatives by displacement reaction with sodium azide on C-5. Separation on silica gel
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

1028
Kefurt, Kefurtova, Markova, Slivova:
column afforded pure 5-azido-5-deoxy-1,2-O-isopropylidene-α-D-xylofuranose (4) and
5-azido-5-deoxy-1,2-O-isopropylidene-3-O-p-toluenesulfonyl-α-D-xylofuranose (5) in
a ratio ca 6 : 1. Azide 4 exhibited consistent melting point, but reversed specific rota-
tion by comparison with the data reported for 4 in literature14,15. Structures of 4 and 5
were also confirmed by elemental analysis and NMR spectra (Table I). Acid hydrolysis
of 4 in the presence of Dowex 50 W (H+) afforded syrupous 5-azido-5-deoxy-D-xylose
(6) which was oxidized with bromine to give 5-azido-5-deoxy-D-xylono-1,4-lactone (7)
in form of the colourless syrup. The assignment of the structure to 7 is based on the
stretching frequencies of the carbonyl and azido groups in its IR spectrum, on ele-
1
mental analysis and H and 13C NMR spectra. Hydrogenation of 7 produced desired
5-amino-5-deoxy-D-xylonolactam (8), possibly in the mixture with corresponding
5-amino-5-deoxy-D-xylonic acid (according to TLC). By crystallization from hot methanol
crystalline lactam 8 was obtained, which exhibited characteristic bands of both hydroxy
and amido groups in the IR spectra, proper elemental analysis and confirming NMR
spectra. NMR spectra of all 5-amino-5-deoxy-D-pentonolactams and their derivatives
will be in detail discussed in the next paper concerning conformation of a six-mem-
bered lactam ring.
The diastereoisomeric D-arabino isomer was prepared in the similar manner. Reaction of
1,2-O-isopropylidene-5-O-p-toluenesulfonyl-β-D-arabinofuranose16 (9) with sodium
azide in N,N-dimethylformamide afforded the corresponding 5-azido-5-deoxy-1,2-O-
isopropylidene-β-D-arabinofuranose (10) in a form of slightly yellow syrup. Its IR and
NMR spectra, as well as elemental analysis confirmed the structure 10 in agreement
with formerly described compound 10 which was characterized17 by its boiling point
and IR spectra. Acid hydrolysis of the 10 in the presence of a cation-exchange resin
afforded the free sugar, 5-azido-5-deoxy-D-arabinofuranose (11) as a colourless syrup
with strongly positive specific rotation, confirming IR and NMR spectra and elemental
analysis. Azide 11 was oxidized with bromine in water to give a syrupous 5-azido-5-
deoxy-D-arabinono-1,4-lactone (12) whose structure confirmed its IR spectra and elemental
analysis. By hydrogenation of 12 in methanol on Pd/C catalyst 5-amino-5-deoxy-D-
arabinonolactam (13) was obtained with a trace of corresponding acid (according to
TLC). Crystallization from methanol afforded solid lactam 13, exhibiting strongly ne-
gative specific rotation, appropriate IR, NMR spectra and elemental analysis.
For the preparation of D-ribo and D-lyxo diastereoisomers of 5-azido-5-deoxy-1,2-O-
isopropylidene-α/β-D-pentofuranose we used reversal of the configuration on C-3 of
derivatives 4 and 10, respectively, via their 3-furanosuloses. This way was already used
for the corresponding 5-O-p-toluenesulfonyl derivatives18. 5-Azido-5-deoxy-1,2-O-iso-
propylidene-α-D-xylofuranose (4) was oxidized by ruthenium dioxide–sodium periodate
way19 to 5-azido-5-deoxy-1,2-O-isopropylidene-α-D-erythro-3-pentofuranosulose (14).
The structure of 14 was confirmed by IR spectra exhibiting stretching absorption on 1 778 cm–1
(C=O), 2 112 cm–1 (azide), bending doublet on 1 386 and 1 378 cm–1 (C(CH3)2), and by
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Amino-5-deoxypentonolactams
1029
1H and 13C NMR spectra (Table I). Reduction of 14 with sodium borohydride in water–
methanol afforded stereoselectively 5-azido-5-deoxy-1,2-O-isopropylidene-α-D-ribo-
furanose (15) isolated in crystalline state. Its IR spectrum exhibited stretching bands of
hydroxy and azido groups. Further proofs of structure of 15 gave NMR spectra (Table I).
R3CH2
R1
N3CH2
R1
N3CH2
R1
O
O
O
OH
O
O
R2
R2
R2
OH
R2
OH
O
R1
R2
R3
R1
R1
R2
OH
H
H
H
H
H
OH
OTs
OTs
N3
OH
H
H
OH
H
H
1
2
6
7
OH
OH
OH
18
20
OTs
OH
3
4
OTs
N3
5
N3
O
14
15
H
OH N3
NH
NH
HO
O
O
R1
R2
R1
R2
HO
HO
OH
R2
R1
R1
R2
OH
H
H
H
OH
H
8
13
23
OH
OH
22
R3CH2
O
N3CH2
N3CH2
O
O
O
R1
R1
OH
O
R1
HO
HO
O
R2
R2
R2
R1
R2
R3
R1
R2
R1
R2
H
H
OH OTs
OH N3
N3
H
OH
H
H
OH
H
9
10
16
17
11
19
12
21
OH
OH
O
OH
H
N3
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

1030
Kefurt, Kefurtova, Markova, Slivova:
TABLE I
1
Chemical shifts (δ-scale, ppm) and J(H,H) coupling constants (Hz) of the H and 13C nuclei of 1,2-
O-isopropylidene derivatives 4, 5, 10, 14, 15–17 in CDCl3
Compounda
14
Chemical shifts
Parameter
4
5
10
15
16
17
H-1
H-2
H-3
H-4
H-5
H-5′
H-O
C-1
C-2
C-3
C-4
C-5
5.96 d
5.92 d
4.67 d
4.78 d
4.29 ddd
3.54 dd
3.24 dd
–
5.95 d
6.15 d
4.39 dd
–
5.85 d
6.08 d
4.50 dd
–
5.80 d
4.53 d
4.57 d
4.59 dd
4.68 dd
4.32 ddd
4.16 ddd
3.65 dd
3.49 dd
2.68 d
4.24 dd
4.29 ddd
3.63 dd
3.59 dd
2.61 d
4.22 d
3.93–3.88 m
3.93–3.88 m
3.70 dd
4.10 ddd
3.62 dd
3.42 dd
3.21 s
4.51 ddd
3.69 dd
3.55 dd
–
4.33 dd
3.61 dd
3.55 dd
–
3.40 dd
2.39 d
104.8
104.8
105.8
103.1
104.7
102.8
105.1
85.4b
78.4b
75.2b
49.2
83.1b
81.7b
77.5b
48.8
86.8b
86.0b
76.3b
52.2
77.8b
208.2
76.1b
51.4
80.1b
79.1b
72.8b
51.4
80.2b
206.9
80.2b
52.1
81.1b
79.3b
69.9b
50.6
Coupling constants (H,H)
J(1,2)
J(2,3)
J(3,4)
J(4,5)
J(4,5′)
J(5,5′)
J(3,OH)
J(2,4)
3.7
0
3.7
0
3.9
0
4.4
–
3.8
4.4
4.3
–
4.2
6.2
c
2.8
6.1
5.9
–12.7
5.1
–
2.8
7.3
5.7
–12.7
–
2.2
7.3
6.1
–12.7
0
–
–
–
6.2
3.2
3.3
–13.2
–
2.4
4.1
6.3
4.0
–13.3
–
8.4
4.8
–13.4
9.2
–12.9
7.1
–
–
~1
–
~0.6
–
a
Other 1H singlets in regions 1.47–1.57 ppm and 1.28–1.43 ppm, as well as 13C signals in regions
112.6–115.1, 26.6–27.4 and 25.0–27.1 ppm were assigned to 1H or 13C nuclei of isopropylidene
groups; b may be interchanged; c undeterminable valve.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Amino-5-deoxypentonolactams
1031
Oxidation of 5-azido-5-deoxy-1,2-O-isopropylidene-β-D-arabinofuranose (10) was
carried out with RuO2–NaIO4 reagent and also with pyridinium dichromate3,20. The
obtained syrupous ketone, 5-azido-5-deoxy-1,2-O-isopropylidene-β-D-threo-3-pento-
furanosulose (16) exhibited stretching bands at 1 776 cm–1 (C=O) and 2 108 cm–1
(azide) in IR spectra and confirming signals in NMR spectra (Table I). Raw ketone 16
was reduced in water–ethanol with sodium borohydride to 5-azido-5-deoxy-1,2-O-iso-
propylidene-β-D-lyxofuranose (17) which was obtained in crystalline state after purifi-
1
cation by chromatography on silica gel. IR, H and 13C NMR spectra confirmed the
assumed structure of 17 (Experimental and Table I).
Synthetic route from 15 and 17 to corresponding 5-amino-5-deoxy-D-ribono/lyxono-
lactams followed the usual procedure. Derivatives 15 and 17 were hydrolyzed to 5-azido-
5-deoxy-D-ribofuranose (18) and 5-azido-5-deoxy-D-lyxofuranose (19), respectively.
Both azidopentoses were obtained as homogeneous (TLC) colourless syrups with the
proper IR data. Their oxidation with bromine in water afforded 5-azido-5-deoxy-D-
ribonolactone (20) and 5-azido-5-deoxy-D-lyxonolactone (21), respectively. Crystalline
lactone 20 as well as syrupous lactone 21 possessed expected bands and signals in IR
and NMR spectra. Hydrogenolysis of azido group in 20 and 21 on Pd/C catalyst in
methanol provided 5-amino-5-deoxy-D-ribonolactam (22) or 5-amino-5-deoxy-D-
lyxonolactam (23), respectively, as major products in addition to minor 5-amino-5-
deoxy-D-ribonic/lyxonic acid (TLC). Lactam 22 agreed in its m.p. and specific rotation
with the described one10. Conclusively, structure of both lactams was confirmed also
using IR and NMR spectra.
The above described synthetic route seems to be useful mainly in the case of preparation
of all four diastereoisomers of 5-amino-5-deoxy-D-pentonolactam. Of course, more ad-
vantageous ways, including the quoted10,11 syntheses of lactam 22, could be found for
the exclusive preparation of the certain single diastereoisomer.
EXPERIMENTAL
Melting points were determined on a Kofler block and are uncorrected. Optical rotations were
measured with an Opton photoelectric polarimeter at 20 °C. Reactions were monitored by TLC on
silica gel G (Merck) using benzene–ethanol 20 : 1 (S1), benzene–acetone 1 : 1 (S2), chloroform–
methanol 20 : 1 (S3), chloroform–methanol 10 : 1 (S4) and chloroform–methanol 5 : 1 (S5) mixtures
for elution, and 1% solution of cerium(IV) sulfate in 10% H2SO4 for detection of the plates. Column
chromatography was carried out on silica gel (100–200 µm, Lachema Brno). NMR spectra were re-
corded at 400 MHz (1H) and 100 MHz (13C) with a Bruker AM-400 instrument in deuteriochloroform,
deuterium oxide or hexadeuterioacetone solutions with tetramethylsilane as internal reference.
Chemical shifts are given in ppm (δ-scale) and coupling constants (J) in Hz. Assignments of
13C signals are tentative and are based on APT experiments and on comparison with published data
of structural analogs. IR spectra (wavenumbers in cm–1) were measured with FT IR Nicolet 740 in-
strument in CHCl3 solutions, KBr pellets or film, according to the state and solubility of measured
matter.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

1032
Kefurt, Kefurtova, Markova, Slivova:
1,2-O-Isopropylidene-5-O-p-toluenesulfonyl-α-D-xylofuranose (2) and 1,2-O-Isopropylidene-
3,5-di-O-p-toluenesulfonyl-α-D-xylofuranose (3)
p-Toluenesulfonyl chloride (13.3 g, 70 mmol) was added during 1 h to the stirred solution of 1,2-O-
isopropylidene-α-D-xylofuranose13 (1; 12.4 g, 65 mmol) in pyridine (55 ml) at room temperature. Re-
action was monitored by TLC in S2 (1: RF 0.15, 2: RF 0.56, 3: RF 0.84). Relative intensity of spots
of compounds 1, 2 and 3 on TLC was constant after 2 h. Reaction mixture was poured into ice water
(700 ml), crystalline product was filtered, washed and dried to obtain 19.1 g mixture 2 and 3 (TLC)
in relation ca 7 : 1, according to specific rotation compared with the data21,22 for pure compounds 2
and 3. This mixture was used in the next step.
5-Azido-5-deoxy-1,2-O-isopropylidene-α-D-xylofuranose (4) and 5-Azido-5-deoxy-1,2-
O-isopropylidene-3-O-p-toluenesulfonyl-α-D-xylofuranose (5)
A solution of the up described mixture of 2 and 3 (3.06 g) in N,N-dimethylformamide (30 ml) was
stirred under nitrogen with water (1.7 ml), sodium azide (0.85 g, 13 mmol) and urea (0.07 g) for 20 h
at 110 °C. Products 4 and 5 were distinguishable from the starting compounds 2 and 3 only accord-
ing to yellow/brown colour change during carbonization of spots in the system S1 as well as in other
tested systems. Reaction mixture was poured into ice water (40 ml), extracted with chloroform (3 × 50 ml)
which was washed with cold solution of sodium bicarbonate and water and dried (MgSO4). After
filtration and evaporation of solvent 1.73 g mixture of 4 and 5 was obtained which was separated on
silica gel column in system S1. Recrystallization of the product obtained by evaporation of combined
fractions from chloroform–hexane 1 : 5 gave 1.2 g of 4, m.p. 60 °C, [α]D –42° (c 1.0, methanol).
Literature14,15 gives m.p. 58.5–60 °C, [α]D +44° (c 1.0, methanol). NMR spectrum: see Table I. For
C8H13N3O4 (215.2) calculated: 44.65% C, 6.09% H, 19.53% N; found: 44.83% C, 6.15% H, 19.65% N.
Syrupous 3-O-tosyl derivative 5 (0.28 g) showed [α]D –8.6° (c 2.0, chloroform); NMR spectrum:
see Table I. For C15H19N3O6S (369.4) calculated: 48.77% C, 5.18% H, 11.38% N, 8.68% S; found:
48.80% C, 5.15% H, 11.11% N, 8.24% S.
5-Azido-5-deoxy-D-xylofuranose (6)
A solution of 4 (850 mg, 3.9 mmol) in water (7.5 ml) was stirred with Dowex 50 W (H+, 100/200 mesh,
3.5 ml) for 45 min at 60 °C. TLC in system S4: 4: RF 0.68, 6: RF 0.2. Decolorization of filtrate,
evaporation, and drying of residue afforded 653 mg (94%) syrupous azido pentose 6, [α]D +52° (c 1.0,
water). IR spectrum (film): 3 372 broad (OH assoc.); 2 932 (CH); 2 108 (azide). For C5H9N3O4
(175.2) calculated: 34.29% C, 5.18% H, 23.99% N; found: 34.28% C, 5.51% H, 23.91% N.
5-Azido-5-deoxy-D-xylono-1,4-lactone (7)
A solution of 6 (490 mg, 2.8 mmol) in water (15 ml) was stirred with bromine (0.2 ml) and barium
carbonate (1.8 g) for 1 h at 0 °C and than 2 h at room temperature. Oxidation was followed by TLC
in system S5 (6: RF 0.55, 7: RF 0.68). After filtration of insoluble salts and removal of the excess
bromine with a stream of air, the colourless solution was stirred for 1 h with silver carbonate (2.5 g)
and desalted on a column of Dowex 50 W (H+ form, 10 ml). The combined filtrates on evaporation
gave 437 mg (90%) colourless syrupous lactone 7, [α]D +50° (c 1.2, chloroform). IR spectrum (film):
1
3 378 broad (OH assoc.); 2 932 (CH); 2 116 (azide); 1 778 (C=O). H NMR spectrum (D2O): 4.67 d,
1 H, J(2,3) = 8.7 (H-2); 4.59 dd, 1 H, J(3,4) = 7.3 (H-3); 3.79 dd, 1 H, J(5,4) = 3.4, J(5,5′) = –13.9
(H-5); 3.73 dd, 1 H, J(5′,4) = 4.7 (H-5′). Signal of the H-4 (≈4.83 ppm) is overlapped by DOH. 13C NMR
spectrum (D2O): 176.5 (C-1); 79.5, 73.6, 72.7 (C-2, C-3, C-4); 50.5 (C-5). For C5H7N3O4 (173.1)
calculated: 34.69% C, 4.08% H, 24.27% N; found: 34.34% C, 4.50% H, 23.99% N.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Amino-5-deoxypentonolactams
1033
5-Amino-5-deoxy-D-xylonolactam (8)
A solution of lactone 7 (1.11 g, 6.4 mmol) in methanol (50 ml) was stirred with 5% Pd/C (0.5 g) in
a renewed hydrogen atmosphere. TLC in system S5 showed gradually disappearing spot of the start-
ing 7 (RF 0.68) and strengthening spot of lactam 8 (RF 0.1) in addition to the slight spot of RF
0
(possibly corresponding amino acid). Removal of the catalyst and evaporation of the solvent afforded
950 mg partially crystalline residue which was recrystallized from methanol to give 180 mg (19%)
of 8, m.p. 177–178 °C, [α]D +6° (c 1.0, water). Further crystalline compound 8 (225 mg, 24%) was
obtained after concentration of mother liquors. IR spectrum (KBr pellet): 3 600–3 200 broad (OH,
NH assoc.); 2 952, 2 919 (CH); 1 684, 1 634 (CONH free, assoc.). For C5H9NO4 (147.1) calculated:
40.82% C, 6.17% H, 9.52% N; found: 40.86% C, 6.27% H, 9.46% N.
5-Azido-5-deoxy-1,2-O-isopropylidene-β-D-arabinofuranose (10)
A mixture of 1,2-O-isopropylidene-5-O-p-toluenesulfonyl-β-D-arabinofuranose16 (9; 1.8 g, 5.2 mmol),
sodium azide (0.43 g, 6.6 mmol) and urea (0.04 g) was stirred in N,N-dimethylformamide (12 ml) for
12 h at 110 °C. Solvent was evaporated and the residue was purified by chromatography on silica gel
column in S4, affording 1.0 g (90%) of syrupous azido derivative 10, [α]D +56.6° (c 1.0, chloroform).
IR spectrum (film): 3 450 broad (OH); 2 103 (azide); 1 378, 1 385 doublet (C(CH3)2). NMR spec-
trum: see Table I. For C8H13N3O4 calculated: 44.65% C, 6.02% H, 19.53% N; found: 44.23% C,
6.24% H, 19.20% N.
5-Azido-5-deoxy-D-arabinofuranose (11)
Solution of isopropylidene derivative 10 (0.86 g, 4 mmol) in water (7.5 ml) was stirred with Dowex 50 W
(H+, 7 ml) for 45 min at 60 °C. Course of hydrolysis was followed by TLC in S4 (10: RF 0.66, 11:
RF 0.25). The filtrate from ion exchanger was decolorized and after evaporation afforded 0.625 g
(89%) of syrupous azido pentose 11, [α]D +159.2° (c 1.0, water). IR spectrum (film): 3 370 broad
(OH); 2 932 (CH); 2 108 (azide). For C5H9N3O4 (175.2) calculated: 34.29% C, 5.18% H, 23.99% N;
found: 34.28% C, 5.5 1% H, 23.86% N.
5-Azido-5-deoxy-D-arabinono-1,4-lactone (12)
Solution of azido pentose 11 (0.5 g, 2.86 mmol) in water (15 ml) was stirred with barium carbonate
(1.8 g) and bromine (0.2 ml) for 2 h at 0 °C. Oxidation was followed by TLC in S5 (11: RF 0.54,
12: RF 0.65). After similar treatment of reaction mixture as described for 6, syrupous lactone 12, [α]D
+98.4° (c 1.0, ethanol), was obtained (0.47 g, 95%). IR spectrum (film): 3 374 broad (OH); 2 933 (CH);
1
2 111 (azide); 1 765 (C=O). H NMR spectrum (D2O): 4.62 d, 1 H, J(2,3) = 9.2 (H-2); 4.44 m, 1 H,
ΣJ = 16.1 (H-4); 4.27 dd, 1 H, J(3,4) = 8.6 (H-3); 3.87 dd, 1 H, J(5,4) = 2.5, J(5,5′) = –14.2 (H-5);
3.62 dd, 1 H, J(5′,4) = 5.3 (H-5′). 13C NMR spectrum (D2O): 176.4 (C-1); 80.3, 74.6, 74.4 (C-2, C-3,
C-4); 51.1 (C-5). For C5H7N3O4 (173.1) calculated: 34.69% C, 4.08% H, 24.27% N; found: 34.45% C,
4.36% H, 23.62% N.
5-Amino-5-deoxy-D-arabinonolactam (13)
Azido lactone 12 (0.41 g, 2.3 mmol) was hydrogenated by the way described for 8. Recrystallization
of the crude product (0.34 g, 98%) from methanol afforded 0.14 g (40%) of lactam 13, m.p. 178 °C,
[α]D –172° (c 1.0, water). IR spectrum (KBr pellet): 3 600–3 200 broad (OH, NH); 2 961, 2 906
(CH); 1 647 (CONH assoc.). For C5H9NO4 (147.1) calculated: 40.82% C, 6.17% H, 9.52% N; found:
40.70% C, 6.35% H, 9.43% N.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

1034
Kefurt, Kefurtova, Markova, Slivova:
5-Azido-5-deoxy-1,2-O-isopropylidene-α-D-erythro-3-pentofuranosulose (14)
Solution of sodium periodate (3.0 g, 14 mmol) in water (30 ml) was added dropwise to the stirred
mixture of the derivative 4 (1.6 g, 7.4 mmol), ruthenium dioxide (0.145 g) and sodium carbonate (0.5 g)
in tetrachloromethane (60 ml). Mixture of two liquid phases was shaked at room temperature for 8 h
and followed by TLC in system S1 (4: RF 0.28, 14: RF 0.45). Further sodium periodate (0.86 g) was
added during this period. Superfluous ruthenium tetraoxide was finally decomposed by 2-propanol (1 ml),
reaction mixture was diluted with water (10 ml) and extracted with chloroform (6 × 50 ml). Syrupous
product 14 (1.12 g, 71%) was obtained after evaporation of the dried chloroform phase. IR spectrum
(chloroform): 3 026, 2 996, 2 939 (CH); 2 112 (azide); 1 778 (C=O); 1 386, 1 378 doublet
(C(CH3)2). NMR spectrum: see Table I.
5-Azido-5-deoxy-1,2-O-isopropylidene-α-D-ribofuranose (15)
Ketone 14 (2.1 g, 9.9 mmol) in mixture ethanol–water (95 ml, 9 : 1) was stirred at 0–5° C with sodium
tetrahydridoborate (0.850 g, 22.4 mmol) for 3 h. Reduction was monitored by TLC in S1 (14: RF 0.45,
15: RF 0.31). The excess of hydride was decomposed by acetic acid (1.0 ml), reaction mixture was
evaporated and the residue extracted with ether (6 × 40 ml). Evaporating of the solution gave crystalline
compound 15 (2.01 g, 95%), m.p. 50.5–51.5 °C (ether–light petroleum 1 : 2), [α]D +65.5° (c 0.5,
chloroform). IR spectrum (chloroform): 3 558 broad (OH); 3 024–2 938 (CH); 2 105 (azide); 1 384,
1 375 doublet (C(CH3)2). NMR spectrum: see Table I. For C8H13N3O4 (215.2) calculated: 44.65% C,
6.09% H, 19.53% N; found: 44.58% C, 6.29% H, 19.53% N.
5-Azido-5-deoxy-1,2-O-isopropylidene-β-D-threo-3-pentosulose (16)
A) Solution of 4.5 g (21 mmol) of sodium periodate in water (50 ml) was dropped to the stirred
mixture of the derivative 10 (2.15 g, 10 mmol), sodium carbonate (1.2 g), ruthenium dioxide (0.12 g),
tetrachloromethane (80 ml) and water (20 ml). Oxidation was monitored by TLC in S3 (10: RF 0.50,
16: RF 0.59). Further portion of sodium periodate (2.1 g) was added in parts during 90 min always
when the yellow-green soluble ruthenium tetraoxide was changed to the black insoluble ruthenium
dioxide. Finally, the superfluous ruthenium tetraoxide was decomposed by 2-propanol (1 ml) and re-
action mixture was extracted with chloroform (6 × 50 ml). Syrupous product 16 (1.4 g, 65%) was
obtained by evaporation of the dried organic phase. IR spectrum (chloroform): 3 026, 2 996, 2 941
(CH); 2 108 (azide); 1 776 (C=O); 1 375, 1 384 doublet (C(CH3)2). NMR spectrum: see Table I.
B) Solution of acetic anhydride (1.7 ml) in dichloromethane (5 ml) was dropped to the mixture of
derivative 10 (2.01 g, 9.4 mmol), pyridinium dichromate20 (7.05 g, 18.8 mmol) and sodium acetate
(1.92 g) stirred at room temperature in dichloromethane (120 ml). Reaction was monitored in S3.
After 75 h, reaction mixture was filtered through a short column of silica gel and the remaining
acetic anhydride was removed from filtrate by shaking with water solution of sodium bicarbonate.
Evaporation of the dried dichloromethane phase afforded 1.92 g (96%) of syrupous pentosulose 16,
conforming in IR spectra with the compound prepared by the way A.
5-Azido-5-deoxy-1,2-O-isopropylidene-β-D-lyxofuranose (17)
Ketone 16 (345 mg, 1.62 mmol) in mixture ethanol–water (12 ml, 10 : 2) was stirred at 0–5 °C with
sodium tetrahydridoborate (110 mg, 2.92 mmol) for 3 h. Reduction was monitored by TLC in S1 (16:
RF 0.54, 17: RF 0.07). Excessing hydride was destroyed with acetic acid (0.1 ml) to the pH 6.5, re-
action mixture was evaporated and the residue was extracted with ether. Evaporating of the ether
solution gave 308 mg (88%) colourless crystalline compound 17, m.p. 48–49 °C (ether–light petroleum
1 : 1), [α]D +45° (c 1.3, CHCl3). IR spectrum (chloroform): 3 534 broad (OH); 3 024, 2 997, 2 943
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

5-Amino-5-deoxypentonolactams
1035
(CH); 2 105 (azide); 1 386, 1 378 doublet (C(CH3)2). NMR spectrum: see Table I. For C8H13N3O4
(215.2) calculated: 44.65% C, 6.02% H, 19.53% N; found: 44.37% C, 6.16% H, 19.32% N.
5-Azido-5-deoxy-D-ribofuranose (18)
By way of hydrolysis used for azido pentoses 6 or 11, isopropylidene derivative 15 (0.84 g, 3.9 mmol)
afforded azido pentose 18 (0.61 g, 88%) in syrupous form, [α]D +105° (c 1.2, water). For C5H9N3O4
(175.2) calculated: 34.29% C, 5.18% H, 23.99% N; found: 34.51% C, 5.17% H, 23.72% N.
5-Azido-5-deoxy-D-lyxofuranose (19)
By the up described way used for hydrolyses of 4, 10 or 15, isopropylidene derivative 17 (1.01 g, 4.7 mmol)
afforded azidopentose 19 (0.72 g, 87%) in syrupous form, [α]D +13° (c 0.4, water). IR spectrum
(film): 3 308 broad (OH); 2 926 (CH); 2 099 (azide). For C5H9N3O4 (175.2) calculated: 34.29% C,
5.18% H, 23.99% N; found: 34.35% C, 5.31% H, 23.80% N.
5-Azido-5-deoxy-D-ribono-1,4-lactone (20)
By way described for preparation of lactones 7 or 12, pentose 18 (1 g, 5.7 mmol) afforded 0.78 g
(79%) lactone 20, m.p. 81–82 °C (ethanol–light petroleum), [α]D +96.8° (c 0.8, ethanol). IR spectrum
1
(KBr pellet): 3 451–3 330 broad (OH); 2 118 (azide); 1 765 (C=O). H NMR spectrum (D2O): 4.81 d,
1 H, J(2,3) = 5.6 (H-2); 4.68 dd, 1 H, J = 9 (H-4); 4.42 d, 1 H, J(3,2) = 5.5 (H-3); 3.79 dd, 1 H,
J(5,4) = 3.6, J(5,5′) = –13.7 (H-5); 3.72 dd, 1 H, J(5′,4) = 5.5 (H-5′). 13C NMR spectrum
(hexadeuterioacetone): 176.2 (C-1); 84.2, 71.2, 70.0 (C-2, C-3, C-4); 53.1 (C-5). For C5H7N3O4
(173.1) calculated: 34.69% C, 4.08% H, 24.27% N; found: 34.34% C, 4.09% H, 23.95% N.
5-Azido-5-deoxy-D-lyxono-1,4-lactone (21)
By way used for preparation of the up described lactones, pentose 19 (0.72 g, 4.1 mmol) afforded
0.71 g (99%) of syrupous lactone 21, [α]D +41° (c 0.3, ethanol). IR spectrum (film): 3 456 broad
1
(OH); 2 941 (CH); 2 106 (azide); 1 776 (C=O). H NMR spectrum (D2O): 4.76 d, 1 H, J(2,3) = 4.8
(H-2); 4.70 ddd, 1 H, ΣJ = 15.6 (H-4); 4.56 dd, 1 H, J(3,4) = 2.9 (H-3); 3.74 dd, 1 H, J(5,4) = 7.5,
J(5,5′) = –13.6 (H-5); 3.69 dd, 1 H, J(5′,4) = 5.0 (H-5′). For C5H7N3O4 (173.1) calculated: 34.69% C,
4.08% H, 24.27% N; found: 34.33% C, 4.28% H, 23.81% N.
5-Amino-5-deoxy-D-ribonolactam (22)
By way described for hydrogenolysis of the azido lactones 7 or 12, lactone 20 (0.7 g, 4.1 mmol)
afforded lactam 22 (0.3 g, 50%), m.p. 244–250 °C (decomp.), [α]D +33.6° (c 0.5, water). IR spectrum
(KBr pellet): 3 600–3 200 broad (OH, NH); 2 921 (CH); 1 641 (CONH assoc.). Refs9,10 give for
lactam 22 m.p. above 240 °C (decomp.), [α]D +33° (c 0.3, water). For C5H9NO4 (147.1) calculated:
40.82% C, 6.17% H, 9.52% N; found: 40.55% C, 6.28% H, 9.32% N.
5-Amino-5-deoxy-D-lyxonolactam (23)
By way used for preparation of the up described lactams, lactone 21 (0.7 g, 4 mmol) afforded 586 mg
(100%) of the crude lactam 23. Foam product crystallized from methanol (10 ml) provided pure com-
pound 23 (240 mg, 41%), m.p. 188–189 °C (decomp.), [α]D –54.7° (c 1.0, water). IR spectrum (KBr
pellet): 3 600–3 170 broad (OH, NH); 2 925, 2 884 (CH); 1 677, 1 634 (CONH free, assoc.). For
C5H9NO4 (147.1) calculated: 40.82% C, 6.17% H, 9.52% N; found: 40.61% C, 6.41% H, 9.23% N.
Collect. Czech. Chem. Commun. (Vol. 61) (1996)

1036
Kefurt, Kefurtova, Markova, Slivova:
The authors are indebted to members of Laboratory of NMR Spectroscopy (Dr R. Hrabal, Head),
Laboratory of Infrared Spectroscopy (Dr M. Novotna, Head) and Laboratory of Organic Analysis (Dr L.
Helesic, Head) of the Prague Institute of Chemical Technology for careful spectral measurements and
analyses.
REFERENCES
1. Kefurt K., Capek K., Kefurtova Z., Jary J.: Collect. Czech. Chem. Commun. 44, 2526 (1979).
2. Kefurt K., Capek K., Kefurtova Z., Jary J.: Collect. Czech. Chem. Commun. 51, 391 (1986).
3. Kefurt K., Kefurtova Z., Jary J.: Collect. Czech. Chem. Commun. 53, 1795 (1988).
4. Kefurt K., Kefurtova Z., Trska P., Blaha K., Fric I., Jary J.: Collect. Czech. Chem. Commun. 54,
2156 (1989).
5. Havlicek J., Kefurt K., Volka K., Ksandr Z.: Vibrational Spectrosc. 3, 139 (1992).
6. Ondracek J., Novotny J., Kefurt K., Havlicek J.: Acta Crystallogr., C 48, 929 (1992).
7. Ondracek J., Havlicek J., Kefurt K., Jary J., Novotny J., Kratochvil B.: Collect. Czech. Chem.
Commun. 57, 2367 (1992).
8. Havlicek J., Kefurt K., Husak M., Novotny J., Kratochvil B.: Collect. Czech. Chem. Commun. 58,
1600 (1993).
9. Hanessian S., Haskell T. H.: J. Heterocycl. Chem. 1, 55 (1964).
10. Hanessian S.: J. Org. Chem. 34, 675 (1969).
11. Herdeis C., Waibel D.: Arch. Pharm. 324, 269 (1991).
12. Gibson W. T.: Eur. Pat. Appl. 334586 (1989); Chem. Abstr. 113, 11926 (1991).
13. Moravcova J., Capkova J., Stanek J.: Carbohydr. Res. 263, 61 (1994).
14. Szarek W. A., Jones J. K. N.: Can. J. Chem. 43, 2345 (1965).
15. Beilstein’s Handbook of Organic Chemistry, Fifth Suppl. Series, Vol. 19/9, p. 308.
16. Levene P. A., Compton J.: J. Biol. Chem. 116, 189 (1936).
17. Hanessian S.: J. Org. Chem. 32, 163 (1967).
18. Defaye J., Horton D., Muesser M.: Carbohydr. Res. 20, 305 (1971).
19. Parikh V. M., Jones J. K. N.: Can. J. Chem. 43, 3452 (1965).
20. Corey E. J., Schmidt G.: Tetrahedron Lett. 1979, 399.
21. Levene P. A., Raymond A. L.: J. Biol. Chem. 102, 317 (1933).
22. Karrer P., Boettcher A.: Helv. Chim. Acta 36, 837 (1953).
Collect. Czech. Chem. Commun. (Vol. 61) (1996)