Carbohydrates to functionalized pyridines: A new synthetic approach via enol-driven ring transformations

Article abstract of DOI:10.1055/s-2008-1042760

An expeditious synthetic protocol for polyhydroxyalkylpyridines and their 3-amino/mercapto-2-pyridinone analogues using unprotected aldoses as biorenewable resources is reported. The synthesis involves enol-driven Michael-type addition of lactones/ketones to aldose-derived 1,3-oxazin-2-ones followed by decarboxylative ring transformation to yield various novel polyhydroxyalkylpyridines. This is a one-pot nanoclay (K-10 clay)-catalyzed process proceeding under conditions of solvent-free microwave irradiation. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1042760

LETTER
529
Carbohydrates to Functionalized Pyridines: A New Synthetic Approach via
Enol-Driven Ring Transformations
Carbohydrates
t
a
o
F
unction
l
alized Pyridin
D
e
s
har Singh Yadav,* Ankita Rai, Vijai Kumar Rai, Chhama Awasthi
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, Uttar Pradesh, India
Fax +91(532)2460533; E-mail: ldsyadav@hotmail.com
Received 20 November 2007
ing to a class of medications called calcium channel
Abstract: An expeditious synthetic protocol for polyhydroxyalkyl-
pyridines and their 3-amino/mercapto-2-pyridinone analogues us-
ing unprotected aldoses as biorenewable resources is reported. The
synthesis involves enol-driven Michael-type addition of lactones/
blockers, was approved by the FDA in 2004, and is pres-
ently in clinical use for the treatment of high blood pres-
sure and angina. Other DHP derivatives, nifedipine1 and
ketones to aldose-derived 1,3-oxazin-2-ones followed by decarbox- nicardipine,2 were also approved by the FDA in 1981 and
ylative ring transformation to yield various novel polyhydroxyal-
1988, respectively, for the same purpose. Isoniazid is be-
kylpyridines. This is a one-pot nanoclay (K-10 clay)-catalyzed
ing popularly used in tuberculosis therapy since its release
process proceeding under conditions of solvent-free microwave ir-
in 1952. Recently, certain pyridine derivatives have been
radiation.
reported as a new class of unnatural anti-HIV agents with
multiple mechanisms of antiviral action.3 The amino and
Key words: carbohydrates, mineral-catalyzed, microwaves, 1,3-
oxazin-2-ones, pyridines, solvent-free
mercapto functions are synthetically and pharmacologi-
cally readily manipulable. Several molecules embedded
with, or derived from, 3-amino/mercaptopyridine-2(1H)-
Pyridines and pyridinones are basic structural motifs
one scaffolds have been found to be HIV-1 reverse tran-
present in various useful medicinal products. Amlodipine
scriptase and thrombin inhibitors, and antihypertensive
(Norvasac®), a dihydropyridine (DHP) derivative belong-
agents.4,5
CHO
(CHOH)n
CH2OH
D
-xylose, n = 3
D-glucose, n = 4
1
O
MW,
K-10 clay
NH2
H2NNH
2
N
O
O
(CHOH)n–2
CH2OH
3a, n = 3
3b, n = 4
S
O
Ph
RCOMe
O
MW
K-10
clay
6
Me
MW
4
N
MW
K-10
clay
O
K-10
clay
O
Ph
5
CH2OH
CH2OH
(CH2OH)n–2
(CH2OH)n–2
CH2OH
HS
O
(CH2OH)n–2
PhCOHN
O
N
H
R
N
R = Ph, 4-ClC6H4,
4-FC6H4, 4-MeOC6H4
N
H
7a, n = 3
7b, n = 4
9a–d, n = 3
9e–h, n = 4
8a, n = 3
8b, n = 4
Scheme 1 Formation of functionalized pyridines 7–9 from xylose/glucose
SYNLETT 2008, No. 4, pp 0529–0534
x
x.
x
x.
2
0
0
8
Advanced online publication: 12.02.2008
DOI: 10.1055/s-2008-1042760; Art ID: G36407ST
© Georg Thieme Verlag Stuttgart · New York

530
L. D. S. Yadav et al.
LETTER
N
HO
CH2OH
CH2OH
HO
N
K-10
clay
NH
NH
O
(CHOH)n–2
(CHOH)n–2
NH2
H
OH
(CHOH)n–2
PhCOHN
O
O
NH2
H2N
O
H3O+
reflux
O
MW
10 min
(CHOH)n–2
CH2OH
CH2OH
N
N
H
11
45 min
H
NH·NH2
N·NH2
NH2
8a, n = 3
8b, n = 4
10a, n = 3
10b, n = 4
HO
HO
N
H
Scheme 2 Debenzoylation of 8 to the corresponding amino ana-
logues 10
O
O
O
O
(CHOH)n–2
(CHOH)n–2
CH2OH
CH2OH
Most of the best-established methods for the synthesis of
pyridines are based on cyclization reactions, for example
the venerable Hantzsch synthesis and its variants. An al-
ternative method for forming the pyridine ring involves
[4+2] cycloaddition reactions using azadienes, especially
heterocyclic rather than acyclic, and electron-rich alkenes
and alkynes.6–8 In these reactions the initial cycloaddition
is followed by a retro-Diels–Alder reaction in which a
small stable molecule, such as HCN, CO2, or N2 is elimi-
nated.
HO
N
N
O
O
O
O
– H2O
– NH2NH2
(CHOH)n–2
(CHOH)n–2
CH2OH
CH2OH
3
Scheme 3 Plausible mechanism for the formation of 1,3-oxazin-2-
ones 3 from xylose/glucose semicarbazone 11
Use of biorenewable resources in organic syntheses is a
promising approach as it is in accordance with the sustain-
able development. The polyhydroxyalkyl dihydropyr-
idines incorporating the NH2 and SH functions reported
herein are hitherto unknown, and neither known synthetic
approaches to pyridines nor functionalization reactions of
heterocycles can be used for their synthesis, although they
appear to be attractive scaffolds for exploiting chemical
diversity and generating drug-like library to screen for
lead candidates. Aside from the simple expectation that
the presence of sugar residues with free hydroxyl groups
in DHP should increase the water solubility and bioavail-
ability, other interesting biological properties may arise
owing to the extensive and essential role of carbohydrates
in the complex machinery of various glycoconjugate bio-
logical activity.9,10
In view of the above mentioned valid points and in contin-
uation of our quest for novel microwave (MW)-assisted
solvent-free heterocyclization processes,11–15 especially
using carbohydrates as starting material,11,12 we report
herein an unprecedented synthesis of functionalized pyr-
idines 7–9 using D-xylose/D-glucose 1 as biorenewable
resources (Scheme 1). In this protocol acid-catalyzed cy-
clization of D-glucose/D-xylose semicarbazones 11 yields
the corresponding precursors 1,3-oxazin-2-ones 3, which
undergo enol-driven deacarboxylative ring transforma-
tion with enolic entities to furnish polyhydroxyalkyl pyr-
idines 7, 8, and 9 (Scheme 4). Compounds 3 and 7–10 are
hitherto unreported.
After considerable experimentation, it was found that the
envisaged synthetic strategy was successful using 1,3-ox-
O
O
CH2OH
O
CH2OH
O
O
N
(CH2OH)n
4
5
2
–
N
1,5-H
shift
(CH2OH)n
2
–
3
HS
O
O
HS
O
O
– PhCOMe
Ph
– CO2
(CHOH)n–2
CH2OH
S
(CHOH)n–2
CH2OH
O
N
SH
N
H
Me
7'
7
O
CH2OH
O
N
CH2OH
O
O
1,5-H
shift
(CH2OH)n–2
N
3
(CH2OH)n
2
–
PhCOHN
O
O
– CO2
PhCOHN
O
O
(CHOH)n
2
–
N
(CHOH)n
N
2 NHCOPh
O
–
Ph
N
8'
CH2OH
8
CH2OH
H
O
O
CH2OH
6
O
O
O
N
(CH2OH)n
3
O
OH
R
2
–
N
N
– H2O
– CO2
R
R
(CHOH)n
CH2OH
2
–
(CHOH)n
CH2OH
2
–
(CHOH)n
CH2OH
R
N
2
–
H
9
Scheme 4 Plausible mechanism for the formation of pyridines 7–9
Synlett 2008, No. 4, 529–534 © Thieme Stuttgart · New York

LETTER
Carbohydrates to Functionalized Pyridines
531
azin-2-ones 3, which were obtained in 79–82% yields via resulted in relatively very low yields of 7, 8, and 9 (19–
Montmorillonite K-10 clay catalyzed domino cyclo- 35%).
isomerization, dehydrazination, and dehydration of glu-
cose/xylose semicarbazones 11 under solvent-free MW
The precursor 1,3-oxazin-2-ones 3 are endowed with two
electrophilic centers, C-2 and C-6, in which the latter is
irradiation conditions in
a
one-pot procedure
highly prone to Michael-type nucleophilic attack due to
the extended conjugation with electron-withdrawing N–
C=O grouping. In the presence of an acid (K-10 clay), the
reaction is possibly initiated by the enol form of the com-
pounds 4, 5, and 6, which acts as a nucleophile and pref-
erentially attacks at the highly electrophilic center C-6 of
the oxazine ring driving the decarboxylative ring transfor-
mation to yield 7, 8, and 9, respectively (Scheme 4).
(Scheme 3).16 The mechanism shown in Scheme 3 is sup-
ported by the formation of hydrazine during the reaction
as detected by p-dimethylaminobenzaldehyde method.17
It was noted that other mineral catalysts, viz. silica gel,
neutral or basic alumina, were far less effective resulting
in either no reaction (in the case of basic alumina) or rel-
atively very low yields (15–28%) of 3 (in the cases of sil-
ica gel and neutral alumina). The solvent-free MW
irradiation of an equimolar mixture of a 1,3-oxazin-2-one
3, oxathiolanone 4, azalactone 5, or a ketone 6, in the pres-
ence of Montmorillonite K-10 clay (particle size 32.7 nm)
afforded the corresponding pyridine analogues 7, 8, or 9
in 83–94% yields (Scheme 1, Table 1).18 Compounds 8
could be easily debenzoylated to furnish the correspond-
ing amino analogues 10 (Scheme 2).19 The use of other
mineral catalysts, viz. silica gel, neutral or basic alumina,
The same products 7, 8, and 9 were obtained even if 2-
thione analogues of 1,3-oxazin-2-ones 3 were used. This
supports the plausible mechanisms outlined in Scheme 4.
It is noteworthy that we could isolate only aromatic 1,2-
dihydropyrimidin-2-ones 7 and 8 instead of the nonaro-
matic 2,3-dihydropyrimidin-2-ones 7¢ and 8¢, which are
related to the former by a 1,5-proton shift.
Table 1 K-10 Clay Catalyzed Microwave-Activated Solvent-Free Synthesis of Functionalized Pyridines 7–9
Entry
Oxazine
Lactone/ketone
Product
Time
Yield
(%)b,c
(min)a
O
SH
SH
N
S
Ph
HN
1
9
89
91
94
92
OH
O
N
HO
O
O
O
O
O
O
O
O
O
Me
OH
OH
OH
7a
O
OH
HO
S
N
N
Ph
HN
OH
2
3
4
10
10
1
HO
O
O
N
Me
OH
7b
O
NHCOPh
HN
OH
O
N
HO
HO
O
Ph
Ph
OH
OH
8a
O
NHCOPh
OH
HO
HN
OH
O
O
N
OH
OH
8b
O
5
7
83
N
O
HO
O
OH
OH
OH
9a
Synlett 2008, No. 4, 529–534 © Thieme Stuttgart · New York

532
L. D. S. Yadav et al.
LETTER
Table 1 K-10 Clay Catalyzed Microwave-Activated Solvent-Free Synthesis of Functionalized Pyridines 7–9 (continued)
Entry
Oxazine
Lactone/ketone
Product
Time
Yield
(%)b,c
(min)a
Cl
O
N
N
N
6
9
8
85
91
N
O
HO
O
O
O
OH
OH
Cl
OH
9b
F
O
7
O
HO
OH
OH
F
OH
9c
MeO
O
8
9
10
87
88
N
O
HO
OH
OH
MeO
OH
9d
O
HO
N
OH
8
HO
O
OH
O
N
OH
OH
9e
Cl
O
HO
N
10
10
92
HO
OH
O
O
OH
N
OH
Cl
OH
9f
F
O
HO
N
11
10
4
HO
OH
O
O
OH
N
OH
F
OH
9g
MeO
O
HO
N
12
11
90
HO
OH
O
O
OH
N
OH
MeO
OH
9h
a Microwave irradiation time at 90 °C.
b Yield of isolated and purified products.
c All compounds gave C, H, and N analyses within 0.35% and satisfactory spectral (IR, 1H NMR, 13C NMR and EIMS) data.
In conclusion, we have devised efficient routes for the amino/mercapto-2-pyridinone analogues of remarkable
synthesis of novel polyhydroxyalkylpyridines and their 3- pharmacological potential from unprotected aldoses as
Synlett 2008, No. 4, 529–534 © Thieme Stuttgart · New York

LETTER
Carbohydrates to Functionalized Pyridines
533
d6): d = 3.88 (ddd, J2¢H,3¢Ha = 5.4 Hz, J1¢H,2¢H = 4.6 Hz,
biorenewable resources. The synthesis is effected under
conditions of K-10 clay catalysis and solvent-free micro-
wave irradiation.
J
2¢H,3¢Hb = 2.7 Hz, 1 H, 2¢H), 4.03 (dd, J3¢Ha,3¢Hb = 10.5 Hz,
J2¢H,3¢Ha = 5.4 Hz, 1 H, 3¢Ha), 4.37 (d, J1¢H,2¢H = 4.6 Hz, 1 H,
1¢H), 4.59 (dd, J3¢Ha,3¢Hb = 10.5 Hz, J2¢H,3¢Hb = 2.7 Hz, 1 H,
3¢Hb), 5.01–5.37 (br s, 3 H, 3 × OH, exch. D2O), 7.51 (d,
J4H,5H = 8.1 Hz, 1 H, 5-H), 7.85 (d, J4H,5H = 8.1 Hz, 1 H, 4-
H). 13C NMR (100 MHz, DMSO-d6): d = 64.3, 65.9, 71.7,
73.5, 86.5, 106.3, 174.8. MS–FAB: m/z = 188 [MH+]. Anal.
Calcd for C7H9NO5: C, 44.92; H, 4.85; N, 7.48. Found: C,
44.69; H, 4.73; N, 7.73.
Acknowledgment
We sincerely thank the DST, Govt. of India, for financial support,
and SAIF, Punjab University, Chandigarh, for providing microana-
lyses and spectra.
(17) L. F.Audrieth, ; B. A.Ogg, The Chemistry of Hydrazines;
John Wiley and Sons, Inc.: New York, 1951.
(18) General Procedure for the Synthesis of 4-Polyhydroxy-
alkyl-1H-pyridin-2-ones 7, 8, and 2-Aryl-4-
References and Notes
(1) Janis, R. A.; Silver, P. J.; Triggle, D. J. Adv. Drug Res. 1987,
16, 309.
polyhydroxyalkylpyridines 9
An intimate solvent-free mixture of 1,3-oxazin-2-one 3 (2.4
mmol) and 1,3-oxathiolan-5-one 4 (2.4 mmol), or 1,3-
oxazol-5-one 5 (2.4 mmol), or ketone 6 (2.4 mmol) in the
presence of Montmorillonite K-10 clay (0.25 g) was taken in
a 20 mL vial and subjected to MW irradiation in a CEM
Discover Focused Microwave Synthesis System at 90 °C for
7–11 min. After completion of the reaction as indicated by
TLC, H2O (10 mL) was added to give the crude product,
which was recrystallized from EtOH to obtain an
analytically pure sample of 7, 8, or 9 as a white solid.
Characterization Data for Representative Compounds
Compound 7a: white solid; mp 178–180 °C. IR (KBr):
3388–3361, 3015, 2550, 1692 cm–1. 1H NMR (400 MHz,
DMSO-d6): d = 1.57 (s, 1 H, SH, exch. D2O), 3.71 (dd,
J2¢Ha,2¢Hb = 10.3 Hz, J1¢H,2¢Ha = 5.4 Hz, 1 H, 2¢Ha), 4.19 (dd,
(2) Bossert, F.; Vater, W. Med. Res. Rev. 1989, 9, 291.
(3) Balzarini, J.; Stevens, M.; De Clercq, E.; Schols, D.;
Pannecouque, C. J. Antimicrob. Chemother. 2005, 55, 135.
(4) Sanderson, P. E. J.; Lyle, T. A.; Cutrona, K. J.; Dyer, D. L.;
Dorsey, B. D.; McDonough, C. M.; Naylor-Olsen, A. M.;
Chen, I.-W.; Chen, Z.; Cook, J. J.; Cooper, C. M.; Gardell,
S. J.; Hare, T. R.; Krueger, J. A.; Lewis, S. D.; Lin, J. H.;
Lucas, B. J. Jr.; Lyle, E. A.; Lynch, J. J. Jr.; Stranieri, M. T.;
Vastag, K.; Yan, Y.; Shafer, J. A.; Vacca, J. P. J. Med. Chem.
1998, 41, 4466.
(5) Elliott, A. J.; Eisenstein, N.; Iorio, L. C. J. Med. Chem. 1980,
23, 333.
(6) Boger, D. L. Tetrahedron 1983, 39, 2869.
(7) Colin, P. FR 1,500,352, 1970; Chem. Abstr. 1970, 72, 31629.
(8) Boger, D. L.; Panck, J. S. J. Org. Chem. 1981, 46, 2179.
(9) Essentials of Glycobiology; Varki, A.; Cummings, R.; Esko,
J.; Freeze, H.; Hart, G.; Marth, J., Eds.; Cold Spring Harbor:
New York, 1999.
(10) Varki, A. Glycobiology 1993, 3, 97.
(11) Yadav, L. D. S.; Awasthi, C.; Rai, V. K.; Rai, A.
Tetrahedron Lett. 2007, 48, 4899.
J2¢Ha,2¢Hb = 10.3 Hz, J1¢H,2¢Hb = 2.8 Hz, 1 H, 2¢Hb), 4.27 (dd,
J1¢H,2¢Ha = 5.4 Hz, J1¢H,2¢Hb = 2.8 Hz, 1 H, 1¢H), 4.97–5.06 (br
s, 2 H, 2 × OH, exch. D2O), 7.98 (d, J5H,6H = 7.8 Hz, 1 H, 5-
H), 8.13 (d, J5H,6H = 7.8 Hz, 1 H, 6-H), 8.51 (br s, 1 H, NH,
exch. D2O). 13C NMR (100 MHz, DMSO-d6): d = 65.1, 74.2,
107.8, 124.9, 131.3, 136.4, 173.2. MS–FAB: m/z = 188
[MH+]. Anal. Calcd for C7H9NO3S: C, 44.91; H, 4.85; N,
7.48. Found: C, 44.79; H, 4.48; N, 7.73.
(12) Yadav, L. D. S.; Rai, A.; Rai, V. K.; Awasthi, C. Synlett
2007, 1905.
Compound 8a: white solid; mp 156–158 °C. IR (KBr):
3398–3367, 3013, 1691, 1665, 1607, 1579, 1454 cm–1. 1H
NMR (400 MHz, DMSO-d6): d = 3.75 (dd, J2¢Ha,2¢Hb = 10.5
Hz, J1¢H,2¢Ha = 5.5 Hz, 1 H, 2¢Ha), 4.17 (dd, J2¢Ha,2¢Hb = 10.5
Hz, J1¢H,2¢Hb = 2.8 Hz, 1 H, 2¢Hb), 4.31 (dd, J1¢H,2¢Ha = 5.5 Hz,
J1¢H,2¢Hb = 2.8 Hz, 1 H, 1¢H), 5.03–5.12 (br s, 2 H, 2 × OH,
exch. D2O), 7.09–7.58 (m, 5 Harom), 7.93 (d, J5H,6H = 7.2 Hz,
1 H, 5-H), 8.09 (d, J5H,6H = 7.2 Hz, 1 H, 6-H), 8.49–8.61 (br
s, 2 H, 2 × NH, exch. D2O). 13C NMR (100 MHz, DMSO-
d6): d = 65.5, 73.6, 105.8, 124.9, 126.9, 128.7, 129.4, 130.5,
131.9, 136.7, 172.5, 173.3. MS–FAB: m/z = 275 [MH+].
Anal. Calcd for C14H14N2O4: C, 61.31; H, 5.14; N, 10.21.
Found: C, 61.63; H, 5.35; N, 10.03.
(13) Yadav, L. D. S.; Yadav, S.; Rai, V. K. Green Chem. 2006, 8,
455.
(14) Yadav, L. D. S.; Yadav, S.; Rai, V. K. Tetrahedron 2005, 61,
10013.
(15) Yadav, L. D. S.; Kapoor, R. J. Org. Chem. 2004, 69, 8118.
(16) General Procedure for the Synthesis of 6-Polyhydroxy-
alkyl-1,3-oxazin-2-ones 3
Thoroughly mixed aldose semicarbazone 11 (2.0 mmol) and
Montmorillonite K-10 clay (0.20 g) were taken in a 20 mL
vial and subjected to MW irradiation in a CEM Discover
Focused Microwave Synthesis System at 90 °C for 10 min.
After completion of the reaction as indicated by TLC, H2O
(10 mL) was added to give the crude product, which was
recrystallized from EtOH to obtain an analytically pure
sample of 3 as a white solid.
Characterization Data for Synthesized Compounds
Compound 3a: white solid; mp 145–148 °C. IR (KBr): 3392,
3386, 3011, 1692 cm–1. 1H NMR (400 MHz, DMSO-d6): d =
4.11 (dd, J2¢Ha,2¢Hb = 10.1 Hz, J1¢H,2¢Ha = 5.4 Hz, 1 H, 2¢Ha),
4.30 (dd, J1¢H,2¢Ha = 5.4 Hz, J1¢H,2¢Hb = 2.9 Hz, 1 H, 1¢H), 4.63
(dd, J2¢Ha,2¢Hb = 10.1 Hz, J1¢H,2¢Hb = 2.9 Hz, 1 H, 2¢Hb), 4.93–
5.21 (br s, 2 H, 2 × OH, exch. D2O), 7.48 (d, J4H,5H = 8.1 Hz,
1 H, 5-H), 7.89 (d, J4H,5H = 8.1 Hz, 1 H, 4-H). 13C NMR (100
MHz, DMSO-d6/TMS): d = 64.5, 65.3, 73.7, 86.2, 105.9,
174.5. MS (FAB): m/z = 158 [MH+]. Anal. Calcd for
C6H7NO4: C, 45.86; H, 4.49; N, 8.91. Found: C, 46.17; H,
4.58; N, 8.79.
Compound 9a: white solid; mp 118–120 °C. IR (KBr): 3393,
3385, 3015, 1608, 1581, 1458 cm–1. 1H NMR (400 MHz,
DMSO-d6): d = 3.73 (dd, 1 H, J2¢Ha,2¢Hb = 10.2 Hz,
J
1¢H,2¢Ha = 5.2 Hz, 2¢Ha), 4.05 (dd, 1 H, J1¢H,2¢Ha = 5.2 Hz,
J1¢H,2¢Hb = 2.7 Hz, 1¢H), 4.21 (dd, 1 H, J2¢Ha,2¢Hb = 10.2 Hz,
1¢H,2¢Hb = 2.7 Hz, 2¢Hb), 4.95–5.13 (br s, 2 H, 2 × OH, exch.
D2O), 7.05–7.51 (m, 5 Harom), 7.67–7.99 (m, 3 Harom). 13
J
C
NMR (DMSO-d6/TMS): d = 65.7, 67.1, 107.8, 126.8, 128.5,
129.7, 131.8, 133.6, 147.5, 149.2, 152.7. MS–FAB:
m/z = 216 [MH+]. Anal. Calcd for C13H13NO2: C, 72.54; H,
6.09; N, 6.51. Found: C, 72.25; H, 6.27; N, 6.69.
(19) General Procedure for the Synthesis of 3-Amino-4-
polyhydroxyalkyl-1H-pyridin-2-ones 10
Compound 8 (2.0 mmol) was refluxed in H2SO4–H2O (15
mL, 4:3, v/v) for 45 min in an oil bath. The reaction mixture
was cooled, and the desired product 10 was precipitated by
Compound 3b: white solid; mp 153–155 °C. IR (KBr):
3399–3382, 3008, 1689 cm–1. 1H NMR (400 MHz, DMSO-
Synlett 2008, No. 4, 529–534 © Thieme Stuttgart · New York

534
L. D. S. Yadav et al.
LETTER
adding concentrated NH4OH (specific gravity 0.88) under
ice cooling and recrystallized from EtOH to obtain an
analytically pure sample of 10.
5.73; N, 16.19.
Compound 10b: white solid; mp 127–128 °C. IR (KBr):
3398–3365, 3009, 1691 cm–1. 1H NMR (400 MHz, DMSO-
d6): d = 3.51 (ddd, J2¢H,3¢Ha = 5.3 Hz, J1¢H,2¢H = 4.2 Hz,
Characterization Data for Synthesized Compounds
Compound 10a: white solid; mp 141–143 °C. IR (KBr):
3391–3367, 3015, 1692 cm–1. 1H NMR (400 MHz, DMSO-
d6): d = 3.77 (dd, J2¢Ha,2¢Hb = 10.3 Hz, J1¢H,2¢Ha = 5.5 Hz, 1 H,
2¢Ha), 4.13 (dd, J2¢Ha,2¢Hb = 10.3 Hz, J1¢H,2¢Hb = 2.8 Hz, 1 H,
2¢Hb), 4.35 (dd, J1¢H,2¢Ha = 5.5 Hz, J1¢H,2¢Hb = 2.8 Hz, 1 H,
1¢H), 4.96–5.18 (br s, 2 H, 2 × OH, exch. D2O), 7.95 (d,
J5H,6H = 7.5 Hz, 1 H, 5-H), 8.13 (d, J5H,6H = 7.5 Hz, 1 H, 6-
H), 8.33–8.59 (br s, 3 H, 3 × NH, exch. D2O). 13C NMR (100
MHz, DMSO-d6): d = 65.2, 73.6, 105.3, 124.9, 131.3, 136.4,
173.2. MS–FAB: m/z = 171 [MH+]. Anal. Calcd for
C7H10N2O3: C, 49.41; H, 5.92; N, 16.46. Found: C, 49.72; H,
J
2¢H,3¢Hb = 2.4 Hz, 1 H, 2¢H), 3.69 (dd, J3¢Ha,3¢Hb = 10.3 Hz,
J2¢H,3¢Ha = 5.3 Hz, 1 H, 3¢Ha), 4.06 (dd, J3¢Ha,3¢Hb = 10.3 Hz,
2¢H,3¢Hb = 2.4 Hz, 1 H, 3¢Hb), 4.17 (d, J1¢H,2¢H = 4.2 Hz, 1 H,
J
1¢H), 5.06–5.37 (br s, 3 H, 3 × OH, exch. D2O), 7.99 (d,
J5H,6H = 7.8 Hz, 1 H, 5-H), 8.12 (d, J5H,6H = 7.8 Hz, 1 H, 6-
H), 8.29–8.65 (br s, 3 H, 3 × NH, exch. D2O). 13C NMR (100
MHz, DMSO-d6/TMS): d = 68.5, 71.1, 73.5, 112.9, 124.7,
129.9, 134.8, 172.9. MS–FAB: m/z = 201 [MH+]. Anal.
Calcd for C8H12N2O4: C, 48.00; H, 6.04; N, 13.99. Found: C,
48.21; H, 5.89; N, 14.16.
Synlett 2008, No. 4, 529–534 © Thieme Stuttgart · New York

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