Divergent synthesis of three classes of aryl N-glycosides by solvent control

Article abstract of DOI:10.1021/jo8020133

Aryl glycosides represent a group of molecules with immense biological applications and implications. While the syntheses of aryl C-glycosides and O-glycosides have been studied extensively, the preparation for aryl N-glycosides is relatively unexplored. By employing 1,4-naphthoquinone and glycosyl azides undergoing a [3 + 2] cycloaddition, we have developed a convenient method for constructing three different classes of aryl N-glycosides that include N-glycosylated 2-aminomethylene-1,3-indanedione, benzazepine-1,5-dione, and 9,10-anthraquinone derivatives via solvent control. It was found that conducting cycloaddition in DMF formed exclusively 9,10-anthraquinone derivatives, while less polar solvent such as toluene offered all three aryl N-glycosides. The synthesis of N-glycosylated 9,10-anthraquinone derivatives is of particular interest since no known example has been documented. The synthesis of these N-glycosylated heterocyclic compounds using traditional glycosylation methods could be challenging. Therefore, our diversity-oriented protocols can be viewed as an alternative and practical glycosylation approach. In addition, we have also demonstrated that alkyl azides can also undergo the same cycloaddition, further expanding the structural repertoire available for a broader interest. Initial anticancer assays have revealed that 19f and 19k exert mean growth percent of 17.58 and-5.95, respectively.

Full text of DOI:10.1021/jo8020133

Divergent Synthesis of Three Classes of Aryl N-Glycosides by
Solvent Control
Jianjun Zhang and Cheng-Wei Tom Chang*
Department of Chemistry and Biochemistry, Utah State UniVersity,
0300 Old Main Hill, Logan, Utah 84322-0300
tom.chang@usu.edu
ReceiVed September 12, 2008
Aryl glycosides represent a group of molecules with immense biological applications and implications.
While the syntheses of aryl C-glycosides and O-glycosides have been studied extensively, the preparation
for aryl N-glycosides is relatively unexplored. By employing 1,4-naphthoquinone and glycosyl azides
undergoing a [3 + 2] cycloaddition, we have developed a convenient method for constructing three
different classes of aryl N-glycosides that include N-glycosylated 2-aminomethylene-1,3-indanedione,
benzazepine-1,5-dione, and 9,10-anthraquinone derivatives via solvent control. It was found that conducting
cycloaddition in DMF formed exclusively 9,10-anthraquinone derivatives, while less polar solvent such
as toluene offered all three aryl N-glycosides. The synthesis of N-glycosylated 9,10-anthraquinone
derivatives is of particular interest since no known example has been documented. The synthesis of
these N-glycosylated heterocyclic compounds using traditional glycosylation methods could be challenging.
Therefore, our diversity-oriented protocols can be viewed as an alternative and practical glycosylation
approach. In addition, we have also demonstrated that alkyl azides can also undergo the same cycloaddition,
further expanding the structural repertoire available for a broader interest. Initial anticancer assays have
revealed that 19f and 19k exert mean growth percent of 17.58 and -5.95, respectively.
Introduction
agents,4 and potential therapeutic for hypotension.5 Benzazepine
analogues have been noted to exert a wide range of pharma-
cological activities.6-9 Anthraquinone, which can be viewed as
part of the structural core of anthracycline, has also been the
focus of synthetic effort in generating novel antibiotics or
anticancer agents.10 Finally, both naphthoquinone and an-
Heterocyclic compounds, such as indanedione, benzazepine,
and anthraquinone, have long attracted great interest due to their
important biological and pharmaceutical applications, leading
to the development and discovery of numerous therapeutics
(Figure 1).1,2 For example, compounds bearing 2-methylene-
1,3-indanedione or 2-methylene-4-cyclopentene-1,3-dione scaf-
folds have been studied for their activity as fungicide,3 antitumor
(1) Lednicer, D., Ed. Strategies for Organic Drug Synthesis and Design;
John Wiley & Sons: New York, 1998.
10.1021/jo8020133 CCC: $40.75
Published on Web 12/04/2008
2009 American Chemical Society
J. Org. Chem. 2009, 74, 685–695 685

Zhang and Chang
FIGURE 1. Examples of cyclic aromatic compounds.
thraquinone are known to uncouple mitochondrial oxidative
phosphorylation, leading to mechanistic investigations in drug
toxicity and related applications.11 The syntheses of these three
classes of cyclic aromatic compounds, in general, require mul-
tistep processes and often begin from various starting mate-
rials.12
Carbohydrates contain multiple stereocenters, and many of
which are commercially available. These advantages make
carbohydrates the ideal building blocks for diversity-oriented
synthesis of molecules of interest.13-15 To circumvent the
challenges and enhance the efficiency of chemical glycosylation,
our laboratory has been interested in utilizing the 1,3-dipolar
cycloaddition, the “click” chemistry,16 for facile incorporation
of 1-azidosugars on structural motif of biological interest.17,18
While various methods for the preparation of O- and C-aryl
glycosides have been documented,19,20 very little has been
devoted to the synthesis of N-aryl glycosides.21 The synthesis
of N-glycosylated heterocyclic compounds is of particular
interest since the amino group on any of these three classes of
compounds is not considered a good nucleophile to undergo
traditional glycosylation via an oxycarbenium ion intermediate.
On the other hand, glycosyl amines are not stable enough to
act as a nucleophile in nucleophilic substitution to make N-
glycosyl compounds.
Azides have been known to undergo [3 + 2] cycloaddition
with alkynes or alkenes.22 The double bond between C2 and
C3 of 1,4-naphthoquinone or R,ꢀ-unsaturated ketones can also
be treated as an electron-deficient alkene. For example, an
intramolecular cycloaddition using 2-alkylazido-1,4-benzoquino-
ne or 1,4-naphthoquinone has been documented (Scheme 1).23
It was reported that following the initial [3 + 2] cycloaddition
carried out at 40 °C in ether, benzene, or CH2Cl2, triazoline 2
was observed. After prolonged heating, compound 1 was
completely consumed and a mixture of azepinedione 4 (ring-
expansion product) and 4-cyclopentene-1,3-dione 5 (ring-
contraction product) was obtained in a 1:1 ratio. A 2-(azidoalky-
l)quinone rearrangement, which may involve a diazoenedione
intermediate 3 was suggested for the formation of compound
5. Alternatively, fragmentation of triazoline 2 can lead to the
formation of compound 4. In addition, an intermolecular
cycloaddition mediated by TMSOTf has recently been reported,
but only azepinedione and 4-cyclopentene-1,3-dione adducts
have been obtained (Scheme 2).24 Similar mechanisms that
involve the degradation of initial triazoline has been proposed
(2) Gringauz, A. Introduction to Medicinal Chemistry, How Drugs Act and
Why?; Wiley-VCH: Weinheim, Germany, 1997.
(3) Babu, K. S.; Li, X.-C.; Jacob, M. R.; Zhang, Q.; Khan, S. I.; Ferreira,
D.; Clark, A. M. J. Med. Chem. 2006, 49, 7877–7886.
(4) (a) Hori, H.; Nagasawa, H.; Ishibashi, M.; Uto, Y.; Hirata, A.; Saijo, K.;
Ohkura, K.; Kirk, K. L.; Uehara, Y. Bioorg. Med. Chem. 2002, 10, 3257–3265.
(b) Inayama, S.; Mamoto, K.; Shibata, T.; Hirose, T. J. Med. Chem. 1976, 19,
433–436.
(5) Baut, L. et al. U.S. Patent No. 4,758,561.
(6) Bra¨se, S.; Gil, C.; Knepper, K. Bioorg. Med. Chem. 2002, 10, 2415–
2437.
(7) Kamal, A.; Reddy, K. L.; Devaiah, V.; Shankaraiah, N.; Reddy, D. R.
Mini.-ReV. Med. Chem. 2006, 6, 53–69.
(8) Guzikowski, A. P.; Cai, S. X.; Espitia, S. A.; Hawkinson, J. A.; Huettner,
J. E.; Nogales, D. F.; Tran, M.; Woodward, R. M.; Weber, E.; Keana, J. F. W.
J. Med. Chem. 1996, 39, 4643–4653.
(9) Sum, F.-W.; Dusza, J.; Santos, E. D.; Grosu, G.; Reich, M.; Du, X.;
Albright, J. D.; Chan, P.; Coupet, J.; Ru, X.; Mazandaranib, H.; Saunders, T.
Bioorg. Med. Chem. Lett. 2003, 13, 2195–2198.
(10) For example: (a) Fan, E.; Shi, W.; Lowary, T. L. J. Org. Chem. 2007,
72, 2917–2928. (b) Zhang, G.; Fang, L.; Zhu, L.; Zhong, Y.; Wang, P. G.; Sun,
D. J. Med. Chem. 2006, 49, 1792–1799.
(11) Wallace, K. B.; Starkov, A. A. Annu. ReV. Pharmacol. Toxicol. 2000,
40, 353–388.
(12) Sartori, M. F. Chem. ReV. 1962, 63, 279–296.
(13) Wong, C.-H., Ed. Carbohydrate-Based Drug DiscoVery; Wiley-VCH:
Weinheim, Germany, 2003.
(19) For examples of O-aryl glycosides, see: (a) Roush, W. R.; Lin, X.-F. J.
Org. Chem. 1991, 56, 5740–5742. (b) Lam, S. N.; Gervay-Hague, J. Org. Lett.
2003, 5, 4219–4222.
(20) For examples of C-aryl glycosides, see: (a) Hart, D. J.; Leroy, V.;
Merriman, G. H.; Young, D. G. J. J. Org. Chem. 1992, 57, 5670–5680. (b)
Palmacci, E. R.; Seeberger, P. H. Org. Lett. 2001, 3, 1547–1550. (c) Toshima,
K.; Matsuo, G.; Ishizuka, T.; Ushiki, Y.; Nakata, M.; Matsumura, S. J. Org.
Chem. 1998, 63, 2307–2313. (d) Hauser, F. M.; Hu, X. Org. Lett. 2002, 4, 977–
978. (e) Kaliappan, K. P.; Subrahmanyam, A. V. Org. Lett. 2007, 9, 1121–
1124. (f) Kaelin, D. E., Jr.; Sparks, S. M.; Plake, H. R.; Martin, S. F. J. Am.
Chem. Soc. 2003, 125, 12994–12995. (g) Chen, C.-L.; Sparks, S. M.; Martin,
S. F. J. Am. Chem. Soc. 2006, 128, 13696–13697.
(14) Klyosov, A. A., Witczak, Z. J., Platt, D., Eds.; Carbohydrate-Based
Drug DiscoVery; ACS Symposium Series; Vol. 932, 2005.
(15) Demchenko, A., Ed.; Frontiers in Carbohydrate Chemistry; ACS
Symposium Series; Vol. 960, 2007.
(16) Huisgen, R. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.;
Wiley: New York, 1984; pp 1-176.
(17) Zhang, J.; Chen, H.-N.; Chiang, F.-I.; Takemoto, J. Y.; Bensaci, M.;
Chang, C.-W. T. J. Comb. Chem. 2007, 9, 17–19.
(21) For examples of N-aryl glycosides, see: (a) Bridiau, N.; Benmansour,
M.; Legoy, M. D.; Maugard, T. Tetrahedron 2007, 63, 4178–4183. (b) Gama,
Y.; Shibuya, I.; Shimizu, M. Chem. Pharm. Bull. 2002, 50, 1517–1519.
(22) For example: (a) Bodnar, B. S.; Miller, M. J. J. Org. Chem. 2007, 72,
3929–3932. (b) Bra¨se, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem.,
Int. Ed. 2005, 44, 5188–5240. (c) Tarabara, I. N.; Kasyan, A. O.; Yarovoi, M. Y.;
Shishkina, S. V.; Shishkin, O. V.; Kas’yan, L. I. Russ. J. Org. Chem. 2004, 40,
992–998.
(18) Zhang, J.; Garrossian, M.; Gardner, D.; Garrossian, A.; Chang, Y.-T.;
Kim, Y. K.; Chang, C.-W. T. Bioorg. Med. Chem. Lett. 2008, 18, 1359–1363.
(23) Schultz, A. G.; McMahon, W. G. J. Org. Chem. 1984, 49, 1676–1678.
(24) Reddy, D. S.; Judd, W. R.; Aube, J. Org. Lett. 2003, 5, 3899–3902.
686 J. Org. Chem. Vol. 74, No. 2, 2009

DiVergent Synthesis of Three Classes of Aryl N-Glycosides
SCHEME 1
N-glycosylated ring-expansion (17) and ring-contraction (18)
products. Lewis acids were employed in cycloaddition of enones
and azides. However, Lewis acids can facilitate the degradation
of triazoline, leading to the formation of only ring-expansion
and ring-contraction adducts.24 Therefore, we intend to focus
on the effect of solvents in directing the distribution of various
adducts from cycloaddition.
By conducting the cycloaddition of 1,4-naphthoquinone and
per-O-acetylated azidoglucose in DMF at 120 °C, only the
oxidized cycloaddition adduct 15a was isolated (Table 1, entry
1). Cycloaddition using dioxane, which has polarity between
toluene and DMF, yielded only 15a and 18a. We proceeded to
apply these findings on solvent effect to other glycosyl and alkyl
azides. To our delight, all the cycloaddition conducted in DMF
furnished exclusiVely the expected products (15a-n) with
modest to excellent yields. Cycloaddition carried out using
toluene as the solvent offered a mixture of 15, 17, and 18. The
first two components (15 and 17) which often have very close
Rf values on TLC can be partially separated by column
chromatography, leaving some fractions a mixture of 15 and
17. The third and most polar product (18) can be readily
separated from 15/17 as the major component.
SCHEME 2
We were intrigued with the initial results, although complex
mixture and difficulties in separating 15/17 mixtures were
encountered. Interestingly, the cycloaddition of azidoxylopy-
ranose 12g in toluene produced a mixture of R and ꢀ anomers
(18g and epi-18g) despite the fact that 12g was in pure ꢀ
configuration. A possible mechanism involving intramolecular
tautomerization is proposed in Scheme 4. Unlike other hexoses,
xylopyranose lacks the equatorial C-6, which lowers the energy
barrier for the formation of a conformation-constrained imine
intermediate, leading to the epimerization at C-1. The cycload-
dition protocol is also applicable for the preparation of 15l by
using a diazido compound 12l.
to explain the formation of 10 and 11. Nonetheless, no triazoline
adduct was isolated or reported in these investigations.
Deprotection of acetyl groups on cycloaddition products (15)
and ring-contraction products (18) was accomplished by using
K2CO3 in MeOH or NaOMe/MeOH (Tables 2 and 3). When
NaOMe/MeOH was employed, the crude product can be readily
purified using solid phase extraction (Amberlite 120(H+))
followed with recrystallization. The concise protocol is advanta-
geous in providing library and scale-up synthesis of compounds
in this class. Unfortunately, deprotection of the acetyl groups
on ring-expansion products (17) under various conditions failed
to yield the desired products. Due to the epimerization of 18g
during the cycloaddition step, deprotection of 18g leads to the
isolation of 20g and epi-20g (Table 3, entry 4). Deprotection
of 18i produces an adduct without a carbohydrate component
(Table 3, entry 5). In general, the yields for the deprotection of
acetyl groups of 18 are lower than that of 15. It is likely that
the 4-cyclopentene-1,3-dione scaffold of 18 may function as a
Design, Results and Discussion
In light of their biological applications, we wish to develop
a method that can lead to the formation of not only azepinedione
and 4-cyclopentene-1,3-dione adducts but also the cycloaddition
adduct, or the oxidized form of triazoline, all of which with
carbohydrate moieties attached. On the basis of the published
studies, it appears that the lack of stability of the initial triazoline
adduct leads to the formation of both ring-expansion (azepinedi-
one) and ring-contraction (4-cyclopentene-1,3-dione) products.
In fact, most of the studies focused on the photo- and thermal-
mediated degradation of triazoline derivatives.25
We expect that, following the initial cycloaddition using
naphthoquinone 6 and azido compounds 12, it is possible to
have a tautomerization that produces the N-glycosylated 9,10-
hydroxyanthraquinone analogue 14, which can be oxidized into
the more stable 9,10-anthraquinone analogue 15 (Scheme 3).
Therefore, we reason that, if the equilibrium can be shifted to
favor the formation of 14, a N-glycosylated cycloaddition adduct
may be obtained. Although triazoline will be afforded in its
oxidized form, this end product resembles both naphthoquinone
and anthraquinone and could possess greater biological signifi-
cance. In contrast, by employing less polar solvent, the initial
triazoline may fragment into 16, which could produce both
(26) With the exception of 15m and 17m, the separation of 15/17 mixture
proves to be challenging. However, for the acetylation of the mixture followed
by aqueous workup, we were amazed to discover that only the 17 component
was present in organic solution. Further purification of 17 by recrystallization
offered the pure desired products.
(27) Among the samples, 19a, 19d, 19f, 19k, 19m, submitted for one-dose
assay, 19f and 19k were selected for further five-dose testing. Please refer to
Supporting Information for more details.
(28) Harmon, R. E.; Earl, R. A.; Gupta, S. K. J. Org. Chem. 1971, 36, 2553–
2556.
(29) Joosten, J. A. F.; Tholen, N. T. H.; Maate, F. A. E.; Brouwer, A. J.;
van Esse, G. W.; Rijkers, D. T. S.; Liskamp, R. M. J.; Pieters, R. J. Eur. J. Org.
Chem. 2005, 3182–3185.
(25) Logothetis, A. L. J. Am. Chem. Soc. 1965, 87, 749–754. Scheiner, P.
J. Am. Chem. Soc. 1968, 90, 988–992. Stout, D. M.; Takaya, T.; Meyers, A. I.
J. Org. Chem. 1975, 40, 563–569.
(30) Alonso, G.; Garcia-Lopez, M. T.; Garcia-Munoz, G.; Madronero, R.;
Rico, M. J. Heterocycl. Chem. 1970, 7, 1269–1272.
J. Org. Chem. Vol. 74, No. 2, 2009 687

Zhang and Chang
SCHEME 3. Proposed Role of Solvent
TABLE 1. Cycloaddition of Naphthoquinone and Azidesa
yield (%)b
entry
1
azido compound
per-O-acetylated ꢀ-D-glucopyranosyl azide (12a)28
solvent
1726
15
18
toluene
dioxane
DMF
toluene
DMF
DMF
DMF
DMF
toluene
DMF
toluene
DMF
DMF
toluene
DMF
DMF
toluene
DMF
DMF
toluene
DMF
toluene
DMF
24%
25%
32%
67%
17%
66%
49%
97%
74%
11%
87%
11%
85%
35%
9%
73%
85%
12%
79%
99%
34%
91%
64%
85%
33%
19%
2
per-O-acetylated ꢀ-D-galactopyranosyl azide (12b)28
17%
34%
3
4
5
6
per-O-acetylated R-D-mannopyranosyl azide (12c)17
per-O-acetylated ꢀ-lactosyl azide (12d)29
per-O-acetylated ꢀ-L-fucopyranosyl azide (12e)17
per-O-acetylated R-L-rhamnopyranosyl azide (12f)17
11%
12%
43%
7
per-O-acetylated ꢀ-xylopyranosyl azide (12g)17
23%c
8
9
per-O-acetylated 2-acetamido-2-deoxy ꢀ-D-glucopyranosyl azide (12h)18
per-O-acetylated ꢀ-cellobiosyl azide (12i)28
9%
36%
20%
10
11
per-O-acetylated ꢀ-cellotriosyl azide (12j)17
per-O-acetylated ꢀ-D-ribofuranosyl azide (12k)30
11%
12
13
per-O-acetylated 1,6-diazido-D-mannitol (12l)
per-O-acetylated 1-azido-D-mannitol (12m)
28%
5%
25%
18%
14
4-(N-tert-Boc-piperidinyl) azide (12n)
a All the cycloaddition reactions were conducted with 2/1 ratio of naphthoquinone/azide at 120 °C for 2 days. b With the exception of 15m and 17m,
the yields of 15 and 17 obtained from cycloaddition in toluene were calculated from the integral ratio of 1H NMR. c Isolated as a mixture of 18g and
epi-18g.
Michael acceptor with a loss of the carbohydrate component
via an addition/elimination process. Deprotection of the Boc
group on 17n and 15n can be fulfilled using TFA in CH2Cl2.
examined due to the presence of electron-withdrawing acetyl
groups and the direct attachment of azide to the anomeric center.
The azido group on 12m should be more electron-rich than 12a
due to the absence of an anomeric center. However, with the
presence of acetyl groups, the azido group on 12m should
be more electron-deficient than the one on alkyl azides (12n
and 7). As indicated in Scheme 2, cycloaddition of 6 and 7
has been reported to generate 10 and 11 but not 15o.
Therefore, it will be interesting to examine our protocol in
generating 15o (Scheme 5).
Investigation of the Reaction Conditions
Since our cycloaddition protocol was conducted using excess
naphthoquinone (2 equiv) and open to air, the nature of oxidant
was unclear. By comparing with the reported results,24 it was
also uncertain regarding the effect of Lewis acid, temperature,
solvent, and alkyl group where the azide is attached. We
employed four different azido compounds including 12a, 12m,
12n, and 724 (benzyl azide) for the investigation of reaction
conditions. The azido group on glycosyl azide (12a) should be
the most electron-deficient among all four azido compounds
A series of cycloaddition reactions in various conditions were
conducted to investigate the product distribution for 15 (9,10-
anthraquinone analogue), 17 (ring-expansion), and 18 (ring-
contraction) (Table 4). We noticed several interesting results.
688 J. Org. Chem. Vol. 74, No. 2, 2009

DiVergent Synthesis of Three Classes of Aryl N-Glycosides
TABLE 3. Deprotection of 18
SCHEME 4. Proposed Mechanism for Epimerization of 18g
entry
reactant
18a
18b
18f
18g/epi-18g
18i
18k
18m
18n
conditiona
product
20a
20b
20f
20g/epi-20g
yield (%)
64%
53%
39%
R: 35%, ꢀ: 53%
decomposed
46%
40%
99%
TABLE 2. Deprotection of 15
1
2
3
4
5
6
7
8
A
A
A
A
A
A
A
B
20k
20m
20n
a A: K2CO3, MeOH, H2O; B: TFA, CH2Cl2.
cycloaddition than heating (temperature effect) when the
electron-deficient azide 12a was used (Table 4, entries 1 and
2). Apparently, the electron-withdrawing nature of anomeric
carbon dramatically reduces the reactivity of glycosyl azides.
The results support that the cycloaddition step is thermodynami-
cally controlled and could be the rate-limiting step. Third,
excellent selectivity for 15 in DMF was obtained regardless of
the electronic environment of azides. For example, under the
condition reported by Aube and co-workers (TMSOTf, CH2Cl2,
rt),24 cycloaddition between 6 and 7 provided only 10 and 11.
In contrast, using our protocol, only 15o was produced (Table
4, entry 11). This result supports our previous speculation that
DMF may favor a fast tautomerization of the initial triazoline
adduct 13 followed by a fast redox reaction with excess
naphthoquinone. When less polar solvents (toluene and CH2Cl2)
were used, the triazoline adduct cannot be tautomerized com-
pletely, which leads to the fragmentation of 13 and the formation
of 17 and 18 under thermodynamic conditions or with the
presence of Lewis acid. Interestingly, the use of Lewis acid
(TMSOTf) was ineffective in facilitating the cycloaddition when
DMF (entry 13) was employed. Fourth, the electronic effect of
azides also plays a role in directing the product formation: the
yield for 15 increases as the electronic environment of azides
changes from electron-deficient to electron-rich. For example,
when the cycloaddition was conducted in degassed toluene under
nitrogen, the yields for 15 varied from 24% (15a), 34% (15m),
43% (15n) to 61% (15o). Electron-rich alkyl azides increase
the rate of oxidation of 14 and produce more 15 while electron-
deficient azides, such as 12a, will lower the rate of oxidation,
allowing for the formation of more fragmentation products (17
and 18).
entry
reactant
conditiona
product
yield (%)
1
2
3
4
5
6
7
8
15a
15b
15c
15d
15e
15f
15g
15h
15i
15j
15k
15l
15m
15n
A
B
A
A
A
B
A
A
A
A
A
A
A
C
19a
19b
19c
19d
19e
19f
19g
19h
19i
19j
19k
19l
19m
19n
99%
46%
62%
99%
41%
33%
79%
56%
99%
57%
57%
23%
97%
94%
9
10
11
12
13
14
a A: NaOMe, MeOH; B: K2CO3, MeOH, H2O; C: TFA, CH2Cl2.
First, with all attempts employing degassed solvents, sodium
ascorbate, or stoichiometric naphthoquinone to avoid the oxida-
tion of the initial triazoline product, the formation of 15 from
the oxidation of the initial triazoline adduct was observed in
all the cases. When stoichiometric naphthoquinone was em-
ployed, the decreased yield of 15 was noted. The results confirm
that the reactant, naphthoquinone, also functions as the oxidant
to oxidize the initial triazoline adducts. Second, the presence
of Lewis acid (TMSOTf) is less effective in facilitating the
The elucidation of the role of naphthoquinone suggests a
possible mode of anticancer activity via the uncoupling of
J. Org. Chem. Vol. 74, No. 2, 2009 689

Zhang and Chang
SCHEME 5
TABLE 4. Investigation of the Effect of TMSOTf and the Potential Oxidanta
entry
reactants (ratio)
solvent, temp, time
additives (equiv)
compounds (yield %)
no reaction; recovered 12a
no reaction; recovered 12a
15a (38%); recovered 12a (43%) and 6 (31%)
15a (61%)
1
2
3
4
5
6
7
8
6/12a (1/1)
6/12a (1/1)
6/12a (1/1)
6/12a (2/1)
6/12m (2/1)
6/12m (1/1)
6/12m (1/1)
6/12n (2/1)
6/12n (2/1)
6/7 (2/1)
degassed toluene, rt, 1 day then 60 °C, 1 day
CH2Cl2, rt, 1 day then reflux, 1 day
degassed DMF, 120 °C, 2 days
degassed DMF, 120 °C, 2 days
degassed toluene, 120 °C, 2 days
degassed toluene, 120 °C, 2 days
degassed toluene, 120 °C, 2 days
degassed toluene, 120 °C, 2 days
degassed DMF, 120 °C, 2 days
degassed toluene, 120 °C, 2 days
degassed DMF, 120 °C, 2 days
CH2Cl2, 0 °C to rt, 10 h
TMSOTf (2)
TMSOTf (2)
15m (34%), 17m (28%), 18m (25%)
15m (32%), 17m (25%), 18m (15%)
15m (34%), 17m (23%), 18m (18%)
15n (43%), 17n (13%), 18n (16%)
15n (85%)
Na ascorbate (1)
9
10
11
12
13
14
15o (61%), 10 (2%),b 11 (2%)b
15o (82%)
6/7 (2/1)
6/7 (1/1.5)
6/7 (2/1)
TMSOTf (2)
TMSOTf (2)
TMSOTf (2)
10 (20%), 11 (40%)
no reaction
15o (39%); recovered 6 (13%)
degassed DMF, 0 °C to rt, 1-2 days
degassed DMF, 120 °C, 2 days
6/7 (2/1)
b
a All the reactions were conducted under N2. Estimated yields from H NMR.
1
HCl (×3), water (×2), saturated NaHCO3(aq) and brine, and dried
over anhydrous Na2SO4. After removal of solvents, the crude
product was re-dissolved in DMF and NaN3 (2.67 g, 0.041 mol)
was added. After being stirred at 80 °C for 1 day, the reaction was
cooled and charcoal was added. After filtration through Celite and
removal of solvents, crystal was formed. The crystal was collected
and washed with a mixture of ether/hexane (1/1) and ether. The
crystal was determined to be hexa-O-acetyl-D-mannitol (2.2 g, 5.07
mmol, 19%). The filtrate was concentrated and purified with a
gradient column chromatography yielding 12l (3.01 g, 7.52 mmol,
28%), 12m (2.21 g, 5.30 mmol, 20%), and trace amount of hexa-
mitochondrial oxidative phosphorylation. The rate of oxidation
of 14 can be tuned by the electronic effect on the employed
azides, suggesting a feasible optimization of redox potential of
compound 19 for disrupting the redox processes involving
coenzyme Q. From the preliminary screening via the DPT/NCI
program, 19f and 19k have shown significant anticancer activity
(mean growth percent of 17.58 and -5.95, respectively) and
are subjected for further investigation.27
Conclusion
1
O-acetyl-D-mannitol: H NMR (CDCl3, 400 MHz) δ 5.37 (d, J )
By varying solvent, three classes of N-glycosylated hetero-
cyclic compounds with immense applications can be synthe-
sized. The cycloaddition between naphthoquinone and glycosyl
and alkyl azides conducted in DMF offers excellent selectivity
for the formation of biologically interesting N-glycosylated 9,10-
anthraquinone analogues. We have also proved that alkyl azide
can undergo the same cycloaddition with naphthoquinone,
further expanding the structural repertoire available for a broader
interest. Ongoing effort has also been directed to the attempts
using 1,4-quinone and 1,4,9,10-anthratetraone as the reactants.
Attempts on optimizing the yield of 17 and the condition for
its sequential deprotection and purification will be performed.
More biological testing will also be conducted shortly.
8.0 Hz, 2H), 5.0 (m, 2H), 3.43 (dd, J ) 13.6, 3.4 Hz, 2H), 3.23
(dd, J ) 13.6, 5.7 Hz, 2H), 2.121 (s, 6H), 2.120 (s, 6H); 13C NMR
(CDCl3, 100 MHz) δ 170.0, 169.9, 68.7, 68.3, 50.8, 20.9, 20.8;
ESI/APCI calcd for C14H20N6O8Na+ ([M + Na]+) m/e 423.1235;
ESI/APCI calcd for C14H21N4O8+ ([M - N2 + H]+) m/e 373.1354;
measured m/e 373.1360.
2,3,4,5,6-Penta-O-acetyl-1-azido-1-deoxy-D-mannitol (12m).
1
Please refer to the procedure for the preparation of 12l: H NMR
(CDCl3, 400 MHz) δ 5.36 (d, J ) 8.8 Hz, 2H), 5.0 (m, 2H), 4.13
(dd, J ) 12.5, 2.6 Hz, 1H), 4.00 (dd, J ) 12.5, 5.2 Hz, 1H), 3.41
(dd, J ) 13.5, 3.3 Hz, 1H), 3.20 (dd, J ) 13.5, 5.6 Hz, 1H), 2.04
(s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 2.00 (s, 3H), 1.98 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 170.6, 170.0, 169.9, 169.82, 169.79,
68.7, 68.3, 68.0, 67.5, 61.9, 50.8, 21.0, 20.9, 20.8, 20.7 (2 carbons);
ESI/APCI calcd for C16H23N3O10Na+ ([M + Na]+) m/e 440.1276;
Compound degraded during the mass spec analysis.
Experimental Section
4-Azido-N-tert-butoxycarbonylpiperidine (12n). To a solution
of 4-hydroxypiperidine (1.0 g, 4.94 mmol) in CH2Cl2 (10 mL) and
Et3N (1.5 mL, 6.92 mmol) was added Boc2O (2.4 g, 5.93 mmol).
After being stirred for 2 h, the reaction was diluted with EtOAc
and washed with saturated NaHCO3, water, and brine, and then
dried over Na2SO4. After removal of solvents, the crude product
was dissolved in anhydrous CH2Cl2 (50 mL) and Et3N (1.0 mL,
7.50 mmol). The reaction mixture was cooled to 0 °C, and MsCl
(0.69 mL, 8.94 mmol) was added slowly. After being stirred for
2 h, the reaction mixture was concentrated and diluted with EtOAc.
The solution was filtered through Celite, and the residue was washed
2,3,4,5-Tetra-O-acetyl-1,6-diazido-1,6-dideoxy-D-mannitol (12l). A
solution of D-mannitol (5.00 g, 0.027 mol), TsCl (7.82 g, 0.041
mol), and catalytic amount of DMAP in anhydrous pyridine (40
mL) was stirred at 0 °C overnight, allowing the reaction temperature
to warm up to room temperature. The reaction mixture was cooled
to 0 °C again, and Ac2O (31 mL, 0.32 mol) was added slowly.
After being stirred for 1 day, the reaction mixture was poured into
a mixture of water/EtOAc and then stirred for several hours. The
aqueous layer was separated from the organic layer and extracted
with EtOAc. The combined organic layers were washed with 1 N
690 J. Org. Chem. Vol. 74, No. 2, 2009

DiVergent Synthesis of Three Classes of Aryl N-Glycosides
with more EtOAc. The filtrate was concentrated and re-dissolved
in DMF (50 mL). After the addition of NaN3 (1.17 g, 18.0 mmol),
the reaction mixture was stirred at 100 °C for 24 h. The reaction
mixture was concentrated and diluted with EtOAc. The solution
was filtered through Celite, and the residue was washed with more
EtOAc. After the removal of solvent and purification with gradient
column chromatography (hexane/EtOAc from 100/0 to 1/1), the
desired product was obtained as an oil (0.90 g, 3.99 mmol, 41%
2.05 (s, 3H), 2.01 (s, 3H), 1.89 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 187.5, 170.5, 170.1, 169.9, 169.7, 168.1, 137.4, 133.9,
133.6, 133.1, 131.9, 130.9, 129.9, 113.8, 82.9, 73.9, 71.3, 67.8,
67.2, 61.4, 20.8 (2 carbons), 20.7, 20.5; ESI/APCI calcd for
C24H25NO11Na+ ([M + Na]+) m/e 526.1320; measured m/e
526.1342.
1-(N-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl))-1H-naph-
1
tho[2,3-d]triazole-4,9-dione (15b): H NMR (CDCl3, 400 MHz)
1
for three steps): H NMR (CDCl3, 300 MHz) δ 3.7 (m, 2H), 3.48
δ 8.35 (dd, J ) 6.9, 1.9 Hz, 1H), 8.28 (dd, J ) 7.2, 2.0 Hz, 1H),
7.87 (td, J ) 6.4, 1.5 Hz, 1H), 7.84 (td, J ) 6.7, 1.6 Hz, 1H), 6.4
(m, 2H), 5.59 (d, J ) 3.2 Hz, 1H), 5.3 (m, 1H), 4.34 (t, J ) 7.0
Hz, 1H), 4.23 (dd, J ) 10.0, 6.9 Hz, 1H), 4.15 (dd, J ) 10.2, 6.9
Hz, 1H), 2.32 (s, 3H), 2.04 (s, 6H), 1.84 (s, 3H); 13C NMR (CDCl3,
100 MHz) δ 176.9, 174.4, 170.6 (2 carbons), 170.2, 169.0, 146.0,
135.5, 134.7, 134.6, 133.1, 133.0, 128.0, 127.8, 86.5, 74.4, 71.5,
67.0, 66.9, 61.5, 20.9, 20.8 (2 carbons), 20.5; ESI/APCI calcd for
C24H23N3O11Na+ ([M + Na]+) m/e 552.1225; measured m/e
552.1230.
(tt, J ) 13.1, 4.8 Hz, 1H), 3.01 (dt, J ) 13.1, 3.4 Hz, 2H), 1.8 (m,
2H), 1.5 (m, 2H), 1.37 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ
154.7, 79.9 (2 carbons), 57.7, 41.6, 30.7 (2 carbons), 28.5 (3
carbons); ESI/APCI calcd for C10H19N4O2 ([M + H]+) m/e
+
227.1503; measured m/e 227.1503.
General Procedure for Cycloaddition. The glycosyl azide (0.20
g, 1 equiv) and naphthoquinone (2 equiv) were dissolved in toluene
or dioxane and were heated at 120 °C for 2 days. After completion
of the reaction monitored by TLC (eluted with hexane/EtOAc )
1/1), the reaction was cooled and the solvents were removed. The
crude products were purified by gradient column chromatography
(eluted with hexane/EtOAc from 100/0 to 55/45). Component 17
is usually the first one being eluted out followed by component
15. In most of the cases, the majority part of 17 was mixed with
15. However, the pure fractions of 17 and 15 can provide
spectroscopic references for the evaluation of the ratio of 15 and
17 in the collected mixture using 1H NMR. The most polar
component 18 can be eluted the last and easily separated from the
previous two components. When DMF was used as the solvent,
only compound 15 was obtained.
2-(N-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl))aminom-
1
ethylene-1,3-indanedione (18b): H NMR (CDCl3, 300 MHz) δ
9.34 (dd, J ) 13.1, 8.6 Hz, 1H), 7.8 (m, 2H), 7.71 (d, J ) 13.4 Hz,
1H), 7.6 (m, 2H), 5.45 (d, J ) 3.4 Hz, 1H), 5.33 (t, J ) 10.3 Hz,
1H), 5.13 (dd, J ) 10.3, 3.4 Hz, 1H), 4.59 (t, J ) 8.6 Hz, 1H), 4.1
(m, 3H), 2.20 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H); 13
C
NMR (CDCl3, 75 MHz) δ 193.1, 189.9, 170.5, 170.2, 170.1, 170.0,
149.3, 140.3, 140.1, 134.0, 133.9, 122.4, 122.2, 107.1, 87.5, 73.0,
70.6, 68.2, 67.0, 61.5, 20.7 (2 carbons), 20.6 (2 carbons); ESI/
APCI calcd for C24H26NO11+ ([M + H]+) m/e 504.1500; measured
m/e 504.1501.
2-(N-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl))-2H-2-ben-
zazepine-1,5-dione (17a): 1H NMR (CDCl3, 400 MHz) δ 8.36 (dd,
J ) 7.4, 1.9 Hz, 1H), 8.16 (dd, J ) 7.0, 2.0 Hz, 1H), 7.8 (m, 2H),
6.94 (d, J ) 11.2 Hz, 1H), 6.34 (d, J ) 9.2 Hz, 1H), 6.06 (d, J )
11.1 Hz, 1H), 5.44 (t, J ) 9.5 Hz, 1H), 5.26 (t, J ) 9.5 Hz, 1H),
5.18 (t, J ) 9.7 Hz, 1H), 4.30 (dd, J ) 12.6, 4.9 Hz, 1H), 4.2 (m,
1H), 4.0 (m, 1H), 2.11 (s, 3H), 2.08 (s, 3H), 2.04 (s, 3H), 1.89 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 187.5, 170.7, 170.1, 169.6,
169.5, 168.1, 137.4, 134.0, 133.6, 133.2, 131.6, 130.9, 129.9, 113.9,
82.5, 75.2, 73.2, 70.1, 68.1, 61.9, 21.0, 20.8 (2 carbons), 20.5; ESI/
APCI calcd for C24H25NO11Na+ ([M + Na]+) m/e 526.1320;
measured m/e 526.1322.
1-(N-(2,3,4,6-Tetra-O-acetyl-r-D-mannopyranosyl))-1H-naph-
1
tho[2,3-d]triazole-4,9-dione (15c): H NMR (CDCl3, 400 MHz)
δ 8.31 (dd, J ) 7.4, 1.4 Hz, 1H), 8.20 (dd, J ) 7.4, 1.2 Hz, 1H),
7.9 (m, 2H), 6.63 (s, 1H), 5.96 (d, J ) 3.0 Hz, 1H), 5.49 (t, J )
10.0 Hz, 1H), 5.39 (dd, J ) 10.0, 3.1 Hz, 1H), 4.3 (m, 2H), 4.2
(m, 1H), 2.18 (s, 3H), 2.12 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) δ 176.6, 175.3, 170.8, 170.3, 170.1, 169.8,
145.1, 135.8, 134.7, 133.8, 133.3, 132.8, 128.2, 127.6, 83.9, 76.3,
71.2, 67.6, 65.7, 62.3, 21.0, 20.9 (2 carbons), 20.8; ESI/APCI calcd
for C24H23N3O11Na+ ([M + Na]+) m/e 552.1225; measured m/e
552.1227.
1-(N-(4-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl)-2,3,6-
tri-O-acetyl-ꢀ-D-glucopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-
dione (15d): 1H NMR (CDCl3, 400 MHz) δ 8.35 (dd, J ) 7.0, 1.5
Hz, 1H), 8.24 (dd, J ) 8.0, 1.6 Hz, 1H), 7.89 (td, J ) 7.2, 1.4 Hz,
1H), 7.86 (td, J ) 7.4, 1.6 Hz, 1H), 6.31 (d, J ) 9.4 Hz, 1H), 6.06
(t, J ) 9.6 Hz, 1H), 5.48 (t, J ) 9.3 Hz, 1H), 5.40 (d, J ) 3.3 Hz,
1H), 5.17 (dd, J ) 10.4, 7.9 Hz, 1H), 5.01 (dd, J ) 10.4, 3.4 Hz,
1H), 4.62 (t, J ) 7.8 Hz, 2H), 4.1 (m, 4H), 4.0 (m, 2H), 2.18 (s,
3H), 2.12 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H), 2.08 (s, 3H), 1.99 (s,
3H), 1.84 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 176.7, 174.4,
170.6, 170.3 (2 carbons), 170.2, 169.9, 169.3 (2 carbons), 146.1,
135.6, 134.7, 134.6, 133.0, 132.9, 128.0, 127.7, 101.2, 85.8, 77.7,
77.4, 77.0, 76.2, 75.4, 72.8, 71.1, 71.0, 69.5, 69.3, 66.9, 61.5, 61.1,
20.9, 20.8, 20.7, 20.4; ESI/APCI calcd for C36H39N3O19Na+ ([M
+ Na]+) m/e 840.2070; measured m/e 840.2088.
1-(N-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl))-1H-naph-
1
tho[2,3-d]triazole-4,9-dione (15a): H NMR (CDCl3, 400 MHz)
δ 8.33 (dd, J ) 6.7, 1.9 Hz, 1H), 8.27 (dd, J ) 7.1, 1.9 Hz, 1H),
7.8 (m, 2H), 6.35 (d, J ) 9.5 Hz, 1H), 6.15 (t, J ) 9.2 Hz, 1H),
5.50 (t, J ) 9.4 Hz, 1H), 5.47 (t, J ) 9.6 Hz, 1H), 4.3 (m, 2H), 4.1
(m, 1H), 2.10 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 1.84 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) δ 176.8, 174.3, 170.7, 170.3, 169.5, 169.1,
147.0, 135.6, 134.8, 134.7, 133.1, 133.0, 128.1, 127.9, 86.1, 75.4,
73.0, 69.3, 67.7, 61.6, 20.9, 20.8 (2 carbons), 20.4; ESI/APCI calcd
for C24H23N3O11Na+ ([M + Na]+) m/e 552.1225; measured m/e
552.1228.
2-(N-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl))aminometh-
ylene-1,3-indanedione (18a): 1H NMR (CDCl3, 400 MHz) δ 9.22
(dd, J ) 13.2, 8.8 Hz, 1H), 7.8 (m, 2H), 7.70 (d, J ) 13.2 Hz,
1H), 7.6 (m, 2H), 5.29 (t, J ) 9.6 Hz, 1H), 5.14 (t, J ) 9.2 Hz,
1H), 5.10 (t, J ) 9.6 Hz, 1H), 4.6 (m, 1H), 4.23 (dd, J ) 4.6, 1.2
Hz, 1H), 4.1 (m, 1H), 3.8 (m, 1H), 2.1 (m, 3H), 2.03 (s, 3H), 2.02
(s, 6H); 13C NMR (CDCl3, 75 MHz) δ 193.2, 189.9, 170.8, 170.2,
170.0, 169.5, 149.3, 140.4, 140.2, 134.2, 134.1, 122.6, 122.3, 107.4,
87.4, 74.4, 72.5, 70.8, 68.0, 61.8, 20.9, 20.8 (2 carbons), 20.7; ESI/
APCI calcd for C24H26NO11+ ([M + H]+) m/e 504.1500; measured
m/e 504.1506.
1-(N-(2,3,4-Tri-O-acetyl-r-D-fucopyranosyl))-1H-naphtho[2,3-
1
d]triazole-4,9-dione (15e): H NMR (CDCl3, 400 MHz) δ 8.32
(dd, J ) 6.8, 1.8 Hz, 1H), 8.26 (dd, J ) 7.2, 1.4 Hz, 1H), 7.86 (td,
J ) 7.4, 1.6 Hz, 1H), 7.83 (td, J ) 7.2, 2.0 Hz, 1H), 6.37 (d, J )
9.4 Hz, 1H), 6.31 (t, J ) 9.6 Hz, 1H), 5.42 (d, J ) 3.2 Hz, 1H),
5.31 (dd, J ) 9.7, 3.4 Hz, 1H), 4.24 (dd, J ) 12.6, 6.2 Hz, 1H),
2.33 (s, 3H), 2.03 (s, 3H), 1.82 (s, 3H), 1.27 (d, J ) 6.4 Hz, 3H);
13C NMR (CDCl3, 100 MHz) δ 176.9, 174.5, 171.0, 170.3, 169.1,
145.9, 135.5, 134.6 (2 carbons), 133.1, 133.0, 128.0, 127.9, 86.4,
73.2, 72.0, 70.0, 67.1, 21.0, 20.8, 20.5, 16.2; ESI/APCI calcd for
C22H21N3O9Na+ ([M + Na]+) m/e 494.1170; measured m/e
494.1180.
2-(N-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl))-2H-2-
benzazepine-1,5-dione (17b): 1H NMR (CDCl3, 400 MHz) δ 8.36
(dd, J ) 7.6, 1.4 Hz, 1H), 8.17 (dd, J ) 7.2, 1.9 Hz, 1H), 7.8 (m,
2H), 7.01 (d, J ) 11.1 Hz, 1H), 6.31 (d, J ) 9.2 Hz, 1H), 6.08 (d,
J ) 11.1 Hz, 1H), 5.53 (d, J ) 3.1 Hz, 1H), 5.39 (t, J ) 9.7 Hz,
1H), 5.25 (dd, J ) 10.1, 3.2 Hz, 1H), 4.2 (m, 3H), 2.23 (s, 3H),
2-(N-(2,3,4-Tri-O-acetyl-r-D-rhamnopyranosyl))-2H-2-benza-
zepine-1,5-dione (17f): 1H NMR (CDCl3, 400 MHz) δ 8.4 (m, 1H),
J. Org. Chem. Vol. 74, No. 2, 2009 691

Zhang and Chang
8.19 (dd, J ) 6.7, 2.2 Hz, 1H), 7.7 (m, 2H), 7.2 (m, 1H), 6.09 (s,
1H), 5.93 (dd, J ) 11.5, 0.7 Hz, 1H), 5.71 (d, J ) 3.4 Hz, 1H),
5.29 (dd, J ) 12.9, 3.4 Hz, 1H), 5.14 (t, J ) 9.7 Hz, 1H), 3.8 (m,
1H), 2.11 (s, 3H), 2.08 (s, 3H), 1.99 (s, 3H), 1.36 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 187.4, 170.1, 169.9 (2 carbons), 167.3, 137.2,
133.9, 133.7, 133.2, 132.8, 130.8, 129.8, 111.4, 82.7, 74.3, 70.6,
70.4, 69.0, 21.0 (2 carbons), 20.8, 17.8; ESI/APCI calcd for
(d, J ) 9.8, 7.8 Hz, 1H), 4.32 (dd, J ) 12.6, 4.9 Hz, 1H), 4.1 (m,
2H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 1.79 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 177.2 (2 carbons), 170.8 (2 carbons), 170.7,
169.6, 146.0, 135.1 (3 carbons), 134.2, 128.2 (3 carbons), 89.6,
75.2, 71.4, 68.2, 61.9, 54.9, 23.3, 20.9, 20.8 (2 carbons); ESI/APCI
calcd for C24H24N4O10Na+ ([M + Na]+) m/e 551.1385; measured
m/e 551.1395.
C22H24NO9 ([M + H]+) m/e 446.1451; measured m/e 446.1446.
+
2-(N-(4-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2,3,6-
tri-O-acetyl-ꢀ-D-glucopyranosyl))-2H-2-benzazepine-1,5-dione
1-(N-(2,3,4-Tri-O-acetyl-r-D-rhamnopyranosyl))-1H-naph-
1
1
tho[2,3-d]triazole-4,9-dione (15f): H NMR (CDCl3, 400 MHz)
(17i): H NMR (CDCl3, 400 MHz) δ 8.34 (dd, J ) 7.4, 1.8 Hz,
δ 8.35 (dd, J ) 7.5, 1.5 Hz, 1H), 8.25 (dd, J ) 7.4, 1.4 Hz, 1H),
7.88 (td, J ) 7.3, 1.5 Hz, 1H), 7.85 (td, J ) 7.3, 1.4 Hz, 1H), 6.68
(d, J ) 0.8 Hz, 1H), 5.89 (t, J ) 0.9 Hz, 1H), 5.4 (m, 2H), 4.0 (m,
1H), 2.21 (s, 3H), 2.13 (s, 3H), 2.05 (s, 3H), 1.42 (d, J ) 6.2 Hz,
3H); 13C NMR (CDCl3, 100 MHz) δ 176.7, 175.0, 170.5, 170.2,
169.9, 145.0, 135.8, 134.7, 133.1, 133.3, 132.8, 128.2, 127.8, 84.0,
74.9, 71.1, 70.2, 68.1, 21.0 (2 carbons), 20.8, 17.7; ESI/APCI calcd
for C22H21N3O9Na+ ([M + Na]+) m/e 494.1170; measured m/e
494.1177.
2-(N-(2,3,4-Tri-O-acetyl-r-D-rhamnopyranosyl))aminometh-
ylene-1,3-indanedione (18f): 1H NMR (CDCl3, 300 MHz) δ 9.41
(dd, J ) 13.2, 8.8 Hz, 1H), 7.82 (d, J ) 13.0 Hz, 1H), 7.7-7.8
(m, 2H), 7.5-7.6 (m, 2H), 5.50 (t, J ) 1.4 Hz, 1H), 5.1 (m, 2H),
5.00 (d, J ) 8.9 Hz, 1H), 3.7 (m, 1H), 2.30 (s, 3H), 2.08 (s, 3H),
1.98 (s, 3H), 1.24 (d, J ) 6.2 Hz, 3H); 13C NMR (CDCl3, 100
MHz) δ 193.5, 189.9, 170.5, 170.4, 170.0, 149.5, 140.3, 140.1,
134.0, 133.9, 122.5, 121.9, 106.7, 84.2, 72.8, 71.1, 69.8, 69.5, 21.0,
20.9, 20.8, 17.7; ESI/APCI calcd for C22H24NO9+ ([M + H]+) m/e
446.1451; measured m/e 446.1439.
1H), 8.15 (dd, J ) 7.9, 2.0 Hz, 1H), 7.8 (m, 2H), 6.87 (d, J ) 11.1
Hz, 1H), 6.28 (d, J ) 9.3 Hz, 1H), 6.01 (d, J ) 11.1 Hz, 1H), 5.41
(t, J ) 8.9 Hz, 1H), 5.1 (m, 3H), 4.96 (t, J ) 8.0 Hz, 1H), 4.56 (d,
J ) 7.9 Hz, 1H), 4.53 (dd, J ) 12.2, 7.9 Hz, 1H), 4.39 (dd, J )
12.5, 4.3 Hz, 1H), 4.16 (dd, J ) 12.1, 4.3 Hz, 1H), 4.08 (dd, J )
12.4, 7.9 Hz, 1H), 3.9 (m, 2H), 3.7 (m, 1H), 2.15 (s, 3H), 2.11 (s,
3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H),1.88 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 187.6, 170.7 (2 carbons),
170.4, 169.7, 169.6, 169.5, 169.2, 168.0, 137.3, 134.0, 133.7, 133.2,
131.5, 130.9, 129.8, 113.7, 100.9, 82.5, 76.2, 76.0, 73.1, 72.7, 72.3,
71.8, 70.2, 67.9, 61.9, 61.8, 21.1, 20.9, 20.8 (3 carbons), 20.7, 20.5;
ESI/APCI calcd for C36H41NO19Na+ ([M + Na]+) m/e 814.2165;
measured m/e 814.2165.
1-(N-(4-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2,3,6-
tri-O-acetyl-ꢀ-D-glucopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-
dione (15i): 1H NMR (CDCl3, 400 MHz) δ 8.30 (dd, J ) 7.8, 1.5
Hz, 1H), 8.19 (dd, J ) 7.3, 1.3 Hz, 1H), 7.84 (td, J )7.4, 1.4 Hz,
1H), 7.81 (td, J ) 7.4, 1.6 Hz, 1H), 6.27 (d, J ) 9.5 Hz, 1H), 6.02
(t, J ) 9.6 Hz, 1H), 5.42 (t, J ) 9.4 Hz, 1H), 5.16 (t, J ) 9.3 Hz,
1H), 5.07 (t, J ) 9.7 Hz, 1H), 4.95 (t, J ) 8.0 Hz, 1H), 4.6 (m,
2H), 4.40 (dd, J ) 12.5, 4.5 Hz, 1H), 4.0 (m, 4H), 3.7 (m, 1H),
2.09 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H),
1.96 (s, 3H), 1.80 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 176.8,
174.5, 170.7, 170.4, 170.3, 169.9, 169.5, 169.3 (2 carbons), 146.2,
135.6, 134.7, 134.6, 133.1, 133.0, 128.1, 127.7, 101.1, 86.0, 76.3,
75.7, 73.1, 72.6, 72.3, 71.8, 69.4, 68.0, 61.8, 61.3, 20.9, 20.8, 20.7
(3 carbons), 20.6, 20.4; ESI/APCI calcd for C36H39N3O19Na+ ([M
+ Na]+) m/e 840.2070; measured m/e 840.2083.
2-(N-(2,3,4-Tri-O-acetyl-ꢀ-D-xylopyranosyl))-2H-2-benzazepine-
1,5-dione (17g): 1H NMR (CDCl3, 400 MHz) δ 8.34 (dd, J ) 2.4,
1.6 Hz, 1H), 8.15 (dd, J ) 6.9, 1.9 Hz, 1H), 7.8 (m, 2H), 6.93 (d,
J ) 11.2 Hz, 1H), 6.24 (d, J ) 9.4 Hz, 1H), 6.03 (d, J ) 11.1 Hz,
1H), 5.44 (t, J ) 9.5 Hz, 1H), 5.19 (t, J ) 9.4 Hz, 1H), 5.10 (dt,
J ) 4.7, 0.7 Hz, 1H), 4.27 (dd, J ) 11.4, 5.7 Hz, 1H), 3.58 (t, J )
10.9 Hz, 1H), 2.08 (s, 3H), 2.05 (s, 3H), 1.87 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ 187.6, 170.1 (2 carbons), 170.0, 168.1, 137.4,
133.9, 133.6, 133.1, 131.7, 130.9, 129.8, 113.7, 83.2, 72.7, 70.3,
+
68.9, 65.7, 20.8 (2 carbons), 20.5; ESI/APCI calcd for C21H22NO9
([M + H]+) m/e 432.1289; measured m/e 432.1294.
2-(N-(4-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2,3,6-
tri-O-acetyl-ꢀ-D-glucopyranosyl))aminomethylene-1,3-indanedi-
1-(N-(2,3,4-Tri-O-acetyl-ꢀ-D-xylopyranosyl))-1H-naphtho[2,3-
d]triazole-4,9-dione (15g): H NMR (CDCl3, 400 MHz) δ 8.32
1
1
one (18i): H NMR (CDCl3, 400 MHz) δ 9.25 (dd, J ) 13.0, 8.2
Hz, 1H), 7.8 (m, 2H), 7.68 (d, J ) 13.1 Hz, 1H), 7.7 (m, 2H), 5.31
(t, J ) 8.9 Hz, 1H), 5.17 (t, J ) 9.1 Hz, 1H), 5.13 (t, J ) 9.6 Hz,
1H), 5.09 (t, J ) 9.9 Hz, 1H), 4.94 (t, J ) 8.0 Hz, 1H), 4.60 (t, J
) 8.7 Hz, 1H), 4.5 (m, 2H), 4.39 (dd, J ) 12.6, 4.5 Hz, 1H), 4.1
(m, 2H), 3.81 (t, J ) 9.0 Hz, 1H), 3.7 (m, 2H), 2.15 (s, 3H), 2.11
(s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H), 1.99
(s, 3H); 13C NMR (CDCl3, 100 MHz) δ 193.3, 189.9, 170.7, 170.4
(2 carbons), 170.1, 169.8, 169.5, 169.3, 149.3, 140.4, 140.2, 134.2,
134.1, 122.6, 122.3, 107.3, 101.1, 87.1, 76.1, 75.2, 73.1, 72.3, 72.0,
71.8, 71.0, 67.9, 61.8, 61.7, 21.1, 20.9, 20.8 (3 carbons), 20.7 (2
carbons); ESI/APCI calcd for C36H41NO19Na+ ([M + Na]+) m/e
814.2165; measured m/e 814.2158.
1-(N-(4-O-(4-O-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-
2,3,6-tri-O-acetyl-ꢀ-D-glucopyranosyl)-2,3,6-tri-O-acetyl-ꢀ-D-glu-
copyranosyl))-1H-naphtho[2,3-d]triazole-4,9-dione (15j): 1H NMR
(CDCl3, 300 MHz) δ 8.33 (dd, J ) 7.2, 1.7 Hz, 1H), 8.24 (dd, J )
7.9, 1.7 Hz, 1H), 7.8 (m, 2H), 6.37 (d, J ) 9.3 Hz, 1H), 5.99 (t, J
) 9.3 Hz, 1H), 5.55 (t, J ) 9.3 Hz, 1H), 5.4 (m, 4H), 5.07 (t, J )
10.0 Hz, 1H), 4.86 (dd, J ) 10.6, 4.1 Hz, 1H), 4.79 (dd, J ) 10.3,
4.1 Hz, 1H), 4.65 (dd, J ) 12.4, 2.4 Hz, 1H), 4.5 (m, 1H), 4.3 (m,
4H), 4.0 (m, 5H), 2.17 (s, 3H), 2.13 (s, 3H), 2.10 (s, 3H), 2.07 (s,
3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.02 (s, 6H), 2.00 (s, 3H), 1.81 (s,
3H); 13C NMR (CDCl3, 75 MHz) δ 176.7, 174.3, 170.7 (2 carbons),
170.6, 170.5, 170.3, 170.2, 170.0, 169.8, 169.5, 169.2, 146.0, 135.5,
134.6, 134.4, 133.0, 132.9, 128.0, 127.7, 96.2, 95.6, 85.5, 75.6,
75.2, 72.9, 72.4, 71.8, 70.6, 70.2, 69.8, 69.4, 69.3, 68.6, 68.0, 62.3,
62.1, 61.4, 21.0, 20.9 (2 carbons), 20.8, 20.7, 20.6 (4 carbons),
(dd, J ) 7.7, 1.9 Hz, 1H), 8.25 (dd, J ) 7.1, 1.8 Hz, 1H), 7.8 (m,
2H), 6.29 (d, J ) 9.2 Hz, 1H), 6.09 (t, J ) 9.3 Hz, 1H), 5.47 (t, J
) 9.4 Hz, 1H), 5.3 (m, 1H), 4.35 (dd, J ) 11.6, 5.6 Hz, 1H), 3.67
(t, J ) 10.2 Hz, 1H), 2.08 (s, 3H), 2.06 (s, 3H), 1.82 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 176.8, 174.5, 170.3, 169.9, 169.2,
146.1, 135.6, 134.7, 134.6, 133.1, 133.0, 128.0, 127.9, 86.7, 72.6,
69.5, 68.6, 65.9, 20.9 (2 carbons), 20.4; ESI/APCI calcd for
C21H19N3O9Na+ ([M + Na]+) m/e 480.1014; measured m/e
480.1007.
2-(N-(2,3,4-Tri-O-acetyl-D-xylopyranosyl))aminomethylene-
1
1,3-indanedione (18g): (R/ꢀ ) 1/1) H NMR (CDCl3, 400 MHz)
δ 9.5 (m, 1H), 9.4 (m, 1H), 7.67 (d, J ) 13.2 Hz, 2H), 7.6-7.8
(m, 8H), 5.3 (m, 2H), 5.14 (dd, J ) 5.7, 2.0 Hz, 1H), 5.0 (m, 3H),
4.8 (m, 1H), 4.61 (t, J ) 5.6 Hz, 1H), 4.2 (m, 1H), 3.9 (m, 1H),
3.8 (m, 1H), 3.5 (m, 1H), 2.20 (s, 3H), 2.09 (s, 6H), 2.05 (s, 3H),
2.02 (s, 3H), 2.01 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 193.7,
193.2, 189.9, 189.8, 170.0, 170.0, 169.9 (2 carbons), 169.8, 169.0,
149.6, 149.5, 140.4 (2 carbons), 140.2, 140.1, 134.2, 134.1 (2
carbons), 134.0, 122.6, 122.5, 122.2, 122.0, 107.3, 107.2, 87.2, 82.4,
71.1, 70.3, 68.3, 68.2, 67.7, 66.9, 64.1, 63.2, 21.0, 20.9 (3 carbons),
20.7 (2 carbons); ESI/APCI calcd for C21H22NO9+ ([M + H]+) m/e
432.1289; measured m/e 432.1303.
1-(N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-ꢀ-D-glucopyra-
nosyl))-1H-naphtho[2,3-d]triazole-4,9-dione (15h): 1H NMR
(CDCl3, 400 MHz) δ 8.36 (d, J ) 5.8 Hz, 1H), 8.35 (d, J ) 5.7
Hz, 1H), 7.9 (m, 2H), 6.59 (d, J ) 9.7 Hz, 1H), 5.83 (t, J ) 9.4
Hz, 1H), 5.76 (d, J ) 7.6 Hz, 1H), 5.27 (t, J ) 9.6 Hz, 1H), 4.60
692 J. Org. Chem. Vol. 74, No. 2, 2009

DiVergent Synthesis of Three Classes of Aryl N-Glycosides
20.3; ESI/APCI calcd for C48H55N3O27Na+ ([M + Na]+) m/e
1128.2915; measured m/e 1128.2903.
67.3, 61.9, 51.4, 21.0, 20.9, 20.8, 20.7, 20.6; ESI/APCI calcd for
C26H27N3O12Na+ ([M + Na]+) m/e 596.1487; measured m/e
596.1502.
2-(N-(2,3,5-Tri-O-acetyl-ꢀ-D-ribofuranosyl))-2H-2-benzazepine-
1,5-dione (17k). Compound 17k was eluted out after compound
2,3,4,5,6-Penta-O-acetyl-1-(aminomethylene-1,3-indanedione)-
1-dideoxy-D-mannitol (18m): 1H NMR (CDCl3, 400 MHz) δ 9.3
(m, 1H), 7.7 (m, 2H), 7.6 (m, 2H), 7.24 (d, J ) 13.8 Hz, 1H), 5.40
(dd, J ) 9.3, 2.2 Hz, 1H), 5.30 (dd, J ) 9.4, 2.3 Hz, 1H), 5.1 (m,
1H), 5.0 (m, 1H), 4.16 (dd, J ) 12.6, 2.7 Hz, 1H), 4.02 (dd, J )
12.6, 5.0 Hz, 1H), 3.5 (m, 1H), 3.4 (m, 1H), 2.15 (s, 3H), 2.08 (s,
3H), 2.06 (s, 6H), 2.01 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
193.5, 190.2, 171.1, 170.8, 170.2, 170.0, 169.8, 152.4, 140.1, 140.0,
133.6, 133.6, 122.2, 121.7, 105.5, 68.2, 67.9, 67.8, 67.3, 62.0, 49.7,
21.0, 21.0, 20.9, 20.8, 20.8; ESI/APCI calcd for C26H30NO12+ ([M
+ H]+) m/e 548.1768; measured m/e 548.1757.
1
15k: H NMR (CDCl3, 400 MHz) δ 8.34 (dd, J ) 9.3, 2.1 Hz,
1H), 8.17 (dd, J ) 9.2, 2.1 Hz, 1H), 7.7-7.8 (m, 2H), 7.07 (d, J
) 11.1 Hz, 1H), 6.30 (d, J ) 4.4 Hz, 1H), 5.97 (d, J ) 11.2 Hz,
1H), 5.38 (t, J ) 5.8 Hz, 1H), 5.34 (d, J ) 5.2 Hz, 1H), 4.4 (m,
3H), 2.14 (s, 3H), 2.09 (s, 6H); 13C NMR (CDCl3, 100 MHz) δ
187.4, 170.4, 169.8, 169.7, 168.0, 137.2, 133.9, 133.6, 133.2, 131.8,
131.3, 129.8, 113.1, 90.6, 79.8, 73.7, 70.1, 63.0, 21.0, 20.7 (2
carbons); ESI/APCI calcd for C21H22NO9 ([M + H]+) m/e
+
432.1295; measured m/e 432.1287.
1-(N-(2,3,5-Tri-O-acetyl-ꢀ-D-ribofuranosyl))-1H-naphtho[2,3-
d]triazole-4,9-dione (15k). Compound 17k was eluted out after
1-(4-(N-tert-Butoxycarbonylpiperidinyl))-1H-naphtho[2,3-
1
1
compound 15k: H NMR (CDCl3, 400 MHz) δ 8.36 (d, J ) 7.4
d]triazole-4,9-dione (15n): H NMR (CDCl3, 300 MHz) δ 8.33
Hz, 1H), 8.25 (d, J ) 7.5 Hz, 1H), 7.9 (m, 2H), 6.97 (d, J ) 2.8
Hz, 1H), 6.2 (m, 1H), 5.84 (t, J ) 5.6 Hz, 1H), 4.6 (m, 1H), 4.48
(dd, J ) 12.4, 3.1 Hz, 1H), 4.23 (dd, J ) 12.4, 4.5 Hz, 1H), 2.17
(s, 3H), 2.16 (s, 3H), 2.07 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
176.7, 175.3, 170.7, 169.7, 169.6, 145.6, 135.7, 134.7, 134.0, 133.2,
132.9, 128.1, 127.8, 89.9, 81.6, 74.2, 70.9, 62.6, 20.8, 20.7 (2
carbons); ESI/APCI calcd for C21H19N3O9Na+ ([M + Na]+) m/e
480.1014; measured m/e 480.1013.
(dd, J ) 7.5, 1.7 Hz, 1H), 8.22 (dd, J ) 6.9, 2.1 Hz, 1H), 7.86 (td,
J ) 7.6, 1.7 Hz, 1H), 7.81 (td, J ) 7.6, 1.7 Hz, 1H), 5.36 (tt, J )
7.2, 4.5 Hz, 1H), 4.3 (m, 2H), 2.97 (t, J ) 11.7 Hz, 2H), 2.1-2.4
(m, 4H), 1.48 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ 177.0, 175.7,
154.6, 145.6, 135.4, 134.5, 133.3, 133.0, 133.0, 127.9, 127.5, 80.3
(2 carbons), 59.2, 42.9, 31.7 (2 carbons), 28.5 (3 carbons); ESI/
APCI calcd for C20H23N4O4+ ([M + H]+) m/e 383.1714; measured
m/e 383.1726.
2-(N-(2,3,5-Tri-O-acetyl-ꢀ-D-ribofuranosyl))aminomethylene-
2-(N-(4-(N-tert-Butoxycarbonylpiperidinyl)))aminomethylene-
1,3-indanedione (18n): H NMR (CDCl3, 400 MHz) δ 9.2 (m,
1
1
1,3-indanedione (18k): H NMR (CDCl3, 400 MHz) δ 9.38 (dd,
J ) 13.0, 8.6 Hz, 1H), 7.75 (d, J ) 13.2 Hz, 1H), 7.7-7.8 (m,
2H), 7.6 (m, 2H), 5.33 (dd, J ) 5.3, 3.4 Hz, 1H), 5.24 (t, J ) 5.5
Hz, 1H), 5.17 (dd, J ) 8.6, 5.6 Hz, 1H), 4.31 (dd, J ) 6.0, 2.9 Hz,
1H), 4.2 - 4.3 (m, 2H), 2.25 (s, 3H), 2.10 (s, 3H), 2.08 (s, 3H);
13C NMR (CDCl3, 100 MHz) δ 193.6, 189.9, 170.8, 169.8, 169.7,
148.9, 140.2, 140.1, 134.1, 133.9, 122.5, 122.0, 106.6, 91.4, 80.7,
1H), 7.74 (d, J ) 14.4 Hz, 1H), 7.7 (m, 2H), 7.6 (m, 2H), 4.1 (m,
2H), 3.4 (m, 1H), 2.86 (t, J ) 11.4 Hz, 2H), 2.0 (m, 2H),
1.6 (m, 2H), 1.43 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 194.0,
190.2, 154.7, 150.0, 140.0, 133.6, 133.5, 122.1, 121.5, 104.8, 80.4,
57.0 (2 carbons), 43.0 (2 carbons), 32.8 (2 carbons), 28.6 (3
carbons); ESI/APCI calcd for C20H25N2O4 ([M + H]+) m/e
+
+
74.9, 71.4, 63.4, 21.1, 20.8, 20.6; ESI/APCI calcd for C21H22NO9
357.1809; measured m/e 357.1807.
([M + H]+) m/e 432.1289; measured m/e 432.1289.
1-Benzyl-1H-naphtho[2,3-d]triazole-4,9-dione (15o): 1H NMR
(CDCl3, 400 MHz) δ 8.30 (dd, J ) 7.5, 1.8 Hz, 1H), 8.20 (dd, J )
7.4, 1.6 Hz, 1H), 7.81 (td, J ) 7.3, 1.6 Hz, 1H), 7.78 (td, J ) 7.1,
1.5 Hz, 1H), 7.5 (m, 2H), 7.3 (m, 3H), 5.99 (s, 2H); 13C NMR
(CDCl3, 100 MHz) δ 177.0, 175.6, 145.9, 135.4 (2 carbons), 134.5
(2 carbons), 134.1, 133.6, 133.3, 133.0, 129.3 (2 carbons), 128.9,
2,3,4,5-Tetra-O-acetyl-1,6-bis(1H-naphtho[2,3-d]triazole-4,9-
dione)-1,6-dideoxy-D-mannitol (15l): 1H NMR (CDCl3, 400 MHz)
δ 8.31 (d, J ) 7.6 Hz, 2H), 8.16 (d, J ) 7.5 Hz, 2H), 7.85 (td, J
) 7.4, 1.1 Hz, 2H), 7.78 (td, J ) 7.5, 1.2 Hz, 2H), 5.56 (d, J ) 7.8
Hz, 2H), 5.49 (t, J ) 9.2 Hz, 2H), 5.09 (dd, J ) 14.2, 2.1 Hz, 2H),
4.94 (dd, J ) 14.2, 9.3 Hz, 2H), 2.23 (s, 6H), 1.94 (s, 6H); 13C
NMR (CDCl3, 100 MHz) δ 176.7 (2 carbons), 175.9 (2 carbons),
170.5 (2 carbons), 169.9 (2 carbons), 145.7 (2 carbons), 135.6 (2
carbons), 134.6 (2 carbons), 133.9 (2 carbons), 133.7 (2 carbons),
132.8 (2 carbons), 128.1 (2 carbons), 127.5 (2 carbons), 68.7 (2
carbons), 68.4 (2 carbons), 51.2 (2 carbons), 20.9 (2 carbons), 20.6
128.1, 127.6, 54.0; ESI/APCI calcd for C17H12N3O2 ([M + H]+)
+
m/e 290.0930; measured m/e 290.0931.
General Procedure for the Deprotection of Acetyl Groups
Using NaOMe/MeOH. To a solution of starting material (0.10 g,
15) in anhydrous MeOH (10 mL), a catalytic amount of NaOMe
(ca. 1 M in MeOH) was added. The solution was stirred at room
temperature for 1 h. After complete consumption of the starting
material, the reaction mixture was loaded to a column packed with
Amberlite 120 (H+) resin, which was balanced with MeOH. The
column was eluted with more MeOH, and the eluent was collected.
After the removal of the solvent, the product was purified by
recrystallization from a mixture of MeOH/EtOAc/hexane.
General Procedure for the Deprotection of Acetyl Groups
Using K2CO3/MeOH/H2O. To a solution of starting material (0.10
g, 18) in MeOH (10 mL) and few drops of water, a catalytic amount
of K2CO3 was added and the solution was stirred at room
temperature for 1 h. After complete consumption of the starting
material, the reaction was quenched with Amberlite 120 (H+) resin
and filtered through Celite. After removal of the solvent, the crude
product was purified by gradient column chromatography (eluted
with CH2Cl2/MeOH from 100/0 to 4/1). The collected product was
further purified by recrystallization from a mixture of MeOH/
EtOAc/hexane.
(2 carbons); ESI/APCI calcd for C34H29N6O12 ([M + H]+) m/e
+
713.1838; measured m/e 713.1851.
2,3,4,5,6-Penta-O-acetyl-1-(2H-2-benzazepine-1,5-dione)-1-
dideoxy-D-mannitol (17m). Compound 17m eluted out after 15m:
1H NMR (CDCl3, 400 MHz) δ 8.4 (m, 1H), 8.2 (m, 1H), 7.7-7.8
(m, 2H), 6.73 (d, J ) 10.9 Hz, 1H), 5.85 (d, J ) 11.0 Hz, 1H),
5.52 (dd, J ) 8.9, 2.3 Hz, 1H), 5.4-5.5 (m, 2H), 5.2 (m, 1H), 4.62
(dd, J ) 12.5, 2.7 Hz, 1H), 4.23 (dd, J ) 12.5, 2.7 Hz, 1H), 4.10
(dd, J ) 12.5, 5.2 Hz, 1H), 3.53 (dd, J ) 13.9, 9.1 Hz, 1H), 2.19
(s, 3H), 2.11 (s, 3H), 2.10 (s, 3H), 2.05 (s, 3H), 1.99 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 187.6, 170.8, 170.6, 170.1 (2 carbons),
170.0, 167.4, 137.9, 137.2, 133.9, 133.7, 133.2, 130.9, 129.8, 112.2,
69.6, 68.3, 68.1, 67.7, 62.0, 54.6, 21.1, 21.0 (2 carbons), 20.9 (2
carbons); ESI/APCI calcd for C26H30NO12 ([M + H]+) m/e
+
548.1768; measured m/e 548.1765.
2,3,4,5,6-Penta-O-acetyl-1-(1H-naphtho[2,3-d]triazole-4,9-di-
1
one)-1-dideoxy-D-mannitol (15m): H NMR (CDCl3, 400 MHz)
δ 8.27 (d, J ) 7.2 Hz, 1H), 8.18 (d, J ) 7.3 Hz, 1H), 7.8 (m, 2H),
5.5 (m, 2H), 5.3 (m, 1H), 5.1 (m, 1H), 5.00 (dd, J ) 14.1, 2.1 Hz,
1H), 4.89 (dd, J ) 12.5, 9.4 Hz, 1H), 4.19 (dd, J ) 12.5, 2.7 Hz,
1H), 4.03 (dd, J ) 12.5, 5.1 Hz, 1H), 2.26 (s, 3H), 2.05 (s, 3H),
2.01 (s, 3H), 1.98 (s, 3H), 1.87 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ 176.7, 175.8, 170.7, 170.6, 170.0, 169.9, 169.8, 145.6,
135.6, 134.5, 133.9, 133.6, 132.8, 128.0, 127.5, 68.9, 68.1, 68.0,
1-(N-(ꢀ-D-Glucopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-di-
one (19a). Please refer to the general procedure for the deprotection
of acetyl groups using NaOMe/MeOH (yield 99%): 1H NMR
(DMSO-d6, 400 MHz) δ 8.2 (m, 2H), 8.0 (m, 2H), 6.15 (d, J )
9.2 Hz, 1H), 5.5 (m, 1H), 5.34 (d, J ) 5.2 Hz, 1H), 5.22 (d, J )
5.6 Hz, 1H), 4.6 (m, 1H), 4.1 (m, 1H), 3.7 (m, 1H), 3.5 (m, 4H);
13C NMR (DMSO-d6, 100 MHz) δ 177.5, 175.4, 145.6, 136.0,
J. Org. Chem. Vol. 74, No. 2, 2009 693

Zhang and Chang
135.4, 135.1, 133.6, 133.4, 127.7, 127.6, 88.2, 81.4, 77.6, 72.2,
70.2, 61.4; ESI/APCI calcd for C16H15N3O7Na+ ([M + Na]+) m/e
384.0802; measured m/e 384.0801.
1-(N-(2-Acetamido-ꢀ-D-glucopyranosyl))-1H-naphtho[2,3-d]tri-
azole-4,9-dione (19h). Please refer to the general procedure for
the deprotection of acetyl groups using NaOMe/MeOH (yield 56%):
1H NMR (DMSO-d6, 400 MHz) δ 8.21 (d, J ) 5.7 Hz, 1H), 8.20
(d, J ) 5.6 Hz, 1H), 7.9 (m, 3H), 6.02 (d, J ) 9.6 Hz, 1H), 5.31
(d, J ) 5.4 Hz, 2H), 4.7 (m, 1H), 4.1 (m, 1H), 3.7 (m, 1H), 3.5 (m,
4H), 1.58 (s, 3H); 13C NMR (DMSO-d6, 100 MHz) δ 177.7, 170.0
(2 carbons), 145.8, 135.5 (3 carbons), 134.6, 127.8 (3 carbons),
91.5, 81.1, 74.2, 70.6, 61.4, 56.1, 23.3; ESI/APCI calcd for
C18H18N4O7Na+ ([M + Na]+) m/e 425.1068; measured m/e
425.1068.
1-(N-(ꢀ-D-Galactopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-
dione (19b). Please refer to the general procedure for the depro-
tection of acetyl groups using K2CO3/MeOH/H2O (yield 46%): 1H
NMR (DMSO-d6, 400 MHz) δ 8.2 (m, 2H), 8.0 (m, 2H), 6.13 (d,
J ) 9.1 Hz, 1H), 5.37 (d, J ) 5.4 Hz, 1H), 5.1 (m, 1H), 4.8 (m,
1H), 4.69 (t, J ) 5.4 Hz, 1H), 4.4 (m, 1H), 3.8 (m, 1H), 3.79 (t, J
) 5.7 Hz, 1H), 3.5 (m, 3H); 13C NMR (DMSO-d6, 100 MHz) δ
177.5, 175.5, 145.5, 135.9, 135.3, 135.1, 133.6, 133.5, 127.7 (2
carbons), 88.4, 79.7, 74.3, 69.5, 68.9, 61.0; ESI/APCI calcd for
C16H15N3O7Na+ ([M + Na]+) m/e 384.0802; measured m/e
384.0801.
1-(N-(r-D-Mannopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-
dione (19c). Please refer to the general procedure for the depro-
tection of acetyl groups using NaOMe/MeOH (yield 62%): 1H NMR
(DMSO-d6, 400 MHz) δ 8.2 (m, 2H), 7.9 (m, 2H), 6.38 (s, 1H),
5.05 (s, 2H), 4.89 (s, 1H), 4.65 (s, 1H), 4.09 (s, 1H), 3.82 (d, J )
11.7 Hz, 1H), 3.5 (m, 4H); 13C NMR (DMSO-d6, 100 MHz) δ
177.7, 175.5, 145.0, 135.9, 135.3, 134.1, 133.6, 133.4, 127.7 (2
carbons), 87.8, 82.1, 74.0, 70.6, 67.0, 61.8; ESI/APCI calcd for
C16H15N3O7Na+ ([M + Na]+) m/e 384.0802; measured m/e
384.0806.
1-(N-(4-O-(ꢀ-D-Glucopyranosyl)-ꢀ-D-glucopyranosyl))-1H-
naphtho[2,3-d]triazole-4,9-dione (19i). Please refer to the general
procedure for the deprotection of acetyl groups using NaOMe/
1
MeOH (yield 99%): H NMR (DMSO-d6, 400 MHz) δ 8.2 (m,
2H), 8.0 (m, 2H), 6.22 (d, J ) 9.2 Hz, 1H), 5.71 (s, 1H), 5.30 (s,
1H), 5.03 (s, 2H), 4.98 (s, 1H), 4.68 (s, 2H), 4.37 (d, J ) 7.8 Hz,
1H), 4.21 (s, 1H), 3.6 (m, 7H), 3.3 (m, 2H), 3.20 (t, J )
8.6 Hz, 1H), 3.08 (t, J ) 9.2 Hz, 1H); 13C NMR (DMSO-d6, 100
MHz) δ 177.5, 175.3, 145.7, 135.9, 135.4, 135.2, 133.6, 133.4,
127.7, 127.6, 103.8, 87.8, 80.1, 79.1, 77.5, 77.1, 75.8, 74.0, 71.9,
70.8, 61.8, 60.7; ESI/APCI calcd for C22H25N3O12Na+ ([M + Na]+)
m/e 546.1330; measured m/e 546.1326.
1-(N-(4-O-(4-O-(ꢀ-D-Glucopyranosyl)-ꢀ-D-glucopyranosyl)-ꢀ-
D-glucopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-dione (19j).
Please refer to the general procedure for the deprotection of acetyl
groups using NaOMe/MeOH (yield 57%): 1H NMR(DMSO-d6, 400
MHz) δ 8.2 (m, 2H), 8.0 (m, 2H), 6.20 (d, J ) 8.9 Hz, 1H), 5.15
(d, J ) 3.6 Hz, 1H), 5.01 (d, J ) 3.6 Hz, 1H), 4.2 (m, 1H), 3.5 (m,
27H); 13C NMR (DMSO-d6, 100 MHz) δ 177.5, 175.3, 145.7, 136.0,
135.3, 135.2, 133.6, 133.4, 127.8, 127.6, 101.5 (2 carbons), 101.3,
80.2, 79.7, 79.3, 77.1, 74.2, 74.0, 73.8, 73.2, 72.7, 72.5, 71.7, 70.6,
61.5, 61.0, 49.3; ESI/APCI calcd for C28H35N3O17Na+ ([M + Na]+)
m/e 708.1859; measured m/e 708.1851.
1-(N-(ꢀ-D-Ribofuranosyl))-1H-naphtho[2,3-d]triazole-4,9-di-
one (19k). Please refer to the general procedure for the deprotection
of acetyl groups using NaOMe/MeOH (yield 57%): 1H NMR
(DMSO-d6, 400 MHz) δ 8.2 (m, 2H), 8.0 (m, 2H), 6.60 (d, J )
3.0 Hz, 1H), 5.73 (s, 1H), 5.34 (s, 1H), 4.7 (m, 1H), 4.35 (t, J )
5.2 Hz, 1H), 4.05 (dd, J ) 13.8, 5.6 Hz, 1H), 3.62 (dd, J ) 11.9,
3.9 Hz, 1H), 3.48 (dd, J ) 11.9, 5.7 Hz, 1H), 3.33 (s, 1H); 13C
NMR (DMSO-d6, 100 MHz) δ 177.6, 175.6, 145.5, 135.8, 135.3,
135.2, 133.7, 133.5, 127.6 (2 carbons), 92.3, 86.7, 74.9, 71.2, 62.2;
ESI/APCI calcd for C15H13N3O6Na+ ([M + Na]+) m/e 354.0697;
measured m/e 354.0703.
1,6-Bis(1H-naphtho[2,3-d]triazole-4,9-dione)-1,6-dideoxy-D-
mannitol (19l). Please refer to the general procedure for the
deprotection of acetyl groups using NaOMe/MeOH (yield 23%):
1H NMR (DMSO-d6, 400 MHz) δ 8.21 (dd, J ) 7.5, 2.3 Hz, 2H),
8.17 (dd, J ) 7.3, 2.4 Hz, 2H), 7.9 (m, 4H), 5.07 (dd, J ) 7.7, 3.3
Hz, 2H), 5.07 (d, J ) 6.3 Hz, 2H), 4.87 (dd, J ) 13.4, 9.4 Hz,
2H), 4.79 (d, J ) 8.2 Hz, 2H), 4.1 (m, 2H), 3.72 (t, J ) 8.4 Hz,
2H); 13C NMR (DMSO-d6, 100 MHz) δ 177.7 (2 carbons), 175.7
(2 carbons), 145.5 (2 carbons), 135.8 (2 carbons), 135.5 (2 carbons),
135.3 (2 carbons), 133.7 (4 carbons), 127.7 (4 carbons), 71.9 (2
carbons), 69.9 (2 carbons), 55.0 (2 carbons); ESI/APCI calcd for
C26H20N6O8Na+ ([M + Na]+) m/e 567.1235; measured m/e
567.1236.
1-(1H-Naphtho[2,3-d]triazole-4,9-dione)-1-dideoxy-D-manni-
tol (19m). Please refer to the general procedure for the deprotection
of acetyl groups using NaOMe/MeOH (yield 97%): 1H NMR
(DMSO-d6, 400 MHz) δ 8.1 (m, 2H), 7.9 (m, 2H), 5.05 (dd, J )
13.4, 3.1 Hz, 1H), 4.97 (d, J ) 6.4 Hz, 1H), 4.83 (dd, J ) 13.4,
9.5 Hz, 1H), 4.63 (d, J ) 7.3 Hz, 1H), 4.50 (d, J ) 4.9 Hz, 1H),
4.40 (s, 1H), 4.27 (d, J ) 7.7 Hz, 1H), 4.1 (m, 1H), 3.71 (t, J )
7.6 Hz, 1H), 3.6 (m, 1H), 3.57 (t, J ) 8.1 Hz, 1H), 3.5 (m, 1H),
3.4 (m, 1H); 13C NMR (DMSO-d6, 100 MHz) δ 177.6, 175.6, 145.4,
135.8, 135.4, 135.3, 133.6 (2 carbons), 127.6, 127.5, 72.0, 71.8,
1-(N-(4-O-(ꢀ-D-Galactopyranosyl)-ꢀ-D-glucopyranosyl))-1H-
naphtho[2,3-d]triazole-4,9-dione (19d): Please refer to the general
procedure for the deprotection of acetyl groups using NaOMe/
1
MeOH (yield 99%): H NMR (DMSO-d6, 400 MHz) δ 8.2 (m,
2H), 7.9 (m, 2H), 6.22 (d, J ) 9.3 Hz, 1H), 5.72 (s, 1H), 5.14 (d,
J ) 4.0 Hz, 1H), 4.99 (s, 1H), 4.83 (s, 1H), 4.68 (s, 1H), 4.65 (s,
1H), 4.56 (s, 1H), 4.31 (d, J ) 7.2 Hz, 1H), 4.2 (m, 1H), 3.8 (m,
1H), 3.6 (m, 7H), 3.3 (m, 3H); 13C NMR (DMSO-d6, 100 MHz) δ
177.5, 175.3, 145.7, 136.0, 135.4, 135.2, 133.6, 133.4, 127.7, 127.6,
104.5, 87.8, 80.4, 79.1, 76.3, 75.7, 73.9, 71.9, 71.2, 68.9, 61.1, 60.7;
ESI/APCI calcd for C22H25N3O12Na+ ([M + Na]+) m/e 546.1330;
measured m/e 546.1331.
1-(N-(r-D-Fucopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-di-
one (19e). Please refer to the general procedure for the deprotection
of acetyl groups using NaOMe/MeOH (yield 41%): 1H NMR
(DMSO-d6, 400 MHz) δ 8.18 (dd, J ) 7.5, 1.8 Hz, 1H), 8.15 (dd,
J ) 6.8, 1.5 Hz, 1H), 7.9 (m, 2H), 6.11 (d, J ) 9.1 Hz, 1H), 5.34
(d, J ) 5.4 Hz, 1H), 5.08 (s, 1H), 4.83 (s, 1H), 4.4 (m, 1H), 3.98
(dd, J ) 12.6, 6.2 Hz, 1H), 3.63 (s, 2H), 1.19 (d, J ) 6.3 Hz, 3H);
13C NMR (DMSO-d6, 100 MHz) δ 177.6, 175.5, 145.5, 135.9,
135.3, 135.0, 133.6, 133.5, 127.6 (2 carbons), 88.3, 74.7, 74.5, 71.7,
69.1, 17.2; ESI/APCI calcd for C16H15N3O6Na+ ([M + Na]+) m/e
368.0853; measured m/e 368.0853.
1-(N-(r-D-Rhamnopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-
dione (19f): Please refer to the general procedure for the depro-
tection of acetyl groups using K2CO3/MeOH/H2O (yield 33%): 1H
NMR (DMSO-d6, 400 MHz) δ 8.1 - 8.2 (m, 2H), 8.0 (m, 2H),
6.36 (s, 1H), 5.08 (d, J ) 5.6 Hz, 1H), 5.02 (d, J ) 5.9 Hz, 1H),
4.89 (d, J ) 5.8 Hz, 1H), 4.1 (m, 1H), 3.6 (m, 2H), 3.4 (m, 1H),
3.33 (d, J ) 6.0 Hz, 3H); 13C NMR (DMSO-d6, 100 MHz) δ 177.7,
175.5, 145.0, 135.9, 135.3, 134.0, 133.5, 133.4, 127.6 (2 carbons),
87.9, 76.6, 73.3, 71.8, 70.7, 18.5; ESI/APCI calcd for C16H15N3-
O6Na+ ([M + Na]+) m/e 368.0853; measured m/e 368.0855.
1-(N-(ꢀ-D-Xylopyranosyl))-1H-naphtho[2,3-d]triazole-4,9-di-
one (19g). Please refer to the general procedure for the deprotection
of acetyl groups using NaOMe/MeOH (yield 79%): 1H NMR
(CDCl3, 400 MHz) δ 8.2 (m, 2H), 8.0 (m, 2H), 6.08 (d, J ) 9.2
Hz, 1H), 5.54 (d, J ) 5.4 Hz, 1H), 5.38 (d, J ) 5.2 Hz, 1H), 5.26
(d, J ) 5.1 Hz, 1H), 4.11 (dt, J ) 12.2, 9.0 Hz, 1H), 3.96 (dd, J
) 11.1, 5.2 Hz, 1H), 3.57 (m, 1H), 3.41(m, 2H); 13C NMR (CDCl3,
100 MHz) δ 177.6, 175.3, 145.7, 135.9, 135.3, 135.1, 133.6, 133.4,
127.7, 127.6, 88.9, 77.6, 72.1, 69.7, 69.4; ESI/APCI calcd for
C15H13N3O6Na+ ([M + Na]+) m/e 354.0697; measured m/e
354.0699.
694 J. Org. Chem. Vol. 74, No. 2, 2009

DiVergent Synthesis of Three Classes of Aryl N-Glycosides
+
70.1, 70.0, 64.4, 55.0; ESI/APCI calcd for C16H18N3O7 ([M +
193.4, 190.7, 151.1 (2 carbons), 139.7, 139.6, 133.7, 133.7, 121.6,
H]+) m/e 364.1139; measured m/e 364.1141.
121.2, 83.9, 70.3, 70.0, 68.5, 65.6; ESI/APCI calcd for C15H16NO6
+
1-(4-Piperidinyl)-1H-naphtho[2,3-d]triazole-4,9-dione (19n).
A solution of 15n (0.13 g, 0.34 mmol) in CH2Cl2 (4 mL) and TFA
(1 mL) was stirred at 0 °C for 30 min. After completion of the
reaction, the reaction mixture was concentrated and purified with
column chromatography (eluted with CH2Cl2/MeOH from 100/0
to 4/1). The desired product was obtained as a solid (0.090 g, 0.32
([M + H]+) m/e 306.0972; measured m/e 306.0977.
2-(N-(ꢀ-D-Xylopyranosyl))aminomethylene-1,3-indanedione
(20g). Please refer to the general procedure for the deprotection of
acetyl groups using K2CO3/MeOH/H2O (yield 53%): 1H NMR
(CD3OD, 300 MHz) δ 7.90 (s, 1H), 7.6-7.7 (m, 4H), 4.52 (d, J )
8.2 Hz, 1H), 3.95 (dd, J ) 11.3, 5.2 Hz, 1H), 3.5 (m, 1H), 3.2-3.4
(m, 3H); 13C NMR (CD3OD, 75 MHz) δ 192.9, 190.9, 150.9, 139.6
(2 carbons), 133.7, 133.6, 121.5, 121.2, 104.8, 89.3, 76.6, 72.9,
1
mmol, 94%): H NMR (D2O, 300 MHz) δ 7.82 (dd, J ) 5.5, 1.1
Hz, 1H), 7.75 (dd, J ) 5.5, 1.0 Hz, 1H), 7.64 (td, J ) 4.5, 0.7 Hz,
1H), 7.60 (td, J ) 4.0, 0.7 Hz, 1H), 5.39 (tt, J ) 14.8, 8.3 Hz,
69.4, 67.6; ESI/APCI calcd for C15H16NO6 ([M + H]+) m/e
+
1H), 3.62 (dt, J ) 13.7, 3.4 Hz, 2H), 3.3 (m, 2H), 2.4 (m, 4H); 13
C
306.0972; measured m/e 306.0976.
NMR (D2O, 100 MHz) δ 178.2, 175.5, 144.8, 135.9, 135.5, 133.7,
2-(N-(ꢀ-D-Ribofuranosyl))aminomethylene-1,3-indanedione
(20k). Please refer to the general procedure for the deprotection of
acetyl groups using K2CO3/MeOH/H2O (yield 46%): 1H NMR
(DMSO-d6, 400 MHz) δ 9.62 (dd, J ) 13.5, 6.7 Hz, 1H), 8.00 (d,
J ) 14.2 Hz, 1H), 7.6-7.7 (m, 4H), 5.31 (d, J ) 6.2 Hz, 1H), 5.1
(m, 3H), 4.06 (dd, J ) 10.5, 5.1 Hz, 1H), 4.0 (m, 1H), 3.85 (d, J
) 2.9 Hz, 1H), 3.5-3.6 (m, 2H); 13C NMR (DMSO-d6, 100 MHz)
δ 192.2, 189.7, 150.9, 140.0, 139.9, 134.4 (2 carbons), 122.1, 121.7,
132.5, 132.1, 127.7, 127.4, 55.8, 42.8 (2 carbons), 27.9 (2 carbons);
ESI/APCI calcd for C15H15N4O2 ([M + H]+) m/e 283.1190;
+
measured m/e 283.1189.
2-(N-(ꢀ-D-Glucopyranosyl))aminomethylene-1,3-indanedi-
one (20a). Please refer to the general procedure for the deprotection
1
of acetyl groups using K2CO3/MeOH/H2O (yield 64%): H NMR
(CD3OD, 400 MHz) δ 8.00 (s, 1H), 7.74 (m, 4H), 4.61 (d, J ) 8.4
Hz, 1H), 3.90 (dd, J ) 12.0, 1.9 Hz, 1H), 3.72 (dd, J ) 12.0, 5.3
Hz, 1H), 3.4 (m, 4H); 13C NMR (CD3OD, 100 MHz) δ 193.1, 191.0,
151.2, 139.8, 139.7, 133.8, 133.7, 121.7, 121.3, 101.8, 88.8, 79.3,
77.1, 73.3, 69.8, 61.3; ESI/APCI calcd for C16H18NO7+ ([M + H]+)
m/e 336.1078; measured m/e 336.1088.
+
104.4, 94.2, 86.2, 75.9, 71.4, 61.9; ESI/APCI calcd for C15H16NO6
([M + H]+) m/e 306.0972; measured m/e 306.0976.
1-(Aminomethylene-1,3-indanedione)-1-dideoxy-D-mannitol
(20m). Please refer to the general procedure for the deprotection
of acetyl groups using K2CO3/MeOH/H2O (yield 40%): H NM-
1
2-(N-(ꢀ-D-Galactopyranosyl))aminomethylene-1,3-indanedi-
R(DMSO-d6, 300 MHz) δ 9.55 (s, 1H), 7.80 (s, 1H), 7.6 (m, 4H),
4.0-5.0 (m, 5H), 3.4-3.7 (m, 8H); 13C (DMSO-d6, 100 MHz) δ
190.2, 189.0, 154.4, 139.8 (2 carbons), 133.9 (2 carbons), 122.0 (2
carbons), 103.5, 71.8, 70.8, 70.0, 69.6, 64.6, 54.2; ESI/APCI calcd
for C16H20NO7+ ([M + H]+) m/e 338.1234; measured m/e 338.1246.
2-(N-(4-Piperidinyl))aminomethylene-1,3-indanedione (20n).
Compound 20n was prepared similarly as the preparation of 19n
one (20b). Please refer to the general procedure for the deprotection
1
of acetyl groups using K2CO3/MeOH/H2O (yield 53%): H NMR
(CD3OD, 400 MHz) δ 8.01 (s, 1H), 7.68 (m, 4H), 4.56 (d, J ) 8.6
Hz, 1H), 3.93 (d, J ) 2.8 Hz, 1H), 3.7-3.8 (m, 4H), 3.59 (dd, J )
9.5, 3.1 Hz, 1H); 13C NMR (CD3OD, 100 MHz) δ 193.2, 191.0,
151.2, 139.8, 139.7, 133.8, 133.7, 121.6, 121.3, 104.8, 89.4, 78.0,
74.0, 70.8, 69.3, 61.4; ESI/APCI calcd for C16H18NO7+ ([M + H]+)
m/e 336.1078; measured m/e 336.1085.
1
(yield 99%): H NMR (D2O, 300 MHz) δ 7.4 (m, 2H), 7.31 (s,
1H), 7.16 (td, J ) 4.5, 1.7 Hz, 1H), 7.06 (td, J ) 4.1, 1.4 Hz, 1H),
3.65 (tt, J ) 11.3, 3.8 Hz, 1H), 3.5 (m, 1H), 3.4 (m, 1H), 3.01 (td,
J ) 13.0, 2.7 Hz, 2H), 2.1 (m, 2H), 1.88 (dd, J ) 14.0, 4.1 Hz,
1H), 1.77 (dd, J ) 13.0, 4.1 Hz, 1H); 13C NMR (D2O, 100 MHz)
δ 193.5, 192.4, 151.0, 138.2 (2 carbons), 134.2, 134.0, 121.6, 121.2,
103.3, 54.6, 42.8 (2 carbons), 28.7 (2 carbons); ESI/APCI calcd
2-(N-(r-D-Rhamnopyranosyl))aminomethylene-1,3-indanedi-
one (20f). Please refer to the general procedure for the deprotection
1
of acetyl groups using K2CO3/MeOH/H2O (yield 39%): H NMR
(DMSO-d6, 400 MHz) δ 9.6 (m, 1H), 8.03 (d, J ) 6.0 Hz, 1H),
7.7 (m, 4H), 5.36 (d, J ) 5.3 Hz, 1H), 4.94 (s, 1H), 4.93 (d, J )
5.3 Hz, 1H), 4.86 (d, J ) 4.3 Hz, 1H), 3.8 (m, 1H), 3.2 (m, 3H),
1.18 (d, J ) 6.0 Hz, 3H); 13C NMR (DMSO-d6, 100 MHz) δ 193.3,
189.5, 151.8, 139.9, 134.5 (2 carbons), 122.2, 121.8 (2 carbons),
104.7, 85.6, 74.6, 73.9, 71.8, 70.6, 18.5; ESI/APCI calcd for
for C15H17N2O2 ([M + H]+) m/e 257.1285; measured m/e
+
257.1293.
Acknowledgment. We acknowledge the support from De-
partment of Chemistry and Biochemistry, Utah State University.
C16H18NO6 ([M + H]+) m/e 320.1129; measured m/e 320.1136.
+
2-(N-(r-D-Xylopyranosyl))aminomethylene-1,3-indanedione
1
Supporting Information Available: H, 13C, and related
(epi-20g). Please refer to the general procedure for the deprotection
1
of acetyl groups using K2CO3/MeOH/H2O (yield 35%): H NMR
spectra of the synthesized compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
(CD3OD, 300 MHz) δ 8.10 (s, 1H), 7.7 (m, 4H), 5.09 (d, J ) 2.4
Hz, 1H), 3.95 (dd, J ) 12.0, 2.8 Hz, 1H), 3.81 (t, J ) 5.5 Hz, 1H),
3.6-3.7 (m, 2H), 3.5 (m, 1H); 13C NMR (CD3OD, 75 MHz) δ
JO8020133
J. Org. Chem. Vol. 74, No. 2, 2009 695