Synthesis of peracetylated C-1-deoxyalditol- and C-glycoside-dipyrranes via dithioacetal derivatives

Article abstract of DOI:10.1016/j.tetlet.2012.12.048

Dipyrranes bearing peracetylated mono- or disaccharidic C-1-deoxyalditol moieties were prepared from d-galactose, d-glucose, d-mannose, and lactose. A partially hydrolyzed polysaccharide (agarose) was also used as starting material for the synthesis of a disaccharide-containing C-glycoside dipyrrane. These compounds were synthesized as follows: the sugar starting materials were first submitted to a mercaptolysis-acetylation one-pot procedure (EtSH/HCl-Ac ₂O/pyridine). The resulting peracetylated diethyl dithioacetals were converted into dipyrranes through carbonyl deprotection (H₅IO ₆, THF-Et₂O) followed by TFA-catalyzed pyrrole condensation with yields up to 62%. Overall yields from sugar starting materials were up to 49%.

Full text of DOI:10.1016/j.tetlet.2012.12.048

Tetrahedron Letters 54 (2013) 1137–1140
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of peracetylated C-1-deoxyalditol- and C-glycoside-dipyrranes via
dithioacetal derivatives
Stephanie M. S. Ló a, Juliana C. Cunico a, Diogo R. B. Ducatti b, Alexandre Orsato b, M. Eugênia R. Duarte b,
Sandra M. W. Barreira a, Miguel D. Noseda b, Alan G. Gonçalves a,
⇑
a Departamento de Farmácia, Universidade Federal do Paraná, Av. Lothario Meissner, 3400, Jardim Botânico, Curitiba, Paraná, Brazil
b Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, PO Box 19046, Curitiba, Paraná, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
Dipyrranes bearing peracetylated mono- or disaccharidic C-1-deoxyalditol moieties were prepared from
Received 20 November 2012
Revised 14 December 2012
Accepted 17 December 2012
Available online 21 December 2012
D
-galactose, D-glucose, D-mannose, and lactose. A partially hydrolyzed polysaccharide (agarose) was also
used as starting material for the synthesis of a disaccharide-containing C-glycoside dipyrrane. These
compounds were synthesized as follows: the sugar starting materials were first submitted to a mercap-
tolysis–acetylation one-pot procedure (EtSH/HCl–Ac2O/pyridine). The resulting peracetylated diethyl
dithioacetals were converted into dipyrranes through carbonyl deprotection (H5IO6, THF–Et2O) followed
by TFA-catalyzed pyrrole condensation with yields up to 62%. Overall yields from sugar starting materials
were up to 49%.
Keywords:
Dipyrranes (dipyrromethanes)
C-Glycosides
Ó 2012 Published by Elsevier Ltd.
Dithioacetals
Agarose
Porphyrin glycoconjugates
Porphyrin glycoconjugates have become of interest because of
the current effort to develop target-specific photosensitizers, which
are particularly promising in the photodynamic therapy for cancer.1
Considering both chemical and enzymatic stabilities of glycopor-
phyrins, synthetic strategies that lead to a carbon–carbon bond link-
ing the carbohydrate moiety to the porphyrin ring are highly
desirable. In this context, dipyrranes (dipyrromethanes)2 prepared
from partially protected 1-hydroxy aldoses3,4 and C-glycosyl alde-
hydes5 are important building blocks for the synthesis of meso-
substituted C-1-deoxyalditol- and C-glycoside-porphyrins. In the
case of the C-1-deoxyalditol derivatives, the use of the correspond-
ing carbohydrate-containing dipyrranes can be indispensable for
porphyrin synthesis.3 In previous works dedicated to the synthesis
of the aforementioned dipyrranes, only monosaccharides, such as,
starting materials, such as algal galactans, which often present
synthetically useful unique structural motifs.7–9
As one of our future objectives involves glycoporphyrin
synthesis from diverse carbohydrate sources, the present work
was devoted to the development of a general strategy for the prep-
aration of dipyrranes from mono-, oligo-, and polysaccharides.
Reactions based on mercaptolysis using EtSH/HCl reactant have
proven to be efficient for the preparation of protected aldehydes
as diethyl dithioacetals from monosaccharides.10,11 More recently,
a multigram production of diethyl dithioacetals containing the rare
residue of 3,6-anhydro-L-galactose was performed using commer-
cial agarose as starting material.8 Here, unmasked aldehydes
obtained from peracetylated diethyl dithioacetals were condensed
with pyrrole to produce mono- and disaccharide C-1-deoxyalditol-
and C-glycoside-dipyrranes (Table 1). This synthetic strategy was
evaluated in terms of its applicability by employing three mono-
D
-glucose, D-galactose, D- and L-arabinose, D-xylose, and D-gulose
have already been utilized as starting materials.3–5 This could be
one of the reasons for the lack of oligosaccharide-containing C-1-
deoxyalditol- or C-glycoside-porphyrins examples in the literature.
The presence of higher sugar moieties in glycoconjugates is consid-
ered important for the anticipated biological activity and targeting.
This is based on the fact that oligosaccharide glycoconjugates have
superior binding constants toward carbohydrate-binding proteins
than do the monosaccharide ones.6 Furthermore, dipyrrane syn-
thetic routes known to date are not suitable for the use of unusual
saccharides (D-galactose 1, D-glucose 2 and D-mannose 3), a disac-
charide (lactose 4), and a polysaccharide (agarose 5) as starting
materials.
In order to synthesize the peracetylated diethyl dithioacetals
shown in Table 1, we developed a one-pot procedure12 that
combines mercaptolysis (EtSH/HCl) and acetylation (Ac2O/pyri-
dine) to produce 6,13 13, and 813 from monosaccharides 1, 2, and
7
3, respectively. These reactions were performed by adding the
acetylating mixture directly into mercaptolysis reaction after its
completion (monitored by TLC analysis). The same approach also
provided the lactose-derivative peracetylated dithioacetal 9.14
⇑
Corresponding author. Tel.: +55 41 33604065; fax: +55 41 33604101.
E-mail address: alan.goncalves@pq.cnpq.br (A.G. Gonçalves).
0040-4039/$ - see front matter Ó 2012 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2012.12.048

Table 1
Synthesis of dipyrranes from sugar starting materials 1–5
R
S
One-pot:
R
sugar
starting material
1. H5IO6, THF-Et2O
2. Pyrrole, TFA
N
H
1. Mercaptolysis
2. Ac2O, pyridine
S
NH
Entry
1
Starting material
Mercaptolysis (Time)a (min)
Peracetylated diethyl dithioacetalb (Yield)c
Dipyrrane (Yield)d
OAc OAc
Overall yield (%)
OH
OAc OAc
O
HO
S
AcO
AcO
AcO
AcO
N
H
OH
30
24
RO
OH
AcO
AcO
AcO
AcO
OAc
OAc
S
NH
1
2
12 (59%)
13 (50%)
14 (50%)
6 (41%)
7 (98%)
8 (95%)
OH
OAc
OAc OAc
OAc
OAc
O
HO
S
S
N
H
AcO
AcO
OH
2
3
180
49
48
HO
OH
OAc
S
OAc
NH
OH
OAc
OAc OAc
OAc
OAc
O
HO
N
H
OH
70
HO
OH
OAc S
OAc
AcO
NH
3
O
OH
OH
AcO
HO
AcO
AcO
AcO
AcO
AcO
AcO
AcO
AcO
O
O
O
O
HO
OH
HO
OH
OH
O AcO
OAc
O AcO
4
240
22
4
S
N
H
AcO
AcO
OAc
S
NH
15 (33%)
16 (62%)
9 (67%)
OH
O
OAc
OAc
H
H
O
O
S
N
H
O
S
O
O
NH
AcO
AcO
O
O
HO
5
60
29
O
O
AcO
AcO
AcO
AcO
HO
OH
OAc
OAc
O
n
5
OAc
OAc
10 (46%)
a
b
c
Mercaptolysis conditions: HCl/EtSH, 0 °C; for agarose (5, entry 5) a partial hydrolysis (1 M TFA, 3 h, 80 °C) was performed before the mercaptolysis step.
Acetylation conditions: Ac2O/pyridine, 18 h, rt.
Isolated yields calculated from starting materials 1–5.
Isolated yields calculated from peracetylated diethyl dithioacetals 6–10.
d

S. M. S. Ló et al. / Tetrahedron Letters 54 (2013) 1137–1140
1139
Table 2
For agarose (5), a TFA-mediated partial hydrolysis was neces-
sary before the mercaptolysis step. Agarose is a polysaccharide
constituted by 3-linked b- -Galp and 4-linked 3,6-An- -Galp
Synthesis of dipyrrane 12 through pyrrole–aldehyde 11 condensationa
D
a-L
Entry Temperature (°C) Atmosphere Aldehyde purification Yield (%)
alternating units, where the glycosidic bonds of the 3,6-anhydrog-
alactopyranosyl units are significantly more acid-labile than the
galactopyranosidic ones.7,8 Under the specific hydrolysis condi-
tions here utilized, disaccharide agarobiose was then preferentially
formed, which resulted in the peracetylated dithioacetal 108 after
mercaptolysis–acetylation one-pot reaction.
1
2
3
4
5
6
7
50
30
0
50
30
30
0
Air
Air
Air
Argon
Argon
Argon
Argon
Extractionb
Extractionb
Extractionb
Extractionb
Extractionb
Chromatographyd
Extractionb
27c
30c
40c
56c
59c
35c,e
40c
Table 1 also shows the differences in the mercaptolysis reaction
time, accordingly to the starting material employed. For example,
mercaptolysis step of 1 had to be interrupted after 30 min, while
reaction time for the other starting materials was at least one hour
long. As previously noted,11 the mercaptolysis reaction mixture of
1 became solid in a few minutes, preventing the starting material
to be completely consumed. Even though the yield obtained for 6
was consequently lower than for 7–10 (Table 1), we took advan-
tage of the distinct behavior of the galactose derivative to prepare
a
b
c
Conditions: aldehyde/pyrrole 1:25, TFA 0.1 equiv, 30 min, solvent-free.
Concentrated chloroform extracts from periodic acid reaction.
Isolated yield for dipyrrane 12 calculated from diethyl dithioacetal 6.
Silica-gel column chromatography of the concentrated chloroform extracts.
60% (aldehyde 11 yield) and 58% (dipyrrane 12 yield).
d
e
b
important for the success of the more straightforward procedure.
In this way, aldehyde–pyrrole condensation conditions were de-
fined in accordance to entry 5 of Table 2.
grams of the hydroxyl-unprotected
D-galactose dithioacetal by
General procedure18 for peracetylated dithioacetals conversion
into dipyrranes (Scheme 1) was also applied to compounds 7–10
to give dipyrranes 13–16, as shown in Table 1. Lactose-derivative
dipyrrane 15 was obtained with a lower yield (33%) in comparison
to the monosaccharide ones (50–59%). However, despite the disac-
charide nature of dipyrrane 16, it presented the highest yield
among all dipyrranes here prepared (62%). This result is consistent
with the C-glycoside-aldehyde being more reactive than the aldi-
tol-aldehydes toward dipyrrane formation. This observation is also
based on the fact that the periodic acid reaction gives about the
same aldehyde yield from either 6 or 10.9
using a crystallization-based purification11 instead of the use of
column chromatography (see Supplementary data).
In order to synthesize dipyrranes from the peracetylated diethyl
dithioacetals, we applied a previously stated8,15 deprotection of
carbonyl of dithioacetal derivatives with periodic acid at 0 °C in
THF–Et2O (first step of Scheme 1 reaction). This procedure over-
comes the use of toxic heavy metal salts that are traditionally em-
ployed in this type of reaction.16
Dipyrrane synthesis was then evaluated using aldehyde 1110,11
as substrate (Table 2 and second step of Scheme 1 reaction). For
these experiments, all condensation reactions were conducted
with excess of pyrrole (1:25, aldehyde/pyrrole) in the presence of
TFA under solvent-free conditions,17 for 30 min. Because dipyrr-
anes easily subside to oxidation after its formation, condensation
reaction was evaluated in terms of reaction temperature and pres-
ence of inert atmosphere. This brief study indicated that the pres-
ence of argon atmosphere was essential for reaching fair yields (in
Table 2, compare entries 2 and 5). Considering the reaction tem-
peratures evaluated in entries 1, 2, and 3 (Table 2), even though
the yields increased by the lowering the temperature, the best
yields were reached at higher temperatures when using argon
atmosphere (Table 2, entries 4, 5, and 7). These results suggest that
the inert atmosphere prevented dipyrrane temperature-mediated
degradation.
Sugar-derived aldehydes can be unstable and also cause diffi-
culties during column chromatography. For this reason, most of
the condensation conditions evaluated in Table 2 were performed
using the aldehyde obtained in the vacuum-dried chloroform ex-
tracts of the periodic acid reaction, without further purification.
Conditions defined in entry 5 were then reassessed by using a
chromatographically purified sample of aldehyde 11 (Table 2, en-
try 6). This comparison (Table 2, entries 5 and 6) demonstrated
that the yield obtained when using the extracted aldehyde (calcu-
lated from peracetylated dithioacetal 6) was higher than that
involving an extensively purified sample of aldehyde 11. This could
be explained by losses during the chromatographic procedure. We
also noted that the immediate use of the extracted aldehyde was
In terms of stability, dipyrranes 12–16 appeared to be indefi-
nitely stable when stored in freezer at ꢀ5 °C. During NMR experi-
ments, we also noted that dipyrranes were quite stable in
deuterated DMSO solution for, at least, 2 days at room tempera-
ture. On the other hand, when employing CDCl3, the originally pale
yellow solutions became dark gray in a few hours.
There are only two examples of acetyl protected C-1-deoxyald-
itol dipyrranes described to date in the literature, being both of
them synthesized by reacting SnCl4/pyrrolylmagnesium-bromide
(1:1) with peracetylated aldoses to give dipyrranes in 35–45%
yield.4 When using protecting groups other than acetyl (benzyl,
isopropylidene, or methyl) the same type of dipyrranes were ob-
tained in yields up to 42% from acid-catalyzed pyrrole condensa-
tion with partially protected 1-hydroxy aldoses.3,4 In all cases,
the given yields were always calculated from the hydroxyl-pro-
tected building block and not from the raw sugar starting material.
Independently of the protecting group, the C-1-deoxyalditol
dipyrranes previously reported3,4 presented one free hydroxyl
group, which was originated from the position involved in the ring
closure of the parent pyranoses or furanoses. In contrast, dipyrr-
anes herein synthesized are fully hydroxyl-protected with acetyl
groups and the yields obtained in dithioacetals conversion into
dipyrromethanes were considerably higher than the previously re-
ported strategies for dipyrrane synthesis.
By observing the peracetylated dipyrrane structures depicted in
Table 1, it is noteworthy that the monosaccharide-derivatives
12–14 represent examples of C-1-deoxyalditol dipyrranes, while
compound 15 corresponds to a C-1-deoxyalditol dipyrrane linked
to a galactopyranose unit through an O-glycosidic bond. Differ-
ently, the agarose-derivative dipyrrane 16 constitutes a strict
H
OAc OAc
N
H5IO6
THF-Et2O, 0 o
O
, TFA
example of a C-glycoside where a b-
linked to the dipyrryl unit through a C-glycosidic linkage. The
b- -threofuranosyl unit was originated from the fivemembered
L-threofuranose residue is
AcO
12
6
Argon, 30 oC
C
AcO
OAc
11
L
ring of the 3,6-anhydrogalactopyranosyl units present in agarose
structure. In conclusion, we established the use of dithioacetal
intermediates to synthesize dipyrranes containing a carbohydrate
(extracted and used)
Scheme 1. Conversion of diethyl dithioacetal 6 into dipyrrane 12.

1140
S. M. S. Ló et al. / Tetrahedron Letters 54 (2013) 1137–1140
17. (a) Lee, C.-H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427; (b) Littler, B. J.; Miller,
M. A.; Hung, C. H.; Wagner, R. W.; O’Shea, D. F.; Boyle, P. D.; Lindsey, J. S. J. Org.
Chem. 1999, 64, 1391–1396.
moiety attached to the dipyrryl unit through a carbon–carbon
bond. This approach allows the use of diverse carbohydrates as
starting materials. Dipyrranes 12–16 are currently being employed
for the synthesis of C-1-deoxyalditol- and C-glycoside-meso-
substituted-porphyrins in our laboratories.
18. To
a cooled (0 °C), stirred mixture of peracetylated diethyl dithioacetal
(1 mmol), THF (2 mL), and Et2O (5 mL), a solution of H5IO6 (2 mmol) in THF
(1 mL) was added drop wise. The resulting mixture was warmed to room
temperature, stirred for 20 min (60 min for 9), diluted with 0.1 M phosphate
buffer, and then extracted with CHCl3. The organic phase containing the freshly
prepared aldehyde was washed with 10% aqueous Na2SO3 solution, dried
(Na2SO4), and concentrated. Pyrrole (25 mmol) and TFA (0.1 mmol) were then
added to the concentrated extract and the resulting mixture was stirred for
30 min under Argon (see details in Supplementary data). Reaction mixture was
then quenched with 0.1 M NaOH and extracted with chloroform. The organic
phase was washed with water, dried over Na2SO4, concentrated under vacuum,
and purified by flash chromatography with ethyl acetate/hexanes as mobile
phase (5:7 for compounds 12–14, 2:1 for 15 and 1:1 for 16).
Acknowledgments
The authors are thankful to Fundação Araucária (15152) and
PRONEX-Carboidratos (14669) for financial support. S.M.S.L.
and A.O. thank the scholarships from REUNI program. M.E.R.D.
and M.D.N. are Research Members of the National Research Council
of Brazil (CNPq). The authors are indebted to Professor Marcelo
Muller dos Santos, M.Sc. Samuel Habib and Dr. Peter Goekjian for
high resolution ESI mass experiments.
Compound 12: ½a 2D2
ꢁ
+12.0 (c 0.5 , CHCl3); 1H NMR (400 MHz, CDCl3) d = 8.52 (b,
1H, NH), 8.26 (b, 1H, NH0), 6.71 (b, 1H, H-1 pyrrole), 6.68 (b, 1H, H-10 pyrrole),
6.13 (b, 1H, H-2 pyrrole), 6.12 (b, 1H, H-20 pyrrole), 6.05 (b, 1H, H-3 pyrrole),
6.02 (b, 1H, H-30 pyrrole), 5.49–5.40 (m, 2H, H-2, H-3), 5.27 (dd, J = 9.5, 1.0 Hz,
1H, H-4), 5.24–5.18 (m, 1H, H-5), 4.32 (d, J = 6.6 Hz, 1H, H-1), 4.27 (dd, J = 11.8,
4.7 Hz, 1H, H-6a), 3.79 (dd, J = 11.8, 7.5 Hz, 1H, H-6b), 2.09, 2.01, 2.01, 2.00,
1.91 (5s, 15H, COCH3). 13C NMR (101 MHz, CDCl3) d = 171.1, 170.6, 170.4,
170.0, 169.9 (5C, C@O), 128.7 (1C, C-4 pyrrole), 127.4 (1C, C-40 pyrrole), 117.9
(1C, C-1 pyrrole), 117.6 (1C, C-10 pyrrole),108.8 (1C, C-2, pyrrole), 108.6 (1C, C-
3 pyrrole), 108.4 (2C, C-20 pyrrole), 106.8 (1C, C-30 pyrrole), 71.7 (1C, C-2), 68.9
(1C, C-3), 68.3 (1C, C-4), 67.9 (1C, C-5), 62.4 (1C, C-6), 39.8 (1C, C-1), 20.9, 20.8,
20.8, 20.7, 20.7 (5C, COCH3). HRMS (ESI): m/z calcd for C24H30N2O10Na+:
529.1793; found: 529.1779.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.12.
048.
Compound 13: ½a 2D2
ꢁ
ꢀ15.9 (c 1.0 , DMSO); 1H NMR (400 MHz, DMSO) d = 10.49
References and notes
(b, 1H, NH), 10.39 (b, 1H, NH0), 6.62 (d, J = 1.6 Hz, 1H, H-1 pyrrole), 6.58 (d,
J = 1.6 Hz, 1H, H-10 pyrrole), 5.95–5.86 (m, 4H, H-2, H-20, H-3, H-30 pyrrole),
5.43 (dd, J = 7.3, 5.2 Hz, 1H, H-2), 5.20 (dd, J = 6.2, 4.8 Hz, 1H, H-4), 5.00–4.91
(m, 2H, H-3, H-5), 4.27 (d, J = 7.4 Hz, 1H, H-1), 4.10 (dd, J = 12.2, 3.1 Hz, 1H, H-
6a), 4.06–3.99 (m, 1H, H-6b), 2.05 2.00, 1.99, 1.89, 1.88 (5s, 15H, COCH3). 13C
NMR (101 MHz, DMSO) d = 170.0, 169.6, 169.3, 169.1, 169.0 (5C, C@O), 128.7
(1C, C-4 pyrrole), 128.4 (1C, C-40 pyrrole), 117.2 (1C, C-1 pyrrole), 117.0 (1C, C-
10 pyrrole), 107.3, 106.9, 106.6, 105.6 (4C, C-2, C-3, C-20, C-30 pyrrole), 72.3 (1C,
C-2), 69.2 (1C, C-3), 68.7 (1C, C-4), 68.6 (1C, C-5), 60.9 (1C, C-6), 38.9 (1C, C-1),
20.4–20.3 (5C, COCH3). HRMS (ESI): m/z calcd for C24H30N2O10Na+: 529.1793;
found: 529.1768.
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Compound 14: ½a 2D2
ꢁ
+19.5 (c 1.0 , DMSO); 1H NMR (400 MHz, DMSO) d = 10.64
(b, 1H, NH pyrrole), 10.34 (b, 1H, NH0 pyrrole), 6.63 (b, 1H, H-1 pyrrole), 6.55 (d,
J = 1.2 Hz, 1H, H-10 pyrrole), 5.98–5.88 (m, 2H, H-2, H-3 pyrrole), 5.88–5.79 (m,
2H, H-20, H-30 pyrrole), 5.56 (dd, J = 8.7, 5.7 Hz, 1H, H-2), 5.42 (d, J = 8.4 Hz, 1H,
H-4), 4.95–4.84 (m, 2H, H-3, H-5), 4.34 (d, J = 8.8 Hz, 1H, H-1), 4.08 (dd, J = 12.4,
2.6 Hz, 1H, H-6a), 4.04–3.97 (m, 1H, H-6b), 2.07, 1.99, 1.89, 1.82, 1.82 (5s, 15H,
COCH3). 13C NMR (101 MHz, DMSO) d = 170.0, 169.5, 169.2, 169.2, 169.2 (5C,
C@O), 129.1 (1C, C-4 pyrrole), 128.5 (1C, C-40 pyrrole), 117.4 (1C, C-1 pyrrole),
116.9 (1C, C-10 pyrrole), 107.2 (1C, C-2 pyrrole), 106.9 (1C, C-20 pyrrole), 106.0
(1C, C-3 pyrrole), 105.8 (1C, C-30 pyrrole), 72.0 (1C, C-2), 68.8 (1C, C-3), 67.7
(1C, C-5), 66.6 (1C, C-4), 61.3 (1C, C-6), 38.9 (1C, C-1), 20.7, 20.5, 20.4, 20.4, 20.4
(COCH3). HRMS (ESI): m/z calcd for C24H30N2O10Na+: 529.1793; found:
529.1773.
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Compound 15: ½a 2D2
ꢁ
ꢀ6.51 (c 0.3 , DMSO); 1H NMR (400 MHz, DMSO) d = 10.31
12. Mercaptolysis–acetylation one-pot procedure: sugar starting material 1–4 (or
agarose 5 hydrolyzate) was dissolved to a concentration of 40 g% in a mixture
of conc HCl (37%)/EtSH (3:2, v/v) at 0 °C. Mercaptolysis was kept at 0 °C for
different reaction times, accordingly to the starting material (see Table 1). The
resulting mixture was then directly added of 22 volumes (in relation to HCl/
EtSH volume) of pyridine/acetic anhydride (6:5, v/v). Reaction was stirred at
0 °C for an hour and then kept at room temperature for 18 h. Ice water was
added to the reaction mixture and the product was extracted with CHCl3. The
organic phase was washed with 5% aqueous CuSO4 solution and then water,
dried over Na2SO4 and concentrated. The residue was purified by flash column
chromatography on silica gel using ethyl acetate/hexanes as mobile phase (1:3
for compounds 6–8, 2:3 for 9 and 1:1 for 10).
(b, 1H, NH), 10.27 (b, 1H, NH0), 6.62 (b, 1H, H-1 pyrrole), 6.55 (b, 1H, H-10
pyrrole), 5.97–5.85 (m, 4H, H-2, H-3, H-20, H-30 pyrrole), 5.56 (t, J = 6.0 Hz, 1H,
H-2), 5.24 (d, J = 3.5 Hz, 1H, H-40), 5.18 (dd, J = 9.5, 3.5 Hz, 1H, H-30), 5.01–4.95
(m, 1H, H-5), 4.93–4.82 (m, 3H, H-3, H-10, H-20), 4.40 (d, J = 6.8 Hz, 1H, H-1),
4.25 (t, J = 6.5 Hz, 1H, H-50), 4.14 (dd, J = 12.0, 2.5 Hz, 1H, H-6a0), 4.08 (t,
J = 4.8 Hz, 1H, H-4), 4.05–3.89 (m, 3H, H-6a, H-6b, H-6b0), 2.13, 2.00, 1.98, 1.97,
1.97, 1.97, 1.91, 1.89 (8s, 24H, COCH3). 13C NMR (101 MHz, DMSO) d = 170.0,
169.9, 169.8, 169.5, 169.4, 169.1, 169.1, 168.8 (8C, C@O), 129.0 (1C, C-4
pyrrole), 128.4 (1C, C-40 pyrrole), 117.2 (1C, C-1 pyrrole), 116.8 (1C, C-10
pyrrole), 107.2, 106.9, 106.8 (3C, C-2, C-20, C-3 pyrrole), 105.2 (1C, C-30 pyrrole),
99.8 (1C, C-10), 75.8 (1C, C-4), 72.4 (1C, C-2), 70.4 (1C, C-30), 70.1, 69.9 (2C, C-5,
C-50), 69.9 (1C, C-3), 69.0 (1C, C-20), 67.2 (1C, C-40), 61.1 (2C, C-6, C-60), 38.3 (1C,
C-1), 20.5, 20.5, 20.4, 20.4, 20.3, 20.3, 20.3, 20.3 (8C, COCH3). HRMS (ESI): m/z
calcd for C36H46N2O18Na+: 817.2638; found: 817.2648.
13. Khan, A. T.; Khan, M. M. Carbohydr. Res. 2010, 335, 21392145.
14. Compound 9: ½a D22
ꢁ
+29.7 (c 1.0, DMSO); 1H NMR (400 MHz, CDCl3) d = 5.76 (dd,
J = 5.7, 4.5 Hz, 1H, H-3), 5.48 (t, J = 5.3 Hz, 1H, H-2), 5.39 (d, J = 3.4 Hz, 1H, H-40),
5.24–5.17 (m, 1H, H-5), 5.14 (dd, J = 10.3, 7.9 Hz, 1H, H-20), 5.02 (dd, J = 10.5,
3.5 Hz, 1H, H-30), 4.75 (d, 1H, J = 7.8 Hz, H-10), 4.47 (dd, J = 12.4, 2.8 Hz, 1H, H-
6a), 4.25 (t, J = 4.6 Hz, 1H, H-4), 4.21–4.09 (m, 4H, H-1, H-6b, H-6a0, H-6b0), 3.92
(t, J = 6.8 Hz, 1H, H-50), 2.79–2.62 (m, 4H, CH2CH3), 2.15, 2.10, 2.09, 2.07, 2.07,
2.06, 2.06, 1.98 (8s, 24H, COCH3), 1.26 (dd, J = 14.1, 7.2 Hz, 6H, CH2CH3). 13C
NMR (101 MHz, CDCl3) d = 170.5, 170.4, 170.1, 170.1, 169.8, 169.7, 169.7, 169.2
(8C, C@O), 100.5 (1C, C-10), 75.4 (1C, C-4), 72.4 (1C, C-2), 71.2 (2C, C-3, C-50),
71.0 (2C, C-5, C-30), 69.1 (1C, C-20), 67.0 (1C, C-40), 62.1 (1C, C-6), 61.4 (1C, C-60),
51.3 (1C, C-1), 25.5, 24.8 (2C, CH2CH3), 20.8 (8C, COCH3), 14.4 (2C, CH2CH3).
HRMS (ESI): m/z calcd for C32H48O18S2Na+: 807.2174; found: 807.2183.
15. Shi, X.-X.; Khanapure, S. P.; Rokach, J. Tetrahedron Lett. 1996, 37, 4331–4334.
16. (a) Wolfrom, M. L.; Konigsberg, M.; Weisblat, D. I. J. Am. Chem. Soc. 1939, 61,
Compound 16: ½a 2D2
ꢁ
+16.4 (c 1.0 , DMSO); 1H NMR (400 MHz, CDCl3) d = 8.47 (b,
1H, NH), 8.44 (b, 1H, NH0), 6.64 (b, 2H, H-1, H-10 pyrrole), 6.13–6.02 (m, 4H, H-
2, H-3, H-20, H-30 pyrrole), 5.67 (dd, J = 8.5, 3.7 Hz, 1H, H-2), 5.39 (d, J = 3.1 Hz,
1H, H-40), 5.13 (dd, J = 10.4, 7.9 Hz, 1H, H-20), 5.00 (dd, J = 10.4, 3.4 Hz, 1H, H-
30), 4.94 (d, J = 4.2 Hz, 1H, H-4), 4.60 (d, J = 7.9 Hz, 1H, H-10), 4.53 (d, J = 8.5 Hz,
1H, H-1), 4.20 (dd, J = 11.4, 6.0 Hz, 1H, H-6a0), 4.13 (dd, J = 11.7, 6.7 Hz, 1H, H-
6b0), 3.98–3.91 (m, 3H, H-5, H-6a, H-50), 3.91–3.84 (m, 2H, H-3, H-6b), 2.14,
2.06, 2.03, 1.96, 1.96, 1.91 (6s, 18H, COCH3). 13C NMR (101 MHz, CDCl3)
d = 170.9, 170.6, 170.3, 170.2, 170.0, 169.6 (6C, C@O), 128.9 (1C, C-4 pyrrole),
128.6 (1C, C-40 pyrrole), 117.4 (2C, C-1, C-10 pyrrole), 108.7 (1C, C-2 pyrrole),
108.3 (1C, C-20 pyrrole), 107.4 (1C, C-3 pyrrole), 106.7 (1C, C-30 pyrrole), 101.6
(1C, C-10), 85.6 (1C, C-5), 83.6 (1C, C-3), 79.7 (1C, C-4), 73.3 (1C, C-2), 71.1 (1C,
C-50), 71.1 (1C, C-6), 70.8 (1C, C-30), 68.8 (1C, C-20), 67.3 (1C, C-40), 61.5 (1C, C-
60), 39.5 (1C, C-1), 21.0, 20.9, 20.6, 20.6, 20.6, 20.6 (6C, COCH3). HRMS (ESI): m/z
calcd for C32H40N2O15Na+: 715.2321; found: 715.2300.
´
574–576; (b) Miljkovic, M.; Dropkin, D.; Hagel, P.; Habash-Marino, M.
Carbohydr. Res. 1984, 128, 11–20.