Synthesis of Glycosyl Amides Using Selenocarboxylates as Traceless Reagents for Amide Bond Formation

Article abstract of DOI:10.1021/acs.joc.6b00832

Carbohydrate-derived amides were successfully prepared in good yields from a broad range of substrates, including furanosyl and pyranosyl derivatives. The methodology successfully relied on the in situ generation of lithium selenocarboxylates from Se/LiEt₃BH and acyl chlorides or carboxylic acids and their reaction with sugar azides. A key aspect of the present protocol is that we start from elemental selenium; isolation and handling of all reactive and sensitive selenium-containing intermediates is avoided, therefore providing the selenocarboxylate the status of a traceless reagent.

Full text of DOI:10.1021/acs.joc.6b00832

Subscriber access provided by UNIV OF NEBRASKA - LINCOLN
Article
Synthesis of Glycosyl Amides Using Selenocarboxylates
as Traceless Reagents for Amide-bond Formation
Luana Silva, Ricardo F Affeldt, and Diogo S. Lüdtke
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00832 • Publication Date (Web): 08 Jun 2016
Downloaded from http://pubs.acs.org on June 10, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Synthesis of Glycosyl Amides Using Selenocarboxylates as Traceless Reagents
for Amide-bond Formation
8
9
Luana Silva, Ricardo F. Affeldt, and Diogo S. Lüdtke*
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Instituto de Química, Universidade Federal do Rio Grande do Sul, UFRGS, Av. Bento Gonçalves 9500,
91501ꢀ970, Porto Alegre, RS, Brazil.
email: dsludtke@iq.ufrgs.br
Phone: +55 51 3308 9637
Abstract. Carbohydrateꢀderived amides were successfully prepared in good
yields from a broad range of substrates, including furanosyl and pyranosyl derivatives.
The methodology successfully relied on the in situ generation of lithium
selenocarboxylates, from Se/LiEt3BH and acyl chlorides or carboxylic acids and their
reaction with sugar azides. A key aspect of the present protocol is that we start from
elemental selenium and isolation and handling all reactive and sensitive seleniumꢀ
containing intermediates is avoided, therefore rendering to the selenocarboxylate the
status of a traceless reagent.
Keywords: amidation, selenium reagents, glycosyl amides
Graphical Abstract:
1
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 35
1
2
3
Introduction
4
5
6
7
8
9
The amide functional group is one of the most important chemical linkage and is
the key connection between amino acids in peptides and proteins. Beyond this well
known role, amides are also present in some of the most important synthetic polymers,
and in a number of pharmaceutical active ingredients.1 The glycosyl amide linkage is an
important connection found in nature, since it is one of the ways in which a sugar unit
can be found attached to other biomolecules and natural products such as Nꢀ
glycosides,2 Nꢀglycopeptides,3 lipopolysaccharides,4 and ceramides.5 Nꢀglycosyl amides
and glycopeptides are known for possessing a wide range of bioactivities, mainly
because these class of carbohydrate derivatives can bind efficiently to specific sites of
proteins6 and are important scaffolds on glycobiology studies.7
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In the context of amide bond formation, several methods have been described.8
Whilst most of them involve the activation of a carboxylic acid with coupling reagents
followed by the reaction with an amine, alternative methods have appeared in the
literature.9 Recent systems include the coupling of amines with carboxylic acids,
promoted by boron compounds,10 αꢀketoacidꢀhydroxylamine reactions11 and Ruꢀ
catalyzed oxidative coupling of alcohols and amines.12 More specifically related to
carbohydrate chemistry, a common method is the Staudinger reaction,13 in which a
glycosyl azide reacts with diphenylphospanylꢀphenyl esters,14 whose main advantage is
to avoid anomeric equilibration, in contrast to catalytic hydrogenation of the glycosyl
azide, followed by acylation procedures that are limited to βꢀglycosyl amides.15
In connection with our current interest on the development of new strategies using
selenium chemistry for the functionalization of carbohydrate derivatives, we sought to
develop an efficient synthesis of glycosyl amides. In order to reduce our plan to practice,
we planned to use a reaction between a selenocarboxylate and a carbohydrateꢀderived
2
ACS Paragon Plus Environment

Page 3 of 35
The Journal of Organic Chemistry
1
2
3
azide. The reaction of selenocarboxylates with azides is a more reactive variation of the
4
5
thioacidꢀazide ligation (Scheme 1, A).16
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1
Precedents can be found in the literature for the reaction of potassium
selenobenzoate with electron deficient azides such as aryl azides bearing electron
withdrawing groups and sulfonyl azides (Scheme 2, B).17,18 More electronꢀrich azides,
particularly alkyl derivatives have only resulted in significantly decreased yields or
recovery of unreacted starting material. One major drawback that hampers further use of
potassium selenobenzoate for amidations is need for isolation of the selenium salt. An
improvement of this protocol was introduced by Hu (Scheme 1, C),19 by the in situ
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 35
1
2
3
4
5
generation of the reactive selenocarboxylate by the reaction of acyl chlorides with
LiAlHSeH (Ishihara reagent20). Our initial attempt to use this protocol for the amidation of
6
7
Dꢀxyloseꢀderived azide 2, didn´t furnish the desired product 3 leading to decomposition
8
9
and partial recovery of unreacted azide 2 (Scheme 1, D).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Therefore, we have decided to reinvestigate this reaction and develop a more
efficient, oneꢀpot protocol, in which we could avoid the isolation and manipulation of
reactive compounds containing selenium. Our plan was to start with the reduction of
elemental selenium, to generate a nucleophilic Se2ꢀ species that would react with an
activated carboxylic acid derivative (e.g. acyl chloride), generating in situ the desired
selenocarboxylate. Introduction of the appropriate sugarꢀbased azide in the reaction
mixture would trigger a cycloadditionꢀtype reaction leading to a selenoꢀtriazoline
intermediate, whose decomposition would generate the desired glycosyl amide,
alongside with harmless gaseous nitrogen and elemental selenium as byꢀproducts
(Scheme 2). The overall transformation should not require the manipulation of any
selenium intermediates and the selenocarboxylate might be therefore considered as a
traceless reagent promoting the amide bond formation.
Scheme 2
4
ACS Paragon Plus Environment

Page 5 of 35
The Journal of Organic Chemistry
1
2
3
Results and Discussion
4
5
6
7
8
9
We started our studies focusing on the in situ generation of the reactive
selenocarboxylate. In order to evaluate the efficiency of our system, we elected 4ꢀ
nitrophenyl azide as the starting material, since it is well known to be an efficient
reaction partner for amidation reaction in previous works.19 The first reducing agent
employed for reduction of elemental selenium was lithium aluminum hydride (Table 1,
entry 1). Therefore, formation of LiAlHSeH and reaction with benzoyl chloride, followed
by introduction of the azide in the reaction mixture resulted only in decomposition and no
product was detected in the crude mixture. Our second attempt was changing the
reducing agent to NaBH4 for the formation of NaHSe.21 In this reaction the desired
amide product was formed, however, in low yield (entry 2). We then decided to test our
methodology for the amidation reaction using lithium triethylborohydride to reduce
elemental selenium to the desired lithium selenide (entry 3). This reaction was first
developed by Gladysz et al22 and has been used for the rapid and efficient synthesis of
selenides and diselenides by our group23 and by others.24 However, it has never been
used for the synthesis of selenocarbonyl compounds. Therefore, we first reacted the in
situ generated Li2Se with benzoyl chloride to generate the corresponding lithium
benzoylselenocarboxylate, which was immediately reacted with 4ꢀnitrophenyl azide,
delivering the desired amide 4 in 75% isolated yield. Increasing the number of
equivalents of the selenocarboxylate led us to obtain amide 4 in essentially quantitative
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
yield, when the reaction was performed at 50 C (entry 4). Lowering the temperature
resulted in decreased isolated yield of the desired product (entry 5). We briefly explored
the scope of the reaction using aryl azides and we have found that the reaction is
tolerant to sensitive functional groups at the azide. The amidation can be performed in
the presence of ester, cyano and trifluoromethyl functional groups and products 5ꢀ7
were isolated in excellent yields (entries 6ꢀ8). Furthermore, heterocyclic azides have
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 35
1
2
3
4
5
6
7
8
9
also proved to be compatible with the amidation conditions. An amide bearing a
tetrahydroacridine moiety 8, was prepared in 70% yield (entry 9). This heterocyclic
compound is derived from the acetylcholinesterase inhibitor tacrine, which was the first
FDAꢀapproved drug for treatment of Alzheimer disease and still serves as a model for
the development of new therapeutic agents for Alzheimer.25 Moreover, a benzoxazoleꢀ
derived 9 amide was also obtained (entry 10). This heterocyclic compound is a
fluorescent molecule and belongs to a class of compounds commonly used as
fluorophores with potential applications as fluorescent probes and optical sensors.26
Alkyl azides were also tested under our conditions and we have found them to be less
reactive substrates. Under our conditions we were not able to obtain product 10 (entry
11), while the product 11 was isolated in 20% yield (entry 12). Despite the modest yield
with benzyl azide, this reveals the promising reactivity of our system, since previous
reports from the literature19 indicate that aliphatic azides do not react at all with sodium
or aluminum selenocarboxylates.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Optimization Studies and Scope with Aryl Azides
Equiv of
Entry Reducing agent
Product
Yield (%)a
selenocarboxylate
1
LiAlH4
1
NR
4
4
4
4
4
2
3
4
5
NaBH4
LiEt3BH
LiEt3BH
LiEt3BH
1
1
4
4
20
75
95
85b
6
ACS Paragon Plus Environment

Page 7 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
LiEt3BH
LiEt3BH
4
4
6
7
96
87
5
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
LiEt3BH
LiEt3BH
LiEt3BH
4
4
4
8
9
95
70
40
7
8
10
9
LiEt3BH
LiEt3BH
4
4
11
12
NR
20
10
11
a Isolated yields. b Reaction performed at r.t.
Having validated this new protocol with aryl azides, we moved on testing the
reaction using a sugarꢀderived azide 2, and gratifyingly we observed an excellent yield
of the glucosyl amide 3, when a xyloseꢀderived azide was used as the reaction partner
(Scheme 3). The best results were achieved using 4 equiv of the selenocarboxylate, 1
equiv of the azide and heating at 50 oC for 48 h.
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 35
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3.
With this promising result in hands, we further investigated the amidation reaction
with a broader range of sugarꢀderived azides. We first evaluated the reactivity of azides
with a furanosyl backbone in combination with a number of different acyl chlorides. The
results of these studies are summarized in Table 2. The reaction of aroyl chlorides as
the starting material, in combination with a xyloseꢀderived azide resulted in the
corresponding amides 3 and 12 in very good yields. The use of acyl chlorides
possessing alkyl side chains was also possible and the corresponding amides 13ꢀ17
were obtained in moderate to excellent yields, varying from 35% to 95%. When a
different xyloꢀfuranosyl azide with a free OH group was used the yields dropped
dramatically and the corresponding products 18 and 19 were isolated in 10% and 12%,
respectively. Different furanosyl azides have also been evaluated and derivatives from
D
ꢀribose (products 20ꢀ26) and Dꢀmannose (products 27ꢀ31) have been successfully
employed in the amidation reaction. Particularly notable are the results achieved for the
synthesis of ribofuranosyl amides, since the reaction proved to be very efficient across a
range of different acyl chlorides used as the selenocarboxylate precursors.
Table 2. Scope of the reaction using furanosyl azidesa,b
8
ACS Paragon Plus Environment

Page 9 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
O
N
H
OMe
O
O
23
95%
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 35
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
b
a Isolated yields. Reactions performed using 0.25 mmol of the furanosyl azide. The
selenocarboxylate (1.0 mmol) was generated in situ by reaction the acyl chloride (1.0
mmol) with Li2Se [(1.0 mmol), formed in situ by reaction of LiEt3BH (2.0 mmol, 1M
THF solution) and Se0 (1.0 mmol)].
Next, the scope was further investigated using azides possessing a pyranosyl
scaffold (Table 3). Amides derived from two different sugars have been studied and five
different galactosyl (products 32ꢀ36) and seven glucosyl amides (products 37ꢀ43) were
prepared. Worth to note is that all glucose derivatives possess the amide linkage at the
βꢀposition on the anomeric center of the sugar. In all examples studied, the configuration
at this carbon was retained, which is a clear advantage of the present method over a
more traditional approach (reduction of the azide to the amine, followed by amide
formation), since it is know that anomeric glucosyl amines are relatively unstable and
prone to mutarotation, resulting in a mixture of anomers.27
10
ACS Paragon Plus Environment

Page 11 of 35
The Journal of Organic Chemistry
1
2
3
Table 3. Scope of the reaction using pyranosyl azidesa,b
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 35
1
2
3
4
5
6
7
b
a Isolated yields. Reactions performed using 0.25 mmol of the pyranosyl azide. The selenocarboxylate
(1.0 mmol) was generated in situ by reaction the acyl chloride (1.0 mmol) with Li2Se [(1.0 mmol), formed in
situ by reaction of LiEt3BH (2.0 mmol, 1M THF solution) and Se0 (1.0 mmol)].
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The reaction is not limited to the use of acyl chlorides as the precursors for the
selenocarboxylates, and we have also successfully used a simple carboxylic acid as the
source of the amidation reagent. For example, 4ꢀphenylbutyric acid was activated by
reaction with ethyl chloroformate and Nꢀmethylmorpholine,28 followed by reaction with
Li2Se for 30 minutes, to generate the corresponding selenocarboxylate (Scheme 4).
o
Introduction of the sugar azide to the reaction mixture and heating at 50 C for 48 h,
resulted in evolution on N2 and precipitation of elemental selenium indicating the
completion of the reaction. The desired product 44 was isolated in 95% yield, after
column chromatography. Notably, the 4ꢀstep sequence occurs without isolation of any
intermediates and only stable, easyꢀtoꢀhandle materials have been manipulated. All
reactive intermediates are generated in situ and their handling avoided. In addition, byꢀ
products formed, Se and N2, are harmless and removed by simple filtration.
Scheme 4. Carboxylic acid as the precursor of selenocarboxylate
12
ACS Paragon Plus Environment

Page 13 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Finally, deprotection of the sugar moieties of selected compounds was performed
(Scheme 5). Thus, compound 32, in which the hydroxy groups were masked as
acetonides, was treated with trifluoroacetic acid and methanol, furnishing the free sugar
moiety in 95% yield. In addition, the tetraacetylated glucose derivative 37 was
deprotected by classic Zemplén methodology29 under very mild conditions using sodium
methoxide in methanol to deliver the corresponding tetraol in nearly quantitative yield.
Worth to point out is that the amide moiety remained untouched under these
deprotection conditions.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 5
Conclusions
In summary, a wide range of sugar derived amides were successfully prepared in
good yields for a broad range of substrates, including substituted aryl, furanosyl and
pyranosyl azides. Our new methodology successfully relied in the in situ generation of
lithium selenocarboxylates, from Se/LiEt3BH and acyl chlorides or carboxylic acids. A
key aspect of the present protocol is that we start from elemental selenium and isolation
and handling all reactive and sensitive seleniumꢀcontaining intermediates is avoided,
therefore rendering to the selenocarboxylate the status of a traceless reagent. Further
applications of the present protocol are underway and will be reported in due course.
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 35
1
2
3
Experimental Section
4
5
6
7
8
9
General Information. NMR spectra were recorded either on a 300 MHz, 400
MHz or 500 MHz spectrometer (for 1H NMR) at room temperature, using a 5ꢀmm internal
diameter probe in chloroform (CDCl3), methanol (CD3OD) or deuterium oxide (D2O).
ESIꢀQTOFꢀMS measurements were performed in the positive ion mode (m/z 50ꢀ2000
range). IR spectra were obtained on an FTIRꢀATR instrument. Melting points were
measured optical microscope apparatus and are uncorrected. Optical rotations were
obtained in polarimeter at 20 oC, unless otherwise noted. Flash column chromatography
was performed using Silica Gel (230ꢀ400 mesh) following the methods described by
Still.30 Thin layer chromatography (TLC) was performed using supported silica gel
GF254, 0.25 mm thickness. For visualization, TLC plates were either placed under
ultraviolet light, or stained with iodine vapor, or acidic vanillin or phosphomolybdic acid.
Lithium triethylborohydride was used as a 1M THF solution. Elemental selenium (ꢀ100
mesh) was dried in oven (80 oC) overnight prior to use. Aryl and sugar azides are known
compounds and were prepared according to literature procedures.3132
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General procedure for the preparation of N-glycosyl amides. Under an argon
atmosphere, lithium triethylborohydride (2.0 mmol, 4 equiv.) was added over selenium
powder (1.0 mmol, 2 equiv.) forming Li2Se as a white solution. THF (2 mL) was added
into the mixture, and after 5 min stirring, the acyl chloride (1.0 mmol, 4 equiv.) was then
added dropwise and the orange/yellow clear solution formed was stirred at room
temperature for 30 min. After this time, a solution of the glycosyl azide (0.25 mmol in 2
mL THF, 1 equiv.) was added. The reaction was allowed to stir at room temperature for
48 h. After consumption of the starting azide, as shown by TLC, selenium powder
precipitated and was removed by filtration, prior to quenching the reaction mixture with
aqueous saturated NaHCO3 (10 mL) and extracted with CH2Cl2 (3x15 mL). The
14
ACS Paragon Plus Environment

Page 15 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
combined organic layers were dried with MgSO4, filtered and concentrated under
reduced pressure. The crude product was purified by flash column chromatography
eluting with a mixture of hexane/ethyl acetate (90:10). Caution: Although the toxicity of
elemental selenium is significantly lower than other forms, care should be taken in its
handling and disposal.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(5ꢀdeoxyꢀ3ꢀOꢀmethylꢀ1,2ꢀOꢀisopropylideneꢀαꢀDꢀxylofuranoside)ꢀ5ꢀbenzamide
(3)
Yellow oil, yield: 0.107 g (70%). [α]D20 = ꢀ 13.9 (c 0.188, CH2Cl2). Rf = 0.4 (10%
ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.77 (d, J = 7.2 Hz, 2H),
7.56 – 7.34 (m, 3H), 6.67 – 6.63 (m, 1H), 5.93 (d, J = 3.8 Hz, 1H), 4.61 (d, J = 3.8 Hz,
1H), 4.41 – 4.34 (m, 1H), 4.10 (ddd, J = 14.3, 7.8, 3.7 Hz, 1H), 3.78 (d, J = 3.3 Hz, 1H),
3.52 – 3.46 (m, 1H), 3.45 (s, 3H), 1.48 (s, 3H), 1.33 (s, 3H). 13C NMR (101 MHz, CDCl3):
δ (ppm) = 167.8, 134.5, 131.6, 128.7, 127.1, 111.9, 105.1, 85.1, 81.9, 78.9, 58.1, 39.2,
26.8, 26.3. IR (νmax, cmꢀ1): 3348, 3064, 2987, 2931, 2825, 1727, 1646, 1539, 1370,
1214, 1072, 1011. HRMS (ESI): m/z, calcd for C16H22NO5 [M+H]+ 308.1498, found
308.1501.
Methyl esterꢀ4ꢀ(benzoylamino)ꢀbenzoic acid (5)
Orange solid, yield: 0.123 g (96%). m.p: 66 ꢀ 68 °C. Rf = 0.2 (10% ethyl acetate/nꢀ
1
hexane). H NMR (300 MHz, CDCl3): δ (ppm) = 8.14 (br, 1H), 8.07 – 8.01 (m, 2H), 7.91
– 7.84 (m, 2H), 7.78 – 7.72 (m, 2H), 7.60 – 7.44 (m, 3H), 3.90 (s, 3H). 13C NMR (75
MHz, CDCl3): δ (ppm) = 166.5, 165.8, 142.1, 134.5, 132.1, 130.8, 128.8, 127.0, 125.8,
119.2, 52.0. IR (νmax, cmꢀ1): 3372, 3219, 2947, 1708, 1666, 1599, 1523, 1273.HRMS
(ESI): m/z, calcd for C15H14NO3 [M+H]+ 256.0974, found 256.0978.
Nꢀ(4ꢀCyanophenyl)ꢀbenzamide (6)
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 35
1
2
3
White solid, yield: 0.097 g (87%). m.p: 166ꢀ168 °C. Rf = 0.1 (10% ethyl acetate/nꢀ
4
5
1
hexane). H NMR (300 MHz, CDCl3): δ (ppm) = 8.15 (br, 1H), 7.91 – 7.77 (m, 4H), 7.68
6
7
8
9
– 7.46 (m, 5H). 13C NMR (75 MHz, CDCl3): δ (ppm) = 165.9, 142.0, 134.0, 133.3, 132.4,
128.9, 127.1, 119.9, 118.8, 107.3. IR (νmax, cmꢀ1): 3351, 2925, 2225, 1659, 1519, 1408.
HRMS (ESI): m/z, calcd for C14H11N2O [M+H]+ 223.0871, found 223.0851.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ[3,5ꢀbis(trifluoromethyl)phenyl]ꢀbenzamide (7)
Pale yellow solid, yield: 0,170 g (95%). m. p.: 112ꢀ114 °C. Rf = 0.5 (10% ethyl
1
acetate/nꢀhexane). H NMR (400 MHz, CDCl3): 8.20 (s, 2H), 8.12 (br, 1H), 7.90 (d, J =
10.0 Hz, 2H), 7.66 (s, 1H), 7.62 (t, J = 7.5 Hz, 1H), 7.53 (t, J = 7.5 Hz, 2H). δ (ppm) =
13C NMR (75 MHz, CDCl3): δ (ppm) = 166.0, 139.4, 132.7, 132.2 (q, J = 33 Hz), 129.1,
127.1, 125.8 (q, J = 273 Hz), 119.8 (m), 117.8 (m). IR (νmax, cmꢀ1): 3264, 2925, 1651,
1559, 1270. HRMS (ESI): m/z, calcd for C15H10F6NO [M+H]+ 334.0667, found 334.0683.
Nꢀ(1,2,3,4ꢀTetrahydroꢀ9ꢀacridinyl)ꢀbenzamide (8)
Yellow Solid, yield: 0.100 g (70%). m.p: 148ꢀ150 °C. Rf = 0.2 (50% ethyl
1
acetate/nꢀhexane). m.p.: 148 – 150 °C. H NMR (500 MHz, CDCl3): δ (ppm) = 8.50 (br,
1H), 7.82 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8,0 Hz, 2H), 7.55 (d, J = 8.0 Hz, 1H), 7.47 –
7.38 (m, 2H), 7.24 – 7.15 (m, 3H), 2.92 (t, J = 6.5 Hz, 2H), 2.55 (t, J = 6.5 Hz, 2H), 1.73
– 1.67 (m, 2H), 1.61 – 1.54 (m, 2H). 13C NMR (126 MHz, CDCl3): δ (ppm) = 166.1,
159.6, 146.6, 138.5, 133.3, 132.0, 128.6, 128.5, 128.4, 127.7, 127.4, 125.6, 123.9,
122.1, 33.7, 25.2, 22.4, 22.1. IR (νmax, cmꢀ1): 2926, 2861, 1647. HRMS (ESI): m/z, calcd
for C20H19N2O [M+H]+ 303.1497, found 303.1509.
Nꢀ[3ꢀ(2ꢀBenzoxazolyl)phenyl]ꢀbenzamide (9)
16
ACS Paragon Plus Environment

Page 17 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
White solid, yield: 0,070 g (40%). m. p.: 191 – 193 °C. Rf = 0.6 (10% ethyl
acetate/nꢀhexane). 1H NMR (500 MHz, DMSOꢀd6): δ (ppm) = 10.53 (s, 1H), 8.81 (s, 1H),
8.03 (d, J = 7.0 Hz, 3H), 7.94 (d, J = 7.9 Hz, 1H), 7.82 (t, J = 8.8 Hz, 2H), 7.65 – 7.52 (m,
4H), 7.48 – 7.38 (m, 2H). 13C NMR (126 MHz, DMSOꢀd6): δ (ppm) = 165.7, 162.2, 150.2,
141.4, 140.0, 134.5, 131.7, 129.6, 128.4 127.7, 126.7, 125.5, 124.8, 123.3, 122.3, 119.8,
118.7, 110.9. IR (νmax, cmꢀ1): 3281, 3060, 1649, 1521, 1419, 1245. HRMS (ESI): m/z,
calcd for C20H15N2O2 [M+H]+ 315.1133, found 315.1137.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4ꢀMethylꢀNꢀ(5ꢀdeoxyꢀ3ꢀOꢀmethylꢀ1,2ꢀOꢀisopropylideneꢀαꢀDꢀxylofuranoside)ꢀ5ꢀ
benzamide (12)
Yellow oil, yield: 0.152 g (95%). [α]D20 = ꢀ 22.4 (c 0.224, CH2Cl2). Rf = 0.4 (10%
ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.67 (d, J = 8.0 Hz, 2H),
7.22 (d, J = 8.0 Hz, 2H), 6.62 (br, 1H), 5.93 (d, J = 3.8 Hz, 1H), 4.60 (d, J = 3.8 Hz, 1H),
4.43 – 4.31 (m, 1H), 4.09 (ddd, J = 14.1, 7.8, 3.6 Hz, 1H), 3.78 (d, J = 3.2 Hz, 1H), 3.50
– 3.45 (m, 1H), 3.44 (s, 3H), 2.39 (s, 3H), 1.48 (s, 3H), 1.32 (s, 3H). 13C NMR (101 MHz,
CDCl3): δ (ppm) = 167.7, 142.0, 131.7, 129.3, 127.1, 111.9, 105.1, 85.1, 81.9, 79.0,
58.1, 39.1, 26.8, 26.3, 21.6. IR (νmax, cmꢀ1): 3355, 3224, 2926, 2360, 1722, 1640, 1537,
1504, 1374, 1259, 1205, 1074, 1020. HRMS (ESI): m/z, calcd for C17H24NO5 [M+H]+
322.1654, found 322.1655.
Nꢀ(5ꢀDeoxyꢀ3ꢀOꢀmethylꢀ1,2ꢀOꢀisopropylideneꢀαꢀDꢀxylofuranoside)ꢀ5ꢀ
benzeneacetamide (13)
Yellow oil, yield: 0.052 g (35%). [α]D20 = ꢀ 10.9 (c 0.464, CH2Cl2). Rf = 0.3 (10%
ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.37 – 7.31 (m, 2H), 7.30
– 7.24 (m, 3H), 5.94 (br, 1H), 5.83 (d, J = 3.9 Hz, 1H), 4.51 (d, J = 3.9 Hz, 1H), 4.24
(ddd, J = 7.5, 4.7, 3.5 Hz, 1H), 3.74 (ddd, J = 14.1, 7.5, 4.7 Hz, 1H), 3.60 (d, J = 3.5 Hz,
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 35
1
2
3
4
5
6
7
8
9
1H), 3.57 (s, 2H), 3.32 (ddd, J = 14.1, 7.2, 4.4 Hz, 1H), 3.24 (s, 3H), 1.46 (s, 3H), 1.30
(s, 3H). 13C NMR (101 MHz, CDCl3): δ (ppm) = 171.3, 135.1, 129.5, 129.0, 127.3, 111.8,
105.0, 84.8, 81.5, 78.3, 57.7, 43.8, 38.6, 26.8, 26.3. IR (νmax, cmꢀ1): 3291, 3065, 3030,
2986, 2933, 2830, 2102, 1645, 1541, 1377, 1214, 1168, 1076, 1011. HRMS (ESI): m/z,
calcd for C17H24NO5 [M+H]+ 322.1654, found 322.1672.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(5ꢀDeoxyꢀ3ꢀOꢀmethylꢀ1,2ꢀOꢀisopropylideneꢀαꢀDꢀxylofuranoside)ꢀ5ꢀ
cyclohexaneacetamide (14)
Orange solid, yield: 0.056 g (72%). [α]D20 = ꢀ 3.5 (c 0.433, CH2Cl2). m. p.: 67ꢀ69
°C. Rf = 0.3 (10% ethyl acetate/nꢀhexane). 1H NMR (500 MHz, CDCl3): δ (ppm) = 5.95 –
5.89 (m, 1H), 5.87 (d, J = 3.8 Hz, 1H), 4.56 (d, J = 3.8 Hz, 1H), 4.26 – 4.20 (m, 1H), 3.87
(ddd, J = 14.0, 8.0, 3.6 Hz, 1H), 3.69 (d, J = 3.2 Hz, 1H), 3.39 (s, 3H), 3.21 (ddd, J =
14.0, 8.3, 3.5 Hz, 1H), 2.03 (d, J = 7.1 Hz, 2H), 1.80 – 1.58 (m, 6H), 1.45 (s, 3H), 1.30
(s, 3H), 1.28 – 1.18 (m, 2H), 1.16 – 1.08 (m, 1H), 0.99 – 0.85 (m, 2H). 13C NMR (126
MHz, CDCl3): δ (ppm) = 172.8, 111.9, 105.0, 84.8, 81.9, 79.1, 58.0, 44.9, 38.5, 35.5,
33.2, 33.2, 26.8, 26.4, 26.3, 26.2. IR (νmax, cmꢀ1): 3331, 2988, 2924, 2847, 1721, 1641,
1544, 1076, 1019. HRMS (ESI): m/z, calcd for C17H30NO5 [M+H]+ 328.2124, found
328.2134.
Nꢀ(5ꢀdeoxyꢀ3ꢀOꢀmethylꢀ1,2ꢀOꢀisopropylideneꢀαꢀDꢀxylofuranoside)ꢀ5ꢀheptanamide
(15)
Yellow oil, yield: 0.044 g (56%). [α]D20 = ꢀ 3.2 (c 0.291, CH2Cl2). Rf = 0.4 (10%
1
ethyl acetate/nꢀhexane). H NMR (300 MHz, CDCl3): δ (ppm) = 5.92 – 5.83 (m, J = 4.7
Hz, 1H), 5.81 (d, J = 3.8 Hz, 1H), 4.49 (d, J = 3.8 Hz, 1H), 4.22 – 4.11 (m, 1H), 3.80
(ddd, J = 14.2, 8.0, 3.5 Hz, 1H), 3.62 (d, J = 3.3 Hz, 1H) , 3.32 (s, 3H), 3.15 (ddd, J =
14.2, 8.4, 3.5 Hz, 1H), 2.09 (t, J = 7.6 Hz, 2H), 1.64 – 1.44 (m, 2H), 1.39 (s, 3H), 1.23 (s,
18
ACS Paragon Plus Environment

Page 19 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
3H), 1.22 – 1.05 (m, 6H), 0.89 – 0.66 (m, 3H).13C NMR (75 MHz, CDCl3): δ (ppm) =
173.6, 111.8, 105.0, 84.8, 81.8, 79.1, 58.0, 38.5, 36.9, 31.6, 29.0, 26.8, 26.3, 25.8, 22.6,
14.2. IR (νmax, cmꢀ1): 3297, 2928, 2859, 2360, 2103, 1646, 1541, 1378, 1216, 1082,
1013. HRMS (ESI): m/z, calcd for C16H30NO5 [M+H]+ 316.2124, found 316.2123.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3,3ꢀDimethylꢀNꢀ(5ꢀdeoxyꢀ3ꢀOꢀmethylꢀ1,2ꢀOꢀisopropylideneꢀ
butanamide (16)
αꢀDꢀxylofuranoside)ꢀ5ꢀ
Orange oil, yield: 0.032 g (45%). [α]D20 = ꢀ 5.3 (c 0.189, CHCl3). Rf = 0.4 (10%
ethyl acetate/nꢀhexane). 1H NMR (300 MHz, CDCl3): δ (ppm) = 5.90 (d, J = 3.8 Hz, 1H),
5.87 – 5.79 (m, 1H), 4.58 (d, J = 3.8 Hz, 1H), 4.26 (dt, J = 8.2, 3.4 Hz, 1H), 3.90 (ddd, J
= 14.2, 8.2, 3.6 Hz, 1H), 3.71 (d, J = 3.4 Hz, 1H), 3.41 (s, 3H), 3.22 (ddd, J = 14.2, 8.2,
3.5 Hz, 1H), 2.06 (s, 2H), 1.47 (s, 3H), 1.32 (s, 3H), 1.03 (s, 9H). 13C NMR (75 MHz,
CDCl3): δ (ppm) = 172.0, 111.9, 105.0, 84.9, 81.9, 79.0, 58.1, 50.8, 38.5, 31.0, 29.9,
26.9, 26.4. IR (νmax, cmꢀ1): 3297, 2955, 2929, 1727, 1639, 1545, 1375, 1217, 1088,
1018. HRMS (ESI): m/z, calcd for C15H28NO5 [M+H]+ 302.1967, found 302.1971.
3ꢀMethylꢀNꢀ(5ꢀdeoxyꢀ3ꢀOꢀmethylꢀ1,2ꢀOꢀisopropylideneꢀ
butanamide (17)
αꢀDꢀxylofuranoside)ꢀ5ꢀ
Yellow oil, yield: 0.074 g (>95%). [α]D20 = ꢀ 6.8 (c 0.232, CH2Cl2). Rf = 0.3 (10%
ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 5.90 (d, J = 3.8 Hz, 1H),
5.88 – 5.82 (m, 1H), 4.58 (d, J = 3.8 Hz, 1H), 4.31 – 4.21 (m, 1H), 3.90 (ddd, J = 14.1,
8.0, 3.6 Hz, 1H), 3.71 (d, J = 3.2 Hz, 1H), 3.41 (s, 3H), 3.24 (ddd, J = 14.1, 8.2, 3.5 Hz,
1H), 2.17 – 2.01 (m, 3H), 1.48 (s, 3H), 1.32 (s, 3H), 0.96 (d, J = 1.6 Hz, 3H), 0.94 (d, J =
1.6 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) = 172.9, 111.9, 105.0, 84.8, 81.9, 79.1,
58.0, 46.2, 38.5, 29.8, 26.8, 26.4, 26.3, 22.6. IR (νmax, cmꢀ1): 3295, 2959, 2929, 1641,
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 35
1
2
3
1544, 1373, 1218, 1081, 1013. HRMS (ESI): m/z, calcd for C14H26NO5 [M+H]+ 288.1811,
4
5
found 288.1808.
6
7
8
9
Nꢀ(1ꢀMethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀribofuranoside)ꢀ5ꢀbenzamide (20)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Yellow oil, yield: 0.105 g (>95%). [α]D20 = ꢀ 65.0 (c 0.620, CH2Cl2). Rf = 0.7 (30% ethyl
acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.82 (d, J = 7.2 Hz, 1H), 7.55
– 7.34 (m, 3H), 7.16 (br, 1H), 5.04 (s, 1H), 4.68 (d, J = 6.0 Hz, 1H), 4.61 (d, J = 6.0 Hz,
1H), 4.53 (t, J = 4.5 Hz, 1H), 3.95 – 3.83 (m, 1H), 3.51 – 3.46 (m, 1H), 3.46 (s, 3H), 1.49
(s, 3H), 1.29 (s, 3H). 13C NMR (101 MHz, CDCl3): δ (ppm) = 167.5, 134.2, 131.7, 128.7,
127.1, 112.6, 110.5, 86.4, 85.8, 82.2, 55.6, 42.6, 26.6, 25.0. IR (νmax, cmꢀ1): 3334, 2986,
2935, 2833, 1737, 1641, 1532, 1371, 1207, 1089, 1043. HRMS (ESI): m/z, calcd for
C15H18NO4 [M−OMe]+ 276.1230, found 276.1213. calcd for C16H22NO5 [M+H]+ 308.1498,
found 308.1483.
4ꢀMethylꢀNꢀ(1ꢀmethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀribofuranoside)ꢀ5ꢀ
benzamide (21)
Yellow solid, yield: 0.105 g (>95%). [α]D20 = ꢀ 63.8 (c 0.779, CH2Cl2). m.p.: 122ꢀ
1
125 °C. Rf = 0.7 (30% ethyl acetate/nꢀhexane). H NMR (300 MHz, CDCl3): δ (ppm) =
7.77 – 7.66 (m, 2H), 7.31 – 7.17 (m, 3H), 7.16 (br, 1H), 5.03 (s, 1H), 4.68 (d, J = 6.0 Hz,
1H), 4.59 (d, J = 6.0 Hz, 1H), 4.51 (t, J = 4.7 Hz, 1H), 3.86 (ddd, J = 14.2, 7.3, 4.7 Hz,
1H), 3.50 – 3.40 (m, 1H), 3.44 (s, 3H), 2.39 (s, 3H), 1.48 (s, 3H), 1.28 (s, 3H). 13C NMR
(75 MHz, CDCl3) δ (ppm): 167.4, 142.0, 131.3, 129.3, 127.0, 112.5, 110.3, 86.3, 85.7,
82.2, 55.5, 42.5, 26.5, 24.9, 21.5. IR (νmax, cmꢀ1): 3306, 2982, 2928, 2360, 2336, 1718,
1630, 1554, 1372, 1274, 1208, 1088, 1054. HRMS (ESI): m/z, calcd for C16H20NO4
[M−OMe]+ 290.1392, found 290.1371; calcd for C17H24NO5 [M+H]+ 322.1654, found
322.1639.
20
ACS Paragon Plus Environment

Page 21 of 35
The Journal of Organic Chemistry
1
2
3
4
5
6
7
Nꢀ(1ꢀMethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀ
benzeneacetamide (22)
Dꢀribofuranoside)ꢀ5ꢀ
8
9
Yellow oil, yield: 0.052 g (50%). [α]D20 = ꢀ 54.2 (c 0.750, CH2Cl2). Rf = 0.6 (30%
ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.39 – 7.23 (m, 5H), 6.16
(br, 1H), 4.84 (s, 1H), 4.47 (d, J = 6.0 Hz, 1H), 4.32 (d, J = 6.0 Hz, 1H), 4.31 – 4.27 (m,
1H), 3.58 (d, J = 3.4 Hz, 2H), 3.56 – 3.47 (m, 1H), 3.33 – 3.25 (m, 1H), 3.13 (s, 3H), 1.43
(s, 3H), 1.25 (s, 3H). 13C NMR (101 MHz, CDCl3): δ (ppm) = 171.4, 134.9, 129.6, 129.1,
127.5, 112.4, 110.1, 85.8, 85.6, 82.0, 55.2, 44.1, 42.4, 26.4, 24.8. IR (νmax, cmꢀ1): 3304,
3061, 3026, 2985, 2933, 2360, 2339, 1650, 1550, 1520, 1497, 1368, 1213, 1197, 1096,
1071, 1046. . HRMS (ESI): m/z, calcd for C16H20NO4 [M−OMe]+ 290.1392, found
290.1371; calcd for C17H24NO5 [M+H]+ 322.1654, found 322.1643.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(1ꢀMethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀribofuranoside)ꢀ5ꢀ
cyclohexaneacetamide (23)
Yellow solid, yield: 0.089 g (>95%). [α]D20 = ꢀ 52.9 (c 0.750, CH2Cl2). m.p.: 93ꢀ95
°C. Rf = 0.6 (30% ethyl acetate/nꢀhexane).1H NMR (500 MHz, CDCl3): δ (ppm) = 6.25
(br, 1H), 4.97 (s, 1H), 4.58 (d, J = 6.0 Hz, 1H), 4.55 (d, J = 6.0 Hz, 1H), 4.34 (t, J = 5.3
Hz, 1H), 3.58 – 3.48 (m, 1H), 3.39 (s, 3H), 3.37 – 3.31 (m, 1H), 2.04 (d, J = 4.0 Hz, 1H),
2.03 (d, J = 4.0 Hz, 1H),1.75 – 1.60 (m, 6H), 1.46 (s, 3H), 1.28 (s, 3H), 1.33 – 1.19 (m,
2H), 1.18 – 1.07 (m, 1H), 1.00 – 0.84 (m, 2H). 13C NMR (126 MHz, CDCl3): δ (ppm) =
172.7, 112.5, 110.2, 86.2, 85.7, 82.2, 55.5, 45.1, 42.2, 35.4, 33.3, 33.3, 26.5, 26.3, 26.2,
26.2, 24.9. IR (νmax, cmꢀ1): 3313, 2989, 2922, 2849, 1730, 1641, 1535, 1376, 1212,
1190, 1161, 1087, 1043. HRMS (ESI): m/z, calcd for C16H26NO4 [M−OMe]+ 296.1862,
found 296.1833; calcd for C17H30NO5 [M+H]+ 328.2124, found 328.2135.
21
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 35
1
2
3
4
5
Nꢀ(1ꢀMethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀ
D
ꢀribofuranoside)ꢀ5ꢀheptanamide
6
7
(24)
8
9
Yellow oil, yield: 0.087 g (>95%). [α]D20 = ꢀ 48.3 (c 0.515, CH2Cl2). Rf = 0.5 (30%
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ethyl acetate/nꢀhexane).1H NMR (400 MHz, CDCl3): δ (ppm) = 6.24 (br, 1H), 4.98 (s,
1H), 4.59 (d, J = 6.0 Hz, 1H), 4.56 (d, J = 6.0 Hz, 1H), 4.35 (t, J = 5.3 Hz, 1H), 3.59 –
3.48 (m, 1H), 3.40 (s, 3H), 3.38 – 3.31 (m, 1H), 2.18 (t, J = 7.6 Hz, 2H), 1.71 – 1.55 (m,
2H), 1.47 (s, 3H), 1.30 (s, 9H), 0.88 (t, J = 6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ
(ppm): 173.5, 112.5, 110.2, 86.3, 85.7, 82.2, 55.5, 42.2, 36.9, 31.6, 29.1, 26.5, 25.7,
25.0, 22.6, 14.1.IR (νmax, cmꢀ1): 3296, 2929, 2854, 2361, 1643, 1544, 1373, 1206, 1160,
1092, 1060, 1045, 867, 489. HRMS (ESI): m/z, calcd for C15H26NO4 [M−OMe]+
284.1862, found 284.1870; calcd for C16H30NO5 [M+H]+ 316.2124, found 316.2109.
3,3ꢀDimethylꢀNꢀ(1ꢀmethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀribofuranoside)ꢀ5ꢀ
butanamide (25)
Orange oil, yield: 0.072 g (80%). [α]D20 = ꢀ 63.7 (c 0.465, CH2Cl2).Rf = 0.4 (30%
1
ethyl acetate/nꢀhexane). H NMR (500 MHz, CDCl3): δ (ppm) = 6.20 (br, 1H), 4.98 (s,
1H), 4.60 (d, J = 5.9 Hz, 1H), 4.57 (d, J = 5.9 Hz, 1H), 4.35 (t, J = 5.4 Hz, 1H), 3.52 –
3.45 (m, 1H), 3.40 (s, 3H), 3.42 – 3.35 (m, 1H), 2.06 (s, 2H), 1.47 (s, 3H), 1.30 (s, 3H),
1.04 (s, 9H).13C NMR (126 MHz, CDCl3): δ (ppm) = 172.0, 112.5, 110.1, 86.2, 85.6,
82.2, 55.5, 50.8, 42.2, 30.9, 29.9, 26.5, 24.9. IR (νmax, cmꢀ1): 3330, 2948, 2359, 2338,
2360, 2337, 1643, 1540, 1369, 1206, 1092, 1061, 1045. HRMS (ESI): m/z, calcd for
C14H24NO4 [M+−OMe]+ 270.1705, found 270.1688; calcd for C15H28NO5 [M+H]+
302.1967, found 302.1957.
22
ACS Paragon Plus Environment

Page 23 of 35
The Journal of Organic Chemistry
1
2
3
3ꢀMethylꢀNꢀ(1ꢀmethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀribofuranoside)ꢀ5ꢀ
4
5
butanamide (26)
6
7
Orange solid, yield: 0.072 g (>95%). [α]D20 = ꢀ 64.9 (c 0.336, CH2Cl2). m.p.: 66ꢀ68
8
9
1
°C. Rf = 0.4 (30% ethyl acetate/nꢀhexane). H NMR (300 MHz, CDCl3): δ (ppm) = 6.25
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(br, 1H), 4.99 (s, 1H), 4.60 (d, J = 6.0 Hz, 1H), 4.57 (d, J = 6.0 Hz, 1H), 4.37 (t, J = 5.4
Hz, 1H), 3.60 – 3.46 (m, 1H), 3.41 (s, 3H), 3.39 – 3.32 (m, 1H), 2.25 – 1.88 (m, 3H), 1.48
(s, 3H), 1.30 (s, 3H), 0.97 (s, 3H), 0.95 (s, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) =
172.7, 112.5, 110.2, 86.2, 85.6, 82.2, 55.5, 46.3, 42.2, 26.5, 26.2, 24.9, 22.6. IR (νmax
,
cmꢀ1): 3288, 2951, 2865, 2356, 1753, 1631, 1538, 1367, 1207, 1161, 1087, 1058, 1041,
1012. HRMS (ESI): m/z, calcd for C13H22NO4 [M−OMe]+ 256.1543, found 256.1549;
calcd for C14H26NO5 [M+H]+ 288.1811, found 288.1835.
Nꢀ(1ꢀMethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀmannofuranoside)ꢀ5ꢀ
benzeneacetamide (27)
Yellow solid, yield: 0.041 g (80%). [α]D20 = + 61.4 (c 0.181, CH2Cl2). m.p.: 78ꢀ80
°C. Rf = 0.4 (30% ethyl acetate/nꢀhexane).1H NMR (300 MHz, CDCl3): δ (ppm): = 7.40 –
7.22 (m, 5H), 5.83 (br, 1H), 4.82 (s, 1H), 4.57 (dd, J = 5.9, 3.6 Hz, 1H), 4.50 (d, J = 5.9
Hz, 1H), 4.03 – 3.94 (m, 1H), 3.75 – 3.61 (m, 1H), 3.58 (s, 2H), 3.55 – 3.39 (m, 1H), 3.22
(s, 3H), 1.37 (s, 3H), 1.25 (s, 3H). 13C NMR (101 MHz, CDCl3): δ (ppm) = 171.3, 135.1,
129.5, 129.1, 127.4, 112.7, 107.1, 85.2, 79.9, 77.6, 54.6, 44.0, 38.8, 26.0, 24.7.IR (νmax
,
cmꢀ1):3340, 3360, 3330, 2988, 2935, 1733, 1647, 1539, 1454, 1424, 1380, 1370, 1356,
1260, 1203, 1160, 1008. HRMS (ESI): m/z, calcd for C16H20NO4 [M−OMe]+ 290.1392,
found 290.1363; calcd for C17H24NO5 [M+H]+ 322.1654, found 322.1656.
23
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 35
1
2
3
4
5
Nꢀ(1ꢀMethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀ
cyclohexaneacetamide (28)
Dꢀmannofuranoside)ꢀ5ꢀ
6
7
8
9
Yellow oil, yield: 0.0252 g (>95%). [α]D20 = + 62.9 (c 0.332, CH2Cl2). Rf = 0.5 (30%
ethyl acetate/nꢀhexane).1H NMR (400 MHz, CDCl3): δ (ppm) = 5.85 (br, 1H), 4.88 (s,
1H), 4.67 (dd, J = 5.9, 3.7 Hz, 1H), 4.56 (d, J = 5.9 Hz, 1H), 4.07 (ddd, J = 7.1, 5.6, 3.7
Hz, 1H), 3.77 – 3.64 (m, 1H), 3.61 – 3.44 (m, 1H), 3.30 (s, 3H), 2.05 (d, J = 7.0 Hz, 2H),
1.84 – 1.59 (m, 5H), 1.47 (s, 3H), 1.31 (s, 3H), 1.30 – 1.06 (m, 4H), 1.02 – 0.81 (m,
2H).13C NMR (101 MHz, CDCl3): δ (ppm) = 172.5, 112.5, 106.9, 85.0, 79.8, 77.6, 54.5,
44.9, 38.3, 35.4, 33.0, 33.0, 26.1, 26.03, 25.9, 24.6. IR (νmax, cmꢀ1): 3315, 2927, 2852,
1729, 1641, 1543, 1441, 1381, 1274, 1260, 1205, 1188, 1163, 1138, 1016. HRMS (ESI):
m/z, calcd for C16H26NO4 [M−OMe]+ 296.1862, found 296.1843; calcd for C17H30NO5
[M+H]+ 328.2124, found 328.2146.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3,3ꢀDimethylꢀNꢀ(1ꢀmethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀmannofuranoside)ꢀ5ꢀ
butanamide (29)
Yellow oil, yield: 0.098 g (65%). [α]D20 = + 68.2 (c 0.251, CH2Cl2). Rf = 0.4 (30%
1
ethyl acetate/nꢀhexane). H NMR (400 MHz, CDCl3): δ (ppm) = 5.89 (br, 1H), 4.87 (s,
1H), 4.66 (dd, J = 5.9, 3.7 Hz, 1H), 4.54 (d, J = 5.9 Hz, 1H), 4.12 – 4.03 (m, 1H), 3.74 –
3.64 (m, 1H), 3.53 – 3.43 (m, 1H), 3.29 (s, 3H), 2.06 (s, 2H), 1.45 (s, 3H), 1.30 (s, 3H),
1.03 (s, 9H). 13C NMR (75 MHz, CDCl3): δ (ppm) = 172.0, 112.7, 107.1, 85.2, 80.0, 77.8,
54.7, 50.7, 38.5, 31.0, 29.9, 26.1, 24.8. IR (νmax, cmꢀ1):3294, 2994, 1730, 1632,
1551,1463, 1368, 1110, 1091, 1033, 1002. HRMS (ESI): m/z, calcd for C14H24NO4
[M−OMe]+ 270.1705, found 270.1713; calcd for C15H28NO5 [M+H]+ 302.1967, found
302.1992.
24
ACS Paragon Plus Environment

Page 25 of 35
The Journal of Organic Chemistry
1
2
3
3ꢀMethylꢀNꢀ(1ꢀmethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀmannofuranoside)ꢀ5ꢀ
4
5
butanamide (30)
6
7
8
9
Yellow solid, yield: 0.113 g (78%). [α]D20 = + 75.6 (c 0.415, CH2Cl2). m.p.: 74ꢀ76
°C. Rf = 0.4 (30% ethyl acetate/nꢀhexane).1H NMR (400 MHz, CDCl3) δ (ppm): 6.00 (br,
1H), 4.88 (s, 1H), 4.68 (dd, J = 5.9, 3.7 Hz, 1H), 4.56 (d, J = 5.9 Hz, 1H), 4.08 (ddd, J =
7.0, 5.5, 3.7 Hz, 1H), 3.71 (ddd, J = 13.9, 6.8, 5.5 Hz, 1H), 3.51 (ddd, J = 13.9, 7.0, 5.3
Hz, 1H), 3.30 (s, 3H), 2.19 – 2.03 (m, 3H, αꢀCH2), 1.46 (s, 3H), 1.31 (s, 3H), 0.97 (s,
3H), 0.95 (s, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) = 172.8, 112.7, 107.0, 85.1, 80.0,
77.7, 54.6, 46.2, 38.4, 26.3, 26.1, 24.7, 22.5, 22.5.IR (νmax, cmꢀ1):3335, 2955, 2926,
1729, 1639, 1546, 1369, 1270, 1205, 1191, 1164, 1107, 1094, 1073, 1010. HRMS (ESI):
m/z, calcd for C13H22NO4 [M−OMe]+ 256.1549, found 256.1541; calcd for C14H26NO5
[M+H]+ 288.1811, found 288.1803.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(1ꢀMethylꢀ5ꢀdeoxyꢀ2,3ꢀOꢀisopropylideneꢀβꢀDꢀmannofuranoside)ꢀ5ꢀheptanamide
(31)
Yellow oil, yield: 0.046 g (30%). [α]D20 = + 66.2 (c 0.244, CH2Cl2). Rf = 0.4 (30%
1
ethyl acetate/nꢀhexane). H NMR (400 MHz, CDCl3): δ (ppm) = 5.88 (br, 1H), 4.89 (s,
1H), 4.68 (dd, J = 5.9, 3.7 Hz, 1H), 4.56 (d, J = 5.9 Hz, 1H), 4.10 – 4.04 (m, 1H), 3.74 –
3.66 (m, 1H), 3.53 (ddd, J = 13.9, 7.0, 5.2 Hz, 1H), 3.31 (s, 3H), 2.19 (t, J = 7.8 Hz, 2H),
1.69 – 1.58 (m, 2H), 1.47 (s, 3H),1.31 (s, 3H), 1.38 – 1.23 (m, 6H), 0.88 (t, J = 6.8 Hz,
3H). 13C NMR (75 MHz, CDCl3): δ (ppm) = 173.6, 112.7, 107.1, 85.2, 80.1, 77.6, 54.7,
38.5, 36.9, 31.7, 29.0, 26.1, 25.8, 24.8, 22.6, 14.2. IR (νmax, cmꢀ1): 3330, 2923, 2851,
1734, 1639, 1542, 1377, 1267, 1203, 1095, 1080, 1052, 1010. HRMS (ESI): m/z, calcd
for C15H26NO4 [M−OMe]+ 284.1862, found 284.1874; calcd for C16H30NO5 [M+H]+
316.2124, found 316.2125.
25
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 35
1
2
3
4
5
Nꢀ(6ꢀdeoxyꢀ1,2:3,4ꢀdiꢀOꢀisopropylideneꢀ
benzeneacetamide (32)
αꢀDꢀgalactopyranose)ꢀ5ꢀ
6
7
8
9
White solid, yield: 0.073 g (76%). [α]D20= ꢀ 21.1 (c 0.416, CH2Cl2). m. p.: 92ꢀ94°C.
1
Rf = 0.4 (30% ethyl acetate/nꢀhexane). H NMR (500 MHz, CDCl3): δ = 7.37 – 7.30 (m,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3H), 7.29 – 7.23 (m, 2H), 6.01 – 5.91 (m, 1H), 5.45 (d, J = 4.9 Hz, 1H), 4.56 (dd, J = 7.9,
2.4 Hz, 1H), 4.27 (dd, J = 4.9, 2.4 Hz, 1H), 4.14 (dd, J = 7.9, 1.8 Hz, 1H), 3.86 (ddd, J =
9.0, 3.6, 1.8 Hz, 1H), 3.70 (ddd, J = 13.7, 7.8, 3.6 Hz, 1H), 3.56 (s, 2H), 3.15 (ddd, J =
13.7, 9.0, 4.0 Hz, 1H), 1.44 (s, 3H), 1.39 (s, 3H), 1.31 (s, 3H), 1.30 (s, 3H). 13C NMR
(126 MHz, CDCl3): δ = 171.5, 135.0, 129.5, 129.0, 127.3, 109.5, 108.9, 96.3, 71.7, 70.9,
70.7, 66.5, 43.9, 40.3, 26.1, 26.0, 25.1, 24.3. IR (νmax, cmꢀ1):3307, 2922, 2849, 2360,
1728, 1639, 1547, 1448, 1371, 1252, 1205, 1165, 1066, 1002, 892. HRMS (ESI): m/z,
calcd for C20H28NO6 [M+H]+ 378.1916, found 378.1938.
Nꢀ(6ꢀdeoxyꢀ1,2:3,4ꢀdiꢀOꢀisopropylideneꢀαꢀDꢀgalactopyranose)ꢀ5ꢀ
cyclohexaneacetamide (33)
Yellow solid, yield: 0.044 g (50%). [α]D20= ꢀ 11.8 (c 0.284, CH2Cl2). m. p.: 76ꢀ78
°C. Rf = 0.3 (30% ethyl acetate/nꢀhexane). 1H NMR (500 MHz, CDCl3): δ (ppm) = 5.97 ꢀ
5.89 (m,1H), 5.51 (d, J = 5.0 Hz, 1H), 4.59 (dd, J = 8.0, 2.3 Hz, 1H), 4.30 (dd, J = 5.0,
2.3 Hz, 1H), 4.20 (dd, J = 8.0, 1.1 Hz, 1H), 3.91 – 3.85 (m, 1H), 3.79 (ddd, J = 13.2, 8.1,
3.2 Hz, 1H), 3.13 (ddd, J = 13.2, 9.2, 2.8 Hz, 1H), 2.08 (dd, J = 13.7, 6.5 Hz, 1H), 2.00
(dd, J = 13.7, 7.2 Hz, 1H), 1.82 – 1.61 (m, 6H), 1.47 (s, 3H), 1.45 (s, 3H), 1.34 (s, 3H),
1.32 (s, 3H), 1.29 – 1.20 (m, 2H), 1.20 – 1.08 (m, 1H), 1.00 – 0.86 (m, 2H). 13C NMR
(126 MHz, CDCl3): δ = 172.6, 109.3, 108.7, 96.2, 71.6, 70.7, 70.5, 66.69, 44.9, 39.7,
35.3, 33.1, 32.9, 26.1, 26.0, 26.0, 25.9, 25.9, 24.9, 24.2. IR (νmax, cmꢀ1): 3304, 2921,
2847, 1726, 1638, 1547, 1448, 1371, 1254, 1207, 1165, 1065, 1001. HRMS (ESI): m/z,
calcd for C20H34NO6 [M+H]+ 384.2386, found 384.2390.
26
ACS Paragon Plus Environment

Page 27 of 35
The Journal of Organic Chemistry
1
2
3
4
5
3,3ꢀDimethylꢀNꢀ(6ꢀdeoxyꢀ1,2:3,4ꢀdiꢀOꢀisopropylideneꢀ
butanamide (34)
αꢀDꢀgalactopyranose)ꢀ5ꢀ
6
7
8
9
White solid, yield: 0.048 g (54%). [α]D20= ꢀ 11.2 (c 0.303, CH2Cl2). m.p.: 110ꢀ112
°C. Rf = 0.5 (30% ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 5.89 –
5.81 (m, 1H), 5.51 (d, J = 5.0 Hz, 1H), 4.59 (dd, J = 8.0, 2.3 Hz, 1H), 4.30 (dd, J = 5.0,
2.3 Hz, 1H), 4.23 – 3.17 (m, 1H), 3.91 – 3.85 (m, 1H), 3.81 (ddd, J = 13.9, 8.2, 3.2 Hz,
1H), 3.13 (ddd, J = 13.9, 9.5, 3.8 Hz, 1H), 2.09 (d, J = 12.9 Hz, 1H), 2.03 (d, J = 12.9 Hz,
1H), 1.47 (s, 3H), 1.45 (s, 3H), 1.34 (s, 3H), 1.32 (s, 3H), 1.04 (s, 9H). 13C NMR (101
MHz, CDCl3): δ (ppm) = 172.0, 109.5, 108.9, 96.4, 71.8, 70.9, 70.7, 66.9, 50.8, 39.9,
30.9, 30.0, 26.2, 26.1, 25.1, 24.4. IR (νmax, cmꢀ1):3362, 2985, 2949, 2868, 1727, 1660,
1533, 1507, 1368, 1245, 1211, 1170, 1099, 1066. HRMS (ESI): m/z, calcd for
C18H32NO6 [M+H]+ 358.2230, found 358.2242.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3ꢀMethylꢀNꢀ(6ꢀdeoxyꢀ1,2:3,4ꢀdiꢀOꢀisopropylideneꢀαꢀDꢀgalactopyranose)ꢀ5ꢀ
butanamide (35)
Yellow solid, yield: 0.046 g (54%). [α]D20= ꢀ 14.5 (c 0.291, CH2Cl2). m.p.: 93ꢀ95
°C. Rf = 0.3 (30% ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 5.98 –
5.86 (m, 1H), 5.51 (d, J = 4.9 Hz, 1H), 4.60 (dd, J = 7.9, 2.3 Hz, 1H), 4.31 (dd, J = 4.9,
2.3 Hz, 1H), 4.21 (dd, J = 7.9, 1.6 Hz, 1H), 3.93 – 3.85 (m, 1H), 3.79 (ddd, J = 14.0, 8.1,
3.3 Hz, 1H), 3.15 (ddd, J = 14.0, 9.4, 3.8 Hz, 1H), 2.15 – 1.97 (m, 3H), 1.47 (s, 3H), 1.45
(s, 3H), 1.34 (s, 3H), 1.32 (s, 3H), 0.96 (s, 3H), 0.95 (s, 3H). 13C NMR (101 MHz,
CDCl3): δ (ppm) = 173.0, 109.5, 108.9, 96.4, 71.8, 70.9, 70.7, 66.8, 46.2, 40.0, 26.3,
26.1, 26.1, 25.1, 24.4, 22.7, 22.5. IR (νmax, cmꢀ1):3285, 2957, 2930, 1634, 1549, 1370,
1255, 1207, 1167, 1109, 1065, 1001. HRMS (ESI): m/z, calcd for C17H30NO6 [M+H]+
344.2073, found 344.2054.
27
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 35
1
2
3
Nꢀ(6ꢀDeoxyꢀ1,2:3,4ꢀdiꢀOꢀisopropylideneꢀαꢀDꢀgalactopyranose)ꢀ5ꢀheptanamide
4
5
(36)
6
7
8
Yellow oil, yield: 0.032 g (35%). [α]D20= ꢀ 36.6 (c 0.190, CH2Cl2). Rf = 0.5 (30%
ethyl acetate/nꢀhexane). 1H NMR (300 MHz, CDCl3): δ (ppm) = 5.91 – 5.88 (m, 1H), 5.51
(d, J = 5.0 Hz, 1H), 4.60 (dd, J = 7.9, 2.4 Hz, 1H), 4.31 (dd, J = 5.0, 2.4 Hz, 1H), 4.21
(dd, J = 7.9, 1.9 Hz, 1H), 3.89 (ddd, J = 9.0, 3.4, 1.9 Hz, 1H), 3.77 (ddd, J = 14.0, 8.0,
3.4 Hz, 1H), 3.16 (ddd, J = 14.0, 9.0, 3.7 Hz, 1H), 2.17 (td, J = 7.3, 1.6 Hz, 2H), 1.68 –
1.55 (m, 2H), 1.48 (s, 3H), 1.45 (s, 3H), 1.34 (s, 3H), 1.32 (s, 3H), 1.31 – 1.22 (m, 6H),
0.88 (t, J = 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) = 173.7, 109.5, 108.9, 96.4,
71.8, 70.9, 70.7, 66.7, 40.0, 37.0, 31.7, 29.1, 26.21, 26.1, 25.9, 25.1, 24.4, 22.6, 14.2. IR
(νmax, cmꢀ1): 3307, 2982, 2952, 2928, 2859, 1647, 1536, 1374, 1251, 1210, 1169, 1068,
1004. HRMS (ESI): m/z, calcd for C19H34NO6 [M+H]+ 372.2386, found 372.2387.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(2,3,4,6ꢀTetraꢀOꢀacetylꢀβꢀDꢀglucopyranosyl)ꢀbenzamide (37)
CAS Registry Number 18918ꢀ50ꢀ8
20
Orange Solid, yield: 0.136 g, (60%). [α]D – 10.4 (c 0.777, CH2Cl2). m.p.: 188ꢀ
190 °C. Rf = 0.5 (30% ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3) δ (ppm): 7.75
(d, J = 7.6 Hz, 2H), 7.52 (t, J = 7.6 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.19 (d, J = 9.1 Hz,
1H), 5.45 (t, J = 9.5 Hz, 1H), 5.38 (t, J = 9.5 Hz, 1H), 5.11 (d, J = 9.5 Hz, 1H), 5.06 (d, J
= 9.1 Hz, 1H), 4.33 (dd, J = 12.5, 4.3 Hz, 1H), 4.12 – 4.06 (m, 1H), 3.90 (ddd, J = 9.5,
4.3, 2.1 Hz, 1H), 2.06 – 2.03 (3s, 12H). 13C NMR (75 MHz, CDCl3) δ (ppm): 171.5,
170.7, 170.0, 169.7, 167.3, 132.8, 132.5, 128.8, 127.3, 78.9, 73.6, 72.7, 70.9, 68.3, 61.7,
20.8, 20.7. IR (νmax, cmꢀ1): 3323, 2970, 2944, 2919, 2118, 1742, 1736, 1662, 1527,
1370, 1242, 1219, 1099, 1031. HRMS (ESI): m/z, calcd for C21H26NO10 [M+H]+
452.1551, found 452.1548.
28
ACS Paragon Plus Environment

Page 29 of 35
The Journal of Organic Chemistry
1
2
3
4ꢀMethylꢀNꢀ(2,3,4,6ꢀtetraꢀOꢀacetylꢀβꢀDꢀglucopyranosyl)ꢀbenzamide (38)
4
5
CAS Registry Number 353264ꢀ43ꢀ4
6
7
8
9
White solid, yield: 0.093 g (40%). [α]D20 ꢀ25.3 (c 0.396, CH2Cl2). m.p.: 185ꢀ187 °C.
Rf = 0.5 (30% ethyl acetate/nꢀhexane). 1H NMR (CDCl3, 400MHz): δ (ppm) = 7.66 (d, J =
8.2 Hz, 2H), 7.25 (d, J = 8.2 Hz, 2H), 7.07 (d, J = 9.1 Hz, 1H), 5.44 (t, J = 9.3 Hz, 1H),
5.39 (t, J = 9.3 Hz, 1H), 5.11 (t, J = 9.2 Hz, 1H), 5.07 (t, J = 9.1 Hz, 1H), 4.34 (dd, J =
12.5, 4.2 Hz, 1H), 4.10 (dd, J = 12.5, 2.1 Hz, 1H), 3.90 (ddd, J = 9.3, 4.2, 2.1 Hz, 1H),
2.40 (s, 3H), 2.08 (s, 3H), 2.05 (2s, 6H), 2.03 (s, 3H). 13C NMR (75 MHz, CDCl3): δ
(ppm) = 171.5, 170.7, 170.0, 169.7, 167.2, 143.1, 130.0, 129.5, 127.4, 79.0, 73.6, 72.7,
70.8, 68.3, 61.7, 21.6, 20.8, 20.85, 20.76, 20.7. IR (νmax, cmꢀ1):3262, 2920, 2850, 2108,
1744, 1648, 1547, 1370, 1218, 1027, 1054. HRMS (ESI): m/z, calcd for C22H27NNaO10
[M+Na]+ 488.1527, found 488.1521.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(2,3,4,6ꢀTetraꢀOꢀacetylꢀβꢀDꢀglucopyranosyl)ꢀbenzeneacetamide (39)
CAS Registry Number 439595ꢀ86ꢀ5
Yellow Solid, yield: 0.104 g, (50%). [α]D20 + 0.3 (c 0.946, CH2Cl2). m.p.: 158ꢀ160
°C. Rf = 0.3 (30% ethyl acetate/nꢀhexane). 1H NMR (400 MHz, CDCl3): δ (ppm) = 7.39 –
7.26 (m, 3H), 7.25 – 7.19 (m, 2H), 6.34 (d, J = 9.6 Hz, 1H), 5.26 (t, J = 9.7 Hz, 1H), 5.21
(t, J = 9,7 Hz, 1H), 5.02 (t, J = 9.6 Hz, 1H), 4.83 (t, J = 9.6 Hz, 1H), 4.30 (dd, J = 12.5,
4.3 Hz, 1H), 4.07 (dd, J = 12.5, 2.1 Hz, 1H), 3.81 (ddd, J = 9.7, 4.3, 2.1 Hz, 1H), 3.58 (d,
J = 15.2 Hz, 1H), 3.49 (d, J = 15.2 Hz, 1H), 2.07 (s, 3H), 2.01 (s, 3H), 1.98 (s, 3H), 1.83
(s, 3H). 13C NMR (75 MHz, CDCl3): δ (ppm) = 171.2, 170.5, 170.4, 169.7, 169.4, 133.7,
129.0, 128.9, 127.4, 78.1, 73.4, 72.5, 70.0, 67.9, 61.5, 43.6, 20.6, 20.4, 20.4, 20.2. IR
(νmax, cmꢀ1):3298, 3063, 3032, 2945, 2359, 2107, 1739, 1674, 1539, 1364, 1214, 1028.
HRMS (ESI): m/z, calcd for C22H28NO10 [M+H]+ 466.1708, found 466.1726.
29
ACS Paragon Plus Environment