Protecting group free synthesis of urea-linked glycoconjugates: Efficient synthesis of β-urea glycosides in aqueous solution

Article abstract of DOI:10.1039/c3ob42452a

A method for the protecting group free synthesis of β-urea-linked glycoconjugates has been developed. The one step process, involving reactions between urea and d-glucose, N-acetyl-d-glucosamine or d-xylose in acidic aqueous solution, furnishes the corresponding β-urea glycosides in modest yields. This simple and efficient procedure is applicable to the synthesis of β-urea tethered amino acid-carbohydrate conjugates. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c3ob42452a

Organic &
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Protecting group free synthesis of urea-linked
glycoconjugates: efficient synthesis of β-urea
glycosides in aqueous solution†
Cite this: Org. Biomol. Chem., 2014,
12, 3924
Yoshiyasu Ichikawa,*a Takahiro Minami,a Shohei Kusaba,a Nobuyoshi Saeki,a
Yuta Tonegawa,a Yumiko Tomita,a Keiji Nakano,a Hiyoshizo Kotsukia and
Toshiya Masudab
A method for the protecting group free synthesis of β-urea-linked glycoconjugates has been developed.
The one step process, involving reactions between urea and D-glucose, N-acetyl-D-glucosamine or D-
xylose in acidic aqueous solution, furnishes the corresponding β-urea glycosides in modest yields. This
simple and efficient procedure is applicable to the synthesis of β-urea tethered amino acid–carbohydrate
conjugates.
Received 11th December 2013,
Accepted 8th March 2014
DOI: 10.1039/c3ob42452a
www.rsc.org/obc
In 1926, Helferich, a former student of Emile Fischer,
reported the reaction of glucose with methyl-harnstoff
Introduction
The urea glycosyl linkage has been known to occur in Nature (N-methylurea) in aqueous 6.5 M HCl to obtain ‘d-glucose-
as a unique and important structural motif found in members monomethyureid’ (eqn (1)).8
of the glycocinnamoylspermidine amino-sugar antibiotic
family.1 In these natural products, two amino sugars are con-
nected via a urea glycosyl bond. Moreover, the synthesis of
neoglycoconjugates, in which native and enzymatically labile
glycosidic bonds are replaced by robust non-native linkers, has
ð1Þ
received considerable recent attention due to the increasing
In 1953, Erickson investigated the reaction of long-chain
need to develop a new type of molecular tool in glycobiology
octadecylurea with D-glucose.9
and potential therapeutic agents.2
The observations made in these two precedents suggest
Replacement of naturally occurring O- and N-glycosyl lin-
that direct coupling of N-substituted ureas with unprotected
kages with urea–glycosyl bonds is one strategy used to design
carbohydrates could serve as a general method for the prepa-
new neoglycoconjugates.3 Although a number of new synthetic
ration of urea glycosides. However, the reliability of the two
methods to access urea glycosides have been devised by us4
reports was questionable owing to the fact that both Helferich
and other groups,5 all methods require the use of protected
and Erickson characterized the reaction products only using
carbohydrates as intermediates. As a result, the reported
melting point, elemental analysis and optical rotation data.
synthetic routes to urea glycosides are often lengthy, as a con-
Furthermore, the yields in the reported reactions were exceed-
sequence of the need for protection/deprotection steps.6
ingly low and the stereochemistry at the anomeric position of
The shortcomings of routes to urea glycosides that rely on
the products was not determined. As a result of these issues,
the use of protected carbohydrates have directed our attention
we have carried out an investigation of the one-step, acid pro-
to a classical method involving acid-catalyzed condensation
moted reactions of N-substituted ureas with carbohydrates.
reaction of glucose with urea in water.7 Although well docu-
This effort has led to the development of a unique and
mented, the application of this process to reaction of N-substi-
efficient protecting group free method for the synthesis of
tuted urea derivatives is both rare and questionable.
urea-linked glycoconjugates.10
aFaculty of Science, Kochi University, Akebono-cho, Kochi 780-8520, Japan.
E-mail: ichikawa@kochi-u.ac.jp
bFaculty of Integrated Arts and Sciences, University of Tokushima, Tokushima
Results and discussion
770-8502, Japan
In the initial phase of this study, we aimed at the characteriz-
ation of the product (d-glucose-monomethyureid) formed in
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ob42452a
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Scheme 2 Synthesis of α-1-methyl-3-glucosylurea from α-glucosyl
isocyanide.
Scheme 1 Synthesis of β-1-methyl-3-glucosylurea from β-glucosyl
isocyanide.
the reaction between glucose and N-methylurea reported by
Helferich. For this purpose, we prepared the anomeric pair of
1-methyl-3-glucosylurea by employing our previously estab-
lished “isocyanide method” (Scheme 1).11 Starting with com-
mercially available pentaacetyl-β-D-glucose (1), β-glucosyl
isocyanide 4 was prepared in a three step sequence involving
(i) azide glucosylation of 1, (ii) catalytic hydrogenation of azide
2 followed by formylation of the produced glucosyl amine, and
(iii) dehydration of glucosyl formamide 3 with triphosgene and
triethylamine. Oxidation of β-glucosyl isocyanide 4 with pyri-
dine N-oxide in the presence of a catalytic amount of iodine
and MS 3A (anhydrous conditions) generated the highly reac-
tive glucosyl isocyanate 5, which, without isolation, was treated
with methylamine. This process formed β-1-methyl-3-glucosy-
lurea 6a in 90% yield. A similar set of transformations starting
with α-glucosyl isocyanide 10, prepared from 1 in four steps,
afforded α-1-methyl-3-glucosylurea 6b in 90% yield (Scheme 2).
With tetraacetyl derivatives of the two anomeric 1-methyl-3-
Scheme 3 Synthesis of 1-methyl-3-glucosylurea.
glucosylureas in hand, we next explored the acid-catalyzed con- pyridine followed by chromatography produced a mixture of
densation reaction of D-glucose (12) with N-methylurea in tetraacetyl β- and α-1-methyl-3-glucosylureas (6a and 6b) in a
water as described by Helferich (Scheme 3). Initial experi- 94 : 6 ratio and a 68% yield. The products of this process were
ments using the reported conditions (2.4 equivalents of found to be identical to the independently synthesized gluco-
N-methylurea, aqueous 6.5 M HCl at 50 °C for 16 d) gave only syl ureas (Schemes 1 and 2).
trace amounts of products. After some experiments using
In order to demonstrate that our approach is truly ‘protect-
varying acid catalysts (HCl, H2SO4, acidic resins), varying ing free’, we further examined the work-up procedure to obtain
amounts of N-methylurea, and a range of temperatures and a non-acylated N-methylurea glucoside. After some experi-
time periods, we found that this reaction, when using 6 M ments, it was found that simply treating the reaction mixture
HCl, a ten equivalent excess N-methylurea, room temperature with methanol and ether led to crystallization of the product.
and a three-day time period, resulted in higher product yields. As a result, non-acylated N-methylurea glucoside 6c was iso-
Specifically, neutralization of the crude reaction mixture with lated as crystals in 70% yield.
sodium bicarbonate followed by concentration in vacuo
The high β-selectivity in this process is presumably the con-
afforded a solid residue, which when treated with Ac2O and sequence of the fact that the reaction most likely proceeds
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under thermodynamically controlled conditions and that able yields (entries A and B, 67% and 56%, respectively) and
the urea group displays only a small anomeric effect.12 high β-selectivities (13a/13b = 93 : 7 and 14a/14b = 93 : 7).13 To
The product distribution dominating the formation of our disappointment, cyclohexylurea and (R)-α-methylbenzyl-
β-anomer 6a over α-isomer 6b seems to reflect the sterically urea, both of which possess α-alkyl branching, reduced the
driven preference for the bulky urea substituents at the pyra- yield considerably (Method A, entries C and D, 26% and 24%,
nose anomeric position to occupy the equatorial position.
respectively). Also, reactions with pyrrolidineurea and N,N-
In order to explore the scope of the process in Scheme 3, we dimethylurea took place in low yields (Method A, entries E and
examined the synthesis of a number of urea glucosides F, 10% and 6%, respectively). In addition to the low yields, we
(Table 1, Method A: 10 equivalents of urea, 6 M HCl, room sometimes encountered problems in purification steps to
temperature and a three-day reaction time). The results show remove excess amounts of urea.
that reactions employing n-butyl and β-phenethyl urea gener-
In order to increase the yield and to reduce the amount of
ated the corresponding urea glucosides 13 and 14 in reason- loading urea, we further investigated the conditions which led
Table 1 Protecting group free synthesis of N-substituted urea glucosides
Method A
Method B
Entrya
A
Urea glucoside (R =)
6 M HCl yieldb (ratio = β/α)c
67% (93 : 7)
2.4 M HCl–solvent (ratio), yield (ratio = β/α)
2.4 M HCl–CH3CN (1 : 4), 65% (92 : 8)
B
C
56% (93 : 7)
26% (92 : 8)
2.4 M HCl–CH3CN (1 : 4), 63% (90 : 10)
2.4 M HCl–AcOEt (1 : 6), 68% (>98 : 2)
D
24% (>98 : 2)
2.4 M HCl–CH3CN (1 : 6), 72% (>98 : 2)
E
F
10% (97 : 3)
6% (97 : 3)
2.4 M HCl–AcOEt (1 : 6), 27% (97 : 3)
2.4 M HCl–AcOEt (1 : 1), 40%b (95 : 5)
2.4 M HCl–AcOEt (1 : 2), 30% (97 : 3)
2.4 M HCl–AcOEt (1 : 1), 51%b (97 : 3)
a The reaction was carried out on the 300 mg scale of D-glucose (12). b Yields obtained employing 10 equiv. of urea. c The ratio was determined by
1H NMR analysis of the crude products after acetylation.
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to the observation that employing 2.4 M HCl, co-solvents such Preliminary experiments, which revealed that acetonitrile is a
as ethyl acetate or acetonitrile, two equivalents of each urea, poor co-solvent to solubilize N-acetyl-D-glucosamine (19),
and a shorter reaction time (ca. 24 h) brought about much suggested that ethyl acetate should be used as the co-solvent.
more efficient glucosyl urea formation (Method B). In the case In addition, five equivalents of urea were necessary to obtain
of n-butylurea and phenethylurea (Method B, entries A and B), reasonable yields. By using modified Method B, we obtained
two equivalents of urea were enough to produce the products the corresponding urea glucosamides 20–23 (entries A to D) in
in similar yields to those of Method A. Glucosylation of cyclo- similar yields to those observed for reactions of D-glucose
hexylurea and (R)-α-methylbenzylurea employing Method B (Table 1, entries A to D). Unfortunately, in the case of pyrrol-
raised the yields considerably (entries C and D; 68 and 72%). idine urea (entry E), a low yield (5%) of the urea glucosamide
Although yields in the case of ureas derived from secondary 24 was obtained. In each case, the β-anomer was formed exclu-
amines were still low even using Method B (entries E and F, 27 sively. The structures of 21, 22 and 24 were unambiguously
and 30%), increases in the amounts of the ureas (10 equiv.) confirmed by comparison with previously reported samples
cause a significant improvement in the yields (Method B, prepared from 19 using the isocyanide method (eqn (2)).3 Pro-
entries E and F, 40 and 51%). It should be noted that all reac- tecting group free synthesis of urea glucosamides shows that
tions using Method B generated products with a high degree this method is a convenient short step synthesis of β-urea glu-
of β-selectivity (>90 : 10). Moreover, due to the high crystalline cosamides in which urea moieties are derived from primary
nature of β-urea glucosides, the minor α-anomers were easily amines.
removed by recrystallization.
Table 2 Synthesis of β-urea glucosamides starting from N-acetyl-D-
glucosamine (19)
ð2Þ
Further studies aimed at broadening the substrate scope of
the process led us to explore the urea forming reaction of
D-xylose (26) using Method B (Table 3). We were delighted to
find that D-xylose (26) is a better substrate than hexoses, giving
good yields of urea xylosides 27–30 (entries A to D, 71–89%)
with a high degree of β-selectivity (≥98 : 2). Even in the
reaction with pyrrolidineurea (entry E), the corresponding
urea xyloside 31 was obtained in modest (41%) yield. The
structures and β/α-selectivity of the products (27–31) were
unambiguously determined by comparison with authentic
samples synthesized by using the isocyanide method
(Scheme 4).14
Having developed an efficient method for the synthesis of
β-urea glycosides starting with unprotected carbohydrates, our
attention was next focused on its application to the synthesis
of urea-tethered amino acid–carbohydrate conjugates. For this
purpose, we examined how to install a urea group on a lysine
derivative 35 (Scheme 5). Amide formation of 35 with
dimethylamine using EDC in the presence of HOBt and depro-
tection of the N-Boc group in 36 with TFA produce the amine
37. Transcarbamoylation of phenyl carbamate with 37 in the
presence of the catalyst dibutyltin maleate furnished urea 38
in 80% yield.15
Entrya
A
Urea glucoside (R =)
Yield (%)
49
B
C
D
45
57
48
E
5
Reactions of urea 38 (2 equiv.) with D-glucose (12) in 2.4 M
HCl and co-solvents were examined (Table 4). Although we
could obtain the desired amino acid–glucose conjugate 39
with high β-selectivity, the yields were low in each co-solvent,
a The reaction was carried out on the 300 mg scale of N-acetyl-D-
glucosamine (19).
The potential generality of the protecting group free syn- acetonitrile (entry A, 9%, β/α = 91 : 9) and ethyl acetate
thesis of urea glycosides was explored using N-acetyl-D-glucos- (entry B, 19%, β/α = 96 : 4). Although raising the stoichiometry
amine (19) as a substrate and Method B conditions (Table 2). of urea 38 to 5 equivalents and the use of acetonitrile as a
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Table 3 Protecting group free urea glycosylation of D-xylose (26)
Entrya
A
Urea glucoside (R =)
2.4 M HCl–solvent (ratio)
2.4 M HCl–CH3CN (1 : 4)
Yieldb (%)
73
β/αb
98 : 2
B
C
2.4 M HCl–CH3CN (1 : 4)
2.4 M HCl–AcOEt (1 : 6)
71
89
>98 : 2
>98 : 2
D
E
2.4 M HCl–CH3CN (1 : 6)
78
>98 : 2
2.4 M HCl–AcOEt (1 : 6)
41
>98 : 2
a The reaction was carried out on the 300 mg scale of D-xylose (26). b The ratio was determined by 1H NMR analysis of the crude products after
acetylation.
Scheme 5 Setting up a urea group on lysine derivative 35.
Scheme 4 Independent synthesis of urea xylosides.
co-solvent gave the product in only 20% yield (entry C),
employing ethyl acetate as a co-solvent improved the yield to
an acceptable level (entry D, 51%, β/α = 95 : 5). The presence of
the α-isomer 39b and the determination of the β/α-selectivities
of the reactions were made possible by the availability
of authentic samples of 39a and 39b, prepared by the
isocyanide method starting with isocyanides
(Scheme 6).
4 and 10
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simple method for the preparation of β-urea glycosides in
which urea moieties contain primary amines. While the yields
are only moderate, the reactions are both scalable and highly
β-selective. This protecting group free method is complemen-
tary to the one developed earlier based on reactions of glycosyl
isocyanide intermediates.
Table 4 Synthesis of urea-tethered amino acid–carbohydrate
conjugate
Experimental
Synthesis of N′-methyl-N-2,3,4,6-tetra-O-acetyl-β-D-
glucopyranosyl urea (6a) employing Method A
A solution of D-glucose (12) (500 mg, 2.78 mmol) and 1-methyl-
urea (2.10 g, 27.8 mmol) in 6 N HCl (2.0 ml) was stirred at
room temperature for 3 days. The reaction mixture was neutral-
ized with solid NaHCO3 and washed with CH2Cl2 to remove
excess 1-methylurea. The aqueous layer was concentrated
under reduced pressure to give crude urea glucoside as solids
(2.68 g), which were dissolved in a mixture of pyridine (12 ml)
and Ac2O (6.0 ml). The solution was stirred at 50 °C for
3 hours, and the resulting reaction mixture was treated with
saturated aqueous NaHCO3. The aqueous layer was extracted
with Et2O, and the combined organic layers were washed with
brine, dried (Na2SO4) and then concentrated under reduced
Entry
Urea (eq)
2.4 M HCl–solvent (ratio)
Yield (%)
β/αa
A
B
C
D
2.0
2.0
5.0
5.0
2.4 M HCl–CH3CN (1 : 4)
2.4 M HCl–AcOEt (1 : 6)
2.4 M HCl–CH3CN (1 : 4)
2.4 M HCl–AcOEt (1 : 6)
9
19
20
51
91 : 9 pressure. The resulting residue was purified by silica gel
96 : 4
chromatography (2 : 1 AcOEt–hexane) to afford a mixture of
92 : 8
95 : 5
1-methyl-3-glucosylurea 6 (764 mg, 68%, 6a : 6b = 94 : 6): Mp
195–196 °C (recrystallized from AcOEt–hexane); [α]2D7 = +2.87
a The ratio was determined by 1H NMR analysis of the crude products
after acetylation.
(c 1.00, CHCl3) IR (KBr) νmax 3323, 2939, 2355, 1755,
1
1739 cm−1; H NMR (CDCl3, 500 MHz) δ 2.01 (s, 3H), 2.03 (s,
3H), 2.05 (s, 3H), 2.07 (s, 3H), 2.76 (d, J = 4.5 Hz, 3H), 3.83
(ddd, J = 9.5, 4.5, 2.5 Hz, 1H), 4.09 (dd, J = 12.0, 2.5 Hz, 1H),
4.30 (dd, J = 12.0, 4.5 Hz, 1H), 4.83 (q, J = 4.5 Hz, 1H), 4.90 (t,
J = 9.5 Hz, 1H), 5.06 (t, J = 9.5 Hz, 1H), 5.17 (t, J = 9.5 Hz, 1H),
5.31 (t, J = 9.5 Hz, 1H), 5.49 (d, J = 9.5 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) δ 20.35, 20.38, 20.5, 26.6, 61.8, 68.2, 70.2,
72.8, 72.9, 79.8, 157.4, 169.5, 169.7, 170.41, 170.46. Anal. calcd
for C16H24N2O10: C, 47.52; H, 5.98; N, 6.93. Found: C, 47.72;
H, 6.03; N, 6.94.
Synthesis and isolation of N′-methyl-N-β-D-glucopyranosyl
urea (6c)
To a solution of D-glucose (12) (1.0 g, 5.74 mmol) and N-methyl
urea (2.0 g, 24.4 mmol) in water (1.0 ml) was added conc. HCl
(1.0 ml). After being stirred at room temperature for 3 days,
MeOH (20 ml) and Et2O (35 mL) were added. After keeping the
mixture at 0 °C for 2 days, the crystals formed were collected,
washed with MeOH (5.0 ml) and Et2O (5.0 ml), and air-dried
to furnish 1-methyl-3-glucosylurea 6c (946 mg, 70%) as color-
less crystals; mp 208–209 °C (recrystallized from methanol and
Scheme 6 Independent synthesis of urea-tethered amino acid–carbo-
hydrate conjugates 39a and 39b.
Conclusion
ether); [α]2D5 −29.9 (c 1.00, H2O); IR (KBr) νmax 3449, 3336,
1
An investigation of the reaction of glucose with N-substituted 2918, 2869, 1672, 1574, 1514, 1301, 1084 cm−1; H NMR (D2O,
urea is revisited over 88 years since the report by Helferich,
which led to a protecting group free method for the synthesis
500 MHz) δ 2.72 (s, 3H), 3.35 (brt, J = 9.5 Hz, 1H), 3.39 (t, J =
9.5 Hz, 1H), 3.48–3.57 (m, 1H), 3.54 (t, J = 9.5 Hz, 1H), 3.71
of urea glycosides. The established process is a good and (dd, J = 12.0, 5.5 Hz, 1H), 3.88 (dd, J = 12.0, 5.5 Hz, 1H), 4.84
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(brd, J = 9.5 Hz, 1H); 13C NMR (D2O, 100 MHz) δ 26.8, 61.3,
67.2, 70.0, 72.5, 77.2, 77.6, 81.7, 160.8. HRMS(ESI): m/z calcd
for C8H17N2O6 [M + H]+ 237.1087, found 237.1081; m/z calcd
for C8H16N2O6Na [M + Na]+ 259.0906, found 259.0917.
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General method for the synthesis of N-substituted urea
glucosides using Method B
N′-Butyl-N-2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl urea (13a).
A solution of D-glucose (12) (300 mg, 1.67 mmol) and n-butyl-
urea (387 mg, 3.33 mmol) dissolved in a mixture of CH3CN
(1.0 mL) and 2.4 N HCl (0.25 mL) was stirred at 50 °C for
1 day, and was then neutralized with solid NaHCO3. The result-
ing reaction mixture was diluted with H2O (ca. 2.0 mL) and
washed with CH2Cl2. The separated aqueous layer was
extracted with n-BuOH, and the combined organic extracts
were concentrated under reduced pressure to afford the solids.
The resulting crude product was dissolved in a mixture of
pyridine (10 mL) and Ac2O (5.0 mL). The solution was stirred
at 50 °C for 3 hours, and diluted with saturated aqueous
NaHCO3. The separated aqueous layer was extracted with Et2O.
The combined organic layers were washed with brine, dried
(Na2SO4) and then concentrated under reduced pressure. The
resulting residue was purified by silica gel chromatography
(2 : 1 AcOEt–hexane) to afford n-butylurea glucoside 13a as a
white solid (485 mg, 65%, β : α = 92 : 8): mp 97–98 °C (recrystal-
lized from AcOEt–hexane); [α]2D6 = +1.46 (c 1.00, CHCl3); IR
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1
(KBr) νmax 3369, 2960, 2875, 2359, 2342, 1752 cm−1; H NMR
(CDCl3, 500 MHz) δ 0.91 (t, J = 7.0 Hz, 3H), 1.32 (sept, J =
7.0 Hz, 2H), 1.45 (quint, J = 7.0 Hz, 2H), 2.01 (s, 3H), 2.03 (s,
3H), 2.05 (s, 3H), 2.07 (s, 3H), 3.10–3.17 (m, 2H), 3.82 (ddd, J =
9.5, 4.5, 2.5 Hz, 1H), 4.09 (dd, J = 12.5, 2.5 Hz, 1H), 4.32 (dd,
J = 12.5, 4.5 Hz, 1H), 4.72 (t, J = 5.5, 1H), 4.90 (t, J = 9.5 Hz,
1H), 5.06 (t, J = 9.5 Hz, 1H), 5.16 (t, J = 9.5 Hz, 1H), 5.30 (t, J =
9.5 Hz, 1H), 5.36 (d, J = 9.5 Hz, 1H); 13C NMR (CDCl3,
125 MHz) δ 13.7, 20.0, 20.5, 20.6, 20.7, 32.0, 40.0, 61.8, 68.3,
70.5, 72.9, 73.0, 80.1, 156.3, 169.6, 169.8, 170.6, 170.9; HRMS
(ESI): m/z calcd for C19H31N2O10 [M + H]+ 447.1979, found
447.1989.
Acknowledgements
Financial support for this study provided by the Kochi Univer-
sity President’s Discretionary Grant is greatly appreciated.
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Notes and references
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537; (c) K. Dobashi, K. Nagaoka, Y. Watanabe, M. Nishida, 10 This work has been communicated in a preliminary form:
M. Hamada, H. Naganawa, T. Takita, T. Takeuchi and
Y. Ichikawa, S. Kusaba, T. Minami, Y. Tomita, K. Nakano
H. Umezawa, J. Antibiot., 1985, 38, 1166–1170;
and H. Kotsuki, Synlett, 2011, 1462–1466.
3930 | Org. Biomol. Chem., 2014, 12, 3924–3931
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Paper
11 (a) Y. Ichikawa, T. Nishiyama and M. Isobe, Synlett, 2000,
1253; (b) Y. Ichikawa, T. Nishiyama and M. Isobe, J. Org.
Chem., 2001, 66, 4200–4205.
of α-urea glucosides 13b, 14b, 16b and 18b were
prepared by the isocyanide method. For their syntheses,
see ESI.†
12 Y. Ichikawa, H. Watanabe, H. Kotsuki and K. Nakano, 14 For the synthesis of an anomeric pair of pyrrolidine urea
Eur. J. Org. Chem., 2010, 6331–6337.
13 For β-urea glucosides 13a, 14a, 15a and 17a and α-urea glu-
cosides 15b and 17b, their structures and stereoselectivities
xylosides 31a and 31b, see ref. 12. Other urea α-xylosides
27b–30b were prepared by the isocyanide method starting
with α-isocyanide 34.
(β/α) were determined by comparing with authentic 15 Y. Ichikawa, Y. Morishita, S. Kusaba, N. Sakiyama, Y. Matsuda,
samples reported in ref. 11 and 4f. Authentic samples
K. Nakano and H. Kotsuki, Synlett, 2010, 1815–1818.
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 3924–3931 | 3931