Synthesis of novel alpha-C-glycosylamino acids and reverse regioselectivity in Larock's heteroannulation for the synthesis of the indole nucleus.

Article abstract of DOI:10.1271/bbb.66.2273

An alpha-C-iodoethynylglucose derivative was coupled with an L-serine-derived zinc-copper reagent to give alpha-C-glucosylpropargyl glycine, which underwent palladium catalyzed-heteroannulation with o-iodoaniline to give not alpha-C-glucosyl-tryptophan bu

Full text of DOI:10.1271/bbb.66.2273

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Synthesis of Novel α-C-Glycosylamino Acids
and Reverse Regioselectivity in Larock's
Heteroannulation for the Synthesis of the Indole
Nucleus
Toshio NISHIKAWAa, Kyoko WADAa & Minoru ISOBEa
a Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya
University Chikusa, Nagoya 464-8601, Japan
Published online: 22 May 2014.
To cite this article: Toshio NISHIKAWA, Kyoko WADA & Minoru ISOBE (2002) Synthesis of Novel α-C-Glycosylamino Acids and
Reverse Regioselectivity in Larock's Heteroannulation for the Synthesis of the Indole Nucleus, Bioscience, Biotechnology,
and Biochemistry, 66:10, 2273-2278, DOI: 10.1271/bbb.66.2273
To link to this article: http://dx.doi.org/10.1271/bbb.66.2273
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Biosci. Biotechnol. Biochem., 66 (10), 2273–2278, 2002
Synthesis of Novel a-C-Glycosylamino Acids and Reverse Regioselectivity
in Larock's Heteroannulation for the Synthesis of the Indole Nucleus
†
Toshio NISHIKAWA, Kyoko WADA, and Minoru ISOBE
Laboratory of Organic Chemistry, Graduate School of Bioagricultural Sciences, Nagoya University,
Chikusa, Nagoya 464-8601, Japan
Received April 24, 2002; Accepted May 31, 2002
An
with an
-glucosylpropargyl glycine, which underwent palladi-
um catalyzed-heteroannulation with -iodoaniline to
give not -glucosyl-tryptophan but -glucosyl-iso
tryptophan. This is the ˆrst observation of complete
reverse regioselectivity to Larock's proposal.
a
-
L
C
-iodoethynylglucose derivative was coupled
b
-
C
-glycosylpropargyl glycine derivatives in diŠerent
ways. These reports prompted us to disclose our un-
reported results of a new convergent synthesis for
-serine-derived zinc-copper reagent to give
a-
C
a
-
o
C
-glucosylpropargyl glycine 3, and the unexpected
a-
C
a
-
C
-
regioselectivity observed in the palladium-catalyzed
heteroannulation between 3 and 4.
The synthesis of
a-C-glucosylpropargyl glycine
was ˆrst examined. Initial attempts to couple lithium
or magnesium acetylide generated from ethynylglu-
Key words:
C
-glycosylamino acid; propargyl glycine;
indole; iso-tryptophan; palladium catalyst
cose 10 (5: R
＝
Bn) with aziridine carboxylic acid 613)
or 3-iodo- b-
L
-serine derivative 714) failed, because of
C
-Glycosylamino acids have attracted considerable
elimination and preferential attack by acetylide to the
carbonyl groups of the carbamate and ester.15,16) We
next turned our attention to an alternative coupling
method with reverse polarity (Scheme 2); that is,
interest for their stable mimic of - and -linked
N
O
glycosylamino acids and glycosidase inhibitors to
elucidate the biological roles of the carbohydrate
moiety of glycopeptide and glycoprotein.1) In the
iodoacetylene 11 as an electrophile and -serine der-
L
course of our synthetic studies on
a
-
C
-mannosyltryp-
ived organozinc-copper reagent 9 as a nucleophile ac-
cording to the Knochel17,18) and Jackson19,20) reports.
Iodoethynylglucose 11 was prepared by iodination21)
tophan (1),2–4) a novel
C
-glycosylamino acid found in
proteins,5,6) we aimed to establish a general synthetic
method for the glucose and galactose analogs of 1 for
a trace analysis of the carbohydrate moiety of this
sugar chain. Our initial synthetic plan for glucose
analog 2 is shown in Scheme 1, which exploits the
palladium-catalyzed heteroannulation developed by
of
sized by highly
derivative with tinacetylene under our established
a
-ethynylglucose 10,11,22) which had been synthe-
a
-selective
C-glycosidation of glucose
conditions,2) while
L
-serine derived Zn-Cu reagent 9
had been prepared from iodoalanine 8 according to
Larock7,8) between
o
-iodoaniline 4 and
C
-glucosyl-
the literature.23,24) These reagents were coupled
together in THF to give a-C-glucosylpropargyl gly-
propargyl glycine 3 as the key reaction. The synthesis
of acetylene counterpart 3 was envisaged by coupling
cine 12 in a moderate yield along with ethynylglucose
10 as a by-product.25) The method described here
should be e‹cient and ‰exible for the synthesis of a
between sugar acetylene 59,10) and an
L
-serine deriva-
tive such as 6 or 7. Dondoni11) and van Boom12) have
independently reported the recent syntheses of and
a
wide variety of C
-glycosylpropargyl glycines.26)
Scheme 1. Retrosynthetic Plan for
a
-
C
-Glycosyltryptophan.
agr.nagoya-u.ac.jp
†
To whom correspondence should be addressed. Fax: +81-52-789-4111; E-mail: isobem
＠

2274
T. NISHIKAWA et al.
Scheme 2. Synthesis of
C
-Glucosylpropargyl Glycine 12.
Scheme 3.
Table. Heteroannulation between Glucosylpropargyl Glycine 12
and -Iodoaniline 4
With the precursor for the heteroannulation in
o
hand, we examined palladium-catalyzed indole syn-
thesis under the conditions reported by Larock7,8)
o
-lodoaniline
Product
z
Yield ( )
(Scheme 3 and Table). When unprotected o-iodoani-
Entry
R
R
line 4a was employed as a coupling partner, a
complex mixture was obtained (entry 1). In sharp
1
2
3
4
4a
H
13a
13b
13c
13d
H
complex mixture
4b
4c
4d
Ac
Boc
Ts
Ac
Boc
Ts
30
30
89
contrast, the reactions with
protected
13b (30
products, but in low yields (entries 2 and 3). We
ˆnally found that -iodo-tosylanilide 4d was the best
coupling partner to aŠord product 13d in about a
90 yield (entry 4). To our surprise, the structures of
N-acetyl and N-Boc-
o
z
-iodoaniline 4b and 4c respectively gave
yield) and 13c (30 yield) as single
z
o
This unexpected result implies unknown important
factor(s) controlling the regioselectivity in this heter-
oannulation. In most of the substrates for the Larock
indole synthesis so far reported, one terminus of the
acetylenes was substituted by a silyl group.31–35) As
tryptophan synthesis by means of the heteroannula-
tion has been reported,36–38) an amino acid functional
group should not interfere with the regioselectivity.
Work on deˆning the origin and mechanism for this
reverse selectivity is currently underway in our
laboratory.
z
these products were determined to be not desired
tryptophan 14, but iso-tryptophan 1327,28) from an
analysis of the NOESY spectra,29) in which correla-
tion between aromatic protons of the Ts group and
the a-proton of the amino acid moiety was observed.
Larock et al. have suggested that the regiochemistry
of this annulation was controlled by steric balance
between two substituents of acetylene to aŠord a
product having a sterically hindered substituent at
the 2-position of indole in high selectivity.7,8,30) As the
carbohydrate moiety of 12 seemed to be larger, a
tryptophan type of product (14) was expected.
However, only iso-tryptophan adducts 13b, 13c and
13d were obtained in these speciˆc cases. To our
knowledge, this is the ˆrst example of complete
reverse regioselectivity in Larock's heteroannulation.
In summary, we developed an e‹cient synthetic
route to
C-glycosylpropargyl glycine and C-glycosyl-
iso-tryptophan. Although the heteroannulation
strategy was revealed to be unsuitable for the synthe-
sis of a-C-glycosyltryptophan, the resulting novel C-
glycosylamino acids might be possible candidates for
biologically active compounds such as enzyme inhibi-

Synthesis of Novel
a
-C-Glycosylamino Acids
2275
tors.39,40)
methyl ester (12). A 20-ml two-necked round-
bottomed ‰ask was charged with zinc-sand (349 mg,
5.34 mmol, Kanto Chemicals) and connected to a
Experimental
vacuum argon line. The ‰ask was evacuated and
W
Infrared spectra were recorded with a Jasco
then ˆlled with argon. This evacuation ˆlling cycle
W
FT IR-8300 spectrophotometer and are reported in
was conducted three times. Dry THF (0.39 ml) and
1,2-dibromoethane (0.019 ml, 0.223 mmol) were
added, and the resulting suspension was heated at
W
wave number (cm„1). Proton nuclear magnetic
resonance (1H-NMR) spectra were recorded with a
Brucker ARX-600 (600 MHz), a Brucker ARX-400
(400 MHz) or a Varian Gemini-2000 (300 MHz) spec-
trometers, and carbon nuclear magnetic resonance
(13C-NMR) spectra were recorded with a ARX-600
(150 MHz), a ARX-400 (100 MHz) or a Varian
Gemini-2000 (75 MHz) spectrometers. Optical rota-
tion values were measured by a Jasco DIP-370 digital
polarimeter, and mass spectra (EI) were recorded by
a Jeol Mstation spectrometer.
609C for 3 min. After cooling to room temperature,
TMSCl (0.023 ml, 0.178 mmol) was added, and the
mixture was sonicated for 30 min. Iodoalanine 8
(586 mg, 1.78 mmol) in dry THF (2.89 ml) was added
via a cannula tubing, and the mixture was sonicated
at 40
zinc reagent as judged by TLC.) The solution of the
zinc reagent was cooled to 0 C, and a solution pre-
9C for 8 hr. (Iodoalanine was converted to the
9
pared from CuCN (159 mg, 1.78 mmol) and LiCl
(151 mg, 3.56 mmol) in dry THF (2.62 ml) was added
2-Iodoethynyl-2,3,4,6-tetra-O-benzyl-
copyranoside (11). To a solution of iodine (454 mg,
1.79 mmol) in benzene (2.4 ml) at 45 C was added
morpholine (0.47 ml, 5.37 mmol) in benzene
(0.57 ml). The dark orange iodo-morpholine com-
plex formed rapidly.
1.79 mmol) in benzene (3.3 ml) was added, and the
mixture was stirred at 45 C for 24 hr. After cooling
a
-
D
-glu-
via a cannula tubing. The mixture was stirred at 0
for 10 min and then cooled to „78 C. The resulting
zinc-copper reagent (9) was added to a stirred
solution of the -1-iodoethynylglucose 11 (307 mg,
0.445 mmol) in THF (2.70 ml) at „78 C in a 30-ml
two-necked round-bottomed ‰ask via a cannula
tubing. The reaction mixture was stirred at „78
for 3 hr, and then at 4 C for an additional 12 hr un-
9C
9
9
a
9
a-1-Ethynylglucose 10 (966 mg,
9
C
9
9
to rt, the hydroiodide salt was removed by suction
ˆltration through ˆlter paper, and the ˆltrate was
diluted with ether. The organic layer was successively
der argon. The reaction was quenched with a saturat-
ed NH4Cl solution, then the mixture was extracted
×
with AcOEt ( 3). The combined organic extract was
successively washed with H2O ( 2), a saturated
washed with a saturated NH4Cl solution (
×
2), satu-
×
×
×
×
×
rated NaHCO3 solution ( 2) and brine ( 2), passed
through a short column packed with anhydrous
Na2SO4, and concentrated. The residue was puriˆed
by silica gel (30 g) column chromatography
NH4Cl solution ( 2) and brine ( 2), dried over
Na2SO4, and concentrated. The residue was puriˆed
by silica gel (30 g) column chromatography
＝
(Et2O:hexane 1:4
ª
1:2) to aŠord 12 (145 mg, 43
z)
(CH2Cl2:hexane
86 ) as a colorless oil. [
IR (KBr)
max cm„1: 3031, 2865, 2178, 1455, 1088. 1H-
NMR (CDCl3, 300 MHz) : 3.60 (1H, dd, 9.5,
9.5 Hz, H-4), 3.65 (1H,
11, 2 Hz, H-6), 3.75 (1H, dd, 11, 3.5 Hz,
9.5 Hz, H-3), 3.93–3.97 (1H,
＝
1:1
ª
2:1) to aŠord 11 (1.02 g,
and -1-ethynylglucose 10 (125 mg, 50
a
z
) as a color-
z
a
]2D3+93.0 (
c
1.11, CHCl3).
less oil. [a
]2D4+72.0 (c 1.05, CHCl3). IR (KBr) nmax
n
cm„1: 3353, 3031, 2876, 2240, 1749, 1718, 1455,
1
d
J
＝
1089. H-NMR (CDCl3, 400 MHz)
d
: 1.38 (9H, s,
16, 5, 2 Hz, H- ),
16, 4, 2 Hz, H- ), 3.58 (1H, dd,
), 3.61 (1H, dd,
＝
＝
6 Hz, H-2), 3.62 (1H, t,
dd,
H-6), 3.92 (1H, t,
m, H-5), 4.47(1H, d,
(1H, d, 12 Hz,
12 Hz, CHA BPh), 4.67 (1H, d,
12.5 Hz, CHC
FPh), 4.83 (1H, d,
J
OC(C
H
3)3), 2.79 (1H, ddd,
J
b
J
＝
J
＝
2.87 (1H, ddd,
J
＝
b
＝
＝
＝
J
J
J
10, 9 Hz, H-4
H-2 ), 3.64 (1H, dd,
COOC 3), 3.71 (1H, dd,
(1H, t,
3.5, 2 Hz, H-5
?
9, 5.5 Hz,
), 3.68 (3H, s,
11, 3.5 Hz, H-6 ), 3.88
＝
H
＝
11, 2 Hz, H-6
J
10 Hz, C
H
EHFPh), 4.47
?
J
?
J
＝
C
AHBPh), 4.60 (1H, d,
H
J
＝
?
＝
J
＝
＝
＝
J
H
J
12.5 Hz,
DPh),
J
9 Hz, H-3
?
), 3.88 (1H, ddd,
10,
AHBPh),
C
H
CHDPh), 4.72 (1H, d,
J
＝
H
?
J
), 4.47 (1H, d,
J
＝
12 Hz, C
H
＝
＝
10.5 Hz, C
4.82 (1H, d,
J
10 Hz, CHE
GHHPh), 4.88 (1H, d,
10.5 Hz, CHG HPh), 7.10–7.38
H
4.48 (1H, d,
H
CHDPh), 4.52 (1H, br
＝
＝
＝
H
＝
J 12 Hz,
J
10.5 Hz, C
H
J
6 Hz, H-1),
dd,
J
8.5, 4.5 Hz, H-
a
) 4.58 (1H, d,
4.99 (1H, d,
J
＝
×
H
CHA
BPh), 4.69 (2H, s, CHEHFPh), 4.70 (1H, dd,
(20H, m, C6H5 4). 13C-NMR (CDCl3, 75 MHz)
d
:
J
5.5, 2 Hz, H-1
?
), 4.81 (1H, d,
J
10.5 Hz,
GHHPh),
＝
CHC
＝
＝
6.0, 68.1, 68.4, 72.9, 73.5, 73.8, 75.3, 75.7, 77.3,
79.0, 83.0, 89.5, 127.66, 127.78, 127.87, 127.98,
128.03, 128.06, 128.14, 128.4, 128.5, 128.6, 137.9,
H
DPh), 4.81 (1H, d,
J
10.5 Hz, C
H
＝
4.98 (1H, d,
J
10.5 Hz, CHGHHPh), 5.54 (1H, d,
＝
J
8.5 Hz, N
7.24–7.39 (18H, m, aromatic). 13C-NMR (CDCl3, 75
MHz ) : 23.3, 28.2, 52.1, 52.6, 66.7, 68.5, 72.8,
H ), 7.12–7.15 (2H, m, aromatic),
138.1, 138.8. MS (FAB) m z 675 (M+H). Anal
.
W
Calcd. for C36H35IO5: C, 64.10; H, 5.23
64.21; H, 5.37
z
. Found: C,
d
z.
73.5, 75.0, 75.7, 77.3, 78.2, 79.0, 80.1, 83.1, 84.5,
127.7, 127.7, 127.9, 128.0, 128.0, 128.1, 128.1,
128.4, 128.5, 138.0, 138.4, 155.3, 171.3. MS (FAB)
(S)-2-tert-Butoxycarbonylamino-5-(2
?,3?,4?,6?-
tetra-O-benzyl- -glucopyranosyl)-pentynoic acid
a
-
D
m z 750 (M+H). Anal. Calcd. for C45H51NO9: C,
W

2276
T. NISHIKAWA et al.
72.07; H, 6.86; N, 1.87
z
. Found: C, 72.09; H, 6.77;
0.030 mmol) in a similar manner to that described for
13b. [
]2D5+6.2 ( 0.39, CHCl3). IR (KBr) nmax cm„1
3336, 3031, 2865, 1733, 1455, 1091. 1H-NMR
(DMSO- 6, at 80 C, 600 MHz) : 1.14 (9H, s,
OC(C 3)3), 1.68 (9H, s, OC(C 3)3), 3.43 (1H, dd,
14, 6 Hz, H- ), 3.52–3.57 (1H, m, H- ), 3.55
(3H, s, COOC
N, 2.00
z.
a
c
:
1-Acetyl-N-(tert-butoxycarbonyl)-3-(2
tetra-O-benzyl- -glucopyranosyl)- -iso-trypto-
phan methyl ester (13b). A 5-ml two-necked round-
bottomed ‰ask was charged with glucosy- -1-
ethynylalanine 12 (29.3 mg, 0.039 mmol), -iodoa-
cetanilide 4b (5.1 mg, 0.0195 mmol), Pd(OAc)2
(1.3 mg, 5.85
10„3 mmol), PPh3 (1.5 mg, 5.85
10„3 mmol),
-Bu4NCl (5.4 mg, 0.0195 mmol) and
Na2CO3 (10.3 mg, 0.0975 mmol) and connected to a
?
,3
?
,4
?
,6
?
-
d
9
d
a
-
D
L
H
H
＝
J
b
H
＝
b
＝
a
3), 3.74 (1H, t,
10.5, 4 Hz, H-6
J
2.5 Hz, H-2
?
J
),
＝
o
3.75 (1H, dd,
10.5, 5 Hz, H-6
4.00 (1H, dd,
12 Hz, C AHBPh), 4.14 (1H, ddd,
H-5 ), 4.39 (1H, d,
(1H, m, H- ), 4.50 (1H, d,
4.53 (1H, d,
11.5 Hz, C
GHHPh), 4.71 (1H, d,
J
?
), 3.78(1H, dd,
＝
?
＝
), 3.92 (1H, dd,
J
8, 5.5 Hz, H-4
?
),
×
n
×
J
5.5, 2.5 Hz, H-3
?), 4.03 (1H, d,
J
＝
＝
H
J
8, 5, 4 Hz,
BPh), 4.48–4.52
12 Hz, C CHDPh),
DPh), 4.58 (1H, d,
EHFPh), 4.69 (1H, d, 12 Hz,
FPh),
＝
12 Hz, CHAH
?
J
＝
vacuum argon line. The ‰ask was evacuated and
a
J
H
W
＝
12 Hz, CHCH
then ˆlled with argon, this evacuation ˆlling cycle
J
W
being conducted three times. These reagents were dis-
solved in DMF (0.88 ml). The mixture was stirred at
J
＝
H
J
＝
＝
H
C
H
J
11.5 Hz, CHE
＝
HPh), 5.38 (1H, d, J
H
＝
90
9
C for 16 hr. After cooling to rt, the reaction was
4.71 (1H, d,
2.5 Hz, H-1
J
12 Hz, CHG
＝
7 Hz, aromatic), 7.06
quenched with a saturated NH4Cl solution, and the
?
), 6.84 (1H, d,
J
×
＝
＝
8 Hz,
mixture was extracted with AcOEt ( 3). The com-
(1H, t,
J
7.5 Hz, aromatic), 7.10 (1H, t,
J
bined organic extract was successively washed with a
H-6), 7.23 (1H, t, J 8 Hz, H-5), 7.25–7.38 (19H, m,
＝
×
×
＝
), 7.50 (1H, d, J
saturated NH4Cl solution ( 2), H2O ( 2) and brine
aromatic & N
H
8 Hz, H-7), 8.01
6, at
: 27.9, 28.0, 28.1, 51.7, 53.0, 68.2,
(
2), passed through a short column packed with
(1H, d,
80
J
8 Hz, H-4). 13C-NMR (DMSO-
d
×
＝
Na2SO4, and concentrated. The residue was puriˆed
by preparative thin-layer chromatography (Et2O:
9
C, 150 MHz)
d
69.6, 71.9, 72.2, 72.7, 74.3, 76.0, 78.5, 79.5, 80.0,
80.1, 80.9, 115.1, 122.2, 123.8, 127.3, 127.4, 127.5,
127.6, 127.7, 127.9, 128.2, 128.28, 128.34, 133.7,
135.8, 138.6, 150.0, 172.4. HRMS(FAB): calcd. for
C56H65N2O11 (M+H), 941.4588; found, 941.4560.
hexane
＝
z
3:1) to aŠord 13b (5.4 mg, 31 ) as a yellow
26
oil. [a
]
+8.2 (
c
0.38, CHCl3). IR (KBr) nmax cm„1
:
D
1
3338, 3029, 2865, 1730, 1677, 1457, 1093. H-NMR
(CDCl3, 400 MHz)
(9H, s, OC(C 3)3), 3.64 (1H, dd,
H- ), 3.65 (1H, t, 2 Hz, H-2
COOC 3), 3.75 (1H, dd,
(1H, dd,
3.5 Hz, H-6
4.01 (1H, dd,
12 Hz,
d
: 1.67 (3H, s, COC
H
3), 1.73
14, 4.5 Hz,
), 3.70 (3H, s,
14, 12 Hz, H- ), 3.82
), 3.87 (1H, dd,
), 3.89 (1H, dd, 5.5, 2 Hz, H-3
), 4.10 (1H, d,
＝
J
H
b
J
＝
?
N-(tert-Butoxycarbonyl)-1-(4-toluenesulfonyl)-3-
＝
?
H
J
b
(2?
,3?
,4
?
,6
?
-tetra-O-benzyl-
a
-
D
-glucopyranosyl)- -
L
＝
?
＝
J
11, 3 Hz, H-6
J
11,
),
iso-tryptophan methyl ester (13d). This was prepared
in an 89 yield by coupling 12 (73 mg, 0.098 mmol)
and 4d (18.2 mg, 0.0488 mmol) in a similar manner
to that described for 13b. [ 0.16, CHCl3).
]2D6+47 (
IR (KBr) nmax cm„1: 3349, 3030, 2867, 1748, 1713,
J
＝
?
z
＝
J
H
8.5, 5.5 Hz, H-4?
AHBPh), 4.31 (1H, d,
J
＝
CHA
C
J
＝
12 Hz,
a
c
＝
H
BPh), 4.32 (1H, ddd,
J
8.5, 3.5, 3 Hz, H-5?),
4.46 (1H, d,
12 Hz,
CHE FPh), 4.58 (1H, d,
4.60 (1H, d, 12 Hz, C GHHPh), 4.71 (1H, d,
12 Hz, CHG HPh), 4.85 (1H, ddd,
H- ), 5.40 (1H, d,
8 Hz, aromatic), 6.90 (1H, d,
J
12 Hz, C
H
CHCPh), 4.50 (1H, d,
12 Hz,
DPh),
1454, 1367, 1175, 1090. 1H-NMR (DMSO-
d
6, at
3)3), 2.09
5.5, 14.5 Hz, H- ),
＝
H3), 3.65 (1H, dd, J 10,
＝
J
＝
C
H
EHFPh), 4.54 (1H, d,
J
＝
80
9
C, 600 MHz)
d
: 1.19 (9H, s, OC(CH
＝
＝
H
J
12 Hz, CHC
H
(3H, s, ArC
H
3), 3.48 (1H, dd,
J
b
J
＝
H
J
＝
3.57 (3H, s, COOC
14.5 Hz, H-
＝
＝
H
J
12, 8, 4.5 Hz,
), 6.90 (1H, d,
8 Hz, aromatic),
b
), 3.64 (1H, t,
J
2.5 Hz, H-2
?
), 3.70
＝
＝
a
＝
J
2 Hz, H-1
?
(1H, dd,
J
4.5, 11 Hz, H-6
?
), 3.72(1H, dd,
J
J
＝
J
＝
5, 11 Hz, H-6
?
), 3.76 (1H, d, J
＝
12 Hz,
＝
5.5, 7.5 Hz, H-4?), 3.89
7.05–7.17 (5H, m, H-6, H-7 & aromatic), 7.23–7.38
(16H, m, H-5 & aromatic), 7.61 (1H, d,
), 8.09 (1H, d,
(CDCl3, 100 MHz)
C
H
AHBPh), 3.83(1H, dd,
J
J
＝
8.5 Hz,
(1H, dd,
J
＝
2.5, 5.5 Hz, H-3
?
), 4.03 (1H, d,
N
H
J
8.5 Hz, H-4). 13C-NMR
J
12 Hz, CHA
H
BPh), 4.06 (1H, ddd,
J
4.5, 5,
＝
＝
＝
＝
d
: 22.6, 28.3, 29.2, 51.4, 52.1,
7.5 Hz, H-5
?
), 4.46 (1H, d,
J
12 Hz, C
H
CHDPh),
68.5, 68.7, 72.2, 72.9, 73.1, 73.3, 73.4, 76.2, 78.4,
80.9, 84.8, 116.2, 116.9, 117.4, 122.6, 124.1, 127.8,
127.8, 127.9, 128.0, 128.4, 128.6, 134.9, 136.0,
137.3, 137.9, 138.3, 150.3, 170.4, 173.1. MS(FAB)
4.49 (1H, d,
J 12 Hz, CHCHDPh), 4.51 (1H, d,
＝
＝
J
11.5 Hz, CHEHFPh), 4.58 (2H, s, CHGHHPh),
＝
11.5 Hz, CHEHFPh), 4.62 (1H, m,
4.63 (1H, d,
H- ), 5.31 (1H, d,
7.5 Hz, aromatic), 7.04 (2H, t,
7.10 (1H, t, 8 Hz, H-6), 7.10 (2H, d,
H-3 of Ts), 7.09–7.11 (1H, aromatic), 7.20 (1H, d,
J
＝ ＝
2.5 Hz, H-1?), 6.69 (2H, d, J
a
J
＝
m z 883 (M+H). HRMS(FAB): calcd. for
J
7.5 Hz, aromatic),
8.5 Hz,
W
C53H59N2O10 (M+H), 883.4170; found, 883.4101.
J
＝
J
＝
!
8 Hz,
＝
＝
8 Hz, H-5),
N,1-bis(tert-Butoxycarbonyl)-3-(2
O-benzyl- -glucopyranosyl)- -iso-tryptophan
methyl ester (13c). This was prepared in a 30 yield
by coupling 12 (22 mg, 0.030 mmol) and 4c (10.0 mg,
?
,3
?
,4
?
,6
?
-tetra-
J
N
H
), 7.26 (1H, t,
J
＝
a
-
D
L
7.23–7.31(15H, m, aromatic), 7.46 (1H, d,
J
8 Hz,
of Ts), 8.01 (1H,
8 Hz, H-4). 13C-NMR (DMSO-
6, at 80 C,
＝
8.5 Hz, H-2!
z
H-7), 7.51 (2H, d,
d,
J
J
＝
d
9

Synthesis of Novel
a
-C-Glycosylamino Acids
2277
stereoselective synthesis of ethylene isosterers of
a-
150 MHz)
d
: 20.8, 28.1, 28.9, 51.8, 54.2, 68.0, 69.4,
and
b-glycosylasparagines. Tetrahedron Lett., 41,
71.9, 72.1, 72.3, 72.7, 74.2, 75.9, 78.6, 79.4, 79.8,
114.6, 121.6, 124.6, 127.3, 127.3, 127.3, 127.4,
127.5, 127.6, 127.7, 128.2, 128.3, 134.1, 136.3,
3483–3486 (2000).
12) Turner, J. J., Leeuwenburgh, M. A., van der Marel,
G. A., and van Boom, J. H., A convenient route to a-
138.5, 145.1, 172.3. MS(FAB) m z 995 (M+H).
HRMS(FAB): calcd. for C58H63N2O11S (M+H),
995.4153; found, 995.4075.
W
amino acids with b-alkyne substituents from a serine
derived aziridine. Tetrahedron Lett., 42, 8713–8716
(2001).
13) Church, N. J., and Young, D. W., Synthesis of
Acknowledgments
stereospeciˆcally labeled
D
-prop-2-ynylglycine and in-
-amino acid oxidase. J.
vestigation of the action of
D
We are grateful to Professor J. M. Cook (Univer-
sity of Wisconsin-Milwaukee) for valuable discussion
and encouragement to publish our preliminary
results. We also thank Mr. K. Koga (analytical
laboratory in this school) for measurement of 2D
NMR spectra. This work was ˆnancially supported
by JSPS-RFTF (96L00504) and by a Grant-in-Aid
for Scientiˆc Research from the Ministry of Educa-
tion, Science, Sports, and Culture of Japan (No.
12760077).
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14) Bajgrowicz, J. A., Hallaoui, A. El., Jacquier, R.,
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