Welcome to LookChem.com Sign In|Join Free

Article Doi

Preparation of C-glycoside pendant β2 - and β2,2 -amino acids

DOI: 10.1246/bcsj.81.606

Source and publish data:

Bulletin of the Chemical Society of Japan p. 606 - 616 (2008)

Update date:2022-08-04

Topics:

Authors:

Inaba, YokoInaba, Yoko

Yano, ShigenobuYano, Shigenobu

Mikata, YujiMikata, Yuji

Read Full Text PDF DownLoad Join now for total 90,000,000 free articles

Article abstract of DOI:10.1246/bcsj.81.606

Facile preparations of C-glycosyl β2- and β2,2-amino acids are described. Selective formation of a β-C-glycoside linkage was achieved by the reaction of a 2,3,4,6-tetra-O-acetyl-a-D-gluco/galactopyranosyl bromide (α-acetobromo- glucose/galactose) with the carbanion of a cyanoacetate ester. Crystallization selectively afforded one of two diastereomers with respect to the chiral center at the α-carbon of the side chain (C-2), however, this compound was found to epimerize during the following nitrile reduction. Separation of the diastereomers was achieved via the Fmoc derivatives. Diastereomerically pure C-glycosyl β2,2-amino acids were prepared by diastereoselective alkylation of C-glycosylated enolate, followed by nitrile hydrogenation. The present procedure serves as an efficient route to C-glycosylated β-amino acids containing a non-biodegradable linkage.

View More

Full text of DOI:10.1246/bcsj.81.606

606 Bull. Chem. Soc. Jpn. Vol. 81, No. 5, 606–616 (2008)  
Ó 2008 The Chemical Society of Japan  
Preparation of C-Glycoside Pendant ꢀ2- and ꢀ2;2-Amino Acids  
y
ꢀ2  
Yoko Inaba,1 Shigenobu Yano,1; and Yuji Mikata  
1Department of Interdisciplinary Materials Science, Nara Women’s University, Nara 630-8506  
2Kyousei Science Center for Life and Nature, Nara Women’s University, Nara 630-8506  
Received August 16, 2007; E-mail: mikata@cc.nara-wu.ac.jp  
Facile preparations of C-glycosyl ꢀ2- and ꢀ2;2-amino acids are described. Selective formation of a ꢀ-C-glycoside  
linkage was achieved by the reaction of a 2,3,4,6-tetra-O-acetyl-ꢁ-D-gluco/galactopyranosyl bromide (ꢁ-acetobromo-  
glucose/galactose) with the carbanion of a cyanoacetate ester. Crystallization selectively afforded one of two diaster-  
eomers with respect to the chiral center at the ꢁ-carbon of the side chain (C-2), however, this compound was found  
to epimerize during the following nitrile reduction. Separation of the diastereomers was achieved via the Fmoc deriv-  
atives. Diastereomerically pure C-glycosyl ꢀ2;2-amino acids were prepared by diastereoselective alkylation of C-glyco-  
sylated enolate, followed by nitrile hydrogenation. The present procedure serves as an efficient route to C-glycosylated  
ꢀ-amino acids containing a non-biodegradable linkage.  
Glycopeptides play key roles in numerous biological pro-  
cesses including metastasis, infection, and inflammation.1  
Generally, oligosaccharide residues of glycopeptides are con-  
nected to the peptide backbone via N- (via asparagine) or O-  
glycoside (via serine or threonine) linkage.2 However, many  
researchers have recently turned their attention to C-glycosyl  
amino acids to probe biological processes, owing to their in-  
creased stability toward chemical and enzymatic hydrolysis.3–6  
Hence, numerous C-glycosyl ꢁ-amino acids (Chart 1, I) have  
been reported.7–16  
In the past decade, ꢀ-amino acids have become an interest-  
ing synthetic target as well as precursors for ꢀ-lactams and  
other medicinally important molecules.17–20 ꢀ-Amino acids  
can be subdivided into three main categories, namely ꢀ2-,  
ꢀ3-, and ꢀ2;3-amino acids, depending on the substitution pat-  
terns of the 3-aminopropanoic acid skeleton. ꢀ-Amino acid  
oligomers, i.e. ꢀ-peptides, have been shown to fold into heli-  
cal, sheet, and turn conformations in solution.21,22 Additional-  
ly, ꢀ-peptides are also known to be more resistant toward pro-  
teolytic degradation as compared to ꢁ-peptides.23,24 Consider-  
ing the aforementioned characteristics, the synthesis of C-gly-  
cosyl ꢀ-amino acids would exhibit significant utility toward  
the development of stable glycosylase- and protease-resistant  
pharmaceuticals and functional materials.  
synthesis of ꢀ2-, ꢀ2;2-amino acids with a glycosyl group  
directly connected to the C2 carbon.  
Results and Discussion  
Synthesis of C-Glycosyl ꢀ2-Amino Acids.  
The SN2  
reaction of 2,3,4,6-tetra-O-acetyl-ꢁ-D-glucopyranosyl bromide  
(ꢁ-acetobromoglucose) with the nucleophilic carbanion of  
t-butyl cyanoacetate affords compound 1a exclusively as the  
ꢀ-anomer. X-ray crystallographic analysis of 1a revealed an  
S absolute configuration of the stereoisomer at the side chain  
C2 (Figure 1).  
Subsequent PtO2-catalyzed hydrogenation of the nitrile  
moiety of 1a in CHCl3/EtOH affords a diastereomeric mixture  
2a and 3a (74:26) via epimerization of compound 1a likely  
due to the acidic nature of the C2-hydrogen. Diastereomerical-  
ly pure 3a was isolated by recrystallization of 2a/3a from  
methanol–ether in 8% recovery. The absolute configuration  
of 3a was determined to be 2S by X-ray crystallography.38  
The difficulty in obtaining diastereomer 2a and the poor recov-  
ery of 3a from repeated recrystallization is far from ideal.  
Changing the ester moiety from t-butyl to ethyl increased the  
recovery of 3 (28% (3b)). Although the absolute configuration  
of 1b was also determined to be 2S by X-ray crystallography  
(Figure 2), compound 3b does not afford single crystals.  
Hence, the absolute configuration of 3b was determined by  
converting to the ꢀ-amino acid 5 and comparing the NMR  
spectra with that obtained from 3a. More specifically, hydrol-  
ysis of amines 3a and 3b in 6 mol dmꢁ3 HCl affords the corre-  
sponding ꢀ-amino acid as the hydrochloride salt in a diastereo-  
merically pure form (Scheme 1).  
Several preparations of C-glycosyl ꢀ3-amino acids (Chart 1,  
III) by Tripathi et al.,25,26 Sharma et al.,27 Dondoni et al.,28–30  
and Palomo et al.31 have been reported. Sharma and co-work-  
ers have reported the synthesis and conformational analysis of  
ꢀ-peptides with C-glycosyl ꢀ3-amino acids.32–36 However,  
there are very few examples describing the preparation of C-  
glycosyl ꢀ2-amino acid derivatives (Chart 1, II).37,38 Further-  
more, the stereoselective synthesis of ꢀ2;2-amino acids with  
a quanternary stereogenic center (Chart 1, IV) remains an im-  
portant challenge.39,40 In this paper, we report the versatile  
A similar procedure was used for the galactose derivatives,  
affording 9(2R)/10(2S) in 33–39% overall yield. The galactose  
derivatives formed the corresponding ꢀ-C-glycoside nitriles  
6a and 6b whose structures were determined by X-ray crystal-  
lography (Figures 3 and 4). However, the amines 7a,7b(2R)/  
8a,8b(2S) currently remain as a mixture of diastereomers.  
To obtain both stereoisomers of the ꢀ-amino acids in dia-  
y Present address: Innovative Collaboration Center, Kyoto Uni-  
versity, Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8520  
Published on the web May 14, 2008; doi:10.1246/bcsj.81.606  
Y. Inaba et al.  
Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
607  
NH2  
NH2  
NH2  
NH2  
2
sugar  
sugar  
sugar  
COOH  
sugar  
2
3
COOH  
COOH  
COOH  
n
n
n
n
R
C-glycosyl β2,2-amino acid  
C-glycosyl α-amino acid  
C-glycosyl β2-amino acid  
C-glycosyl β3-amino acid  
I
II  
III  
IV  
Chart 1.  
R2  
R2 OAc  
R2 OAc  
OH  
R2 OAc  
•
•
NH2 HCl  
6'  
NH2 HCl  
(ii)  
CN  
2
(iii)  
(i)  
3
4'  
O
5'  
R1  
AcO  
O
O
O
R1  
AcO  
R1  
AcO  
R1  
HO  
CO2R3  
2
CO2R3  
2
CO2H  
1
2' HO 1'  
AcO  
AcO  
AcO  
3'  
Br  
1a (R1 = OAc, R2 = H, R3 = But ): 57%  
1b (R1 = OAc, R2 = H, R3 = Et): 45%  
6a (R1 = H, R2 = OAc, R3 = But ):42%  
6b (R1 = H, R2 = OAc, R3 = Et): 37%  
2a (2R) / 3a (2S ) (R1 = OAc, R2 = H, R3 = But): 99% (74/26)  
2b (2R) / 3b (2S ) (R1 = OAc, R2 = H, R3 = Et): 98% (66/34)  
7a (2R) / 8a (2S ) (R1 = H, R2 = OAc, R3 = But): 98% (73/27)  
7b (2R) / 8b (2S ) (R1 = H, R2 = OAc, R3 = Et): 96% (74/26)  
4 (2R) / 5 (2S) (R1 = OH, R2 = H): 84%  
9 (2R) / 10 (2S) (R1 = H, R2 = OH): 85-100%  
recrystallization  
OH  
OAc  
•
•
NH2 HCl  
NH2 HCl  
(iii)  
O
O
HO  
HO  
AcO  
AcO  
2
CO2H  
2
CO2R  
AcO  
HO  
3a (R = But ): 8%a (31%)b  
3b (R = Et): 28%a (82%)b  
5: 96-100%  
Scheme 1. Synthesis of C-glycosyl ꢀ2-amino acids. Reagents and conditions: (i) t-butyl cyanoacetate or ethyl cyanoacetate, NaH,  
DMF, 0 ꢂC, 2 h; (ii) H2, PtO2, CHCl3, EtOH, overnight; (iii) 6 mol dmꢁ3 HCl, reflux, 2 h–overnight. a) Recovery from total 2/3.  
b) Recovery of 3 from the mixture of 2/3.  
O11  
C17  
C17  
C20  
C16  
C5  
C16  
C21  
O4  
C6  
C6  
O11  
O5  
C19  
O10  
O10  
N1  
C19  
N1  
O4  
C4  
O3  
O7  
O7  
O5  
C7  
C5  
C18  
O3  
O2  
C7  
C8  
C14  
O2  
C9  
C18  
C14  
C15  
C15  
C3  
C4  
C1  
O6  
C9  
C1  
C2  
O1  
C2  
O1  
C10  
C11  
C8  
C12  
C3  
C13  
O6  
C12  
C13  
O8  
C10  
O8  
O9  
O9  
C11  
Figure 1. ORTEP plot for 1a.  
Figure 2. ORTEP plot for 1b.  
stereomerically pure forms, the amines 2a/3a (74/26) and 7a/  
8a (73/27) were converted to the corresponding Fmoc-  
derivatives (Fmoc = 9-fluorenylmethoxycarbonyl) 11/12 and  
15/16 by Fmoc-succinate and triethylamine in MeOH/  
CH3CN. The diastereomers were then successfully separated  
by silica gel column chromatography. Deprotection of the  
t-butyl groups with formic acid led to both (2R)- and (2S)-  
Fmoc-protected C-glycosyl ꢀ2-amino acids 13/14 and  
17/18, useful synthons for solid-phase peptide synthesis  
(Scheme 2). Assignments of the absolute configurations of  
glucose derivatives 11 (Figure 5) and 1438 were established  
by crystallographic analysis. The configuration of the galac-  
tose derivatives were predicted by comparing the 1H NMR  
chemical shifts of the C2-hydrogen NMR with the glucose  
derivatives (2.8 ppm for 11 and 15, 2.7 ppm for 12 and 16).  
A similar product ratio for the glucose 11/12 and galactose  
derivatives 15/16 also supports this prediction.  
C15  
O11  
C16  
C17  
C14  
O4  
C6  
O3  
O10  
N1  
C5  
C4  
O5  
O6  
C9  
C1  
C18  
C19  
C3  
C12  
C7  
O7  
C8  
C2  
O2  
C21  
C13  
O8  
O9  
O1  
C10  
C11  
C20  
Figure 3. ORTEP plot for 6a.  
608 Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
Preparation of C-Glycosyl ꢀ-Amino Acids  
O13  
26  
C27  
C
C28  
Figure 5. ORTEP plot for 11.  
Figure 4. ORTEP plot for 6b.  
R2  
R1  
AcO  
R2  
OAc  
OAc  
NHFmoc  
CO2But  
NHFmoc  
(iii)  
R1  
O
O
AcO  
CO2H  
AcO  
AcO  
11 (R1 = OAc, R2 = H): 44%  
15 (R1 = H, R2 = OAc): 46%  
13 (R1 = OAc, R2 = H): 97%  
17 (R1 = H, R2 = OAc): 75%  
R2  
OAc  
•
NH2 HCl  
(i)  
(ii)  
O
R1  
CO2But  
AcO  
AcO  
R2  
R1  
AcO  
R2  
OAc  
OAc  
2a (2R) / 3a (2S) (R1 = OAc, R2 = H) (73/27)  
7a (2R) / 8a (2S) (R1 = H, R2 = OAc) (75/25)  
NHFmoc  
CO2But  
NHFmoc  
CO2H  
(iii)  
O
O
R1  
AcO  
AcO  
AcO  
12 (R1 = OAc, R2 = H): 18%  
16 (R1 = H, R2 = OAc): 16%  
14 (R1 = OAc, R2 = H): 96%  
18 (R1 = H, R2 = OAc): 84%  
Scheme 2. Synthesis of Fmoc-protected amino acids. Reagents and conditions: (i) FmocOSu, Et3N, MeOH, CH3CN, rt, 3 h;  
(ii) silica gel column chromatography; (iii) HCOOH, rt, 3 h.  
OAc  
OAc  
OH  
•
•
NH2 HCl  
NH2 HCl  
CN  
(iii)  
(iv)  
O
O
O
AcO  
AcO  
HO  
HO  
AcO  
AcO  
Me  
Me  
CO2R1  
Me  
AcO  
AcO  
HO  
CO2R1  
CO2H  
21a (R1 = But ): 84%  
21b (R1 = Et): 95%  
19a (R1 = But ): 16%  
19b (R1 =Et): 3%*  
OAc  
23: 77-100%  
(i)  
O
AcO  
AcO  
AcO  
(ii)  
Br  
OAc  
OAc  
•
OH  
O
•
NH2 HCl  
NH2 HCl  
CN  
O
(iii)  
(iv)  
O
AcO  
AcO  
HO  
HO  
AcO  
AcO  
CO2R1  
Me  
CO2R1  
CO2H  
Me  
AcO  
AcO  
HO  
Me  
20a (R1 = But ): 15%  
20b (R1 =Et): 12%*  
22a (R1 = But): 99%  
22b (R1 = Et): 77%  
24: 56-91%  
Scheme 3. Synthesis of C-glycosyl ꢀ2;2-amino acids. Reagents and conditions: (i) t-butyl or ethyl 2-cyanopropionate, NaH, DMF,  
0 ꢂC, 2 h; (ii) silica gel column chromatography and recrystallization; (iii) H2, PtO2, CHCl3, EtOH, overnight; (iv) 6 mol dmꢁ3  
HCl, reflux, overnight. ꢀ) Unresolved mixture of 19b and 20b: 44%.  
Synthesis of C-Glycosyl ꢀ2;2-Amino Acids. Our studies  
suggested that C-glycosylated cyanoacetate 1 was subject to  
epimerization owing to the high acidity of C2-H as previously  
described. We thus attempted to inhibit this isomerization by  
substituting the C2 hydrogen with an alkyl group to afford a  
ꢀ2;2-amino acid.  
Compounds 19a,19b/20a,20b, in which the C2-H of 1a and  
1b is exchanged for a methyl group, were prepared by a similar  
procedure to that described above using t-butyl/ethyl 2-cyano-  
propionate in place of 2-cyanoacetate ester. Two diastereomers  
with respect to the quaternary carbon (C2) in the side chain  
were obtained in approximately 1:1 ratio and were separated  
by silica gel column chromatography and recrystallization.  
No isomerization was observed in the subsequent nitrile hydro-  
genation. Thus, both stereoisomers of the ꢀ2;2-amino acids  
23 and 24 were obtained in diastereomerically pure form  
(Scheme 3). Introduction of a methyl group at the C-2 carbon  
of 1a and 1b suppresses epimerization and allows efficient  
separation of the nitrile diastereomers. X-ray crystallography  
of 19a and 19b reveals the configuration of the C-2 carbon  
(Figures 6 and 7).  
Cativiela and co-workers have reported that diastereoselec-  
tive alkylation of the enolate form of alkylcyano[(1S,2R,4R)-  
1-(dicyclohexylsulfamoylmethyl)-7,7-dimethylbicyclo[2,2,1]-  
heptan-2-yl]acetates affords diastereomerically pure ꢀ2;2-di-  
alkylcyanoacetate.41 We employed this alternative method  
Y. Inaba et al.  
Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
609  
19  
Figure 6. ORTEP plot for 19a.  
Figure 7. ORTEP plot for 19b.  
R2  
R2  
OAc  
OAc  
CN  
CN  
i) LDA  
ii) R4X, HMPA  
O
O
R1  
R1  
AcO  
*
R4  
CO2R3  
AcO  
AcO  
AcO  
CO2R3  
1a (R1 = OAc, R2 = H, R3 = But)  
1b (R1 = OAc, R2 = H, R3 = Et)  
6b (R1 = H, R2 = OAc, R3 = Et)  
19a (2R) / 20a (2S) (R1 = OAc, R2 = H, R3 = But, R4 = Me)  
19b (2R) / 20b (2S) (R1 = OAc, R2 = H, R3 = Et, R4 = Me)  
25 (2R) / 26 (2S) (R1 = OAc, R2 = H, R3 = Et, R4 = Et)  
27 (2R) / 28 (2S) (R1 = OAc, R2 = H, R3 = Et, R4 = Pri)  
29 (2R) / 30 (2S) (R1 = H, R2 = OAc, R3 = Et, R4 = Me)  
Scheme 4. Alkylations of 1a, 1b, and 6b.  
20  
Figure 8. ORTEP plot for 25.  
Figure 9. ORTEP plot for 29.  
for the diastereoselective preparation of C-glycosyl ꢀ2;2-amino  
acids using the sugar moiety of 1a and 1b as a chiral auxiliary.  
The enolates of the C-glycosylated cyanoacetate esters 1a, 1b,  
and 6b generated by lithium diisopropylamide in dry THF  
at ꢁ78 ꢂC were alkylated with MeI, EtI, and i-PrI in the pres-  
ence of hexamethylphosphoric triamide (HMPA) (Scheme 4  
and Table 1). The absolute configuration of the isolated prod-  
ucts 25 and 29 were determined by X-ray crystallography  
(Figures 8 and 9).  
We initially examined the alkylation of t-butyl/ethyl (2S)-  
(2,3,4,6-tetra-O-acetyl-ꢀ-D-glucopyranosyl)cyanoacetate 1a/  
1b with methyl iodide (Table 1, Entries 1 and 2). As the ethyl  
ester 1b was isolated in higher yield than the t-butyl ester 1a  
without loss of diastereoselectivity, further experiments were  
Table 1. Diastereoselective Alkylation of 1a, 1b, and 6b  
Starting  
material  
Entry  
Product R4X  
Yielda)/% dr(2R/2S)b)  
1
2
3
4
5
1a  
1b  
1b  
1b  
6b  
19a/20a CH3I  
19b/20b CH3I  
48 (38)  
80 (25)  
CH3CH2I 41 (35)  
81/19  
81/19  
92/8  
87/13c)  
82/18  
25/26  
27/28  
29/30  
(CH3)2CHI  
CH3I  
6
86 (66)  
a) Yield of a diastereomer mixture. Values in parentheses in-  
dicates isolated yield of the major isomer. b) Derived from  
1H NMR integral ratio of unresolved product. c) The absolute  
configuration was not determined.  
610 Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
Preparation of C-Glycosyl ꢀ-Amino Acids  
R2  
R2  
TMS or solvent signals. Mass spectra were obtained by electro-  
spray ionization-mass spectrometry (ESI-MS) on a JEOL JMS-T  
100LC.  
OAc  
R
•
NH2 HCl  
CN  
R3  
CO2Et  
(i)  
O
O
R
R1  
R1  
AcO  
R3  
R
CO2R4  
AcO  
31 (R = R1 = OAc, R2 = H, R3 = Et, R4 = Et): 78%  
32 (R = R1 = OH, R2 = R4 = H, R3 = Et): 100%  
t-Butyl (2S)-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-  
25 (R1 = OAc, R2 = H, R3 = Et)  
29 (R1 = H, R2 = OAc, R3 = Me)  
(ii)  
(ii)  
cyanoacetate (1a).  
To a solution of t-butyl cyanoacetate  
(4.24 g, 30.0 mmol) in 12 mL of dmf was added sodium hydride  
(1.32 g, 33.0 mmol; previously washed with hexane) by portions  
with stirring at 0 ꢂC. After the evolution of hydrogen gas ceased,  
a solution of ꢁ-acetobromoglucose (4.12 g, 10.0 mmol) in 8 mL of  
dmf was slowly added dropwise with stirring at 0 ꢂC and the reac-  
tion mixture was stirred for 2 h. After aqueous acetic acid (10%)  
was added, the yellow precipitate was filtered and washed with  
water. The product was dissolved in dichloromethane (120 mL)  
and dried over sodium sulfate and concentrated in vacuo. The res-  
idue was recrystallized in ethanol to afford 1a as colorless needles  
(2.72 g, 5.76 mmol) in 57% yield. Mp 138–139 ꢂC (EtOH);  
1H NMR (CDCl3, Me4Si): ꢂ 5.28–5.09 (3H, m, H-30, H-20, H-  
40), 4.20 (1H, dd, J ¼ 2:4, 12.2 Hz, H-60a), 4.15–4.07 (2H, m,  
H-60b, H-10), 3.72 (1H, ddd, J ¼ 2:4, 4.9, 9.8 Hz, H-50), 3.60  
(1H, d, J ¼ 2:4 Hz, H-2), 2.07 (3H, s, COCH3), 2.06 (3H, s,  
COCH3), 2.04 (3H, s, COCH3), 2.02 (3H, s, COCH3), 1.53 (9H,  
s, (CH3)3C). 13C NMR (CDCl3): ꢂ 170.55, 170.31, 169.26,  
169.11 (COCH3), 162.25 (COOBut), 112.82 (CN), 85.24  
((CH3)3C), 76.24 (C-50), 75.30 (C-10), 73.76 (C-30), 69.70 (C-  
20), 68.02 (C-40), 61.90 (C-60), 41.42 (C-2), 27.78, 27.70  
((CH3)3C), 20.60 (COCH3). ESI-MS Calcd for C21H29NO11Na  
(½M þ Naꢃþ): 494.16. Found: 494.09. Anal. Found: C, 53.48; H,  
6.25; N, 2.98%. Calcd for C21H29NO11: C, 53.50; H, 6.20; N,  
33 (R = R2 = OAc, R1 = H, R3 = Me, R4 = Et): 91%  
34 (R = R2 = OH, R1 = R4 = H, R3 = Me): 87%  
Scheme 5. Synthesis of diastereomerically pure C-glycosyl  
ꢀ2;2-amino acids. Reagents and conditions: (i) H2, PtO2,  
CHCl3, EtOH, overnight; (ii) 6 mol dmꢁ3 HCl, reflux,  
overnight.  
conducted using ethyl esters 1b and 6b.  
As seen in Entries 3 and 4 in Table 1, larger alkyl halides  
result in slightly better diastereoselectivity along with signifi-  
cant loss of product yield. In the case of the isopropyl deriva-  
tives, we were unable to isolate 27/28 from the reaction mix-  
ture, preventing further investigation.  
The methylation of galactose derivative 6b proceeds in sim-  
ilar yield and selectivity as compared to the glucose derivative.  
Thus, the close proximity of the attached C-glycoside moiety  
to the reaction center acts as an efficient chiral auxiliary for  
the diastereoselective preparation of C-glycosylated ꢀ2;2-ami-  
no acids. The nitriles 25 and 29 were converted to ꢀ2;2-amino  
acids 32 and 34 under the same conditions described above  
(Scheme 5).  
Summary  
2.97%. Crystal data: monoclinic, space group C2, a ¼  
3
˚
˚
˚
˚
24:21ð3Þ A, b ¼ 5:838ð6Þ A, c ¼ 17:15ð2Þ A, V ¼ 2414:7ð44Þ A ,  
We have developed a facile preparation of diastereomerical-  
ly pure C-glycosyl ꢀ2- and ꢀ2;2-amino acids. Although epimer-  
ization with respect to C-glycosylated cyanoacetate 1 during  
nitrile reduction was unavoidable owing to the high acidity  
of C2-H, diastereomerically pure C-glycosyl ꢀ2-amino acids  
were obtained after recrystallization or Fmoc derivatization  
of amines. The yields of C-glycoside formation are moderate  
(31% to 57%), and the following two steps proceeded with  
nearly quantitative yield. Fmoc derivatives (R)-13 and (S)-14  
were prepared from D-glucose in five steps without any special  
techniques, which is in contrast to Sharma’s method to obtain  
amine-protected analogues.40 The present procedure is appli-  
cable to other sugar moieties to display a library of C-glycosyl  
ꢀ2- and ꢀ2;2-amino acids. Readily available, well-resolved dia-  
stereomers of C-glycosyl ꢀ2- and ꢀ2;2-amino acids should be  
useful carbohydrate-containing ꢀ-amino acid building blocks  
for glycopeptide research and application to pharmaceuti-  
cals.42–44 The synthesis and investigation of C-glycosyl ꢀ2-  
peptides incorporating these sugar amino acids is currently  
underway.  
2
Z ¼ 4, R ¼ 0:092, Rw ¼ 0:271, GOF ¼ 1:055.  
Ethyl (2S)-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)cya-  
noacetate (1b): Compound 1b was prepared by a method similar  
to the preparation of 1a using ethyl cyanoacetate in place of t-bu-  
1
tyl cyanoacetate. Yield: 45%. Mp 138–139 ꢂC (EtOH); H NMR  
(CDCl3, Me4Si): ꢂ 5.26 (1H, dd, J ¼ 8:7, 9.2 Hz, H-30), 5.18  
(1H, dd, J ¼ 8:7, 9.5 Hz, H-20), 5.14 (1H, dd, J ¼ 9:2, 9.9 Hz,  
H-40), 4.32 (2H, q, J ¼ 7:0 Hz, CH2CH3), 4.17 (2H, d,  
J ¼ 3:7 Hz, H-60a, H-60b), 4.14 (1H, dd, J ¼ 2:7, 9.5 Hz, H-10),  
3.73 (1H, m, H-50), 3.68 (1H, d, J ¼ 2:7 Hz, H-2), 2.08 (3H, s,  
COCH3), 2.07 (3H, s, COCH3), 2.04 (3H, s, COCH3), 2.02  
(3H, s, COCH3), 1.35 (3H, t, J ¼ 7:0 Hz, CH2CH3). 13C NMR  
(CDCl3): ꢂ 170.55, 170.25, 169.23, 169.14 (COCH3), 163.40  
(COOEt), 112.50 (CN), 76.01 (C-50), 75.04 (C-10), 73.57 (C-30),  
69.67 (C-20), 67.81 (C-40), 63.52 (CH2CH3), 61.60 (C-60), 40.45  
(C-2), 20.55 (COCH3), 13.90 (CH2CH3). ESI-MS Calcd for  
C19H25NO11Na (½M þ Naꢃþ): 466.13. Found: 466.08. Anal.  
Found: C, 51.52; H, 5.77; N, 3.20%. Calcd for C19H25NO11: C,  
51.47; H, 5.68; N, 3.16%. Crystal data: orthorhombic, space group  
˚
˚
2
˚
P212121, a ¼ 7:0872ð15Þ A, b ¼ 12:529ð3Þ A, c ¼ 25:424ð6Þ A,  
3
˚
V ¼ 2257:5ð8Þ A , Z ¼ 4, R ¼ 0:052, Rw ¼ 0:166, GOF ¼  
0:982.  
Experimental  
General. All reagents and solvents were from commercial  
sources and used as received. N,N-Dimethylformamide (dmf,  
Wako) was dried over CaSO4 and distilled under reduced pres-  
sure. Tetrahydrofuran was distilled over sodium metal and benzo-  
phenone. TLC was performed on Merck silica gel 60 aluminium  
sheets. Melting points were determined on a Yanaco MP-J3 micro  
hotstage. Optical rotations were measured at room temperature  
(20 ꢂC) with a Jasco DIP-140 digital polarimeter. 1H NMR  
(300.07 MHz) and 13C NMR (75.00 MHz) spectra were recorded  
on a Varian GEMINI 2000 spectrometer and referenced to internal  
t-Butyl (2S)-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl)-  
cyanoacetate (6a): Compound 6a was prepared by a method  
similar to the preparation of 1a using 2,3,4,6-tetra-O-acetyl-ꢁ-D-  
galactopyranosyl bromide (ꢁ-acetobromogalactose) in place of  
ꢁ-acetobromoglucose. Yield: 42%. Mp 151–152 ꢂC (EtOH);  
1H NMR (CDCl3, Me4Si): ꢂ 5.44 (1H, dd, J ¼ 0:92, 3.4 Hz, H-  
40), 5.38 (1H, dd, J ¼ 9:8, 10.1 Hz, H-20), 5.09 (1H, dd,  
J ¼ 3:4, 10.1 Hz, H-30), 4.18–4.04 (3H, m, H-1, H-60a, H-60b),  
3.95 (1H, ddd, J ¼ 0:92, 5.5, 5.5 Hz, H-50), 3.60 (1H, d,  
J ¼ 2:7 Hz, H-2), 2.18 (3H, s, COCH3), 2.08 (3H, s, COCH3),  
Y. Inaba et al.  
Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
611  
2.02 (3H, s, COCH3), 2.00 (3H, s, COCH3), 1.53 (9H, s,  
(CH3)3C). 13C NMR (CDCl3): ꢂ 170.25, 170.03, 169.29 (COCH3),  
162.45 (COOBut), 112.97 (CN), 85.07 ((CH3)3C), 75.77, 74.62,  
71.63, 67.13, 61.56, 41.68 (C-2), 27.78, 27.67 ((CH3)3C), 20.61  
(COCH3). HRMS (ESI) Calcd for C17H21NO11Na (½M ꢁ  
But þ H þ Naꢃþ): 438.10123. Found: 438.10091. Anal. Found:  
C, 53.52; H, 6.21; N, 3.02%. Calcd for C21H29NO11: C, 53.50;  
H, 6.20; N, 2.97%. Crystal data: monoclinic, space group  
ESI-MS Calcd for C18H23NO11Na (½M ꢁ But þ H þ Naꢃþ):  
452.12. Found: 452.07. Anal. Found: C, 54.24; H, 6.44; N,  
2.84%. Calcd for C22H31NO11: C, 54.43; H, 6.44; N, 2.89%.  
˚
Crystal data: monoclinic, space group P21, a ¼ 6:394ð2Þ A,  
˚
˚
b ¼ 21:419ð5Þ A,  
c ¼ 9:530ð3Þ A,  
ꢀ ¼ 108:259ð3Þꢂ,  
V ¼  
3
2
˚
1239:3ð6Þ A , Z ¼ 2, R ¼ 0:036, Rw ¼ 0:084, GOF ¼ 1:118.  
t-Butyl (2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-  
20  
2-cyanopropanoate (20a): Mp 175–177 ꢂC (EtOH); ½ꢁꢃD  
¼
1
˚
˚
˚
P21, a ¼ 10:237ð2Þ A, b ¼ 9:770ð2Þ A, c ¼ 12:894ð3Þ A, ꢀ ¼  
0:811 (c ¼ 1:01, CHCl3); H NMR (CDCl3, Me4Si): ꢂ 5.30 (1H,  
dd, J ¼ 9:2, 9.6 Hz, H-20), 5.20 (1H, dd, J ¼ 9:2, 9.5 Hz, H-30),  
5.08 (1H, dd, J ¼ 9:5, 9.8 Hz, H-40), 4.20 (1H, dd, J ¼ 5:2,  
12.4 Hz, H-60a), 4.14 (1H, dd, J ¼ 2:4, 12.4 Hz, H-60b), 3.95  
(1H, d, J ¼ 9:6 Hz, H-10), 3.73 (1H, ddd, J ¼ 2:4, 5.2, 9.8 Hz,  
H-50), 2.07 (3H, s, COCH3), 2.04 (6H, s, COCH3), 2.01 (3H, s,  
COCH3), 1.54 (12H, s, 2-CH3, (CH3)3C). 13C NMR (CDCl3):  
ꢂ 170.49, 170.23, 169.23, 168.90 (COCH3), 164.91 (COOBut),  
117.63 (CN), 84.75 ((CH3)3C), 78.21 (C-10), 76.09 (C-50), 74.25  
(C-30), 68.91 (C-20), 67.89 (C-40), 61.73 (C-60), 47.73 (C-2),  
27.67 ((CH3)3C), 20.57, 20.47 (COCH3), 18.45 (2-CH3). ESI-  
MS Calcd for C18H23NO11Na (½M ꢁ But þ H þ Naꢃþ): 452.12.  
Found: 452.04. Anal. Found: C, 54.40; H, 6.18; N, 2.82%. Calcd  
for C22H31NO11: C, 54.43; H, 6.44; N, 2.89%.  
3
2
101:4403ð10Þꢂ, V ¼ 1263:9ð5Þ A , Z ¼ 2, R ¼ 0:051, Rw  
¼
˚
0:156, GOF ¼ 1:084.  
Ethyl (2S)-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl)-  
cyanoacetate (6b): Compound 6b was prepared by a method  
similar to the preparation of 1b using ꢁ-acetobromogalactose in  
place of ꢁ-acetobromoglucose and purified by silica gel column  
chromatography with hexane/ethyl acetate 1:1 (Rf ¼ 0:25). Yield:  
37%. Mp 121–123 ꢂC (EtOH); H NMR (CDCl3, Me4Si): ꢂ 5.44  
1
(1H, dd, J ¼ 0:92, 3.2 Hz, H-40), 5.38 (1H, dd, J ¼ 9:8, 10.1 Hz,  
H-20), 5.09 (1H, dd, J ¼ 3:2, 9.8 Hz, H-30), 4.32 (2H, q,  
J ¼ 7:0 Hz, CH2CH3), 4.11 (2H, dd, J ¼ 1:1, 7.0 Hz, H-60a, H-  
60b), 4.09 (1H, dd, J ¼ 2:7, 10.1 Hz, H-10), 3.96 (1H, ddd,  
J ¼ 1:1, 7.0, 7.0 Hz, H-50), 3.67 (1H, d, J ¼ 2:7 Hz, H-2), 2.18  
(3H, s, COCH3), 2.08 (3H, s, COCH3), 2.03 (3H, s, COCH3),  
2.00 (3H, s, COCH3), 1.35 (3H, t, J ¼ 7:0 Hz, CH2CH3).  
13C NMR (CDCl3): ꢂ 170.21, 169.99, 169.36 (COCH3), 163.61  
(COOEt), 112.64 (CN), 75.54, 75.48, 74.44, 71.52, 66.94, 63.41,  
61.18, 40.98 (C-2), 20.60, 20.42 (COCH3), 13.85 (CH2CH3).  
ESI-MS Calcd for C19H25NO11Na (½M þ Naꢃþ): 466.13. Found:  
466.03. Anal. Found: C, 51.41; H, 5.69; N, 3.17%. Calcd for  
C19H25NO11: C, 51.47; H, 5.68; N, 3.16%. Crystal data: mono-  
Ethyl (2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-  
20  
cyanopropanoate (19b): Mp 114–116 ꢂC (EtOH); ½ꢁꢃD ¼ 6:27  
1
(c ¼ 0:996, CHCl3); H NMR (CDCl3, Me4Si): ꢂ 5.29–5.21 (2H,  
m, H-20, H-30), 5.07 (1H, dd, J ¼ 9:5, 10.1 Hz, H-40), 4.29 (2H,  
tq, J ¼ 3:3, 7.0 Hz, CH2CH3), 4.18–4.08 (3H, m, H-1, H-60a, H-  
60b), 3.70 (1H, ddd, J ¼ 2:8, 4.9, 10.1 Hz, H-50), 2.07 (3H, s,  
COCH3), 2.06 (3H, s, COCH3), 2.04 (3H, s, COCH3), 2.01  
(3H, s, COCH3), 1.65 (3H, s, 2-CH3), 1.34 (3H, t, J ¼ 7:0 Hz,  
CH2CH3). 13C NMR (CDCl3): ꢂ 170.44, 170.18, 169.31  
(COCH3), 166.09 (COOEt), 116.82 (CN), 77.81 (C-10), 76.26  
(C-50), 73.94 (C-30), 68.83 (C-20), 68.04 (C-40), 63.20 (CH2CH3),  
61.84 (C-60), 45.30 (C-2), 20.53 (COCH3), 17.26 (2-CH3), 13.96  
(CH2CH3). ESI-MS Calcd for C20H27NO11Na (½M þ Naꢃþ):  
480.15. Found: 480.12. Anal. Found: C, 52.42; H, 6.04; N,  
3.15%. Calcd for C20H27NO11: C, 52.51; H, 5.95; N, 3.06%.  
˚
˚
clinic, space group P21, a ¼ 9:2023ð5Þ A, b ¼ 8:3030ð4Þ A, c ¼  
ꢂ
3
˚
˚
14:3389ð7Þ A, ꢀ ¼ 97:0267ð10Þ , V ¼ 1087:36ð10Þ A , Z ¼ 2,  
2
R ¼ 0:057, Rw ¼ 0:175, GOF ¼ 1:117.  
General Procedure for Alkylation. To a dry THF solution  
(10 mL) of lithium diisopropylamide (2.0 M solution, 0.275 mL,  
0.55 mmol) was added a solution of 1a, 1b, and 6b (0.5 mmol)  
in dry THF (9.0 mL) under argon at ꢁ78 ꢂC. After 1 h, a solution  
of iodomethane (0.31 mL, 5.0 mmol)/iodoethane (0.40 mL, 5.0  
mmol)/2-iodopropane (0.50 mL, 5.0 mmol) and HMPA (0.13  
mL, 0.75 mmol) in dry THF (5.0 mL) was added by syringe.  
The reaction mixture was allowed to warm to room temperature  
and stirring was continued for 1 day. The reaction mixture was  
then quenched with saturated aqueous NH4Cl solution (5 mL).  
An ether extraction, washing by water, drying over Na2SO4 and  
concentration in vacuo yielded a mixture of diastereomers of  
corresponding 2-alkylated 2-cyano ester as a crude oil, which  
was chromatographed on a silica gel column (eluent: hexane/ethyl  
acetate 1:1).  
˚
Crystal data: monoclinic, space group C2, a ¼ 27:446ð9Þ A,  
b ¼ 6:190ð2Þ A, c ¼ 13:991ð5Þ A, ꢀ ¼ 101:5687ð10Þꢂ, V ¼  
˚
3
˚
2
˚
2328:5ð13Þ A , Z ¼ 4, R ¼ 0:053, Rw ¼ 0:146, GOF ¼ 1:062.  
Ethyl (2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-  
20  
cyanopropanoate (20b):  
Mp 125–127 ꢂC (EtOH); ½ꢁꢃD  
¼
ꢁ4:35 (c ¼ 1:00, CHCl3); 1H NMR (CDCl3, Me4Si): ꢂ 5.25–  
5.17 (2H, m, H-20, H-30), 5.07 (1H, dd, J ¼ 9:5, 10.1 Hz, H-40),  
4.39–4.19 (3H, m, CH2CH3, H-60a), 4.13 (1H, dd, J ¼ 2:4,  
12.1 Hz, H-60b), 4.04 (1H, m, H-10), 3.76 (1H, ddd, J ¼ 2:4,  
5.5, 10.1 Hz, H-50), 2.09 (3H, s, COCH3), 2.04 (3H, s, COCH3),  
2.00 (3H, s, COCH3), 1.99 (3H, s, COCH3), 1.58 (3H, s, 2-  
CH3), 1.37 (3H, t, J ¼ 7:0 Hz, CH2CH3). 13C NMR (CDCl3): ꢂ  
170.57, 170.26, 169.29, 168.84 (COCH3), 166.01 (COOEt),  
117.53 (CN), 78.05 (C-10), 76.29 (C-50), 74.17 (C-30), 68.57 (C-  
20), 67.99 (C-40), 63.28 (CH2CH3), 61.73 (C-60), 46.71 (C-2),  
20.61, 20.53, 20.48 (COCH3), 17.47 (2-CH3), 13.90 (CH2CH3).  
HRMS (ESI) Calcd for C20H27NO11Na (½M þ Naꢃþ):  
480.14818. Found: 480.14721. Anal. Found: C, 52.48; H, 6.03;  
N, 3.08%. Calcd for C20H27NO11: C, 52.51; H, 5.95; N, 3.06%.  
Ethyl (2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-  
t-Butyl (2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-  
20  
2-cyanopropanoate (19a):  
Mp 96–100 ꢂC (EtOH); ½ꢁꢃD  
¼
1
9:83 (c ¼ 0:999, CHCl3); H NMR (CDCl3, Me4Si): ꢂ 5.27 (1H,  
dd, J ¼ 9:2, 9.3 Hz, H-30), 5.21 (1H, dd, J ¼ 7:9, 9.2 Hz, H-20),  
5.05 (1H, dd, J ¼ 9:3, 9.8 Hz, H-40), 4.15 (1H, dd, J ¼ 4:8,  
12.5 Hz, H-60a), 4.13 (1H, d, J ¼ 7:9 Hz, H-10), 4.07 (1H, dd,  
J ¼ 2:4, 12.5 Hz, H-60b), 3.69 (1H, ddd, J ¼ 2:4, 4.8, 9.8 Hz,  
H-50), 2.09 (3H, s, COCH3), 2.04 (3H, s, COCH3), 2.03 (3H, s,  
COCH3), 2.01 (3H, s, COCH3), 1.56 (3H, s, 2-CH3), 1.52 (9H,  
s, (CH3)3C). 13C NMR (CDCl3): ꢂ 170.39, 170.07, 169.55,  
169.26 (COCH3), 164.42 (COOBut), 117.39 (CN), 84.33  
((CH3)3C), 77.78 (C-10), 76.21 (C-50), 73.91 (C-30), 68.34  
(C-20), 68.00 (C-40), 61.97 (C-60), 45.19 (C-2), 27.68, 27.65  
((CH3)3C), 20.79, 20.57, 20.53, 20.47 (COCH3), 15.82 (2-CH3).  
20  
cyanobutanoate (25): Mp 120–122 ꢂC (EtOH); ½ꢁꢃD ¼ ꢁ3:20  
(c ¼ 1:00, CHCl3); 1H NMR (CDCl3, Me4Si): ꢂ 5.33 (1H, dd,  
J ¼ 9:2, 9.8 Hz, H-20), 5.21 (1H, dd, J ¼ 9:2, 9.3 Hz, H-30),  
5.12 (1H, dd, J ¼ 9:3, 9.8 Hz, H-40), 4.31–4.21 (3H, m,  
OCH2CH3, H-60a), 4.16 (1H, dd, J ¼ 2:7, 4.6 Hz, H-60b), 3.97  
612 Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
Preparation of C-Glycosyl ꢀ-Amino Acids  
(1H, d, J ¼ 9:8 Hz, H-10), 3.71 (1H, ddd, J ¼ 2:7, 4.6, 9.8 Hz,  
H-50), 2.23 (1H, ddd, J ¼ 7:5, 7.5, 7.5 Hz, 2-CH2CH3), 2.09  
(3H, s, COCH3), 2.05–1.92 (1H, m, 2-CH2CH3), 2.04 (3H, s,  
COCH3), 2.00 (3H, s, COCH3), 1.98 (3H, s, COCH3), 1.35 (3H,  
t, J ¼ 7:0 Hz, OCH2CH3), 1.06 (3H, t, J ¼ 7:5 Hz, 2-CH2CH3).  
13C NMR (CDCl3): ꢂ 170.52, 170.31, 169.21, 168.45 (COCH3),  
166.09 (COOEt), 115.59 (CN), 78.00 (C-10), 76.32 (C-50), 74.02  
(C-30), 69.99 (C-20), 67.92 (C-40), 62.86 (COOCH2CH3), 61.69  
(C-60), 53.39 (C-2), 27.43 (2-CH2CH3), 20.63, 20.48 (COCH3),  
13.98 (OCH2CH3), 9.17 (2-CH2CH3). HRMS (ESI) Calcd for  
C21H29NO11Na (½M þ Naꢃþ): 494.16383. Found: 494.16341.  
Anal. Found: C, 53.29; H, 6.13; N, 3.01%. Calcd for C21H29NO11:  
C, 53.50; H, 6.20; N, 2.97%. Crystal data: monoclinic, space  
was prepared by a method similar to the preparation of 3a using  
1b in place of 1a. Recrystallization from methanol–ether gave a  
single diastereomer 3b as colorless needles in 27% yield. Mp  
20  
194–196 ꢂC (MeOH, ether); ½ꢁꢃD ¼ 6:11 (c ¼ 0:999, MeOH);  
1H NMR (D2O, DSS): ꢂ 5.37 (1H, dd, J ¼ 9:5, 9.2 Hz, H-30),  
5.17 (1H, dd, J ¼ 9:5, 9.9 Hz, H-20), 5.10 (1H, dd, J ¼ 9:2,  
10.1 Hz, H-40), 4.42 (1H, dd, J ¼ 2:7, 9.9 Hz, H-10), 4.35–4.16  
(4H, m, H-60, CH2CH3), 3.99 (1H, m, H-50), 3.42 (2H, d,  
J ¼ 5:2 Hz, H-3a, H-3b), 3.09 (1H, br, H-2), 2.10 (6H, s, COCH3),  
2.09 (3H, s, COCH3), 2.06 (3H, s, COCH3), 1.29 (3H, t,  
J ¼ 7:2 Hz, CH2CH3). 13C NMR (D2O, dioxane): ꢂ 173.69,  
173.14, 172.74, 171.62 (COCH3, COOEt), 76.22 (C-10), 75.35  
(C-50), 74.28 (C-30), 69.20 (C-20), 68.20 (C-40), 63.07 (C-60),  
62.03 (CH2CH3), 42.83 (C-2), 35.84 (C-3), 20.05, 19.93  
(COCH3), 13.14 (CH2CH3). HRMS (ESI) Calcd for C19H30NO11  
(½M ꢁ Clꢃþ): 448.1813. Found: 448.1812. Anal. Found: C, 46.96;  
H, 6.23; N, 2.83%. Calcd for C19H30NO11Cl: C, 47.16; H, 6.25; N,  
2.89%.  
˚
˚
˚
group C2, a ¼ 35:450ð3Þ A, b ¼ 12:3686ð8Þ A, c ¼ 25:189ð2Þ A,  
ꢀ ¼ 121:121ð3Þꢂ, V ¼ 9455:2ð13Þ A , Z ¼ 16, R ¼ 0:0872,  
3
˚
2
Rw ¼ 0:3048, GOF ¼ 1:349.  
Ethyl (2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl)-  
20  
2-cyanopropanoate (29):  
Mp 109–111 ꢂC (EtOH); ½ꢁꢃD  
¼
1
19:7 (c ¼ 0:995, CHCl3); H NMR (CDCl3, Me4Si): ꢂ 5.47–5.40  
(2H, m, H-40, H-20), 5.08 (1H, dd, J ¼ 3:6, 10.1 Hz, H-30), 4.28  
(2H, tq, J ¼ 3:7, 7.3 Hz, CH2CH3), 4.11 (1H, d, J ¼ 9:8 Hz,  
H-10), 4.06 (2H, d, J ¼ 5:8 Hz, H-60a, H-60b), 3.93 (1H, dd,  
J ¼ 5:8, 7.0 Hz, H-50), 2.17 (3H, s, COCH3), 2.08 (3H, s,  
COCH3), 2.03 (3H, s, COCH3), 1.99 (3H, s, COCH3), 1.67 (3H,  
s, 2-CH3), 1.35 (3H, t, J ¼ 7:3 Hz, CH2CH3). 13C NMR (CDCl3):  
ꢂ 170.18, 170.03, 169.95, 169.44 (COCH3), 166.07 (COOEt),  
117.05 (CN), 78.26 (C-10), 74.80 (C-50), 71.95 (C-30), 67.23  
(C-40), 65.92 (C-20), 63.09 (CH2CH3), 61.37 (C-60), 45.17  
(C-20), 20.79, 20.53, 20.50, 20.44 (COCH3), 16.76 (2-CH3),  
13.88 (CH2CH3). HRMS (ESI) Calcd for C20H27NO11Na  
(½M þ Naꢃþ): 480.14818. Found: 480.14722. Anal. Found: C,  
52.42; H, 5.92; N, 3.17%. Calcd for C20H27NO11: C, 52.51;  
H, 5.95; N, 3.06%. Crystal data: orthorhombic, space group  
t-Butyl (2R)/(2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyr-  
anosyl)-3-aminopropanoate Monohydrochloride (7a/8a):  
Compound 7a/8a (diastereomer ratio: 70/30) was prepared by a  
method similar to the preparation of 3a using 6a in place of 1a.  
Yield: 98%. 1H NMR (D2O, DSS): ꢂ 5.71 (0.7H, dd, J ¼ 9:8,  
10.1 Hz, H-20 (7a)), 5.51 (1H, m, H-40 (7a), H-40 (8a)), 5.18  
(1.3H, m, H-30 (7a), H-30 (8a), H-20 (8a)), 4.37 (0.3H, dd,  
J ¼ 2:4, 9.3 Hz, H-10 (8a)), 4.17 (2.7H, m, H-60a (7a), H-60b  
(7a), H-60a (8a), H-60b (8a), H-50 (7a)), 4.00 (1H, m, H-10 (7a),  
H-50 (8a)), 3.37 (2H, m, H-3a (7a), H-3b (7a), H-3a (8a), H-3b  
(8a)), 3.11 (0.7H, m, H-2 (7a)), 3.04 (0.3H, m, H-2 (8a)), 2.23,  
2.22, 2.16, 2.13, 2.11, 2.07, 2.06, and 2.02 (12H, s, COCH3),  
1.55 (7H, s, C(CH3)3), 1.51 (3H, s, C(CH3)3). 13C NMR (D2O, di-  
oxane): ꢂ 173.53, 173.43, 173.11, 172.95, 172.72, 172.67, 172.58,  
170.70, 169.97, 169.66 (COCH3, COOBut), 84.75 (C(CH3)3),  
77.02, 76.73, 76.60, 74.77, 73.75, 72.99, 72.71, 72.24, 68.52,  
67.28, 67.05, 62.52 (C-60 (8a)), 62.03 (C-60 (7a)), 43.49 (C-2  
(8a)), 42.15 (C-2 (7a)), 39.50 (C-3 (7a)), 35.66 (C-3 (8a)),  
27.23 (C(CH3)3 (7a)), 27.13 (C(CH3)3 (8a)), 20.26, 20.13, 20.00  
(COCH3). HRMS (ESI) Calcd for C21H33NO11Na (½M ꢁ  
HCl þ Naꢃþ): 498.19513. Found: 498.19546.  
˚
˚
˚
P212121, a ¼ 7:585ð2Þ A, b ¼ 14:418ð4Þ A, c ¼ 21:154ð7Þ A, V ¼  
3
2
˚
2313:5ð12Þ A , Z ¼ 4, R ¼ 0:0488, Rw ¼ 0:1257, GOF ¼ 1:114.  
t-Butyl (2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-  
3-aminopropanoate Monohydrochloride (3a). To a solution  
of 1a (290 mg, 0.61 mmol) in chloroform (6 mL) and ethanol  
(30 mL) was added platinum(IV) oxide (100 mg). The suspension  
was hydrogenated under atmospheric pressure hydrogen at room  
temperature overnight. After removal of the catalyst by filtration,  
the solvent was removed by evaporation to give a mixture of  
amines (2a/3a = 74/26) as a white powder (311 mg, 0.608 mmol)  
in 99% yield. Recrystallization from methanol–ether gave a single  
diastereomer 3a (23 mg, 0.049 mmol) as colorless needles in 8%  
Ethyl (2R)/(2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyr-  
anosyl)-3-aminopropanoate Monohydrochloride (7b/8b):  
Compound 7b/8b (diastereomer ratio: 78/22) was prepared by a  
method similar to the preparation of 3a using 6b in place of 1a.  
Yield: 96%. 1H NMR (D2O, DSS): ꢂ 5.56 (1H, dd, J ¼ 9:8,  
10.1 Hz, H-20 (7b), H-20 (8b)), 5.49 (0.78H, d, J ¼ 3:4 Hz, H-40  
(7b)), 5.26 (0.22H, m, H-40 (8b)), 5.20 (1H, dd, J ¼ 3:4, 9.8 Hz,  
H-30 (7b), H-30 (8b)), 4.40–4.12 (6H, m, H-10 (7b), H-10 (8b),  
H-50 (7b), H-50 (8b), H-60a (7b), H-60a (8b), CH2CH3 (7b),  
CH2CH3 (8b)), 3.43 (2H, m, H-3a (7b), H-3b (7b), H-3a (8b),  
H-3b (8b)), 3.25 (0.78H, m, H-2 (7b)), 3.12 (0.22H, m, H-2  
(8b)), 2.21, 2.20, 2.12, 2.08, 2.02, and 2.01 (12H, s, COCH3),  
1.35 (3H, t, J ¼ 7:0 Hz, CH2CH3 (7b), CH2CH3 (8b)). 13C NMR  
(D2O, dioxane): ꢂ 173.74, 173.45, 173.42, 173.09, 172.90, 172.64,  
172.53, 171.59, 170.70, 170.57 (COCH3 (7b), COCH3 (8b),  
COOEt (7b), COOEt (8b)), 76.60 (C-10 (8b)), 76.47 (C-10 (7b)),  
74.62 (C-50 (8b)), 73.98 (C-50 (7b)), 72.62 (C-30 (7b)), 72.21  
(C-30 (8b)), 68.43 (C-20 (7b)), 67.33 (C-20 (8b)), 66.95 (C-40  
(7b)), 66.86 (C-40 (8b)), 63.04 (C-60 (8b)), 62.75 (C-60 (7b)),  
62.13 (CH2CH3 (8b)), 62.02 (CH2CH3 (7b)), 43.17 (C-2 (8b)),  
42.04 (C-2 (7b)), 38.83 (C-3 (7b)), 35.95 (C-3 (8b)), 20.16,  
20.00 (COCH3 (7b), COCH3 (8b)), 13.41 (CH2CH3 (7b)), 13.25  
(CH2CH3 (8b)). HRMS (ESI) Calcd for C19H29NO11Na  
20  
yield. Mp 189–191 ꢂC (MeOH, ether); ½ꢁꢃD ¼ 5:96 (c ¼ 0:999,  
MeOH); 1H NMR (D2O, DSS): ꢂ 5.38 (1H, dd, J ¼ 9:3, 9.5 Hz,  
H-30), 5.17 (1H, dd, J ¼ 9:5, 10.3 Hz, H-20), 5.09 (1H, dd,  
J ¼ 9:3, 10.1 Hz, H-40), 4.40 (1H, dd, J ¼ 2:4, 10.3 Hz, H-10),  
4.30 (1H, dd, J ¼ 5:2, 12.5 Hz, H-60a), 4.18 (1H, dd, J ¼ 2:7,  
12.5 Hz, H-60b), 4.01 (1H, m, H-50), 3.36 (2H, m, H-3a, H-3b),  
3.01 (1H, br, H-2), 2.11 (3H, s, COCH3), 2.09 (6H, s, COCH3),  
2.07 (3H, s, COCH3), 1.50 (9H, s, (CH3)3C). 13C NMR (D2O, di-  
oxane): ꢂ 173.68, 173.14, 172.74, 170.75 (COCH3, COOBut),  
84.75 ((CH3)C), 76.73 (C-10), 75.50 (C-50), 74.28 (C-30), 68.81  
(C-20), 68.26 (C-40), 62.31 (C-60), 43.06 (C-2), 35.58 (C-3),  
27.05 ((CH3)C), 20.02, 19.97 (COCH3). HRMS (ESI) Calcd for  
C21H34NO11 (½M ꢁ Clꢃþ): 476.2126. Found: 476.2124. Anal.  
Found: C, 47.66; H, 6.44; N, 2.74%. Calcd for C21H36NO12Cl:  
C, 47.59; H, 6.85; N, 2.64%.  
Ethyl (2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-3-  
aminopropanoate Monohydrochloride (3b):  
Compound 3b  
Y. Inaba et al.  
Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
613  
(½M ꢁ HCl þ Naꢃþ): 470.16383. Found: 470.16344.  
CH2CH3), 4.03 (1H, ddd, J ¼ 2:1, 2.4, 9.9 Hz, H-50), 3.40 (1H,  
d, J ¼ 13:4 Hz, H-3a), 3.32 (1H, d, J ¼ 13:4 Hz, H-3b), 2.12  
(3H, s, COCH3), 2.09 (3H, s, COCH3), 2.04 (6H, s, COCH3),  
1.40 (3H, s, 2-CH3), 1.31 (3H, t, J ¼ 7:2 Hz, CH2CH3). 13C NMR  
(D2O, dioxane): ꢂ 173.76, 173.06, 172.64, 172.25 (COCH3,  
COOEt), 78.65 (C-10), 75.38 (C-50), 74.82 (C-30), 68.64 (C-20),  
68.07 (C-40), 63.20 (CH2CH3), 61.92 (C-60), 46.84 (C-2), 43.59  
(C-3), 20.16, 20.05 (COCH3), 13.82 (2-CH3), 13.11 (CH2CH3).  
HRMS (ESI) Calcd for C20H31NO11Na (½M ꢁ HCl þ Naꢃþ):  
484.17948. Found: 484.18249.  
t-Butyl (2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-  
3-amino-2-methylpropanoate Monohydrochloride  
Compound 21a was prepared by a method similar to the prepara-  
tion of 3a using 19a in place of 1a. Yield: 84%. ½ꢁꢃD ¼ ꢁ4:86  
(21a):  
20  
(c ¼ 0:830, MeOH); 1H NMR (CD3OD): ꢂ 5.42 (1H, dd,  
J ¼ 9:2, 9.6 Hz, H-20), 5.26 (1H, dd, J ¼ 9:2, 9.5 Hz, H-30),  
5.07 (1H, dd, J ¼ 9:5, 10.1 Hz, H-40), 4.29 (1H, dd, J ¼ 5:0,  
12.5 Hz, H-60a), 4.21 (1H, dd, J ¼ 2:4, 12.5 Hz, H-60b), 3.95  
(1H, ddd, J ¼ 2:4, 5.0, 10.1 Hz, H-50), 3.31 (1H, d, J ¼ 13:4 Hz,  
H-3a), 3.16 (1H, d, J ¼ 13:4 Hz, H-3b), 2.09 (3H, s, COCH3),  
2.06 (3H, s, COCH3), 2.03 (3H, s, COCH3), 2.00 (3H, s, COCH3),  
1.59 (9H, s, C(CH3)3), 1.36 (3H, s, 2-CH3). 13C NMR (CD3OD):  
ꢂ 172.91, 172.31, 171.63, 171.22, 171.16 (COCH3, COOBut),  
84.63 (C(CH3)3), 80.57 (C-10), 77.15 (C-50), 76.21 (C-30), 70.44  
(C-20), 69.26 (C-40), 63.08 (C-60), 48.77 (C-2), 44.24 (C-3),  
28.40, 28.11 (C(CH3)3), 20.99, 20.73, 20.54 (COCH3), 18.89  
(2-CH3). HRMS (ESI) Calcd for C22H35NO11Na (½M ꢁ HCl þ  
Naꢃþ): 512.21078. Found: 512.21091.  
Ethyl (2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-2-  
aminomethylbutanoate Monohydrochloride (31): Compound  
31 was prepared by a method similar to the preparation of 3a us-  
1
ing 25 in place of 1a. Yield: 78%. H NMR (D2O, DSS): ꢂ 5.44–  
5.31 (2H, m, H-20, H-30), 5.10 (1H, dd, J ¼ 9:5, 10.1 Hz, H-40),  
4.35–4.24 (5H, m, OCH2CH3, H-60, H-10), 4.02 (1H, m, H-50),  
3.40 (1H, d, J ¼ 14:0 Hz, H-3a), 3.34 (1H, d, J ¼ 14:0 Hz, H-  
3b), 2.12 (3H, s, COCH3), 2.09 (3H, s, COCH3), 2.05 (3H, s,  
COCH3), 2.04 (3H, s, COCH3), 1.95 (2H, q, J ¼ 7:5 Hz, 2-  
CH2CH3), 1.32 (3H, t, J ¼ 7:3 Hz, OCH2CH3), 0.90 (3H, t,  
J ¼ 7:5 Hz, 2-CH2CH3). 13C NMR (D2O, dioxane): ꢂ 173.69,  
173.01, 172.70, 172.62, 172.35 (COCH3, COOEt), 79.09, 75.66,  
74.83, 68.77, 68.13, 62.89, 62.07, 49.84, 38.99, 24.43 (2-  
CH2CH3), 20.10, 20.05, 19.98, 19.92 (COCH3), 13.11  
(OCH2CH3), 7.15 (2-CH2CH3). HRMS (ESI) Calcd for  
C21H33NO11Na (½M þ Naꢃþ): 498.19513. Found: 498.20049.  
Ethyl (2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl)-  
3-amino-2-methylpropanoate Monohydrochloride (33): Com-  
pound 33 was prepared by a method similar to the preparation of  
t-Butyl (2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-  
3-amino-2-methylpropanoate Monohydrochloride  
Compound 22a was prepared by a method similar to the prepara-  
tion of 3a using 20a in place of 1a. Yield: 99%. ½ꢁꢃD ¼ 24:3  
(22a):  
20  
(c ¼ 0:983, MeOH); 1H NMR (CD3OD): ꢂ 5.36 (1H, dd,  
J ¼ 9:2, 9.2 Hz, H-30), 5.25 (1H, dd, J ¼ 9:2, 10.1 Hz, H-20),  
5.13 (1H, dd, J ¼ 9:2, 10.1 Hz, H-40), 4.29–4.23 (3H, m, H-60a,  
H-60b, H-10), 3.95 (1H, ddd, J ¼ 3:4, 4.3, 10.1 Hz, H-50), 3.30  
(1H, d, J ¼ 13:7 Hz, H-3a), 3.23 (1H, d, J ¼ 13:7 Hz, H-3b),  
2.10 (3H, s, COCH3), 2.07 (3H, s, COCH3), 2.06 (3H, s, COCH3),  
2.01 (3H, s, COCH3), 1.58 (9H, s, C(CH3)3), 1.22 (3H, s, 2-CH3).  
13C NMR (CD3OD): ꢂ 172.82, 172.66, 171.58, 171.30, 171.26  
(COCH3, COOBut), 84.43 (C(CH3)3), 81.41 (C-10), 77.65 (C-  
50), 75.73 (C-30), 69.92 (C-20), 69.47 (C-40), 63.45 (C-60), 49.10  
(C-2), 44.02 (C-3), 28.27 (C(CH3)3), 20.88, 20.80, 20.54, 20.49  
(COCH3), 17.43 (2-CH3). ESI-MS Calcd for C22H35NO11Na  
(½M ꢁ HCl þ Naꢃþ): 512.21. Found: 512.18. Anal. Found: C,  
49.72; H, 6.80; N, 2.72%. Calcd for C45H76N2O23Cl2: C, 49.86;  
H, 7.07; N, 2.58%.  
20  
3a using 29 in place of 1a. Yield: 91%. ½ꢁꢃD ¼ 15:3 (c ¼ 1:16,  
MeOH); 1H NMR (CD3OD): ꢂ 5.47 (1H, d, J ¼ 3:4 Hz, H-40),  
5.35 (1H, dd, J ¼ 9:9, 10.1 Hz, H-20), 5.17 (1H, dd, J ¼ 3:4,  
9.9 Hz, H-30), 4.42–4.32 (1H, m, CH2CH3-a), 4.28–4.11 (5H, m,  
H-60a, H-60b, H-50, H-10, CH2CH3-b), 3.45 (1H, d, J ¼ 12:8 Hz,  
H-3a), 3.15 (1H, d, J ¼ 13:1 Hz, H-3b), 2.18 (3H, s, COCH3),  
2.08 (3H, s, COCH3), 2.02 (3H, s, COCH3), 1.97 (3H, s, COCH3),  
1.45 (3H, s, 2-CH3), 1.39 (3H, t, J ¼ 7:2 Hz, CH2CH3). 13C NMR  
(CD3OD): ꢂ 173.81, 172.15, 171.77, 171.34, 171.16 (COCH3,  
COOEt), 80.91 (C-10), 76.20 (C-50), 73.74 (C-30), 69.27 (C-40),  
67.38 (C-20), 63.08 (CH2CH3), 62.82 (C-60), 47.95 (C-2), 42.59  
(C-3), 20.94, 20.72, 20.56, 20.46 (COCH3), 18.68 (2-CH3),  
14.31 (CH2CH3). HRMS (ESI) Calcd for C20H31NO11Na  
(½M þ Naꢃþ): 484.17948. Found: 484.17885.  
Ethyl (2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-3-  
amino-2-methylpropanoate Monohydrochloride (21b): Com-  
pound 21b was prepared by a method similar to the preparation of  
20  
3a using 19b in place of 1a. Yield: 95%. ½ꢁꢃD ¼ ꢁ10:1  
1
(c ¼ 0:990, MeOH); H NMR (D2O, DSS): ꢂ 5.35–5.27 (2H, m,  
H-20, H-30), 5.08 (1H, dd, J ¼ 9:5, 10.1 Hz, H-40), 4.31–4.18  
(5H, m, H-60, H-10, CH2CH3), 4.00 (1H, ddd, J ¼ 4:0, 9.8,  
10.4 Hz, H-50), 3.35 (1H, d, J ¼ 13:4 Hz, H-3a), 3.25 (1H, d,  
J ¼ 13:4 Hz, H-3b), 2.11 (3H, s, COCH3), 2.08 (3H, s, COCH3),  
2.06 (3H, s, COCH3), 2.04 (3H, s, COCH3), 1.40 (3H, s, 2-CH3),  
1.32 (3H, t, J ¼ 7:2 Hz, CH2CH3). 13C NMR (D2O, dioxane):  
ꢂ 173.66, 173.43, 173.04, 172.69 (COCH3), 172.38 (COOEt),  
78.98 (C-10), 75.29 (C-50), 74.96 (C-30), 68.91 (C-20), 68.01  
(C-40), 62.97 (CH2CH3), 61.92 (C-60), 46.47 (C-2), 41.81 (C-3),  
19.95 (COCH3), 17.64 (2-CH3), 13.06 (CH2CH3). HRMS (ESI)  
Calcd for C20H31NO11Na (½M ꢁ HCl þ Naꢃþ): 484.17948. Found:  
484.17864.  
(2S)-3-Amino-2-(ꢀ-D-glucopyranosyl)propanoic Acid Mono-  
hydrochloride (5). 3a (20 mg, 0.040 mmol) was added 6 mol  
dmꢁ3 HCl (7 mL) and refluxed for 2 h. The solution was evaporat-  
ed to 1 mL and decolorized with active carbon. To the filtrate  
was added EtOH and solvent was evaporated in vacuo to afford  
5 as colorless crystalline material (12 mg, 0.040 mmol) in 100%  
20  
yield. ½ꢁꢃD ¼ 6:97 (c ¼ 2:97, MeOH); 1H NMR (D2O, DSS): ꢂ  
3.96 (1H, dd, J ¼ 2:1, 9.8 Hz, H-50), 3.85 (1H, d, J ¼ 12:5 Hz,  
H-60a), 3.68 (1H, dd, J ¼ 3:7, 12.5 Hz, H-60b), 3.51 (1H, m, H-  
30), 3.44–3.38 (5H, m, H-20, H-40, H-3), 3.22 (1H, m, H-2).  
13C NMR (D2O, dioxane): ꢂ 175.08 (COO), 80.09 (C-10), 78.65  
(C-50), 77.28 (C-30), 70.40 (C-20), 69.45 (C-40), 60.72 (C-60),  
42.78 (C-2), 35.99 (C-3). HRMS (ESI) Calcd for C9H18NO7  
(½M ꢁ Clꢃþ): 252.1078. Found: 252.1080. Anal. Found: C,  
Ethyl (2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-3-  
amino-2-methylpropanoate Monohydrochloride (22b): Com-  
pound 22b was prepared by a method similar to the preparation of  
34.16; H, 6.96; N, 4.04%. Calcd for C9H18NO7Cl 1.5H2O: C,  
ꢄ
20  
3a using 20b in place of 1a. Yield: 77%. ½ꢁꢃD ¼ 19:7 (c ¼ 0:807,  
34.35; H, 6.73; N, 4.45%.  
MeOH); 1H NMR (D2O, DSS): ꢂ 5.33 (1H, dd, J ¼ 9:2, 9.3 Hz,  
H-30), 5.22 (1H, dd, J ¼ 9:2, 9.8 Hz, H-20), 5.12 (1H, dd, J ¼  
9:3, 9.9 Hz, H-40), 4.41–4.22 (5H, m, H-60a, H-60b, H-10,  
(2R)/(2S)-3-Amino-2-(  
Monohydrochloride (9/10):  
ꢀ
-D  
-galactopyranosyl)propanoic Acid  
Compound 9/10 was prepared  
by a method similar to the preparation of 5 using 7a/8a in place  
614 Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
Preparation of C-Glycosyl ꢀ-Amino Acids  
of 3a. Yield: 100%. 1H NMR (D2O, DSS): ꢂ 3.97 (1H, dd,  
J ¼ 2:7, 3.4 Hz, H-40 (9), H-40 (10)), 3.87 (1H, dd, J ¼ 9:5,  
9.8 Hz, H-20 (9), H-20 (10)), 3.78–3.62 (5H, m, H-10 (9), H-10  
(10), H-30 (9), H-30 (10), H-50 (9), H-50 (10), H-60a (9), H-60a  
(10), H-60b (9), H-60b (10)), 3.51–3.41 (2H, m, H-3a (9), H-3b  
(9), H-3a (10), H-3b (10)), 3.37–3.21 (1H, m, H-2 (9), H-2  
(10)). 13C NMR (D2O, dioxane): ꢂ 174.82, 173.27 (COO), 79.43  
(C-10), 79.20, 79.07 (C-50), 73.98 (C-30), 69.12, 68.98 (C-40),  
67.75, 67.62 (C-20), 61.18 (C-60), 42.68, 42.46 (C-2), 38.40,  
35.97 (C-3). HRMS (ESI) Calcd for C9H17NO7Na (½M ꢁ HCl þ  
Naꢃþ): 274.09027. Found: 274.09051.  
followed by the dropwise addition of Et3N (1.26 mL, 3.60 mmol)  
in order to maintain pH 8–9 (monitored by pH-test paper). After  
1 h, TLC (chloroform/methanol 9:1) indicated no starting material  
(Rf ¼ 0:4). Sufficient hydrochloric acid (1 mol dmꢁ3) was added  
to reach pH 2. The aqueous layer was extracted with dichloro-  
methane (2 ꢅ 50 mL) and combined extracts were washed with  
brine (50 mL), dried (Na2SO4), and concentrated in vacuo. The  
residue was purified by silica gel column chromatography (eluent:  
chloroform/ethyl acetate 8:1 to 4:1) to afford 11 (Rf ¼ 0:35  
(chloroform/ethyl acetate, 4:1), 743 mg, 1.07 mmol) in 44% and  
12 (Rf ¼ 0:4 (chloroform/ethyl acetate, 4:1), 306 mg, 0.44 mmol)  
in 18% yield, respectively. For 11: mp 175–176 ꢂC (MeOH);  
(2R)-3-Amino-2-(ꢀ-D-glucopyranosyl)-2-methylpropanoic  
20  
Acid Monohydrochloride (23): Compound 23 was prepared by  
a method similar to the preparation of 5 using 21a in place of 3a.  
½ꢁꢃD ¼ ꢁ24:5 (c ¼ 0:993, CHCl3); 1H NMR (CDCl3, Me4Si):  
ꢂ 7.76 (2H, d, J ¼ 7:3 Hz, Fmoc-Ar-4), 7.58 (2H, d, J ¼ 7:3 Hz,  
Fmoc-Ar-1), 7.40 (2H, dd, J ¼ 7:3, 7.5 Hz, Fmoc-Ar-3), 7.31  
(2H, dd, J ¼ 7:3, 7.5 Hz, Fmoc-Ar-2), 5.38 (1H, dd, J ¼ 9:2,  
9.5 Hz, H-20), 5.32 (1H, dd, J ¼ 5:5, 5.5 Hz, NHCOO), 5.12  
(1H, dd, J ¼ 9:2, 9.5 Hz, H-30), 5.05 (1H, dd, J ¼ 9:2, 9.5 Hz,  
H-40), 4.39 (2H, m, Fmoc-CH2O), 4.23–4.02 (3H, m, Fmoc-CH,  
H-60a, H-60b), 3.67 (1H, dd, J ¼ 9:5 Hz, H-10), 3.58 (1H, m,  
H-50), 3.49 (2H, m, H-3a, H-3b), 2.77 (1H, m, H-2), 2.03 (6H,  
s, COCH3), 2.02 (3H, s, COCH3), 2.00 (3H, s, COCH3), 1.50  
(9H, s, (CH3)3C). 13C NMR (CDCl3): ꢂ 170.52, 170.39, 169.34,  
169.23 (COCH3, COOBut), 156.40 (NHCOO), 143.79, 141.25  
(Fmoc-Ar-C), 127.68 (Fmoc-Ar-3), 126.98 (Fmoc-Ar-2), 124.96  
(Fmoc-Ar-1), 119.96 (Fmoc-Ar-4), 82.32 ((CH3)3C), 76.58 (C-  
10), 75.95 (C-50), 74.74 (C-30), 69.70 (C-20), 67.99 (C-40), 66.65  
(Fmoc-CH2O), 61.84 (C-60), 47.15 (Fmoc-CH), 45.85 (C-2),  
40.21 (C-3), 28.12, 28.02 ((CH3)3C)), 20.63, 20.50 (COCH3).  
ESI-MS Calcd for C36H43NO13Na (½M þ Naꢃþ): 720.26. Found:  
720.15. Anal. Found: C, 61.86; H, 6.26; N, 2.04%. Calcd for  
C36H43NO13: C, 61.97; H, 6.21; N, 2.01%. Crystal data: ortho-  
20  
Yield: 100%. ½ꢁꢃD ¼ 1:28 (c ¼ 0:736, MeOH); 1H NMR (D2O,  
DSS): ꢂ 3.88 (1H, d, J ¼ 12:5 Hz, H-60a), 3.74–3.66 (2H, m, H-  
60b, H-10), 3.49–3.28 (6H, m, H-20, H-30, H-40, H-50, H-3a, H-  
3b), 1.43 (3H, s, 2-CH3). 13C NMR (D2O, dioxane): ꢂ 176.56  
(COO), 81.26 (C-10), 80.04 (C-50), 77.58 (C-30), 70.50 (C-20),  
69.54 (C-40), 60.82 (C-60), 46.19 (C-2), 41.94 (C-3), 17.70  
(2-CH3). HRMS (ESI) Calcd for C10H19NO7Na (½M ꢁ HCl þ  
Naꢃþ): 288.10592. Found: 288.10633.  
(2S)-3-Amino-2-(ꢀ-D-glucopyranosyl)-2-methylpropanoic  
Acid Monohydrochloride (24): Compound 24 was prepared by  
a method similar to the preparation of 5 using 22a in place of 3a.  
20  
Yield: 91% ½ꢁꢃD ¼ 13:2 (c ¼ 1:00, MeOH); 1H NMR (D2O,  
DSS): ꢂ 3.94–3.85 (2H, m, H-60a, H-10), 3.68 (1H, dd, J ¼ 5:4,  
12.4 Hz, H-60b), 3.50–3.46 (2H, m, H-20, H-30), 3.42–3.37 (2H,  
m, H-40, H-50), 3.32 (2H, s, H-3a, H-3b), 1.32 (3H, s, 2-CH3).  
13C NMR (D2O, dioxane): ꢂ 176.38 (COO), 80.51 (C-10), 79.82  
(C-50), 77.49 (C-30), 70.36 (C-20), 69.41 (C-40), 60.76 (C-60),  
46.76 (C-2), 43.80 (C-3), 14.85 (2-CH3). HRMS (ESI) Calcd for  
C10H20NO7 (½M ꢁ Clꢃþ): 266.1240. Found: 266.1244.  
˚
rhombic, space group with P212121, a ¼ 10:8622ð5Þ A, b ¼  
3
˚
2
˚
˚
(2R)-2-Aminomethyl-2-(ꢀ-D-glucopyranosyl)butanoic Acid  
Monohydrochloride (32): Compound 32 was prepared by a  
method similar to the preparation of 5 using 31 in place of 3a.  
12:9881ð7Þ A, c ¼ 25:340ð1Þ A, V ¼ 3575:0ð3Þ A , Z ¼ 4, R ¼  
20  
0:083, Rw ¼ 0:120, GOF ¼ 0:912. For 12: ½ꢁꢃD ¼ ꢁ21:4  
(c ¼ 0:999, CHCl3); 1H NMR (CDCl3, Me4Si): ꢂ 7.75 (2H, d,  
J ¼ 7:6 Hz, Fmoc-Ar-4), 7.58 (2H, d, J ¼ 7:0 Hz, Fmoc-Ar-1),  
7.38 (2H, dd, J ¼ 7:3, 7.6 Hz, Fmoc-Ar-3), 7.29 (2H, dd,  
J ¼ 7:0, 7.3 Hz, Fmoc-Ar-2), 5.41 (1H, dd, J ¼ 5:5, 6.1 Hz,  
NHCOO), 5.32 (1H, dd, J ¼ 9:0, 9.8 Hz, H-30), 5.13 (1H, dd,  
J ¼ 9:0, 9.3 Hz, H-20), 5.05 (1H, dd, J ¼ 9:3, 9.8 Hz, H-40),  
4.34 (2H, d, J ¼ 7:0 Hz, Fmoc-CH2O), 4.22–4.06 (4H, m,  
Fmoc-CH, H-60a, H-60b, H-10), 3.68–3.60 (1H, m, H-50), 3.49–  
3.40 (2H, m, H-3a, H-3b), 2.70 (1H, m, H-2), 2.06 (3H, s,  
COCH3), 2.03 (3H, s, COCH3), 2.02 (3H, s, COCH3), 2.01  
(3H, s, COCH3), 1.47 (9H, s, (CH3)3C). 13C NMR (CDCl3):  
ꢂ 170.47, 170.25, 170.16, 169.37, 169.27 (COCH3, COOBut),  
156.01 (NHCOO), 143.90, 143,76, 141.11 (Fmoc-Ar-C), 127.51  
(Fmoc-Ar-3), 126.85 (Fmoc-Ar-2), 125.01 (Fmoc-Ar-1), 119.80  
(Fmoc-Ar-4), 81.73 ((CH3)3C), 77.10 (C-10), 76.30 (C-50), 74.22  
(C-30), 69.12 (C-20), 68.39 (C-40), 66.58 (Fmoc-CH2O), 62.16  
(C-60), 47.04 (Fmoc-CH), 45.90 (C-2), 37.20 (C-3), 27.94, 27.85  
((CH3)3C), 20.53, 20.45, 20.40 (COCH3). HRMS (ESI) Calcd  
for C36H43NO13Na (½M þ Naꢃþ): 720.26321. Found: 720.26201.  
t-Butyl (2R)- and (2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galac-  
topyranosyl)-N-(9-fluorenylmethoxycarbonyl)-ꢀ-alaninate (15  
and 16): Compound 15/16 was prepared by a method similar  
to the preparation of 11/12 using 7a/8a in place of 2a/2a. Yield:  
20  
Yield: 100%. ½ꢁꢃD ¼ 1:20 (c ¼ 0:309, MeOH); 1H NMR (D2O,  
DSS): ꢂ 3.89 (1H, d, J ¼ 12:3 Hz, H-60a), 3.85 (1H, m, H-10),  
3.70 (1H, dd, J ¼ 12:3, 3.0 Hz, H-60b), 3.52 (2H, m, H-20, H-  
30), 3.41 (4H, m, H-3a, H-3b, H-40, H-50), 1.95 (2H, m, 2-  
CH2CH3), 0.92 (3H, t, J ¼ 7:3 Hz, 2-CH2CH3). 13C NMR (D2O,  
dioxane): ꢂ 175.52 (CO), 81.71 (C-10), 80.63 (C-50), 77.50  
(C-30), 70.58 (C-20), 69.56 (C-40), 60.76 (C-60), 49.27 (C-2),  
38.67 (C-3), 24.69 (2-CH2CH3), 7.15 (2-CH2CH3). HRMS (ESI)  
Calcd for C11H21NO7Na (½M ꢁ HCl þ Naꢃþ): 302.12157. Found:  
302.12244.  
(2R)-3-Amino-2-(ꢀ-D-galactopyranosyl)-2-methylpropanoic  
Acid Monohydrochloride (34): Compound 34 was prepared by  
a method similar to the preparation of 5 using 33 in place of 3a.  
20  
Yield: 87%. ½ꢁꢃD ¼ 14:7 (c ¼ 0:911, MeOH); 1H NMR (D2O,  
DSS): ꢂ 3.96 (1H, d, J ¼ 2:4 Hz, H-40), 3.75–3.62 (6H, m, H-10,  
H-20, H-30, H-50, H-60a, H-60b), 3.39 (2H, q, J ¼ 13:6 Hz, H-3a,  
H-3b), 1.45 (3H, s, 2-CH3). 13C NMR (D2O, dioxane): ꢂ 176.67  
(COO), 82.02, 79.48, 74.25, 69.02 (C-40), 67.83, 61.23 (C-60),  
46.11 (C-2), 41.83 (C-3), 17.99 (2-CH3). HRMS (ESI) Calcd for  
C10H19NO7Na (½M þ Naꢃþ): 288.10592. Found: 288.10631.  
t-Butyl (2R)- and (2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-gluco-  
pyranosyl)-N-(9-fluorenylmethoxycarbonyl)-ꢀ-alaninate (11  
and 12). A mixture of compounds 2a/3a (1.229 g, 2.40 mmol,  
2a/3a = 72/28) was dissolved in methanol (15 mL) and aceto-  
nitrile (15 mL) and stirred at room temperature. A solution of  
FmocOSu (1.214 g, 3.60 mmol) in acetonitrile (15 mL) was added,  
20  
46% (15) and 16% (16). For 15: ½ꢁꢃD ¼ ꢁ13:3 (c ¼ 0:999,  
CHCl3); 1H NMR (CDCl3, Me4Si): ꢂ 7.63 (2H, d, J ¼ 7:5 Hz,  
Fmoc-Ar-4), 7.58 (2H, d, J ¼ 7:3 Hz, Fmoc-Ar-1), 7.40 (2H, dd,  
J ¼ 7:0, 7.5 Hz, Fmoc-Ar-3), 7.31 (2H, dd, J ¼ 7:0, 7.3 Hz,  
Y. Inaba et al.  
Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
615  
Fmoc-Ar-2), 5.61 (1H, dd, J ¼ 9:8, 10.0 Hz, H-20), 5.41 (1H, d,  
J ¼ 3:2 Hz, H-40), 5.33 (1H, t, J ¼ 6:3 Hz, NHCOO), 4.97 (1H,  
dd, J ¼ 3:2, 10.0 Hz, H-30), 4.39 (2H, d, J ¼ 6:9 Hz, Fmoc-  
CH2O), 4.21 (1H, t, J ¼ 6:9 Hz, Fmoc-CH), 4.04 (2H, d,  
J ¼ 6:6 Hz, H-60a, H-60b), 3.83 (1H, dd, J ¼ 6:5, 6.5 Hz, H-50),  
3.65 (1H, dd, J ¼ 7:8, 9.8 Hz, H-10), 3.51 (2H, dd, J ¼ 6:3,  
6.3 Hz, H-3a, H-3b), 2.78 (1H, m, H-2), 2.14 (3H, s, COCH3),  
2.03 (3H, s, COCH3), 2.00 (3H, s, COCH3), 1.98 (3H, s, COCH3),  
1.53 (9H, s, (CH3)3C). 13C NMR (CDCl3): ꢂ 170.28, 170.15,  
169.95, 169.37, 169.19 (COCH3, COOBut), 156.43 (NHCOO),  
143.84, 143.76, 141.23 (Fmoc-Ar-C), 127.64 (Fmoc-Ar-3),  
126.96 (Fmoc-Ar-2), 124.94 (Fmoc-Ar-1), 119.93 (Fmoc-Ar-4),  
82.05 ((CH3)3C), 77.50 (C-10), 74.28 (C-50), 72.62 (C-30), 67.55  
(C-40), 66.81 (C-20), 66.63 (Fmoc-CH2O), 61.14 (C-60), 47.13  
(Fmoc-CH), 45.72 (C-2), 40.30 (C-3), 27.96 ((CH3)3C), 20.73,  
HRMS (ESI) Calcd for C32H34NO13Na2 (½M ꢁ H þ 2Naꢃþ):  
686.18255. Found: 686.18287.  
(2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-glucopyranosyl)-N-(9-  
fluorenylmethoxycarbonyl)-ꢀ-alanine (14): Compound 14 was  
prepared by a method similar to the preparation of 13 using 12 in  
20  
place of 11. Yield: 96%. Mp 95–96 ꢂC (MeOH); ½ꢁꢃD ¼ ꢁ15:8  
(c ¼ 1:01, CHCl3); 1H NMR (CD3OD): ꢂ 7.83 (2H, d, J ¼  
7:5 Hz, Fmoc-Ar-4), 7.69 (2H, d, J ¼ 7:3 Hz, Fmoc-Ar-1), 7.43  
(2H, dd, J ¼ 7:0, 7.5 Hz, Fmoc-Ar-3), 7.35 (2H, dd, J ¼ 7:0,  
7.3 Hz, Fmoc-Ar-2), 5.25 (1H, dd, J ¼ 9:2, 9.5 Hz, H-30), 5.12  
(1H, dd, J ¼ 9:5, 9.8 Hz, H-20), 5.07 (1H, dd, J ¼ 9:2, 9.2 Hz,  
H-40), 4.36–4.26 (4H, m, Fmoc-CH2O, Fmoc-CH, H-60a), 4.14–  
4.06 (2H, m, H-60b, H-10), 3.82 (1H, m, H-50), 3.54 (2H, m,  
H-3a, H-3b), 2.83 (1H, m, H-2), 2.06 (6H, s, COCH3), 2.03  
(3H, s, COCH3), 1.99 (3H, s, COCH3). 13C NMR (CD3OD):  
ꢂ 174.54, 172.34, 171.76, 171.24, 171.21 (COCH3, COOH),  
158.51 (NHCOO), 145.34, 145.25, 142.50 (Fmoc-Ar-C), 128.75  
(Fmoc-Ar-3), 128.14 (Fmoc-Ar-2), 126.24 (Fmoc-Ar-1), 120.90  
(Fmoc-Ar-4), 77.87 (C-10), 75.83 (C-50), 75.83 (C-30), 71.94  
(C-20), 69.76 (C-40), 67.80 (Fmoc-CH2O), 63.34 (C-60), 48.37  
(Fmoc-CH), 47.88 (C-2), 39.50 (C-3), 20.64 (COCH3). ESI-MS  
Calcd for C32H35NO13Na (½M þ Naꢃþ): 664.20. Found: 664.22.  
Anal. Found: C, 59.12; H, 5.58; N, 2.21%. Calcd for C33H39NO14:  
C, 58.84; H, 5.84; N, 2.08%.  
20.63, 20.53 (COCH3). HRMS (ESI) Calcd for C36H43NO13Na  
20  
(½M þ Naꢃþ): 720.26321. Found: 720.26354. For 16: ½ꢁꢃD  
¼
ꢁ3:24 (c ¼ 0:997, CHCl3); 1H NMR (CDCl3, Me4Si): ꢂ 7.76  
(2H, d, J ¼ 7:5 Hz, Fmoc-Ar-4), 7.59 (2H, d, J ¼ 7:0 Hz, Fmoc-  
Ar-1), 7.39 (2H, dd, J ¼ 7:0, 7.5 Hz, Fmoc-Ar-3), 7.30 (2H, dd,  
J ¼ 7:0, 7.0 Hz, Fmoc-Ar-2), 5.42 (1H, d, J ¼ 3:4 Hz, H-40), 5.36  
(1H, br, NHCOO), 5.32 (1H, dd, J ¼ 9:9, 9.9 Hz, H-20), 5.05  
(1H, dd, J ¼ 3:4, 9.9 Hz, H-30), 4.35 (2H, d, J ¼ 7:4 Hz, Fmoc-  
CH2O), 4.22 (1H, t, J ¼ 7:4 Hz, Fmoc-CH), 4.15–4.02 (3H, d,  
m, H-60, H-10), 3.87 (1H, dd, J ¼ 5:8, 5.8 Hz, H-50), 3.70 (1H,  
m, H-3a), 3.50 (1H, m, H-3b), 2.72 (1H, m, H-2), 2.13 (3H, s,  
COCH3), 2.07 (3H, s, COCH3), 2.02 (3H, s, COCH3), 1.99  
(3H, s, COCH3), 1.47 (9H, s, (CH3)3C). 13C NMR (CDCl3):  
ꢂ 170.36, 170.13, 169.52 (COCH3, COOBut), 156.02 (NHCOO),  
144.05, 143.84, 141.19 (Fmoc-Ar-C), 127.58 (Fmoc-Ar-3),  
126.90 (Fmoc-Ar-2), 125.04 (Fmoc-Ar-1), 119.88 (Fmoc-Ar-4),  
81.77 ((CH3)3C), 77.58 (C-10), 75.01 (C-50), 72.36 (C-30), 67.78  
(C-40), 66.68 (Fmoc-CH2O), 66.61 (C-20), 61.76 (C-60), 47.13  
(Fmoc-CH), 46.11 (C-2), 37.38 (C-3), 27.98 ((CH3)3C), 20.65,  
20.53 (COCH3). HRMS (ESI) Calcd for C36H43NO13Na  
(½M þ Naꢃþ): 720.26321. Found: 720.26441.  
(2R)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl)-N-(9-  
fluorenylmethoxycarbonyl)-ꢀ-alanine (17): Compound 17 was  
prepared by a method similar to the preparation of 13 using 15 in  
20  
place of 11. Yield: 75%. ½ꢁꢃD ¼ ꢁ12:0 (c ¼ 1:00, CHCl3);  
1H NMR (CD3OD): ꢂ 7.84 (2H, d, J ¼ 7:0 Hz, Fmoc-Ar-4),  
7.69 (2H, d, J ¼ 7:3 Hz, Fmoc-Ar-1), 7.45–7.33 (2H, m, Fmoc-  
Ar-2,3), 5.54 (1H, dd, J ¼ 10:1, 10.1 Hz, H-20), 5.43 (1H, d,  
J ¼ 3:1 Hz, H-40), 5.11 (1H, dd, J ¼ 3:1, 10.1 Hz, H-30), 4.41  
(2H, dd, J ¼ 3:4, 6.1 Hz, Fmoc-CH2O), 4.25 (1H, t, J ¼ 6:1 Hz,  
Fmoc-CH), 4.12 (2H, dd, J ¼ 6:2, 10.5 Hz, H-60a, H-60b), 4.03  
(1H, ddd, J ¼ 6:2, 10.5, 11.0 Hz, H-50), 3.90 (1H, dd, J ¼ 2:4,  
10.1 Hz, H-10), 3.48 (2H, dd, J ¼ 2:4, 7.0 Hz, H-3a, H-3b), 2.94  
(1H, dd, J ¼ 2:4, 4.8 Hz, H-2), 2.15 (3H, s, COCH3), 2.05 (3H,  
s, COCH3), 2.01 (3H, s, COCH3), 1.98 (3H, s, COCH3). 13C NMR  
(CD3OD): ꢂ 173.41, 172.16, 172.10, 171.68, 171.27 (COCH3,  
COOH), 158.70 (NHCO), 145.35, 145.24, 142.62 (Fmoc-Ar-C),  
128.82 (Fmoc-Ar-3), 128.20 (Fmoc-Ar-2), 126.15 (Fmoc-Ar-1),  
120.95 (Fmoc-Ar-4), 77.43 (C-10), 75.62 (C-50), 74.29 (C-30),  
69.27 (C-40), 68.48 (C-20), 67.66 (Fmoc-CH2O), 62.64 (C-60),  
48.43 (Fmoc-CH), 46.67 (C-2), 39.83 (C-3), 20.77, 20.59, 20.52  
(COCH3). HRMS (ESI) Calcd for C32H34NO13Na2 (½M ꢁ H þ  
2Naꢃþ): 686.18255. Found for: 686.18184.  
(2R)-2-(2,3,4,6-Tetra-O-acetyl-  
fluorenylmethoxycarbonyl)-ꢀ-alanine (13).  
ꢀ
-
D
-glucopyranosyl)-N-(9-  
Compound 11  
(209 mg, 0.30 mmol) was dissolved in formic acid (10 mL) and  
stirred at room temperature for 3 h. TLC (ethyl acetate) indicated  
no starting material (Rf ¼ 0:7). Water (30 mL) was added and the  
aqueous layer was extracted with chloroform (2 ꢅ 40 mL), dried  
(Na2SO4), and concentrated. The residue was purified by silica  
gel column chromatography (chloroform/ethyl acetate/methanol  
7:1:0 to 40:2:3) to afford 13 as colorless needles (Rf ¼ 0:3,  
20  
192 mg, 0.29 mmol) in 97% yield. ½ꢁꢃD ¼ ꢁ22:3 (c ¼ 1:0,  
CHCl3); 1H NMR (CD3OD): ꢂ 7.83 (2H, d, J ¼ 7:3 Hz, Fmoc-  
Ar-4), 7.69 (2H, d, J ¼ 7:3 Hz, Fmoc-Ar-1), 7.43 (2H, dd,  
J ¼ 6:7, 7.3 Hz, Fmoc-Ar-3), 7.36 (2H, dd, J ¼ 7:3, 6.7 Hz,  
Fmoc-Ar-2), 7.09 (1H, br, NHCOO), 5.34 (1H, dd, J ¼ 9:3,  
9.8 Hz, H-20), 5.22 (1H, dd, J ¼ 9:3, 9.6 Hz, H-30), 5.05 (1H,  
dd, J ¼ 9:6, 9.8 Hz, H-40), 4.42 (2H, m, Fmoc-CH2O), 4.26–  
4.10 (3H, m, H-60a, H-60b, Fmoc-CH), 3.86 (1H, dd, J ¼ 2:4,  
9.8 Hz, H-10), 3.75 (1H, m, H-50), 3.73 (2H, m, H-3a, H-3b),  
2.92 (1H, m, H-2), 2.06 (3H, s, COCH3), 2.05 (3H, s, COCH3),  
2.00 (3H, s, COCH3), 1.99 (3H, s, COCH3). 13C NMR (CD3OD):  
ꢂ 173.13, 172.37, 171.85, 171.22, 171.06 (COCH3, COOH),  
158.64 (NHCOO), 145.27, 145.17, 142.55 (Fmoc-Ar-C), 128.80  
(Fmoc-Ar-3), 128.17 (Fmoc-Ar-2), 126.10 (Fmoc-Ar-1), 120.94  
(Fmoc-Ar-4), 76.98 (C-50, C-10), 76.20 (C-30), 70.99 (C-20),  
69.53 (C-40), 67.56 (Fmoc-CH2O), 63.22 (C-60), 48.43 (Fmoc-  
CH), 46.28 (C-2), 39.79 (C-3), 20.65, 20.62, 20.52 (COCH3).  
(2S)-2-(2,3,4,6-Tetra-O-acetyl-ꢀ-D-galactopyranosyl)-N-(9-  
fluorenylmethoxycarbonyl)-ꢀ-alanine (18): Compound 18 was  
prepared by a method similar to the preparation of 13 using 16 in  
20  
place of 11. Yield: 84%. ½ꢁꢃD ¼ ꢁ0:02 (c ¼ 0:981, CHCl3);  
1H NMR (CD3OD): ꢂ 7.83 (2H, d, J ¼ 7:6 Hz, Fmoc-Ar-4),  
7.69 (2H, d, J ¼ 7:0 Hz, Fmoc-Ar-1), 7.43 (2H, dd, J ¼ 7:2,  
7.6 Hz, Fmoc-Ar-3), 7.35 (2H, dd, J ¼ 7:0, 7.2 Hz, Fmoc-Ar-2),  
5.45 (1H, d, J ¼ 3:2 Hz, H-40), 5.31 (1H, dd, J ¼ 9:8, 10.1 Hz,  
H-20), 5.15 (1H, dd, J ¼ 3:2, 9.8 Hz, H-30), 4.34 (2H, dd,  
J ¼ 3:1, 7.9 Hz, Fmoc-CH2O), 4.26 (1H, t, J ¼ 6:7 Hz, Fmoc-  
CH), 4.19–4.06 (4H, m, H-60a, H-60b, H-10, H-50), 3.61 (1H, dd,  
J ¼ 5:0, 14.0 Hz, H-3a), 3.51 (1H, dd, J ¼ 8:3, 14.0 Hz, H-3b),  
2.87 (1H, m, H-2), 2.15 (3H, s, COCH3), 2.05 (3H, s, COCH3),  
2.04 (3H, s, COCH3), 1.97 (3H, s, COCH3). 13C NMR (CD3OD):  
ꢂ 174.70, 172.15, 172.02, 171.56, 171.47 (COCH3, COOBut),  
158.51 (NHCOO), 145.37, 145.27, 142.54 (Fmoc-Ar-C), 128.77  
616 Bull. Chem. Soc. Jpn. Vol. 81, No. 5 (2008)  
Preparation of C-Glycosyl ꢀ-Amino Acids  
(Fmoc-Ar-3), 128.15 (Fmoc-Ar-2), 126.26 (Fmoc-Ar-1), 120.92  
(Fmoc-Ar-4), 78.29 (C-10), 75.81 (C-50), 73.85 (C-20), 69.37  
(C-40), 69.26 (C-30), 67.88 (Fmoc-CH2O), 62.69 (C-60), 48.39  
(Fmoc-CH), 47.95 (C-2), 39.55 (C-3), 20.73, 20.56 (COCH3).  
HRMS (ESI) Calcd for C32H34NO13Na2 (½M ꢁ H þ 2Naꢃþ):  
686.18255. Found for: 686.18273.  
20 J. Mittendorf, F. Kunisch, M. Matzke, H.-C. Militzer,  
A. Schmidt, W. Schonfeld, Bioorg. Med. Chem. Lett. 2003, 13,  
433.  
21 R. P. Cheng, S. H. Gellman, W. F. DeGrado, Chem. Rev.  
2001, 101, 3219.  
¨
22 D. Seebach, D. F. Hook, A. Glattli, Pept. Sci. 2006, 84, 23.  
¨
X-ray Crystallography. Crystallographic data have been de-  
posited with Cambridge Crystallographic Data Centre: Deposition  
numbers CCDC-674992–675000 for compounds 1a, 1b, 6a, 6b,  
19b, 11, 19a, 29, and 25, respectively. Copies of the data can  
be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/  
retrieving.html (or from the Cambridge Crystallographic Data  
Centre, 12, Union Road, Cambridge, CB2 1EZ, UK; Fax: +44  
1223 336033; e-mail: deposit@ccdc.cam.ac.uk).  
23 J. Frackenpohl, P. I. Arvidsson, J. V. Schreiber, D.  
Seebach, ChemBioChem 2001, 2, 445.  
24 J. V. Schreiber, J. Frackenpohl, F. Moser, T. Fleischmann,  
H.-P. E. Kohler, D. Seebach, ChemBioChem 2002, 3, 424.  
25 R. P. Tripathi, R. Tripathi, V. K. Tiwari, L. Bala, S. Sinha,  
A. Srivastava, R. Srivastava, B. S. Srivastava, Eur. J. Med. Chem.  
2002, 37, 773.  
26 R. C. Mishra, R. Tripathi, D. Katiyar, N. Tewari, D. Singh,  
R. P. Tripathi, Bioorg. Med. Chem. 2003, 11, 5363.  
27 G. V. M. Sharma, V. G. Reddy, A. S. Chander, K. R.  
Reddy, Tetrahedron: Asymmetry 2002, 13, 21.  
28 A. Dondoni, A. Massi, S. Sabbatini, V. Bertolasi, Tetra-  
hedron Lett. 2004, 45, 2381.  
This work was supported by the Sasakawa Scientific Re-  
search Grant from The Japan Science Society. The authors  
thank Dr. Tim Storr of Stanford University for critical reading  
of the manuscript.  
29 A. Dondoni, A. Massi, S. Sabbatini, Chem.—Eur. J. 2005,  
11, 7110.  
30 A. Dondoni, A. Massi, E. Minghini, Synlett 2006, 539.  
References  
´
31 C. Palomo, M. Oiarbide, A. Landa, M. C. Gonzalez-Rego,  
1
2
R. A. Dwek, Chem. Rev. 1996, 96, 683.  
H. Herzner, T. Reipen, M. Schultz, H. Kunz, Chem. Rev.  
´
´
´
J. M. Garcıa, A. Gonzalez, J. M. Odriozola, M. Martın-Pastor,  
A. Linden, J. Am. Chem. Soc. 2002, 124, 8637.  
32 G. V. M. Sharma, K. R. Reddy, P. R. Krishna, A. R.  
Sankar, K. Narsimulu, S. K. Kumar, P. Jayaprakash, B.  
Jagannadh, A. C. Kunwar, J. Am. Chem. Soc. 2003, 125, 13670.  
33 G. V. M. Sharma, K. R. Reddy, P. R. Krishna, A. R.  
Sankar, P. Jayaprakash, B. Jagannadh, A. C. Kunwar, Angew.  
Chem., Int. Ed. 2004, 43, 3961.  
2000, 100, 4495.  
J. F. Espinosa, E. Montero, A. Vian, J. L. Garcıa, H.  
´
Dietrich, R. R. Schmidt, M. Martın-Lomas, A. Imberty, F. J.  
3
´
Can˜ada, J. Jimenez-Barbero, J. Am. Chem. Soc. 1998, 120, 1309.  
´
L. A. Marcaurelle, C. R. Bertozzi, Chem.—Eur. J. 1999, 5,  
4
1384.  
5
Q. Wang, M. Wolff, T. Polat, Y. Du, R. J. Linhardt, Bio-  
org. Med. Chem. Lett. 2000, 10, 941.  
T. Gustafsson, M. Hedenstrom, J. Kihlberg, J. Org. Chem.  
2006, 71, 1911.  
34 G. V. M. Sharma, P. Nagendar, P. Jayaprakash, P. R.  
Krishna, K. V. S. Ramakrishna, A. C. Kunwar, Angew. Chem.,  
Int. Ed. 2005, 44, 5878.  
6
¨
7
8
A. Dondoni, A. Marra, Chem. Rev. 2000, 100, 4395.  
S. P. Vincent, A. Schleyer, C.-H. Wong, J. Org. Chem.  
35 G. V. M. Sharma, V. Subash, K. Narsimulu, A. R. Sankar,  
A. C. Kunwar, Angew. Chem., Int. Ed. 2006, 45, 8207.  
36 G. Srinivasulu, S. K. Kumar, G. V. M. Sharma, A. C.  
Kunwar, J. Org. Chem. 2006, 71, 8395.  
37 G. V. M. Sharma, K. L. Reddy, P. S. Lakshmi, R. Ravi,  
A. C. Kunwar, J. Org. Chem. 2006, 71, 3967.  
2000, 65, 4440.  
9
F. Schweizer, T. Inazu, Org. Lett. 2001, 3, 4115.  
10 L. Colombo, M. di Giacomo, P. Ciceri, Tetrahedron 2002,  
58, 9381.  
11 P. Brown, D. S. Eggleston, R. C. Haltiwanger, R. L.  
Jarvest, L. Mensah, P. J. O’Hanlon, A. J. Pope, Bioorg. Med.  
Chem. Lett. 2001, 11, 711.  
12 J. D. Parrish, R. D. Little, Org. Lett. 2002, 4, 1439.  
13 E. Brenna, C. Fuganti, P. Grasselli, S. Serra, S. Zambotti,  
Chem.—Eur. J. 2002, 8, 1872.  
38 Y. Inaba, S. Yano, Y. Mikata, Tetrahedron Lett. 2007,  
48, 993.  
39 S. Abele, D. Seebach, Eur. J. Org. Chem. 2000, 1.  
40 A. Guerrini, G. Varchi, A. Battaglia, J. Org. Chem. 2006,  
71, 6785.  
´
41 C. Cativiela, M. D. Diaz-de-Villegas, J. A. Galvez, J. Org.  
14 T. Gustafsson, M. Saxin, J. Kihlberg, J. Org. Chem. 2003,  
68, 2506.  
15 S. B. McNabb, M. Ueda, T. Naito, Org. Lett. 2004, 6,  
1911.  
16 M. Ousmer, V. Boucard, N. Lubin-Germain, J. Uziel,  
Chem. 1994, 59, 2497.  
42 G. V. Subbaraju, T. Golakoti, G. M. L. Patterson, R. E.  
Moore, J. Nat. Prod. 1997, 60, 302.  
43 S. Chaganty, T. Golakoti, C. Heltzel, R. E. Moore, W. Y.  
Yoshida, J. Nat. Prod. 2004, 67, 1403.  
˚
44 J. K. Ekegren, N. Ginman, A. Johansson, H. Wallberg,  
´
J. Auge, Eur. J. Org. Chem. 2006, 1216.  
17 M. Liu, M. P. Sibi, Tetrahedron 2002, 58, 7991.  
18 N. Sewald, Angew. Chem., Int. Ed. 2003, 42, 5794.  
19 G. Lelais, D. Seebach, Pept. Sci. 2004, 76, 206.  
M. Larhed, B. Samuelsson, T. Unge, A. Hallberg, J. Med. Chem.  
2006, 49, 1828.  

Products guided by the article

Product name:(2R)-3-amino-2-(β-D-glucopyranosyl)-2-methylpropanoic acid monohydrochloride

Cas No:1038534-75-6

1038534-75-6

R&D Labs maybe for 1038534-75-6

Relevant to this article

Hot Product