Synthesis of unsaturated c-glycosyl glycines

Article abstract of DOI:10.1081/CAR-100103957

Palladium(0)-catalyzed alkylation of 2,3-unsaturated aryl glycoside with ethyl nitroacetate or N-(diphenylmethylene)glycine ethyl ester in the presence of N,O-bis(trimethylsilyl)acetamide/KOAc afforded ethyl 2-(4,5-di-O-benzyl-2,3-dideoxy-α-D-erythro-hex-

Full text of DOI:10.1081/CAR-100103957

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SYNTHESIS OF UNSATURATED C-GLYCOSYL GLYCINES
Angelika Wernicke a & Denis Sinou b
a Université Claude Bernard Lyon 1 , Laboratoire de Synthèse Asymétrique, associé
au CNRS, CPE Lyon, 43, boulevard du 11 novembre 1918, 69622 Villeurbanne Ce´dex,
France
b Université Claude Bernard Lyon 1 , Laboratoire de Synthèse Asymétrique, associé
au CNRS, CPE Lyon, 43, boulevard du 11 novembre 1918, 69622 Villeurbanne Ce´dex,
France
Published online: 16 Aug 2006.
To cite this article: Angelika Wernicke & Denis Sinou (2001) SYNTHESIS OF UNSATURATED C-GLYCOSYL GLYCINES, Journal
of Carbohydrate Chemistry, 20:2, 181-190, DOI: 10.1081/CAR-100103957
To link to this article: http://dx.doi.org/10.1081/CAR-100103957
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J. CARBOHYDRATE CHEMISTRY, 20(2), 181–190 (2001)
SYNTHESIS OF UNSATURATED C-GLYCOSYL
GLYCINES
Angelika Wernicke and Denis Sinou*
Laboratoire de Synthèse Asymétrique, associé au CNRS, CPE Lyon,
Université Claude Bernard Lyon 1, 43,
boulevard du 11 novembre 1918, 69622 Villeurbanne Cédex, France
ABSTRACT
Palladium(0)-catalyzed alkylation of 2,3-unsaturated aryl glycoside with ethyl
nitroacetate or N-(diphenylmethylene)glycine ethyl ester in the presence of
N,O-bis(trimethylsilyl)acetamide/KOAc afforded ethyl 2-(4,5-di-O-benzyl-
2,3-dideoxy-ꢀ-D-erythro-hex-2-enopyranosyl)-2(R,S)-nitroacetate (2) and
ethyl 2-(4,6-di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-hex-2-enopyranosyl)-
2(R,S)-[(N-diphenylmethylene)amino)]acetate (7), respectively. Hydrogena-
tion of compound 2 afforded the saturated aminoesters, while compound 7
was readily transformed into 2-(4,6-di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-
hex-2-enopyranosyl)-2(R,S)-glycine (10) by acidic hydrolysis followedby
saponification.
INTRODUCTION
O-Linked glycopeptides represent an important group of glycoconjugates
which are involved in various cellular and biological processess.1,2 However, since
glycopeptides contain the natural O- or N-glycosidic linkage, they are chemically
and enzymatically unstable, and these drawbacks sometimes limit their uses. Con-
sequently, there is a need to have access to C-analogues of O-glycosylated
aminoacids in order to increase their stability towards hydrolysis. These analogues
can also be used to probe and understand the mechanisms of a number of key cel-
*Corresponding author. E-mail: sinou@univ-lyon1.fr
181
Copyright © 2001 by Marcel Dekker, Inc.
www.dekker.com

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WERNICKE AND SINOU
lular processes; effectively a simple modification could provide useful information
on the specific role of the carbohydrate moiety of glycopeptides. They can also be
readily incorporated into larger and biologically more relevant molecular frame-
works. Much effort has therefore been invested in developing new methodologies
for the construction of C-glycosyl aminoacids. Different approaches to C-glycosyl
glycine,3–8 C-glycosyl alanine,9–12 C-glycosyl serine,13–28 C-glycosyl as-
paragine,21, 28–30 C-glycosyl tyrosine,31 as well as more complex C-glycosyl
aminoacids29, 32–34 have been described.
We have previously described the stereoselective synthesis of various func-
tionalized unsaturated C-glycosides via palladium(0)-catalyzed alkylation of 2,3-
unsaturated O-aryl glycosides with various active methylene compounds.35, 36 We
expect that these compounds could be suitable precursors to unsaturated C-glyco-
syl amino acids given a judicious choice of the active methylene compound. We
describe in this paper the application of this methodology to the synthesis of
unsaturated C-glycosyl glycines using ethyl nitroacetate and N-(diphenylmethy-
lene)glycine ethyl ester as the nucleophiles.
RESULTS AND DISCUSSION
We have previously shown that palladium(0)-catalyzed alkylation of the unsat-
urated carbohydrate 1 occurs regio and stereospecifically at the anomeric center to
give the ꢀ-anomer 2 as the sole product (Scheme 1).35 However, the reaction is not
stereoselective at C-2, a mixture of epimers in a ratio of 75/25 being obtained. In or-
der to increase this selectivity, we attempted some palladium(0)-catalyzed coupling
reaction in the presence of the chiral diphosphines (S,S)-DIOP [(S,S)-(2,3)-O-iso-
propylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane], (S,S)-BDPP [(S,S)-
(2,4)-bis(diphenylphosphinohexane], and (S)-Prophos [(S)-1,2-bis(diphenylphos-
Scheme 1.

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SYNTHESIS OF UNSATURATED C-GLYCOSYL GLYCINES
183
Scheme 2.
phino)propane], at 60°C in THF as the solvent; unfortunately we obtained a quite sim-
ilar ratio of the two epimers: 76/24, 75/25, and 72/28, respectively.
The alkylation reaction was extended to p-tert-butylphenyl 4-O-benzyl-6-de-
oxy-2,3-dideoxy-ꢀ-L-erythro-hex-2-enopyranoside37 (4) using ethyl nitroacetate
as the nucleophile; the corresponding unsaturated ꢀ-C-glycoside 5 was obtained in
90% yield as a 65/35 mixture of the two epimers at C-2 (Scheme 1).
The unsaturated C-glycosides 2 and 5 were stirred in ethanol under a hydro-
gen atmosphere in the presence of Pd/C (10%) in order to access the C-glycosidic
amino esters (Scheme 1). The corresponding saturated amino esters 3 and 6 were
obtained in 30% yield as mixtures of the two epimers (70/30 for 3 and 55/45 for 6).
We then examined the use of N-(diphenylmethylene)glycine ethyl ester as the
nucleophile in this palladium(0)-catalyzed alkylation reaction (Scheme 2). No re-
action was observed when the condensation between the unsaturated carbohydrate
1 and N-(diphenylmethylene)glycine ethyl ester was performed in the absence of a
base at 70°C. We therefore used the anion of N-(diphenylmethylene)glycine ethyl
ester obtained by treating this iminoester with NaH. We observed the formation of
a single compound 8 in 52% yield; the structure of this compound was confirmed
by NMR using COSY and HMBC sequences, altough the E/Z stereochemistry of
the double bond was not determined.
We next performed the coupling reaction using N,O-bis(trimethylsilyl)ac-
etamide (BSA) as the base and KOAc. Under identical conditions, the unsaturated
ꢀ-C-glycoside 7 was obtained in 60% yield as a 50/50 mixture of the two epimers.
It is to be noticed that heating compound 7 in THF in the presence of one equiva-
lent of NaH afforded quantitatively the isomerized C-glycoside 8. The conversion
to the aminoacid was performed according to the litterature.38 Treatment of com-
pound 7 by HCl 10% gave the unsaturated amino ester 9 in 69% yield as a 80/20

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WERNICKE AND SINOU
mixture of the two epimers, that was readily transformed by saponification in 74%
yield into the unsaturated C-glycosyl glycine 10.
CONCLUSION
In conclusion, we have shown that palladium(0)-catalyzed alkylation of
2,3-unsaturated aryl glycoside with N-(diphenylmethylene)glycine ethyl ester in
the presence of N,O-bis(trimethylsilyl)acetamide and KOAc afforded ethyl
2-(4,6-di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-hex-2-enopyranosyl)-2(R,S)-[(N-
diphenylmethylene)amino]acetate. This compound was readily transformed into 2-
(4,6-di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-hex-2-enopyranosyl)-2(R,S)-glycine
by acidic hydrolysis followed by saponification.
EXPERIMENTAL
General Methods. All reactions were monitored by thin-layer chromatog-
raphy carried out on 0.25 mm silica gel plates (60 F-254, Merck). Compounds were
visualized under UV light (254 nm) or by spraying with an H2SO4 solution and heat-
ing. Column chromatography was performed on silica gel 60 (40–63 mesh, Merck).
NMR spectra were recorded on Bruker AC 200 and AM 300 spectrometers, and
chemical shifts are given in ppm on the ꢁ scale from internal tetramethylsilane. Re-
actions involving palladium complexes were carried out in a Schlenk tube under a
nitrogen atmosphere. THF was distilled from sodium/benzophenone and stored un-
der a nitrogen atmosphere. Ethyl 2-(4,5-di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-
hex-2-enopyranosyl)-2(R,S)-nitroacetate (2) has already been described.35
Ethyl 2-(4-O-Benzyl-2,3,6-trideoxy-ꢀ-L-erythro-hex-2-enopyranosyl)-
2(R,S)-nitroacetate (5). A solution of 22.9 mg (0.025 mmol) of Pd2(dba)3 and
40 mg (0.1 mmol) of dppb in tetrahydrofuran (5 mL) was added under argon to a
Schlenk tube containing 176.5 mg (0.5 mmol) of the unsaturated carbohydrate 437
and 99.8 mg (0.75 mmol) of ethyl nitroacetate in tetrahydrofuran (5 mL). The so-
lution was stirred at 70°C and the reaction followed by TLC. After completion of
the reaction, the solvent was evaporated under reduced pressure to give an oil that
was purified by column chromatography on silica gel using petroleum ether/ethyl
acetate (4/1) as the eluent to give 151 mg of the unsaturated C-alkylated carbohy-
drate 5 (as a 65/35 mixture of the two epimers) (90% yield). Oil; Rf 0.66; 1H NMR
(300 MHz, CDCl3) ꢁ 1.25 (d, 0.35 ꢂ 3H, J ꢃ 5.7 Hz, CHCH3), 1.27 (d, 0.75 ꢂ 3H,
J ꢃ 5.7 Hz, CHCH3), 1.30 (t, 0.65 ꢂ 3H, J ꢃ 7.1 Hz, CH2CH3), 1.32 (t, 0.35
ꢂ 3H, J ꢃ 7.1 Hz, CH2CH3), 3.67 (m, 1H, H-4), 3.72 (dq, 1H, J ꢃ 7.5, 5.8 Hz, H-
5), 4.29 (q, 0.65 ꢂ 2H, J ꢃ 7.1 Hz, OCH2CH3), 4.30 (q, 0.35 ꢂ 2H, J ꢃ 7.1 Hz,
OCH2CH3), 4.56 (d, 0.65 ꢂ 1H, J ꢃ 11.5 Hz, CH2Ph), 4.57 (d, 0.35 ꢂ 1H,
J ꢃ 11.5 Hz, CH2Ph), 4.66 (d, 0.35 ꢂ 1H, J ꢃ 11.5 Hz, CH2Ph), 4.67 (d, 0.65 ꢂ
1H, J ꢃ 11.5 Hz, CH2Ph), 4.92–4.98 (m, 1H, H-1), 5.27 (d, 0.35 ꢂ 1H, J ꢃ 8.5

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SYNTHESIS OF UNSATURATED C-GLYCOSYL GLYCINES
185
Hz, CHNO2), 5.34 (d, 0.65 ꢂ 1H, J ꢃ 8.5 Hz, CHNO2), 5.91 (ddd, 1H, J ꢃ 10.4,
3.0, 1.3 Hz, H-3), 6.15 (bd, 1H, J ꢃ 10.4 Hz, H-2), 7.27–7.39 (m, 5H, Har); 13C (50
MHz, CDCl3) ꢁ maj (65%) 13.8 (CH3), 18.0 (CH3), 63.3 (OCH2), 69.0 (C-4), 70.8
(C-1), 71.4 (CH2Ph), 75.0 (C-5), 88.5 (CHNO2), 124.4, 127.9, 128.0, 130.6, 137.8
(C-2, C-3, Car), 161.9 (CO2); ꢁ min (35%) 13.9 (CH3), 17.8 (CH3), 63.2 (OCH2),
69.8 (C-4), 70.2 (C-1), 71.0 (CH2Ph), 74.4 (C-5), 88.4 (CHNO2), 124.8, 128.5,
129.7, 137.9 (C-2, C-3, Car), 162.5 (CO2).
Anal. Calcd for C17H21NO6 (335.36): C, 60.89; H, 6.31. Found: C, 61.85; H,
6.67.
Ethyl 2-(4,6-Di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-hex-2-enopyranosyl)-
2(R,S)-[(N-diphenylmethylene)amino]acetate (7). A solution of 22.9 mg
(0.025 mmol) of Pd2(dba)3 and 40 mg (0.1 mmol) of dppb in tetrahydrofuran (5
mL) was added under argon to a Schlenk tube containing 230 mg (0.5 mmol) of the
unsaturated carbohydrate 1 and 400 mg (1.5 mmol) of N-(diphenylmethylene)-
glycine ethyl ester in the presence of 304 mg (1.5 mmol) of N,O-bis(trimethylsi-
lyl)acetamide and 147 mg (1.5 mmol) of KOAc in tetrahydrofuran (5 mL). The
solution was stirred at 70°C and the reaction followed by TLC. After completion
of the reaction, the solvent was evaporated under reduced pressure to give an oil
that was purified by column chromatography on silica gel using petroleum
ether/ethyl acetate (4/1) as the eluent to give 172 mg of the unsaturated C-alkylated
carbohydrate 7 as a 50/50 mixture of the two epimers (60% yield). Oil; isomer Rf
0.44; 1H NMR (300 MHz, CDCl3) ꢁ 1.19 (t, 3H, J ꢃ 7.2 Hz, CH3), 3.57 (dd, 1H,
J ꢃ 11.1, 3.3 Hz, H-6), 3.62 (dd, 1H, J ꢃ 11.1, 4.0 Hz, H-6), 3.69 (ddd, 1H,
J ꢃ 7.4, 4.0, 3.3 Hz, H-5), 4.08 (m, 2H, CH2CH3), 4.10 (dd, 1H, J ꢃ 7.3, 1.5 Hz,
H-4), 4.39 (d, 1H, J ꢃ 7.4 Hz, CHN), 4.45 (d, 1H, J ꢃ 11.8 Hz, CH2Ph), 4.46 (d,
1H, J ꢃ 12.1 Hz, CH2Ph), 4.54 (d, 1H, J ꢃ 12.1 Hz, CH2Ph), 4.56 (d, 1H, J ꢃ 11.8
Hz, CH2Ph), 4.95 (dd, 1H, J ꢃ 7.4, 1.8 Hz, H-1), 5.98 (dd, 1H, J ꢃ 10.4, 1.8 Hz,
H-2), 6.04 (dd, 1H, J ꢃ 10.4, 1.5 Hz, H-3), 7.10–7.70 (m, 20H, Har); 13C (75 MHz,
CDCl3) ꢁ 14.3 (CH3), 61.1 (CH2CH3), 68.9 (CHN), 69.4 (C-6), 69.9 (C-1), 70.6
(CH2Ph), 73.4 (CH2Ph), 72.5 (C-5), 74.0 (C-4), 127.5–129.0, 130.5, 130.6, 136.0,
136.1, 138.5, 139.4, 139.7 (C-2, C-3, Car), 170.1 (NꢃC), 171.3 (CO2); isomer Rf
0.40; 1H NMR (300 MHz, CDCl3) ꢁ 1.29 (t, 3H, J ꢃ 7.2 Hz, CH3), 3.60 (dd, 1H,
J ꢃ 11.1, 3.3 Hz, H-6), 3.67 (dd, 1H, J ꢃ 11.1, 4.0 Hz, H-6), 3.68–3.77 (m, 1H, H-
5), 3.99–4.27 (m, 3H, CH2CH3, H-4), 4.32 (d, 1H, J ꢃ 5.9 Hz, CHN), 4.45 (d, 1H,
J ꢃ 11.8 Hz, CH2Ph), 4.46 (d, 1H, J ꢃ 12.1 Hz, CH2Ph), 4.54 (d, 1H, J ꢃ 12.1 Hz,
CH2Ph), 4.56 (d, 1H, J ꢃ 11.8 Hz, CH2Ph), 4.87 (dd, 1H, J ꢃ 5.9, 2.6 Hz, H-1),
5.73 (ddd, 1H, J ꢃ 10.7, 2.6, 1.8 Hz, H-2), 6.07 (dd, 1H, J ꢃ 10.7, 1.8 Hz, H-3),
7.13–7.73 (m, 20H, Har); 13C (75 MHz, CDCl3) ꢁ 14.2 (CH3), 61.1 (CH2CH3), 69.0
(CHN), 69.3 (C-6), 69.8 (C-1), 70.8 (CH2Ph), 73.4 (CH2Ph), 72.6 (C-5), 74.4 (C-
4), 128.0–129.2, 130.1, 130.4, 132.5, 136.1, 136.2, 138.3, 138.5, 139.3 (C-2, C-3,
Car), 170.1 (NꢃC), 172.1 (CO2).
Anal. Calcd for C37H37NO5 (575.71): C, 77.19; H, 6.48. Found: C, 77.02; H,
6.32.

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WERNICKE AND SINOU
Ethyl 2-(4,6-Di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-hex-2-enopyranosyl)-
2-(benzhydrylimino)acetate (8). A solution of 22.9 mg (0.025 mmol) of
Pd2(dba)3 and 40 mg (0.1 mmol) of dppb in tetrahydrofuran (5 mL) was added un-
der argon to a Schlenk tube containing 230 mg (0.5 mmol) of the unsaturated car-
bohydrate 1 and 400 mg (1.5 mmol) of N-(diphenylmethylene)glycine ethyl ester
in the presence of 36 mg (1.5 mmol) of NaH in tetrahydrofuran (5 mL). The solu-
tion was stirred at the desired temperature and the reaction followed by TLC. Af-
ter completion of the reaction, the solvent was evaporated under reduced pressure
to give an oil that was purified by column chromatography on silica gel using
petroleum ether/ethyl acetate (4/1) as the eluent to give 150 mg of the unsaturated
C-alkylated carbohydrate 8 (52% yield). Oil; Rf 0.39; 1H NMR (300 MHz, CDCl3)
ꢁ 1.18 (t, 3H, J ꢃ 7.0 Hz, CH3), 3.48 (dd, 1H, J ꢃ 14.8, 5.5 Hz, H-6), 3.51 (dd, 1H,
J ꢃ 14.8, 6.3 Hz, H-6), 3.95 (m, 1H, H-5), 4.10 (m, 2H, CH2CH3), 4.23 (d, 1H,
J ꢃ 11.8 Hz, CH2Ph), 4.38 (dd, 1H, J ꢃ 10.3, 5.2 Hz, H-4), 4.49 (d, 1H, J ꢃ 14.7
Hz, CH2Ph), 4.50 (d, 1H, J ꢃ 14.7 Hz, CH2Ph), 4.51 (d, 1H, J ꢃ 11.8 Hz, CH2Ph),
5.68 (dd, 1H, J ꢃ 10.3, 10.3 Hz, H-3), 6.57 (dd, 1H, J ꢃ 12.5, 10.3 Hz, H-2), 6.69
(d, 1H, J ꢃ 12.5 Hz, H-1), 7.15–7.60 (m, 20H, Har), 7.79 (d, 1H, J ꢃ 7.4 Hz,
CHPh2); 13C (75 MHz, CDCl3) ꢁ 14.3 (CH3), 61.1 (CH2CH3), 70.3 (CH2Ph), 70.7
(C-6), 72.6 (C-5), 73.5 (CH2Ph), 74.6 (C-4), 127.7, 127.8, 127.9, 128.1, 128.3,
128.4, 128.8, 129.3, 131.3, 131.9,138.0, 141.4 (C-2, C-3, Car), 138.0 (CꢃN), 171.6
(CO2).
Anal. Calcd for C37H37NO5 (575.71): C, 77.19; H, 6.48. Found: C, 76.84; H,
6.47.
Isomerization of Compound 7. A solution of 130 mg (0.23 mmol) of the
iminoester 7 and 64 mg (2.66 mmol) of NaH in tetrahydrofuran (6 mL) was stirred
under nitrogen at 60°C for 5h. The solution was diluted with water (2 mL), and the
organic product was extracted with CH2Cl2 (2 ꢂ 10 mL). Evaporation of the sol-
vent gave quantitatively an oil that was identical to compound 8.
Hydrogenation of Nitrocompounds 2 and 5. A solution of 1 mmol of the
glycosidic nitroester 2 or 5 in 15 mL of ethanol was stirred for 24 h under hydro-
gen (1 atm) in the presence of 10% Pd/C (10%). After filtration, the solvent was
evaporated and the residue purified on silica using methanol as the eluent to afford
the aminoester 3 or 6, respectively.
Ethyl 2(R,S)-amino-2-(4,6-di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-hexopy-
ranosyl)acetate (3) (as a 70/30 mixture). Yield 30%; oil; Rf 0.50 (methanol); 1H
NMR (200 MHz, CDCl3) ꢁ 1.18–1.28 (m, 2H, H-2, H-3), 1.22 (t, 3H, J ꢃ 7.1 Hz,
CHCH3), 1.50–1.61 (m, 2H, H-2, H-3), 2.14–2.45 (m, 2H, NH2), 3.38–3.79 (m,
6H, H-1, H-4, H-5, H-6, CHNH2), 4.15 (q, 0.3 ꢂ 2H, J ꢃ 7.1 Hz, CH2CH3), 4.16
(q, 0.7 ꢂ 2H, J ꢃ 7.1 Hz, CH2CH3), 4.42 (d, 1H, J ꢃ 12.0 Hz, CH2Ph), 4.52 (d,
1H, J ꢃ 12.0 Hz, CH2Ph), 4.57 (d, 1H, J ꢃ 11.2 Hz, CH2Ph), 4.60 (d, 1H, J ꢃ 11.2
Hz, CH2Ph), 7.28–7.32 (m, 10H, Har); 13C (50 MHz, CDCl3) ꢁ 14.2 (CH3), 24.0
and 28.8 (C-2, C-3 maj), 25.0 and 29.7 (C-2, C-3 min), 61.1 (OCH2 min), 61.2

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SYNTHESIS OF UNSATURATED C-GLYCOSYL GLYCINES
187
(OCH2 maj), 69.0 (C-6 min), 69.8 (C-6 maj), 70.6 (CH2Ph min), 71.0 (CH2Ph maj),
72.1 (C-4), 73.0 (C-5), 73.3 (CH2Ph), 74.5 (C-1), 80.8 (CHNH2), 127.5, 127.6,
127.7, 127.8, 128.3, 138.3, 138.4 (Car), 162.5 (CO2).
Ethyl 2(R,S)-amino-(4-O-benzyl-2,3,6-trideoxy-ꢀ-L-erythro-hexopyra-
nosyl)acetate (6) (as a 55/45 mixture). Yield 30%; oil; Rf 0.31 (ethyl acetate); 1H
NMR (200 MHz, CDCl3) ꢁ 1.24 (m, 3H, CHCH3), 1.25 (d, 3H, J ꢃ 5.7 Hz, CHCH3),
1.40–2.10 (m, 4H, H-2, H-3), 2.20–2.40 (m, 2H, NH2), 2.90 (3.40 (m, 2H, H-4, H-
5), 3.60–4.05 (m, 2H, H-1, H-2), 4.20 (q, 2H, J ꢃ 7.0 Hz, OCH2CH3), 4.51 (d, 1H,
J ꢃ 12.0 Hz, CH2Ph), 4.56 (d, 1H, J ꢃ 12.0 Hz, CH2Ph), 7.32–7.44 (m, 5H, Har);
13C (50 MHz, CDCl3) ꢁ 14.2 (CH3), 17.1 (CH3 maj), 18.6 (CH3 min), 22.0 and 29.7
(C-2, C-3 min), 23.1 and 28.8 (C-2, C-3 maj), 61.0 (CH2CH3), 70.4 (CH2Ph min),
71.0 (CH2Ph maj), 71.4 (C-4), 76.3 (C-5), 76.5 (C-1 min), 77.4 (C-1 maj), 77.7
(CHNH2 min), 78.7 (CHNH2 maj), 127.6, 127.7, 128.4, 135.6 (Car), 161.9 (CO2).
Anal. Calcd for C17H25NO4 (307.39): C, 66.43; H, 8.20. Found: C, 66.33; H,
8.52.
Ethyl 2(R,S)-Amino-2-(4,6-di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-hex-2-
enopyranosyl)acetate (9). A solution of 262 mg (0.46 mmol) of the iminoester
7 in diethyl ether (5 mL) was stirred at room temperature in the presence of a so-
lution of HCl (10%, 2.5 mL). After 1 h, the organic layer was separated, the aque-
ous phase was washed with diethyl ether and neutralized with sodium hydrogen-
carbonate. The organic substrate was extracted with diethyl ether (10 mL).
Evaporation of the solvent gave a residue that was purified by chromatography us-
ing methanol as the eluent to give 131 mg of compound 9 (as a 80/20 mixture of
the two epimers) as an oil (69% yield). Rf 0.74 (methanol); major isomer 1H NMR
(300 MHz, CDCl3) ꢁ 1.26 (t, 3H, J ꢃ 7.2 Hz, CH3), 1.92 (bs, 2H, NH2), 3.54–3.72
(m, 3H, H-5, H-6), 3.92 (m, 1H, CHNH2), 4.01 (dd, 1H, J ꢃ 10.3, 4.8 Hz, H-4),
4.10–4.26 (m, 2H, CH2CH3), 4.39 (ddd, 1H, J ꢃ 5.9, 4.4, 2.2 Hz, H-1), 4.51 (d, 1H,
J ꢃ 12.1 Hz, CH2Ph), 4.52 (d, 1H, J ꢃ 11.8 Hz, CH2Ph), 4.58 (d, 1H, J ꢃ 12.1 Hz,
CH2Ph), 4.60 (d, 1H, J ꢃ 11.8 Hz, CH2Ph), 5.92 (ddd, 1H, J ꢃ 10.7, 2.2, 1.5 Hz,
H-2), 6.08 (ddd, 1H, J ꢃ 10.7, 2.6, 2.6 Hz, H-3), 7.23–7.38 (m, 10H, Har); 13C (75
MHz, CDCl3) ꢁ 14.2 (CH3), 57.7 (CHN), 61.3 (C-6), 69.1 (CH2Ph), 69.3 (C-1),
70.8 (CH2CH3), 72.8 (C-5), 73.4 (CH2Ph), 73.5 (C-4), 127.2, 127.7, 127.8, 127.9,
1
128.4, 128.5, 138.1, 138.2 (C-2, C-3, Car), 172.8 (CO2); minor isomer H NMR
(300 MHz, CDCl3) ꢁ 1.24 (t, 3H, J ꢃ 7.2 Hz, CH3), 1.79 (bs, 2H, NH2), 3.54–3.68
(m, 3H, H-5, H-6), 3.92 (m, 1H, CHNH2), 3.96–4.05 (m, 1H, H-4), 4.10–4.26 (m,
2H, CH2CH3), 4.35 (ddd, 1H, J ꢃ 5.5, 4.4, 2.2 Hz, H-1), 4.50 (d, 1H, J ꢃ 12.1 Hz,
CH2Ph), 4.51 (d, 1H, J ꢃ 11.8 Hz, CH2Ph), 4.59 (d, 1H, J ꢃ 12.1 Hz, CH2Ph), 4.60
(d, 1H, J ꢃ 11.8 Hz, CH2Ph), 5.84 (ddd, 1H, J ꢃ 10.3, 2.2, 1.5 Hz, H-2), 6.08 (ddd,
1H, J ꢃ 10.3, 2.2, 2.2 Hz, H-3), 7.23–7.38 (m, 10H, Har); 13C (75 MHz, CDCl3) ꢁ
14.2 (CH3), 58.1 (CHN), 61.1 (C-6), 70.9 (CH2Ph), 69.3 (C-1), 70.9 (CH2CH3),
73.0 (C-5), 73.4 (CH2Ph), 73.7 (C-4), 127.2, 127.7, 127.8, 127.9, 128.4, 128.7,
138.1, 138.2 (C-2, C-3, Car), 173.6 (CO2). HRMS calcd for C24H29NO5 (CI)
412.2124. Found: 412.2122.

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2-(4,6-Di-O-benzyl-2,3-dideoxy-ꢀ-D-erythro-hex-2-enopyranosyl)-
2(R,S)-glycine (10). A solution of 68 mg (0.17 mmol) of the aminoester 9 in
methanol (0.5 mL) and aqueous sodium hydroxide 1N (0.5 mL) was stirred for 2 h
at room temperature. After filtration on a Dowex 50WX4 (1 g), the residue was dis-
solved in methanol. Evaporation of the solvent gave 47 mg of the aminoacid 10 as
an oil (74% yield): 1H NMR (300 MHz, CDCl3) ꢁ 2.19 (s, 2H, NH2), 3.30–3.70 (m,
3H, H-5, H-6), 3.86 (dm, 1H, J ꢃ 9.5 Hz, H-4), 4.10 (m, 1H, CHNH2), 4.25–4.75
(m, 5H, H-1, CH2Ph), 5.92 (bd, 1H, J ꢃ 11.4 Hz, H-2), 6.05 (bd, 1H, J ꢃ 11.4 Hz,
H-3), 7.10–8.05 (m, 10H, Har), 10.0 (bs, 1H, CO2H); 13C (75 MHz, CDCl3) ꢁ 68.5,
68.7, 70.5, 70.7, 77.3 (CHN, C-1, C-4, C-5, C-6), 73.2 (CH2Ph), 127.0, 127.6,
127.8, 128.0, 128.1, 128.4, 128.5, 129.0, 129.8, 137.9, 138.0 (C-2, C-3, Car), 171.3
(CO2). Mass spectra for C22H25NO5 (CI): 340 (100%) (MHꢄ - CO2).
ACKNOWLEDGMENTS
One of us (A. W.) thanks the the French Government for a fellowship.
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Received November 8, 2000
Accepted December 6, 2000

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