Enantioselective synthesis of erythro-β-hydroxyglutamic acid

Article abstract of DOI:10.1081/SCC-200048467

An enantioselective synthesis of N-Boc-(2S,3S)-3-hydroxy glutamic acid dimethyl ester (92% ee) is described. Starting from enantiomerically enriched (93% ee) (2S,3S)-2,3-epoxy-5-hexen-1-ol, easily available by Sharpless asymmetric epoxidation, the protect

Full text of DOI:10.1081/SCC-200048467

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Enantioselective Synthesis of
erythro‐β‐Hydroxyglutamic
Acid
Xavier Ginesta a , Miquel A. Pericàs a & Prof. Antoni
Riera a
a Parc Científic de Barcelona and Departament de
Química Orgànica, Universitat de Barcelona, Josep
Samitier, 1‐5, Barcelona, 08028, Spain
Version of record first published: 28 Jul 2007.
To cite this article: Xavier Ginesta , Miquel A. Pericàs & Prof. Antoni Riera
(2005): Enantioselective Synthesis of erythro‐β‐Hydroxyglutamic Acid, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 35:2, 289-297
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Synthetic Communicationsw, 35: 289–297, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200048467
Enantioselective Synthesis of
erythro-b-Hydroxyglutamic Acid
`
Xavier Ginesta, Miquel A. Pericas, and Antoni Riera
`
´ ´
Parc Cientıfic de Barcelona and Departament de Quımica Organica,
Universitat de Barcelona, Barcelona, Spain
Abstract: An enantioselective synthesis of N-Boc-(2S,3S)–3-hydroxy glutamic acid
dimethyl ester (92% ee) is described. Starting from enantiomerically enriched
(93% ee) (2S,3S)-2,3-epoxy-5-hexen-1-ol, easily available by Sharpless asymmetric
epoxidation, the protected amino acid was prepared in 11 steps.
Keywords: b-Hydroxyglutamic, Sharpless epoxidation, epoxide ring opening
INTRODUCTION
b-Hydroxy-a-amino acids are constituents of many biologically active natural
products and medicinally important compounds.[1–9] Because both the
relative and absolute stereochemistry of their chiral centers are crucial for
its biological activity, many stereoselective syntheses have been reported
up to now.[2–12] Although some of these synthetic approaches are
highly efficient, most of them involve unfunctionalised side chains. In
contrast, few syntheses of erythro-b-hydroxy-glutamic acid (1) have been
developed,[13–17] despite its biological activity and its interest as a glutamic
acid analogue.[18–22] For instance, some analogues of the anticancer drug
methotrexate (MTX) have shown to be potent inhibitors of dihydrofolate
reductase.[23]
Received in the UK May 11, 2004
Address correspondence to Prof. Antoni Riera, Parc Cientıfic de Barcelona and
´ `
Departament de Quımica Organica, Universitat de Barcelona, Josep Samitier, 1-5,
´
Barcelona 08028, Spain. E-mail: ariera@pcb.ub.es

´
X. Ginesta, M. A. Pericas, and A. Riera
290
During the last several years we have been involved in a project directed
to the synthesis of amino acids from epoxy alcohols [see inter alia:[24–30]
]
because these compounds are easily available in any configuration by
Sharpless epoxidation.[31,32] The C-2 ring opening of an epoxy alcohol
affords a 2-amino-1,3-diol with anti stereoselectivity, ideally suited for the
preparation of erythro-b-hydroxy-a-amino acids. We planned the enantio-
selective preparation of erythro-b-hydroxyglutamic acid setting the stereo-
chemistry of the diol by a regio and estereoselective ring opening of
the readily available epoxy alcohol 2 and using a terminal alkene as a
masked carboxylic acid function.
Up to now, the most reliable method for the regioselective C-2 ring
opening of epoxy alcohols is the intramolecular cyclization of benzyl
carbamate, developed by Roush and Adam.[33] However, very often it has
the drawback that the reaction product is a mixture of isomeric oxazolidinones
due to the easy acyl-migration in these compounds.[34,35] Some years ago, we
found that the use of NaHMDS as a base in the carbamate cyclization
minimize this acyl migration so we decided to explore this approach.[36]
We describe here the enantioselective synthesis of a protected form of
3-hydroxy glutamic acid 1, based on the C-2 ring opening of the easily
available 2,3-epoxy-5-hexen-1-ol (2).
RESULTS
Our synthesis of the unsaturated b-hydroxy-a-amino acid is outlined in
Scheme 1. Epoxy alcohol 2 was prepared in 93% ee by Sharpless epoxidation
of 2,5-hexadien-1-ol.[37] The benzyl carbamate of 2 was prepared by treatment
with benzylisocyanate in ether, and it was cyclized to oxazolidinone 4 using
sodium bistrimethylsilylamide as a base[36] in high yield. Under these
1
conditions, only 7% of the trans-acyl isomer was observed by H NMR.
Our initial approach was to protect the secondary alcohol as tert-butyl-
dimethylsilyl ether and liberate the primary alcohol by hydrolysis of the
carbamate, but, unfortunately, this protecting group was not stable to
the carbamate hydrolysis. Consequently, we hydrolyzed carbamate 4 by
treatment with NaOH and protected the amine as a Boc-derivative,
affording diol 5 in good yield. Protection of the secondary alcohol could
be conveniently performed by silylation of both alcohols followed by
selective hydrolysis of the primary one. Alcohol oxidation in 7 gave the

Enantioselective Synthesis of erythro-b-Hydroxyglutamic Acid
291
Scheme 1. (a) Bn-NCO, THF reflux (95%). (b) NaN(TMS)2, THF (91%). (c) NaOH,
reflux, 16 hr (78% yield). (d) Boc2O, NaHCO3, MeOH, 3.5 hr (78% yield) (e) tBuMe2-
SiTf, Lutidine, (86% yield), (f) PTSA cat, MeOH, 2.5 hr (70% yield). (g) TEMPO,
NaClO, NaHCO3, KBr. (h) NaClO2, KH2PO4, 2-methyl-2-butene tBuOH, 16 hr
room temperature. (i) MeI, KHCO3, DMF (65% three steps).
fully protected 3-hydroxy-4-amino-5-hexenoic acid, which was converted
into its methyl ester 8 to facilitate isolation and characterization. It is worth
noting that this synthetic scheme should allow the preparation of many
other b-hydroxy-a-amino acids.
The final steps in our synthesis were performed as shown in Scheme 2.
Oxidative cleavage of the terminal olefin gave the corresponding amino
acid that was esterified with methyl iodide/sodium bicarbonate to afford
diester 9 in good yield. Compound 9 is a fully protected form of the target
erythro-b-hydroxyglutamic acid. If desired, the preparation and purification
of 8 can be skipped. To this end, the carboxylic acid obtained in the
oxidation of 7 was treated with NaIO4/RuCl3, and the diacid was esterified
with MeI to give diester 9 in 28% overall yield from 7 (four steps).
The sometimes problematic deprotection of the benzyl group was
achieved, after some experimentation, by hydrogenolysis catalyzed by
palladium chloride. Somewhat surprisingly, this treatment also cleaved the
silyl ether, yielding the known[13] N-Boc-b-hydroxyglutamic dimethyl ester
1
(10). All compounds gave satisfactory H and 13C NMR spectra with no
detectable impurities above 5%.
Scheme 2. (a) RuCl3 cat, NaIO4. (b) MeI, KHCO3, DMF (50% two steps), (c) PdCl2,
H2, 16 hr (73% yield).

´
X. Ginesta, M. A. Pericas, and A. Riera
292
Compound 10 was derivatized to the corresponding Mosher’s esters
by treatment with (R) and (S)-2-methoxy-2-trifluoromethylphenylacetic acid
chlorides, NEt3, and DMAP in CH2Cl2. Analysis by 1H NMR of both
reaction crudes established an enantiomeric excess of 92% ee for 10, in
complete agreement with the optical purity of the starting epoxy alcohol.
In summary, starting from 2,3-epoxy-5-pentenol, we have described
an enantioselective synthesis of (2S, 3S)-2-tert-butoxycarbonyl-3-hydroxy
glutamic acid dimethyl ester (92% ee), a protected derivative of the biologi-
cally important erythro-b-hydroxyglutamic acid. The key steps in our
approach are asymmetric Sharpless epoxidation, regioselective C-2 ring
opening of an epoxy carbamate and use of a terminal double bond as a
masked carboxylic acid group.
EXPERIMENTAL
General
Optical rotations were measured at room temperature on a Perkin–Elmer
241MC automatic polarimeter (concentration in g/100 mL). Melting points
were determined on a Gallenkamp apparatus and have not been corrected.
Infrared spectra were recorded on a Nicolet 510FT-IR instrument using
NaCl film or KBr pellet techniques. NMR spectra were acquired on a
1
Varian XL-200 or Varian Mercury 400 instruments. H-NMR were obtained
at 200 or 400 MHz (s ¼ singlet, d ¼ doublet, t ¼ triplet, dt ¼ double triplet,
m ¼ multiplet, and b ¼ broad). 13C-NMR were obtained at 50.3 MHz or
1
100.6 MHz. H chemical shifts are quoted relative to TMS and 13C shifts
relative to solvent signals. High-resolution mass spectra (CI) were measured
´
by the Servicio de Espectrometrıa de Masas de la Universidad de Santiago
de Compostela. Chromatographic separations were carried out by using
NEt3-pretreated (2.5% v/v) SiO2 (70–230 mesh) and eluting with hexane/
ethyl acetate mixtures of increasing polarity. (2S,3S)-2,3-Epoxy-5-hexen-1-
ol (2) was prepared according to the procedure described by Ref. [37].
(2S, 3S)-N-Benzyl-carbamic Acid 3-allyl-oxiranylmethyl Ester (3)
To a solution of epoxide 2 (263 mg, 2.30 mmol) in ether (20 mL), NEt3
(698 mL, 4.95 mmol, 2.15 eq.) was slowly added, and the mixture was
stirred 15 min under nitrogen. Benzyl isocyanate (428 mL 3.45 mmol) was
added, and the resulting mixture was stirred at reflux during 16 hr. It
was allowed to cool at room temperature, and NH4Cl (20 mL) was added.
The organic layer was washed with brine, dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by chromatography to afford
539 mg (2.18 mmol, 95%) of 3 as a white solid. M.p. 43–468C [a]D ¼ 2 23.4

Enantioselective Synthesis of erythro-b-Hydroxyglutamic Acid
293
(c ¼ 1.1 in CHCl3) 1H NMR (200 MHz, CDCl3) d 2.33–2.38 (m, 2H),
2.94–3.05 (m, 2H), 3.94 (dd, J1 ¼ 5.8 Hz, J2 ¼ 12 Hz, 1H), 4.30–4.50
(m, 3H), 5.00–5.20 (m, 2H). 5.70–5.90 (m, 1H), 7.20–7.40 (m, 5H) ppm.
13C NMR (50 MHz, CDCl3) 29.7 35.5, 45.1, 55.2, 64.1, 117.8, 127.4, 127.5,
128.6, 132.4 ppm. IR (NaCl): n ¼ 3322, 2927, 1692 cm21. HRMS (CI,
CH4) Calc. for C14H18NO3 (M þ Hþ) 248.1287, found 248.1275.
(4R, 10S)-N-Benzyl-4(1-hydroxy-3-butenyl)-oxazolidin-2-one (4)
To a solution of epoxycarbamate 3 (2.64 g, 10.69 mmol) in anhydrous THF
(250 mL) at room temperature, a solution of sodium bistrimethylsilylamide
(11.76 mmol) in THF (50 mL) was added dropwise under nitrogen. The
reaction mixture was stirred for 30 min, being monitored by TLC. When
the reaction was complete, the mixture was quenched with 120 mL of
ammonium chloride-saturated solution. The stirring was maintained 10 min,
the mixture was extracted with dichloromethane, and the combined organic
phases were washed with brine, dried (sodium sulfate), and evaporated. The
residue was purified by column chromatography eluting with hexanes/ethyl
acetate mixtures to afford 2.40 g (9.71 mmol, 91%) of 4 (as a 13 : 1 mixture
of 4 and its trans-acyl isomer). [a]D ¼ 2 5.14 (c ¼ 0.56 in CHCl3).
1H NMR(400 MHz, CDCl3) d 1.60 (bs, 1H), 2.00–2.20 (m, 2H), 3.66 (ddd,
J1 ¼ 2 Hz, J2 ¼ 6.8 Hz, J3 ¼ 9.2 Hz, 1H), 3.87 (t, J ¼ 6 Hz, 1H), 4.21
(t, J ¼ 8.8 Hz, 1H), 4.28–4.36 (m, 2H), 4.70 (d, J ¼ 15.2 Hz, 1H),
5.07–5.13 (m, 2H) 5.60–5.80 (m, 1H) 7.20–7.40 (m, 5H) ppm. 13C NMR
(100.6 MHz, CDCl3) d 36.7, 46.1, 58.0, 62.0, 66.7, 118.3, 128.0, 128.8,
128.9, 133.3, 135.8, 159.1 ppm. IR (NaCl): v ¼ 3413, 2925, 1728 cm21
.
HRMS (CI, CH4) Calc. for C14H18NO3 (M þ Hþ) 248.1287, found 248.1282.
(2R, 3S)-N-Benzyl-N-tert-butoxycarbonyl-2-amino-5-hexen-1,3-diol (5)
To a solution of carbamate 4 (300 mg, 1.21 mmol) in MeOH/H2O 9 : 1
(25 mL) was added 6N NaOH (6 mL), and the mixture was heated under
reflux 16 hr. Then it was allowed to reach the room temperature and the
mixture was extracted with diethyl ether. The organic layer was dried
(MgSO4) and concentrated under reduced pressure affording 209 mg of an
oil that was dissolved in MeOH (4 mL). To this solution, NaHCO3 (239 mg,
2.85 mmol) and Boc2O (227 mg, 1.04 mmol) in MeOH (6 mL) were added
and the mixture stirred 2.5 hr at room temperature. Then inorganic salts
were filtered and solvent was removed under reduced pressure. The residue
was taken with ether (30 mL) and filtered again. The ethereal solution was
concentrated and purified by chromatography to afford 235 mg (0.73 mmol,
60%) of 5 as an oil. [a]D ¼ 2 12.4 (0.65, CHCl3) 1HNMR (400 MHz,
˙
CDCl3) d 1.47 (s, 9H), 1.65 (bs, 1H), 2.15–2.33 (m, 2H), 3.25 (bs, 1H),
3.75–4.15 (m, 3H), 4.34–4.58 (m, 2H), 5.00–5.10 (m, 2H), 5.62–5.74

´
X. Ginesta, M. A. Pericas, and A. Riera
294
13
˙
(m, 1H), 7.20–7.36 (m, 5H) ppm. CNMR (100.6 MHz, CDCl3) d 28.4, 39.3,
53.4ꢀ, 53.7, 62.1, 64.2, 71.4, 81.1, 117.8, 127.5, 127.6, 128.6, 134.6 ppm
(signals marked with an asterisk correspond to a rotamer). IR (film)
v ¼ 3412, 2976, 2931, 1666 cm21. HRMS (CI, CH4) for C18H28NO4
(M þ Hþ) 322.2018, found 322.2017.
(1R, 2S)-N-Benzyl-N-tert-butoxycarbonyl-2-tert-
butyldimethylsilanyloxy-1-tert-butydimethylsilanyloxymethyl-4-
pentenylamine (6)
To a solution 5 (465 mg, 1.44 mmol) in CH2Cl2 (10 mL) at 08C, 2,6-lutidine
(504 mL, 4.36 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate
(826 mL, 3.59 mmol) were added. After 2 hr stirring, H2O (10 mL) was
added, the organic layer was washed with sat NaHCO3, dried, and concen-
trated in vacuo to give an oil that was purified by chromatography affording
680 mg (1.24 mmol, 86%) of 6 as an oil. [a]D ¼ þ15.1 (0.75, CHCl3).
1H NMR (400 MHz, CDCl3) d 0.0 (s, 12H), 0.85 (s, 18H) 1.28 (s, 5H) 1.47
(s, 4H), 1.94–2.30 (m, 2H), 3.65–4.00 (m, 4H), 4.36 (s, 1H), 4.45 (s, 1H)
4.86–5.00 (m, 2H), 5.60–5.78 (m, 1H), 7.14–7.34 (m, 5H) ppm. 13C NMR
˙
(400 MHz, CDCl3) d 25.5, 25.4, 24.6, 23.8, 18.0, 18.2, 25.9, 28.2, 28.5,
38.5ꢀ, 38.9, 51.0 (b), 61.3, 63.2 (b), 71.2, 71.6ꢀ, 79.4, 79.9ꢀ, 117.2, 126.5,
126.7ꢀ, 127.3, 128.0, 128.2ꢀ, 134.4, 140.2 (b), 155.7 (b) ppm (signals
marked with an asterisk correspond to a rotamer). IR (film): v ¼ 2929,
2857, 1696 cm21. HRMS (CI, CH4) for C30H56NO4Si2 (M þ Hþ) 550.3748,
found 550.3738.
(2R, 3S)-N-Benzyl-N-tert-butoxycarbonyl-2-amino-3-tert-
butydimethylsilyloxy-5-hexen-1-ol (7)
A solution of 6 (620 mg, 1.13 mmol) and p-toluenesulfonic acid (21 mg,
0.11 mmol) in MeOH (30 mL) was stirred 2.5 hr at room temperature. The
reaction was monitored by TLC. When complete, sat NaHCO3 (20 mL) was
added, and extracted with CH2Cl2 (2 ꢁ 60 mL). The combined organic
phases were dried, concentrated, and purified by chromatography to afford
345 mg (0.85 mmol, 70%) of 7 as an oil. [a]D ¼ þ19.8 (0.5, CHCl3).
1
˙
H NMR (400 MHz, CDCl3) d 0.0 (s, 6H), 0.80 (s, 9H) 1.33 (s, 9H)
2.15–2.25 (m, 2H), 3.11 (sa, 1H) 3.40–3.75 (m, 3H), 4.00–4.38 (m, 2H),
4.61 (d, J ¼ 15.6 Hz, 1H) 4.98–5.05 (m, 2H), 5.70–5.85 (m, 1H), 7.14–
7.26 (m, 5H) ppm. 13C NMR (100 MHz, CDCl3) d 24.8, 24.2, 18.0, 25.9,
28.4, 39.1, 52.4 (b), 62.7, 63.6 (b), 70.6 (b), 80.6, 117.6 (b), 127.3, 128.6,
134.2 (b), 139.2, 156.6 ppm. IR (film): v ¼ 3446, 2929, 2857, 1694 cm21
.
HRMS (CI, CH4) for C24H42NO4Si (M þ Hþ) 436.2883, found 436.2884.

Enantioselective Synthesis of erythro-b-Hydroxyglutamic Acid
295
(2S, 3S)-N-Benzyl-N-tert-butoxycarbonyl-2-amino-3-tert-
butydimethylsilyloxy-5-hexenoic Acid Methyl Ester (8)
To a solution of 7 (65 mg, 0.149 mmol) in sat. NaHCO3 (1 mL) and acetone
(2 mL) at 08C, TEMPO (26 mg, 0.164 mmol), KBr (2 mg, 0.015 mmol) and
NaClO (353 mL, 0.55M, 0.194 mmol) were added. The mixture was stirred
1 hr, NaClO (180 mL, 0.55M, 0.1 mmol) was added, and it was stirred for an
additional 1 hr. It was concentrated in vacuo and extracted with CH2Cl2.
The combined organic extracts were dried and concentrated to give an oil
t
(80 mg) that was dissolved in BuOH (2 mL). To this solution, 2-methyl-2-
butene (57 mL, 0.51 mmol) in THF (1 mL), a solution of NaClO2 (20 mg,
0.23mmol) and NaH2PO4 (28 mg, 0.20 mmol) in H2O (1 mL) were sequen-
tially added and the mixture stirred 258C for 15 hr. Then, it was extracted
with CH2Cl2 dried with MgSO4 and evaporated affording an oil (60 mg)
that was dissolved in DMF (3 mL). To this solution, KHCO3(45 mg,
0.45 mmol) and MeI (55 mL, 0.89 mmol) were added, and the mixture
stirred 16 hr under nitrogen. H2O (20 mL) was added, and it was extracted
with CH2Cl2 (20 mL). The combined organic phases were dried (MgSO4)
and evaporated. The crude was chromatographed to afford 45 mg
1
(0.097 mmol, 65%) of 8 as an oil. [a]D ¼ þ17.5 (0.5, CHCl3) H NMR
(400 MHz, CDCl3) d 0.02 (s, 3H), 0.05 (s, 3H), 0.83 (s, 9H) 1.33, 1.47
(m, 9H) 2.00–2.45 (m, 2H), 3.52 (s, 3H), 4.26–4.36 (m, 2H), 4.45–4.48
(m, 1H) 4.52–4.76 (m, 1H) 5.00–5.10 (m, 2H), 5.74–5.86 (m, 1H),
7.14–7.32 (m, 5H) ppm. 13C NMR (400 MHz, CDCl3) 25.0, 24.1, 18.0,
25.8, 28.2, 38.4 (b), 49.5, 51.5, 61.9 (b), 63.0ꢀ (b), 71.2 (b), 80.7 (b), 117.8,
126.7 (b), 128.1, 134.0, 139.0, 155.5, 170.7 ppm. (Signals marked with an
asterisk correspond to a rotamer.) IR (film): n ¼ 2929, 1744, 1703 cm21
.
HRMS (CI, CH4) for C25H42NO5Si (M þ Hþ) 464.2832, found 464.2835.
(2S, 3S)-N-Benzyl-N-tert-butoxycarbonyl-3-tert-
butyldimethylsilanyloxy Glutamic Acid Dimethyl Ester (9)
A suspension of 8 (45 mg, 0.097 mmol), NaIO4 (144 mg, 0.68 mmol) and
.
RuCl3 H2O (3 mg, 0.014 mmol, 0.14) in CCl4 (1 mL), CH3CN (1 mL),
and H2O (1.5 mL) was stirred 3 hr at room temperature. The mixture was
extracted with CH2Cl2 (3 ꢁ 15 mL), and the combined organic phases were
dried (MgSO4) and evaporated. The crude product was solved in DMF
(3 mL) and, to this solution, KHCO3 (28 mg, 0.28 mmol, 3 eq.) and MeI
(36 mL, 0.56 mmol, 6 eq) were added. The mixture was stirred 16 hr under
nitrogen. After workup with H2O (20 mL) and CH2Cl2 (20 mL), the
combined organic phases were dried (MgSO4) and evaporated. The crude
product was purified by chromatography (SiO2/NEt3) to afford 25 mg
1
(0.050 mmol, 52%) of 9 as an oil. [a]D ¼ 235.4 (0.55, CHCl3). H NMR
˙
(400 MHz, CDCl3) d 0.02 (s, 3H), 0.05 (s, 3H), 0.80 (s, 9H) 1.37–1.48

´
X. Ginesta, M. A. Pericas, and A. Riera
296
(m, 9H) 2.16–2.80 (m, 2H), 3.45 (s, 3H), 3.66 (s, 3H), 4.45–4.70 (m, 3H),
4.76–4.85 (m, 1H) 7.17–7.32 (m, 5H) ppm. 13C NMR (400 MHz, CDCl3)
25.1, 24.8, 17.9, 25.7, 28.2, 38.3, 49.8 (b), 50.7ꢀ (b), 51.6, 62.9 (b), 64.0ꢀ
(b), 68.8, 80.7 (b), 127.0 (b), 128.4, 138.5 (b), 155.6, 170.0, 171.8 ppm.
(Signals marked with an asterisk correspond to a rotamer.) IR (film):
v ¼ 2953, 1744, 1703 cm21. HRMS (CI, CH4) for C25H42NO7Si (M þ Hþ)
496.2731, found 496.2743.
N-Boc-(2S, 3S)-3-hydroxy Glutamic Acid Dimethyl Ester (10)
A suspension of 9 (14 mg, 0.028 mmol), and PdCl2 (5 mg) in MeOH (2 mL)
was stirred 20 hr under hydrogen atmosphere (balloon). When the reaction
was complete by TLC, it was filtered through a celite pad, and the solvent
was removed under reduced pressure. The crude was purified by column
chromatography affording 10 (6 mg, 73%) as an oil. [a]D ¼ þ 19.0 (0.5,
1
˙
CHCl3). H NMR (400 MHz, CDCl3) d 1.45 (ds, 9H), 1.60 (bs, 1H), 2.60
(dd, J1 ¼ 16.8 Hz, J2 ¼ 3.6 Hz, 1H), 2.68 (dd, J1 ¼ 16.8 Hz, J2 ¼ 8.8 Hz,
1H) 3.71 (s, 3H), 3.78 (s, 3H), 4.31–4.40 (m, 2H), 5.48 (bs, 1H) ppm.
13C NMR (400 MHz, CDCl3), 28.2, 37.7, 51.9, 52.6, 57.7, 69.6, 80.6, 155.7,
172.4, 173.4 ppm. IR (film): n ¼ 3380, 2956, 1739, 1716 cm21. HRMS
(CI, CH4) for C12H22NO7 (M þ Hþ) 292.1396, found 292.1390.
ACKNOWLEDGMENTS
Financial support from CIRIT (2001SGR-00050) and DGICIT (BQU2002-
02459) is gratefully acknowledged. XG thank CIRIT (Generalitat de
Catalunya) for fellowship.
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