A concise C-glycosyl amino acid synthesis by alkenyl C-glycoside-vinyloxazolidine cross-metathesis. Synthesis of glycosyl serine, asparagine and hydroxynorvaline isosteres

Article abstract of DOI:10.1039/b106029p

A convergent synthesis has been developed to afford C-linked glycosyl amino acids by cross-metathesis of vinyl, allyl, and butenyl C-glycosides with N-Boc-vinyloxazolidine using the Grubbs 1,3-dimesityl-4,5-dihydroimidazol-2-ylideneruthenium carbene. The method has been employed to introduce through an α-linkage, an α-aminopentanoic acid chain at the anomeric carbon of β-D-C-gentiobiose to give a totally artificial glycosyl α-amino acid of a disaccharide. This compound represents the isostere of the α-linked glycosylasparagine moiety of the natural glycopeptide nephritogenoside.

Full text of DOI:10.1039/b106029p

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A concise C-glycosyl amino acid synthesis by alkenyl C-glycoside–
vinyloxazolidine cross-metathesis. Synthesis of glycosyl serine,
asparagine and hydroxynorvaline isosteres
1
Alessandro Dondoni,* Pier Paolo Giovannini and Alberto Marra*
Dipartimento di Chimica, Laboratorio di Chimica Organica, Università di Ferrara, Via L.
Borsari 46, I-44100 Ferrara, Italy. E-mail: adn@dns.unife.it
Received (in Cambridge, UK) 5th July 2001, Accepted 10th August 2001
First published as an Advance Article on the web 18th September 2001
A convergent synthesis has been developed to afford C-linked glycosyl amino acids by cross-metathesis of vinyl,
allyl, and butenyl C-glycosides with N-Boc-vinyloxazolidine using the Grubbs 1,3-dimesityl-4,5-dihydroimidazol-2-
ylideneruthenium carbene. The method has been employed to introduce through an α-linkage, an α-aminopentanoic
acid chain at the anomeric carbon of β--C-gentiobiose to give a totally artificial glycosyl α-amino acid of a
disaccharide. This compound represents the isostere of the α-linked glycosylasparagine moiety of the natural
glycopeptide nephritogenoside.
Introduction
The current interest in synthetic methods leading to C-glycosyl
amino acids, primarily isosteres of O-serine, O-threonine and
N-asparagine glycoconjugates, is mainly due to the need of
usable quantities of these building blocks in studies of the
complex biological machinery involving glycoproteins1 as well
as the development of glycosidase inhibitors and lead com-
pounds for drug design.2 The stereoselective introduction of
amino acid moieties at the anomeric carbon of sugars has been
described via various carbon–carbon bond-forming processes.3
Substantial efforts in our laboratory have been recently focused
toward the synthesis of C-glycosyl serines and asparagines via
either direct C-glycosidation reaction or coupling of functional-
ized C-glycosides (methylenephosphorane, formyl, ethynyl)
with amino acid equivalents.4 Nevertheless further innovations
homocoupling products as main reaction products. The recent
advent of tetracoordinated ruthenium carbene complexes
reported by Grubbs and co-workers9 has considerably
expanded the scope of all types of alkene metathesis reactions.
These pre-catalysts show both high tolerance toward various
heteroatoms, particularly oxygen-containing functional groups,
and ability to suppress the formation of self-metathesis
products. Hence, some examples of selective CM reactions have
recently appeared in the literature.7,10
are still required focusing mainly on the search for methods
endowed with conciseness and simplicity. Hence, we have been
stimulated to develop a convergent synthetic approach to
C-glycosyl amino acids via cross-metathesis (CM) reaction of
the N-Boc-vinyloxazolidine5 1, a vinylglycine equivalent, with
sugar olefins whose double bond was linked to the anomeric
carbon of the glycoside moiety through alkyl chains of variable
length. We sought the α-amino acid equivalence of 1 on the
basis of the racemization-free one-step oxidative cleavage of the
N-Boc-oxazolidine ring into the glycinyl moiety [CH(NH2)-
CO2H] using the Jones reagent.6 A single example of the CM-
based approach to C-glycosyl amino acids has been recently
reported using racemic allylglycine and an allyl -C-mannoside
derivative.7 The resulting mixture of E and Z alkenes contain-
ing epimeric glycinyl moieties was not transformed into usable
building blocks for glycopeptide synthesis. Hence, we have
carried out a wider investigation into this synthetic approach
directed toward this main objective and report here the relevant
results of our study.
Results and discussion
Heating a mixture of the allyl β--C-glucopyranoside 3a, the
vinyloxazolidine 1 (2 equiv.) and the ‘second generation’
Grubbs 1,3-dimesityl-4,5-dihydroimidazol-2-ylideneruthenium
carbene11 2 (0.2 equiv.) in CCl4 at 100 ЊC (screw-capped vial)
afforded after 3.5 h the corresponding CM product 4a as a
mixture of E and Z isomers in 50% isolated yield by column
chromatography (Scheme 1). A substantial amount of un-
changed 3a (ca. 30%) was also isolated whereas the mixture of
homodimers did not exceed 10%. On the other hand the
homodimers were the only products obtained by the use of
the ‘standard’ Grubbs ruthenium carbene complex [RuCl2-
As compared with the metal (Mo, W, Ru) alkylidene-
promoted ring-closing metathesis (RCM) of alkenes employed
for the synthesis of carbo- and heterocyclic systems,8 the CM
reaction in which two different alkenes are used to form a
new acyclic product has so far found much less application.
The limited scope of the latter intermolecular process appears
to be due to concomitant self-metathesis reactions leading to
(᎐CHPh)(PCy ) ]. Comparable yields of CM products 4b–e and
᎐
3
2
unchanged sugar alkenes were obtained in reactions of 1 with
the allyl C-pyranosides 3b and 3c as well as the C-butenyl
derivatives 3d and 3e whereas the yield of 4f from the reaction
with the vinyl β--C-glucopyranoside 3f was much lower (Table
2380
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This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b106029p

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in our laboratory by Wittig-type coupling of perbenzylated
formyl C-glucopyranoside with glucose 6-phosphorane.17 Treat-
ment of 7 with the in situ generated diimide from p-tolylsulfonyl
hydrazine and sodium acetate17 allowed the reduction of the
double bond without removal of the O-benzyl groups. The
resulting perbenzylated O-methyl β--C-gentiobioside 8 was
then transformed by hydrolysis and acetylation into the acetate
9 and this product was glycosidated with allyltrimethylsilane to
give the corresponding α-linked C-allyl derivative 10. The cross-
metathesis of 10 with 1 under the activation of the Grubbs
ruthenium carbene 2 gave the alkene 11 as an E,Z mixture in
40% isolated yield. Also this mixture of alkenes was suitably
elaborated as described for the CM products in Table 1 to give
the oxazolidine derivative 12 and then the glycosyl α-amino
acid 13 in 67% overall yield. This compound represents, to our
knowledge, the first example of a C-glycosyl α-amino acid of a
C-disaccharide.
Quite interestingly compound 13 appears to be the isostere of
the major fragment of the asparagine-linked core trisaccharide
14 of the natural glycopeptide nephritogenoside 15. The name
of this compound stems from its activity to induce a progressive
chronic glomerulonephritis in animals.18 The glycopeptide 15 is
uniquely distinct from common glycoproteins as it contains an
α--glucopyranose as the glycan linker to the amide group of
-asparagine.19 Hence compound 13 can be used as a probe in
recognition-specificity studies regarding the biological activity
of 15.
In conclusion, the methodology via olefin CM reaction
described above appears to be a viable route to various C-glyco-
syl amino acids with a great degree of structural diversity. The
products of this synthetic approach can be transformed into
suitable building blocks for the synthesis of modified glyco-
peptides possessing enhanced stability and eventually different
biological activity with respect to the natural analogues.
Scheme 1 Reagents and conditions: a) H2, Pd(OH)2, t-BuOH–THF, 1
bar, rt, 3 h; b) Ac2O, pyridine, rt, 3 h; c) 1 M Jones, acetone, 0 ЊC to rt,
3.5 h.
1). Very likely the well known instability12 of vinyl C-glycosides
constitutes a serious limitation on the use of these compounds
as partners in CM reactions. However in order to elaborate
upon this methodology, all alkenes 4a–f were transformed into
the corresponding peracetylated N-Boc-oxazolidine derivatives
5a–f by hydrogenation over Pd(OH)2 and acetylation. Finally,
oxidative cleavage of the oxazolidine ring by the Jones reagent
afforded the α-amino acids 6a–f. Based on precedent examples
of the latter transformation in our6 and others’ laboratory,13
the same configuration for the resulting glycinyl moiety as that
for the precursor N-Boc-oxazolidine ring was assigned. All
compounds 6a–f were adequately characterized through their
corresponding methyl ester. It has to be noted that compounds
6a–c are ethylene isosteres of N-glycosylasparagines and 6f
is the methylene isostere of O-glycosylserine. Of the two
α-aminohexanoic acids 6d and 6e, the latter compound has
recently attracted some attention in immunological studies as
the C-linked isostere of β--galactosyl hydroxynorvaline.14 All
compounds 5a–f with O-acetyl15 and N-Boc16 protecting
groups appear to be orthogonally protected building blocks
suitable for glycopeptide synthesis.
Experimental
All moisture-sensitive reactions were performed under a
nitrogen atmosphere using oven-dried glassware. Anhydrous
solvents were dried over standard drying agents20 and freshly
distilled prior to use. Commercially available powdered 4 Å
molecular sieves (5 µm average particle size) were used without
further activation. Reactions were monitored by TLC on silica
gel 60 F254 with detection by charring with sulfuric acid. Flash
column chromatography21 was performed on silica gel 60 (230–
400 mesh). Melting points were determined with a capillary
apparatus and are uncorrected. Optical rotations were meas-
ured at 20 2 ЊC in the stated solvent; [α]D-values are given
in 10Ϫ1 deg cm2 gϪ1. H (300 MHz) and 13C (75 MHz) NMR
1
As an expanded scope of the methodology we considered the
introduction of the C-tethered α-amino acid group in a more
complex carbohydrate moiety such as a C-disaccharide to give
a totally artificial C-glycoconjugate. For this endeavour we
started from the sugar alkene 7 (Scheme 2) which was available
spectra were recorded at room temperature unless otherwise
specified; chemical shifts are in ppm (δ) from SiMe4 (TMS)
as internal standard; J-values are given in Hz; assignments
were aided by homo- and heteronuclear two-dimensional
experiments. MALDI-TOF mass spectra were acquired using
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Table 1 Other C-glycosyl amino acids prepared by cross-metathesis reactions of sugar alkenes and the vinyloxazolidine 1a
Sugar alkene CM-Product Oxazolidine Amino acid
a For the catalyst and reaction conditions, see Scheme 1. Yields in parentheses refer to isolated products.
α-cyano-4-hydroxycinnamic acid as the matrix. The allyl
β-C-glucoside 3a, α-C-glucoside 3b and α-C-galactoside 3c
were prepared as described.22 The butenyl β-C-glucoside 3d,
prepared as reported,23 had mp 87–88 ЊC (from MeOH); [α]D
0.0 (c 1.4 in CHCl3) {lit.,23 mp 83–84 ЊC (from Et2O); [α]D ϩ3
(c 1.2 in CHCl3); lit.,24 mp 84–85 ЊC (from light petroleum); [α]D
Ϫ1.7}. The butenyl β-C-galactoside 3e, prepared as described,25
had [α]D Ϫ3.0 (c 1.0 in CHCl3) {lit.25 [α]D not reported}. The
preparation of the vinyl C-glucoside 3f was previously
described by Kraus and Molina26 but the physical data of
this compound were not reported. Hence, our synthesis and the
full characterization of 3f are described below. The Grubbs
catalyst, tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-
4,5-dihydroimidazol-2-ylidene][benzylidene]ruthenium()
dichloride, was purchased from Strem Chemicals, Inc.,
Bischheim, France.
at pH 7 (60 cm3) and extracted with Et2O (2 × 100 cm3).
The combined organic phases were dried (Na2SO4) and
concentrated. The residue was eluted from a column of silica
gel with cyclohexane–AcOEt (from 5 : 1 to 4 : 1) to give 2,3,4,6-
tetra-O-benzyl-1-C-vinyl--glucopyranose (1.00 g, 59%) as a
syrup.
To a cooled (Ϫ40 ЊC), stirred solution of the hemiketal and
triethylsilane (1.40 cm3, 8.8 mmol) in anhydrous acetonitrile
(17 cm3) was slowly added freshly distilled boron trifluoride–
diethyl ether (0.22 cm3, 1.76 mmol). The solution was stirred for
2 h at Ϫ40 ЊC, then diluted with triethylamine (0.5 cm3),
warmed to room temperature, and concentrated. The residue
was eluted from a column of silica gel with 10 : 1 cyclohexane–
AcOEt (containing 0.3% of triethylamine) to give 3f (0.53 g,
55%) as a white solid; mp 68–69 ЊC (from pentane); [α]D ϩ28.0
(c 0.2 in CHCl3) (Found: C, 78.70; H, 7.03. Calc. for C36H38O5:
1
C, 78.52; H, 6.96%); H NMR (CDCl3) δ 7.40–7.17 (m, 20 H,
4 × Ph), 6.00 (ddd, 1 H, J1a,2 17.0, J1b,2 10.6, J2,3 6.5, H-2), 5.49
(ddd, 1 H, J1a,1b 1.6, J1a,3 1.2, H-1a), 5.32 (ddd, 1 H, J1b,3 0.8,
H-1b), 4.95 and 4.90 (2 d, 2 H, J 11.2, PhCH2), 4.85 and 4.59
(2 d, 2 H, J 10.8, PhCH2), 4.78 and 4.68 (2 d, 2 H, J 10.8,
PhCH2), 4.66 and 4.58 (2 d, 2 H, J 11.2, PhCH2), 3.80 (dddd,
1 H, J3,4 9.6, H-3), 3.76–3.64 (m, 4 H, H-5, H-6, 2 × H-8), 3.50
(ddd, 1 H, J6,7 9.2, J7,8a = J7,8b = 3.2, H-7), 3.36 (dd, 1 H, J4,5 8.5,
H-4); MALDI-TOF MS (550.7) m/z, 573.6 (M ϩ Na), 589.9
(M ϩ K).
3,7-Anhydro-4,5,6,8-tetra-O-benzyl-1,2-dideoxy-D-glycero-D-
gulo-oct-1-enitol 3f
To a cooled (Ϫ70 ЊC), stirred solution of 2,3,4,6-tetra-O-
benzyl--gluconolactone (1.61 g, 3.0 mmol) in anhydrous Et2O
(30 cm3) was added commercially available vinylmagnesium
bromide (4.5 cm3, 4.5 mmol; a 1.0 M solution in THF) over a
20 min period. The reaction mixture was allowed to warm
to Ϫ55 ЊC in 1.5 h, then was diluted with 1 M phosphate buffer
2382
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Scheme 2 Reagents and conditions: a) TsNHNH2, AcONa, DME–water, 85 ЊC, 4 h; b) 10 : 1 AcOH–1 M H2SO4, 100 ЊC, 75 min; c) Ac2O, pyridine,
rt; d) AllSiMe3, TMSOTf, CH2Cl2, rt, 1 h; e) 1 (2 equiv.), 2 (0.2 equiv.), CCl4, 100 ЊC, 3.5 h; f ) H2, Pd(OH)2, t-BuOH–THF, 1 bar, rt; g) Ac2O,
pyridine, rt; h) 1 M Jones, acetone, 0 ЊC to rt, 3.5 h.
6,10-Anhydro-7,8,9,11-tetra-O-benzyl-2,3,4,5-tetradeoxy-1-O,2-
N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
galacto-undec-3-enitol 4a
PhCH2), 4.57 and 4.52 (2 d, 2 H, J 12.2, PhCH2), 4.27
(ddd, 1 H, J1a,2 6.3, J1b,2 2.5, H-2), 3.98 (dd, 1 H, J1a,1b 8.8,
H-1a); MALDI-TOF MS (764.0) m/z, 787.1 (M ϩ Na), 803.2
(M ϩ K).
A solution of the allyl β-C-glucopyranoside 3a (282 mg,
0.50 mmol), the vinyloxazolidine 1 (227 mg, 1.00 mmol),
and the Grubbs catalyst 2 (85 mg, 0.10 mmol) in anhydrous
CCl4 (10 cm3) was stirred in a screw-capped vial at 100 ЊC
(oil-bath temperature) for 3.5 h, then cooled to room temper-
ature and concentrated. The residue was eluted from a column
of silica gel with cyclohexane–AcOEt (from 9 : 1 to 5 : 1) to
give, first, unchanged 3a (84 mg, 30% recovery). Eluted second
was the dimer of 3a slightly contaminated by uncharacterized
by-products (27 mg, ca. 10%); MALDI-TOF MS (1101.5)
m/z, 1124.4 (M ϩ Na), 1140.9 (M ϩ K). Eluted third was 4a
(191 mg, 50%) as a ca. 5 : 1 E : Z mixture (Found: C, 74.08; H,
7.66; N, 2.01. Calc. for C47H57NO8: C, 73.89; H, 7.52; N,
1.83%); 1H NMR (DMSO-d6; 140 ЊC) selected data of the
E isomer: δ 5.69 (ddd, 1 H, J3,4 15.6, J4,5a = J4,5b = 6.7, H-4),
5.51 (dd, 1 H, J2,3 6.8, H-3), 4.83 (s, 2 H, PhCH2), 4.80 and 4.66
(2 d, 2 H, J 11.6, PhCH2), 4.75 and 4.62 (2 d, 2 H, J 11.5,
6,10-Anhydro-7,8,9,11-tetra-O-benzyl-2,3,4,5-tetradeoxy-1-O,2-
N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
gulo-undec-3-enitol 4b
Cross-metathesis of the allyl α-C-glucopyranoside 3b (226 mg,
0.40 mmol) with the vinyloxazolidine 1 (182 mg, 0.80 mmol) as
described for the preparation of 4a afforded, after column
chromatography with cyclohexane–AcOEt (from 8 : 1 to 5 : 1),
4b (156 mg, 51%) as a ca. 5 : 1 E : Z mixture (Found: C, 73.78;
H, 7.76; N, 1.94. Calc. for C47H57NO8: C, 73.89; H, 7.52; N,
1.83%); 1H NMR (DMSO-d6; 160 ЊC) selected data of the
E isomer: δ 5.65 (ddd, 1 H, J3,4 15.6, J4,5a = J4,5b = 6.3 Hz, H-4),
5.56 (dd, 1 H, J2,3 5.9, H-3), 4.27 (ddd, 1 H, J1a,2 6.4, J1b,2 3.0,
H-2), 4.03 (ddd, 1 H, J5a,6 9.1, J5b,6 = J6,7 = 5.0, H-6), 3.98
(dd, 1 H, J1a,1b 8.8, H-1a); MALDI-TOF MS (764.0): m/z, 787.3
(M ϩ Na), 803.1 (M ϩ K).
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6,10-Anhydro-7,8,9,11-tetra-O-benzyl-2,3,4,5-tetradeoxy-1-O,2-
N-isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-gulo-
undec-3-enitol 4c
THF (10 cm3) was degassed under vacuum and saturated with
hydrogen (by an H2-filled balloon) three times. The suspension
was stirred at room temperature for 3 h under a slightly positive
pressure of hydrogen (balloon), then filtered through a plug of
cotton and concentrated. A solution of the residue in pyridine
(3 cm3) and acetic anhydride (3 cm3) was kept at room temper-
ature for 3 h, then concentrated. The residue was eluted from a
column of silica gel with 2 : 1 cyclohexane–AcOEt to give 5a
(96 mg, 84%) as a syrup; [α]D ϩ3.4 (c 1.2 in CHCl3) (Found: C,
56.40; H, 7.61; N, 2.28. Calc. for C27H43NO12: C, 56.53; H, 7.56;
N, 2.44%); 1H NMR (CDCl3): δ 5.18 (dd, 1 H, J7,8 9.4, J8,9 9.3,
H-8), 5.07 (dd, 1 H, J9,10 10.0, H-9), 4.89 (dd, 1 H, J6,7 9.3, H-7),
4.26 (dd, 1 H, J10,11a 4.9, J11a,11b 12.2, H-11a), 4.09 (dd, 1 H,
J10,11b 2.2, H-11b), 3.94 (dd, 1 H, J1a,2 6.4, J1a,1b 8.6, H-1a), 3.90–
3.72 (m, 2 H, H-1b, H-2), 3.63 (ddd, 1 H, H-10), 3.45–3.35 (m,
1 H, H-6), 2.11, 2.07, 2.04, and 2.02 (4 s, 12 H, 4 × Ac), 1.83–
1.28 (m, 6 H, 2 × H-3, 2 × H-4, 2 × H-5), 1.58 and 1.52 (2 s, 6 H,
2 × CH3), 1.51 (s, 9 H, t-Bu); MALDI-TOF MS (573.6): m/z,
596.8 (M ϩ Na), 612.9 (M ϩ K).
Cross-metathesis of the allyl α-C-galactopyranoside 3c (226
mg, 0.40 mmol) with the vinyloxazolidine 1 (182 mg, 0.80
mmol) as described for the preparation of 4a afforded, after
column chromatography with cyclohexane–AcOEt (from 8 : 1
to 5 : 1), 4c (144 mg, 47%) as a ca. 5 : 1 E : Z mixture (Found: C,
73.67; H, 7.62; N, 1.98. Calc. for C47H57NO8: C, 73.89; H, 7.52;
1
N, 1.83%); H NMR (CDCl3) selected data: δ 5.62–5.40 (m,
2 H, H-3, H-4), 2.48–2.30 (m, 2 H, 2 × H-5); MALDI-TOF MS
(764.0): m/z, 787.6 (M ϩ Na), 803.6 (M ϩ K).
7,11-Anhydro-8,9,10,12-tetra-O-benzyl-2,3,4,5,6-pentadeoxy-1-
O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-
L-galacto-dodec-3-enitol 4d
Cross-metathesis of the butenyl β-C-glucopyranoside 3d (289
mg, 0.50 mmol) with the vinyloxazolidine 1 (227 mg, 1.00
mmol) as described for the preparation of 4a afforded, after
column chromatography with cyclohexane–AcOEt (from 9 : 1
to 6 : 1), 4d (163 mg, 42%) as a ca. 5 : 1 E : Z mixture (Found: C,
74.38; H, 7.69; N, 1.68. Calc. for C48H59NO8: C, 74.10; H, 7.64;
7,8,9,11-Tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetradeoxy-1-O,2-
N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
gulo-undecitol 5b
1
N, 1.80%); H NMR (DMSO-d6; 120 ЊC) selected data of the
Hydrogenation and acetylation of 4b (153 mg, 0.20 mmol) as
described for the preparation of 5a afforded, after column
chromatography with 1.5 : 1 cyclohexane–AcOEt, 5b (93 mg,
81%) as a syrup; [α]D ϩ62.6 (c 1.0 in CHCl3) (Found: C, 56.31;
H, 7.70; N, 2.41. Calc. for C27H43NO12: C, 56.53; H, 7.56; N,
2.44%); 1H NMR (DMSO-d6; 140 ЊC): δ 5.22 (dd, 1 H, J7,8 8.6,
J8,9 8.2, H-8), 4.94 (dd, 1 H, J6,7 5.4, H-7), 4.86 (dd, 1 H, J9,10 8.7,
H-9), 4.18 (dd, 1 H, J10,11a 5.8, J11a,11b 12.0, H-11a), 4.09 (dd,
1 H, J10,11b 3.3, H-11b), 4.11–4.05 (m, 1 H, H-6), 3.95 (dd, 1 H,
J1a,2 6.0, J1a,1b 8.7, H-1a), 3.92 (ddd, 1 H, H-10), 3.82 (dddd,
1 H, J1b,2 2.0, J2,3a 3.8, J2,3b 8.2, H-2), 3.69 (dd, 1 H, H-1b),
2.03, 2.02, 2.01, and 1.99 (4 s, 12 H, 4 × Ac), 1.86–1.24 (m, 6 H,
2 × H-3, 2 × H-4, 2 × H-5), 1.52 and 1.46 (2 s, 6 H, 2 × CH3),
1.47 (s, 9 H, t-Bu); MALDI-TOF MS (573.6): m/z, 596.6
(M ϩ Na), 612.8 (M ϩ K).
E isomer: δ 5.60 (ddd, 1 H, J3,4 15.5, J4,5a = J4,5b = 6.5, H-4), 5.40
(dd, 1 H, J2,3 7.0, H-3), 4.83 (s, 2 H, PhCH2), 4.80 and 4.61 (2 d,
2 H, J 11.2, PhCH2), 4.76 and 4.64 (2 d, 2 H, J 11.6, PhCH2),
4.57 and 4.53 (2 d, 2 H, J 12.0, PhCH2), 4.25 (ddd, 1 H, J1a,2 6.3,
J1b,2 2.6, H-2), 3.99 (dd, 1 H, J1a,1b 8.8, H-1a); MALDI-TOF
MS (778.0): m/z, 800.8 (M ϩ Na), 817.0 (M ϩ K).
7,11-Anhydro-8,9,10,12-tetra-O-benzyl-2,3,4,5,6-pentadeoxy-1-
O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-
galacto-dodec-3-enitol 4e
Cross-metathesis of the butenyl β-C-galactopyranoside 3e (174
mg, 0.30 mmol) with the vinyloxazolidine 1 (136 mg, 0.60
mmol) as described for the preparation of 4a afforded, after
column chromatography with cyclohexane–AcOEt (from 10 : 1
to 6 : 1), 4e (96 mg, 41%) as a ca. 5 : 1 E : Z mixture (Found: C,
74.34; H, 7.75; N, 1.67. Calc. for C48H59NO8: C, 74.10; H, 7.64;
7,8,9,11-Tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetradeoxy-1-O,2-
N-isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-gulo-
undecitol 5c
1
N, 1.80%); H NMR (DMSO-d6; 120 ЊC) selected data of the
E isomer: δ 5.58 (ddd, 1 H, J3,4 15.8, J4,5a = J4,5b = 6.5, H-4), 5.40
(dd, 1 H, J2,3 7.0, H-3), 4.84 and 4.62 (2 d, 2 H, J 11.4, PhCH2),
4.84 and 4.56 (2 d, 2 H, J 11.6, PhCH2), 4.79 and 4.67 (2 d, 2 H,
J 12.0, PhCH2), 4.54 and 4.48 (2 d, 2 H, J 12.2, PhCH2), 4.23
(ddd, 1 H, J1a,2 6.4, J1b,2 2.5, H-2), 4.04 (dd, 1 H, J9,10 2.6, J10,11
0.5, H-10), 3.98 (dd, 1 H, J1a,1b = 8.9, H-1a), 3.23 (ddd, 1 H, J6a,7
3.0, J6b,7 = J7,8 = 9.0, H-7); MALDI-TOF MS (778.0): m/z, 801.4
(M ϩ Na), 817.2 (M ϩ K).
Hydrogenation and acetylation of 4c (153 mg, 0.20 mmol) as
described for the preparation of 5a afforded, after column
chromatography with 1.5 : 1 cyclohexane–AcOEt, 5c (94 mg,
82%) as a syrup; [α]D ϩ70.2 (c 1.2 in CHCl3) (Found: C, 56.46;
H, 7.65; N, 2.31. Calc. for C27H43NO12: C, 56.53; H, 7.56; N,
1
2.44%); H NMR (CDCl3): δ 5.42 (dd, 1 H, J8,9 3.0, J9,10 2.3,
H-9), 5.29 (dd, 1 H, J6,7 5.1, J7,8 9.6, H-7), 5.20 (dd, 1 H, H-8),
4.26–4.15 (m, 2 H, H-6, H-11a), 4.10 (dd, 1 H, J10,11b 5.2, J11a,11b
11.4, H-11b), 4.02 (ddd, 1 H, J10,11a 7.0, H-10), 3.94 (dd, 1 H,
J1a,2 6.0, J1a,1b 8.3, H-1a), 3.93–3.86 (m, 1 H, H-2), 3.74 (d, 1 H,
H-1b), 2.14, 2.09, 2.07, and 2.04 (4 s, 12 H, 4 × Ac), 1.85–
1.46 (m, 6 H, 2 × H-3, 2 × H-4, 2 × H-5), 1.49 and 1.44 (2 s, 6 H,
2 × CH3), 1.49 (s, 9 H, t-Bu); MALDI-TOF MS (573.6): m/z,
597.3 (M ϩ Na), 613.4 (M ϩ K).
5,9-Anhydro-6,7,8,10-tetra-O-benzyl-2,3,4-trideoxy-1-O,2-N-
isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
galacto-dec-3-enitol 4f
Cross-metathesis of the vinyl β-C-glucopyranoside 3f (275 mg,
0.50 mmol) with the vinyloxazolidine 1 (227 mg, 1.00 mmol) as
described for the preparation of 4a afforded, after column
chromatography with cyclohexane–AcOEt (from 9 : 1 to 6 : 1),
4f (60 mg, 16%) as a ca. 5 : 1 E : Z mixture (Found: C, 73.40; H,
7.53; N, 1.70. Calc. for C46H55NO8: C, 73.67; H, 7.39; N,
8,9,10,12-Tetra-O-acetyl-7,11-anhydro-2,3,4,5,6-pentadeoxy-1-
O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-
L-galacto-dodecitol 5d
1
1.87%); H NMR (CDCl3) selected data: δ 5.70–5.42 (m, 2 H,
Hydrogenation and acetylation of 4d (156 mg, 0.20 mmol) as
described for the preparation of 5a afforded, after column
chromatography with 1.5 : 1 cyclohexane–AcOEt, 5d (95 mg,
81%) as a syrup; [α]D ϩ5.0 (c 0.5 in CHCl3) (Found: C, 57.40; H,
7.79; N, 2.25. Calc. for C28H45NO12: C, 57.23; H, 7.72; N,
2.38%); 1H NMR (DMSO-d6; 160 ЊC): δ 5.16 (dd, 1 H, J8,9 9.2,
J9,10 9.4, H-9), 4.88 (dd, 1 H, J10,11 9.6, H-10), 4.74 (dd, 1 H, J7,8
9.6, H-8), 4.14 (dd, 1 H, J11,12a 5.0, J12a,12b 12.0, H-12a), 4.09 (dd,
1 H, J11,12b 3.2, H-12b), 3.94 (dd, 1 H, J1a,2 6.0, J1a,1b 8.6, H-1a),
H-3, H-4); MALDI-TOF MS (749.9): m/z, 772.9 (M ϩ Na),
789.4 (M ϩ K).
7,8,9,11-Tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetradeoxy-1-O,2-
N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
galacto-undecitol 5a
A vigorously stirred mixture of 4a (153 mg, 0.20 mmol), 20%
palladium hydroxide on carbon (75 mg), and 1 : 1 t-BuOH–
2384
J. Chem. Soc., Perkin Trans. 1, 2001, 2380–2388

View Article Online
3.82–3.77 (m, 1 H, H-2), 3.81 (ddd, 1 H, H-11), 3.68 (dd,
1 H, J1b,2 2.3 Hz, H-1b), 3.62–3.54 (m, 1 H, H-7), 2.01, 2.00,
1.99, and 1.94 (4 s, 12 H, 4 × Ac), 1.72–1.25 (m, 8 H, 2 × H-3,
2 × H-4, 2 × H-5, 2 × H-6), 1.51 and 1.45 (2 s, 6 H, 2 × CH3),
1.47 (s, 9 H, t-Bu); MALDI-TOF MS (587.7): m/z, 611.2
(M ϩ Na), 627.3 (M ϩ K).
as described for the preparation of 6a gave 6b (101 mg, ca. 92%)
as a syrup ca. 95% pure by 1H NMR analysis. 1H NMR
(CDCl3): δ 5.32 (dd, 1 H, J7,8 9.5, J8,9 8.9, H-8), 5.08 (dd, 1 H,
J6,7 5.8, H-7), 5.08 (d, 1 H, J2,NH 8.5, NH), 4.99 (dd, 1 H, J9,10
9.5, H-9), 4.38–4.30 (m, 1 H, H-2), 4.26 (dd, 1 H, J10,11a 5.4,
J11a,11b 12.0, H-11a), 4.18 (ddd, 1 H, J5a,6 2.7, J5b,6 8.5, H-6), 4.09
(dd, 1 H, J10,11b 2.5, H-11b), 3.84 (ddd, 1 H, H-10), 2.12, 2.08,
2.06, and 2.05 (4 s, 12 H, 4 × Ac), 1.98–1.41 (m, 6 H, 2 × H-3,
2 × H-4, 2 × H-5), 1.46 (s, 9 H, t-Bu).
8,9,10,12-Tetra-O-acetyl-7,11-anhydro-2,3,4,5,6-pentadeoxy-1-
O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-
galacto-dodecitol 5e
7,8,9,11-Tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetradeoxy-1-O,
2- N-isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-
gulo-undeconic acid 6c
Hydrogenation and acetylation of 4e (117 mg, 0.15 mmol) as
described for the preparation of 5a afforded, after column
chromatography with 2 : 1 cyclohexane–AcOEt, 5e (72 mg,
82%) as a syrup; [α]D ϩ12.5 (c 1.0 in CHCl3) (Found: C, 57.01;
H, 7.86; N, 2.28. Calc. for C28H45NO12: C, 57.23; H, 7.72; N,
2.38%); 1H NMR (DMSO-d6; 120 ЊC): δ 5.33 (dd, 1 H, J9,10 3.5,
J10,11 0.5, H-10), 5.11 (dd, 1 H, J8,9 9.9, H-9), 4.92 (dd, 1 H, J7,8
9.6, H-8), 4.08–4.00 (m, 3 H, H-11, 2 × H-12), 3.92 (dd, 1 H,
J1a,2 6.0, J1a,1b 8.6, H-1a), 3.82–3.74 (m, 1 H, H-2), 3.68 (dd, 1 H,
J1b,2 2.1, H-1b), 3.59–3.52 (m, 1 H, H-7), 2.10, 2.02, 1.98, and
1.93 (4 s, 12 H, 4 × Ac), 1.70–1.22 (m, 8 H, 2 × H-3, 2 × H-4,
2 × H-5, 2 × H-6), 1.51 and 1.45 (2 s, 6 H, 2 × CH3), 1.49 (s, 9 H,
t-Bu); MALDI-TOF MS (587.7): m/z, 610.9 (M ϩ Na), 627.0
(M ϩ K).
Treatment of the oxazolidine derivative 5c (86 mg, 0.15 mmol)
as described for the preparation of 6a gave 6c (74 mg, ca. 90%)
as a syrup ca. 95% pure by 1H NMR analysis. 1H NMR
(CDCl3): δ 5.42 (dd, 1 H, J8,9 3.1, J9,10 2.0, H-9), 5.27 (dd, 1 H,
J6,7 4.9, J7,8 9.5, H-7), 5.20 (dd, 1 H, H-8), 5.14 (d, 1 H, J2,NH
8.0, NH), 4.38–4.17 and 4.12–4.02 (2 m, 5 H, H-2, H-6, H-10,
2 × H-11), 2.15, 2.10, 2.09, and 2.04 (4 s, 12 H, 4 × Ac), 1.93–
1.40 (m, 6 H, 2 × H-3, 2 × H-4, 2 × H-5), 1.46 (s, 9 H, t-Bu).
8,9,10,12-Tetra-O-acetyl-7,11-anhydro-2,3,4,5,6-pentadeoxy-1-
O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-
L-galacto-dodeconic acid 6d
6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-1-O,2-N-
isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
galacto-decitol 5f
Treatment of the oxazolidine derivative 5d (117 mg, 0.20 mmol)
as described for the preparation of 6a gave 6d (105 mg, ca. 94%)
as a syrup ca. 95% pure by 1H NMR analysis. 1H NMR
(CDCl3): δ 5.17 (dd, 1 H, J8,9 9.3, J9,10 9.5, H-9), 5.06 (dd, 1 H,
J10,11 9.8, H-10), 5.04 (d, 1 H, J2,NH 8.0, NH), 4.89 (dd, 1 H, J7,8
9.5, H-8), 4.34–4.26 (m, 1 H, H-2), 4.26 (dd, 1 H, J11,12a 5.0,
J12a,12b 12.4, H-12a), 4.13 (dd, 1 H, J11,12b 2.1, H-12b), 3.63
(ddd, 1 H, H-11), 3.43–3.36 (m, 1 H, H-7), 2.11, 2.06, 2.04, and
2.02 (4 s, 12 H, 4 × Ac), 1.84–1.30 (m, 8 H, 2 × H-3, 2 × H-4,
2 × H-5, 2 × H-6), 1.46 (s, 9 H, t-Bu).
Hydrogenation and acetylation of 4f (75 mg, 0.10 mmol) as
described for the preparation of 5a afforded, after column
chromatography with 1.5 : 1 cyclohexane–AcOEt, 5f (42 mg,
74%) as a syrup; [α]D ϩ8.1 (c 0.6 in CHCl3) (Found: C, 55.73; H,
7.47; N, 2.17. Calc. for C26H41NO12: C, 55.80; H, 7.38; N,
2.50%); 1H NMR (DMSO-d6; 120 ЊC): δ 5.17 (dd, 1 H, J6,7 9.4,
J7,8 9.2, H-7), 4.88 (dd, 1 H, J8,9 10.0, H-8), 4.72 (dd, 1 H,
J5,6 9.6, H-6), 4.13 (dd, 1 H, J9,10a 5.6, J10a,10b 12.0, H-10a),
4.07 (dd, 1 H, J9,10b 2.8, H-10b), 3.91 (dd, 1 H, J1a,2 6.5, J1a,1b 8.7,
H-1a), 3.86–3.78 (m, 2 H, H-2, H-9), 3.66 (dd, 1 H, J1b,2 1.8,
H-1b), 3.58 (ddd, 1 H, J4a,5 2.8, J4b,5 8.1, H-5), 2.05–1.80 and
1.66–1.30 (2 m, 4 H, 2 × H-3, 2 × H-4), 2.00 and 1.95 (2 s, 12 H,
4 × Ac), 1.50 and 1.43 (2 s, 6 H, 2 × CH3), 1.45 (s, 9 H,
t-Bu); MALDI-TOF MS (559.6): m/z, 583.0 (M ϩ Na), 598.8
(M ϩ K).
8,9,10,12-Tetra-O-acetyl-7,11-anhydro-2,3,4,5,6-pentadeoxy-1-
O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-threo-L-
galacto-dodeconic acid 6e
Treatment of the oxazolidine derivative 5e (88 mg, 0.15 mmol)
as described for the preparation of 6a gave 6e (79 mg, ca. 94%)
as a syrup ca. 95% pure by 1H NMR analysis. 1H NMR
(CDCl3): δ 5.43 (dd, 1 H, J9,10 3.1, J10,11 0.8, H-10), 5.10 (dd,
1 H, J7,8 9.0, J8,9 9.6, H-8), 5.01 (d, 1 H, J2,NH 8.0, NH), 5.01
(dd, 1 H, H-9), 4.31 (ddd, 1 H, J2,3a 5.5, J2,3b 8.0, H-2), 4.17 (dd,
1 H, J11,12a 6.8, J12a,12b 11.4, H-12a), 4.06 (dd, 1 H, J11,12b 6.6,
H-12b), 3.85 (ddd, 1 H, H-11), 3.43–3.35 (md, 1 H, H-7), 2.18,
2.07, and 2.00 (3 s, 12 H, 4 × Ac), 1.85–1.34 (m, 8 H, 2 × H-3, 2
× H-4, 2 × H-5, 2 × H-6), 1.47 (s, 9 H, t-Bu).
7,8,9,11-Tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetradeoxy-1-O,2-
N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
galacto-undeconic acid 6a
To a cooled (0 ЊC), stirred solution of 5a (115 mg, 0.20 mmol) in
acetone (4 cm3) was added freshly prepared 1 M Jones reagent
(0.60 cm3, 0.6 mmol). The mixture was allowed to warm to
room temperture during 30 min, then was stirred for an addi-
tional 3 h. To the orange suspension was added dropwise
propan-2-ol until a green colour was observed, then the reac-
tion mixture was diluted with CH2Cl2 (60 cm3) and washed with
brine (3 × 20 cm3). The organic phase was dried (Na2SO4) and
concentrated to afford 6a (99 mg, ca. 91%) as a syrup ca. 95%
pure by 1H NMR analysis. 1H NMR (CDCl3): δ 5.18 (dd, 1 H,
J7,8 9.1, J8,9 9.5, H-8), 5.08 (d, 1 H, J2,NH 8.0, NH), 5.06 (dd, 1 H,
J9,10 9.9 Hz, H-9), 4.88 (dd, 1 H, J6,7 9.9, H-7), 4.33–4.26 (m,
1 H, H-2), 4.26 (dd, 1 H, J10,11a 4.9, J11a,11b 12.3, H-11a), 4.11
(dd, 1 H, J10,11b 2.3, H-11b), 3.64 (ddd, 1 H, H-10), 3.42 (ddd,
1 H, J5a,6 3.3, J5b,6 7.8, H-6), 2.11, 2.06, 2.04, and 2.01 (4 s, 12 H,
4 × Ac), 1.93–1.48 (m, 6 H, 2 × H-3, 2 × H-4, 2 × H-5), 1.46
(s, 9 H, t-Bu).
6,7,8,10-Tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-1-O,2-N-
isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
galacto-deconic acid 6f
Treatment of the oxazolidine derivative 5f (56 mg, 0.10 mmol)
as described for the preparation of 6a gave 6f (49 mg, ca. 91%)
as a syrup ca. 95% pure by 1H NMR analysis. 1H NMR
(CDCl3): δ 5.19 (dd, 1 H, J6,7 9.4, J7,8 9.3, H-7), 5.17 (d, 1 H,
J2,NH 9.0, NH), 5.05 (dd, 1 H, J8,9 10.0, H-8), 4.90 (dd, 1 H, J5,6
9.9, H-6), 4.33–4.25 (m, 1 H, H-2), 4.23 (dd, 1 H, J9,10a 5.1,
J10a,10b 12.3, H-10a), 4.13 (dd, 1 H, J9,10b 2.2, H-10b), 3.66 (ddd,
1 H, H-9), 3.50 (ddd, 1 H, J4a,5 2.6, J4b,5 8.0, H-5), 2.11, 2.06,
2.04, and 2.02 (4 s, 12 H, 4 × Ac), 2.01–1.44 (m, 4 H, 2 × H-3,
2 × H-4), 1.46 (s, 9 H, t-Bu).
7,8,9,11-Tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetradeoxy-1-O,2-
N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-L-
gulo-undeconic acid 6b
Methyl 7,8,9,11-tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetra-
deoxy-1-O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-
erythro-L-galacto-undeconate 6a Me ester
Treatment of the oxazolidine derivative 5b (115 mg, 0.20 mmol)
Treatment of a solution of crude acid 6a in 1 : 1 Et2O–MeOH
J. Chem. Soc., Perkin Trans. 1, 2001, 2380–2388
2385

View Article Online
with ethereal diazomethane at 0 ЊC for 5 min gave, after column
chromatography on silica gel (1 : 1 cyclohexane–AcOEt), 6a Me
ester as a syrup; [α]D Ϫ1.5 (c 1.0 in CHCl3) (Found: C, 53.69;
H, 7.10; N, 2.41. Calc. for C25H39NO13: C, 53.47; H, 7.00; N,
54.52; H, 7.29; N, 2.36. Calc. for C26H41NO13: C, 54.25; H, 7.18;
N, 2.43%); 1H NMR (CDCl3): δ 5.17 (dd, 1 H, J8,9 9.3, J9,10 9.5,
H-9), 5.06 (dd, 1 H, J10,11 9.8, H-10), 5.03 (d, 1 H, J2,NH 8.0,
NH), 4.88 (dd, 1 H, J7,8 9.5, H-8), 4.34–4.26 (m, 1 H, H-2), 4.26
(dd, 1 H, J11,12a 5.0, J12a,12b 12.4, H-12a), 4.10 (dd, 1 H, J11,12b 2.1,
H-12b), 3.76 (s, 3 H, OCH3), 3.63 (ddd, 1 H, H-11), 3.43–3.36
(m, 1 H, H-7), 2.11, 2.06, 2.04, and 2.01 (4 s, 12 H, 4 × Ac),
1.84–1.26 (m, 8 H, 2 × H-3, 2 × H-4, 2 × H-5, 2 × H-6), 1.46
(s, 9 H, t-Bu); 13C NMR (CDCl3): δC 173.3, 170.7, 170.4, 169.7,
1
2.49%); H NMR (CDCl3): δ 5.18 (dd, 1 H, J7,8 9.1, J8,9 9.5,
H-8), 5.06 (dd, 1 H, J9,10 9.9, H-9), 5.03 (d, 1 H, J2,NH 8.0, NH),
4.88 (dd, 1 H, J6,7 9.9, H-7), 4.33–4.26 (m, 1 H, H-2), 4.26 (dd,
1 H, J10,11a 4.9, J11a,11b 12.3, H-11a), 4.10 (dd, 1 H, J10,11b 2.3,
H-11b), 3.76 (s, 3 H, OCH3), 3.63 (ddd, 1 H, H-10), 3.40 (ddd,
1 H, J5a,6 3.3, J5b,6 7.8, H-6), 2.11, 2.06, 2.04, and 2.01 (4 s, 12 H,
4 × Ac), 1.86–1.34 (m, 6 H, 2 × H-3, 2 × H-4, 2 × H-5), 1.46
(s, 9 H, t-Bu); 13C NMR (CDCl3): δC 173.2, 170.7, 170.4, 169.7,
169.5, and 155.3 (C᎐O), 79.9 (CMe ), 77.7 (C-7), 75.6 (C-11),
᎐
3
74.4 (C-9), 71.9 (C-8), 68.7 (C-10), 62.3 (C-12), 53.3 (C-2), 52.2
(OMe), 32.7, 31.0, 25.1, and 24.7 (C-3, C-4, C-5, C-6), 28.3
(CMe3), 20.7 and 20.6 (MeCO); MALDI-TOF MS (575.6): m/z,
598.6 (M ϩ Na), 614.9 (M ϩ K).
and 155.3 (C᎐O), 79.9 (CMe ), 77.5 (C-6), 75.7 (C-10), 74.3
᎐
3
(C-8), 71.8 (C-7), 68.6 (C-9), 62.3 (C-11), 53.3 (C-2), 52.2
(OMe), 32.3, 30.7, and 21.0 (C-3, C-4, C-5), 28.3 (CMe3),
20.7 and 20.6 (MeCO); MALDI-TOF MS (561.6): m/z, 584.1
(M ϩ Na), 600.2 (M ϩ K).
Methyl 8,9,10,12-tetra-O-acetyl-7,11-anhydro-2,3,4,5,6-penta-
deoxy-1-O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-
threo-L-galacto-dodeconate 6e Me ester
Methyl 7,8,9,11-tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetra-
deoxy-1-O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-
erythro-L-gulo-undeconate 6b Me ester
Treatment of a solution of crude acid 6e in 1 : 1 Et2O–MeOH
with ethereal diazomethane at 0 ЊC for 5 min gave, after column
chromatography on silica gel (1.5 : 1 cyclohexane–AcOEt), 6e
Me ester as a syrup; [α]D ϩ5.8 (c 1.0 in CHCl3) (Found: C,
54.16; H, 7.36; N, 2.31. Calc. for C26H41NO13: C, 54.25; H, 7.18;
N, 2.43%); 1H NMR (CDCl3): δ 5.43 (dd, 1 H, J9,10 3.1, J10,11 0.8,
H-10), 5.09 (dd, 1 H, J7,8 9.0, J8,9 9.6, H-8), 5.02 (d, 1 H, J2,NH
8.0, NH), 5.01 (dd, 1 H, H-9), 4.31 (ddd, 1 H, J2,3a 5.5, J2,3b 8.0,
H-2), 4.16 (dd, 1 H, J11,12a 6.8, J12a,12b 11.4, H-12a), 4.08 (dd,
1 H, J11,12b 6.6, H-12b), 3.85 (ddd, 1 H, H-11), 3.76 (s, 3 H,
OCH3), 3.37 (ddd, 1 H, J6a,7 6.0, J6b,7 9.1, H-7), 2.18, 2.07,
and 2.00 (3 s, 12 H, 4 × Ac), 1.85–1.34 (m, 8 H, 2 × H-3,
2 × H-4, 2 × H-5, 2 × H-6), 1.46 (s, 9 H, t-Bu); 13C NMR
Treatment of a solution of crude acid 6b in 1 : 1 Et2O–MeOH
with ethereal diazomethane at 0 ЊC for 5 min gave, after column
chromatography on silica gel (1 : 1 cyclohexane–AcOEt), 6b Me
ester as a syrup; [α]D ϩ54.9 (c 1.0 in CHCl3) (Found: C, 53.31;
H, 7.19; N, 2.30. Calc. for C25H39NO13: C, 53.47; H, 7.00; N,
1
2.49%); H NMR (CDCl3): δ 5.32 (dd, 1 H, J7,8 9.5, J8,9 8.9,
H-8), 5.07 (dd, 1 H, J6,7 5.8, H-7), 5.04 (d, 1 H, J2,NH 8.5, NH),
4.94 (dd, 1 H, J9,10 9.5, H-9), 4.38–4.30 (m, 1 H, H-2), 4.27 (dd,
1 H, J10,11a 5.4, J11a,11b 12.0, H-11a), 4.16 (ddd, 1 H, J5a,6 2.7, J5b,6
8.5, H-6), 4.08 (dd, 1 H, J10,11b 2.5, H-11b), 3.83 (ddd, 1 H,
H-10), 3.77 (s, 3 H, OCH3), 2.13, 2.09, 2.06, and 2.05 (4 s, 12 H,
4 × Ac), 1.94–1.36 (m, 6 H, 2 × H-3, 2 × H-4, 2 × H-5), 1.46
(s, 9 H, t-Bu); 13C NMR (CDCl3): δC 173.1, 170.7, 170.1, 169.7,
(CDCl ): δ 173.3, 170.4, 170.3, 170.2, 169.8, and 155.3 (C᎐O),
᎐
3
C
79.9 (CMe3), 78.1 (C-7), 74.1 (C-11), 72.2 (C-9), 69.4 (C-8), 67.7
(C-10), 61.6 (C- 12), 53.3 (C-2), 52.2 (OMe), 32.7, 31.2, 25.1,
and 24.7 (C-3, C-4, C-5, C-6), 28.3 (CMe3), 20.8, 20.7, and 20.6
(MeCO); MALDI-TOF MS (575.6): m/z, 598.6 (M ϩ Na),
614.7 (M ϩ K).
and 155.3 (C᎐O), 80.0 (CMe ), 72.5 (C-6), 70.3 (C-7, C-8),
᎐
3
68.8 (C-9), 68.7 (C-10), 62.3 (C-11), 53.0 (C-2), 52.3 (OMe),
32.4, 24.7, and 20.9 (C-3, C-4, C-5), 28.3 (CMe3), 20.7
(MeCO); MALDI-TOF MS (561.6): m/z, 584.6 (M ϩ Na),
600.7 (M ϩ K).
Methyl 6,7,8,10-tetra-O-acetyl-5,9-anhydro-2,3,4-trideoxy-1-
O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-erythro-
L-galacto-deconate 6f Me ester
Methyl 7,8,9,11-tetra-O-acetyl-6,10-anhydro-2,3,4,5-tetra-
deoxy-1-O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-
threo-L-gulo-undeconate 6c Me ester
Treatment of a solution of crude acid 6f in 1 : 1 Et2O–MeOH
with ethereal diazomethane at 0 ЊC for 5 min gave, after column
chromatography on silica gel (1 : 1 cyclohexane–AcOEt), 6f
Me ester as a white solid; mp 109–111 ЊC (from AcOEt–
cyclohexane); [α]D Ϫ4.0 (c 0.6 in CHCl3) (Found: C, 52.80; H,
6.76; N, 2.46. Calc. for C24H37NO13: C, 52.64; H, 6.81; N,
Treatment of a solution of crude acid 6c in 1 : 1 Et2O–MeOH
with ethereal diazomethane at 0 ЊC for 5 min gave, after column
chromatography on silica gel (1 : 1 cyclohexane–AcOEt), 6c Me
ester as a syrup; [α]D ϩ67.7 (c 0.9 in CHCl3) (Found: C, 53.70;
H, 7.11; N, 2.36. Calc. for C25H39NO13: C, 53.47; H, 7.00; N,
1
2.56%); H NMR (CDCl3): δ 5.19 (dd, 1 H, J6,7 9.4, J7,8 9.3,
1
2.49%); H NMR (CDCl3): δ 5.42 (dd, 1 H, J8,9 3.1, J9,10 2.0,
H-7), 5.06 (d, 1 H, J2,NH 8.0, NH), 5.05 (dd, 1 H, J8,9 10.0, H-8),
4.89 (dd, 1 H, J5,6 9.9, H-6), 4.33–4.25 (m, 1 H, H-2), 4.24 (dd,
1 H, J9,10a 5.1, J10a,10b 12.3, H-10a), 4.11 (dd, 1 H, J9,10b 2.2,
H-10b), 3.76 (s, 3 H, OCH3), 3.65 (ddd, 1 H, H-9), 3.48 (ddd,
1 H, J4a,5 2.6, J4b,5 8.0, H-5), 2.11, 2.06, 2.04, and 2.02 (4 s, 12 H,
4 × Ac), 2.01–1.44 (m, 4 H, 2 × H-3, 2 × H-4), 1.46 (s, 9 H,
t-Bu); 13C NMR (CDCl3): δC 175.0, 173.0, 170.7, 170.3, 169.7,
H-9), 5.27 (dd, 1 H, J6,7 4.9, J7,8 9.5, H-7), 5.20 (dd, 1 H, H-8),
5.06 (d, 1 H, J2,NH 8.5, NH), 4.37–4.28 (m, 1 H, H-2), 4.27 (dd,
1 H, J10,11a 6.7, J11a,11b 10.8, H-11a), 4.24–4.16 (m, 1 H, H-6),
4.11–4.01 (m, 2 H, H-10, H-11b), 3.77 (s, 3 H, OCH3), 2.15,
2.10, 2.09, and 2.04 (4 s, 12 H, 4 × Ac), 1.93–1.31 (m, 6 H,
2 × H-3, 2 × H-4, 2 × H-5), 1.46 (s, 9 H, t-Bu); 13C NMR
(CDCl3): δC 173.1, 170.6, 170.1, 169.9, and 155.3 (C᎐O), 79.9
169.5, and 155.5 (C᎐O), 80.0 (CMe ), 76.8 (C-5), 75.7 (C-9),
᎐
᎐
3
(CMe3), 71.9 (C-6), 68.3 (C-7), 68.1 (C-10), 67.9 (C-8), 67.6
(C-9), 61.5 (C- 11), 53.1 (C-2), 52.3 (OMe), 32.3, 25.1, and 21.2
(C-3, C-4, C-5), 28.3 (CMe3), 20.7 (MeCO); MALDI-TOF MS
(561.6): m/z, 584.2 (M ϩ Na), 600.4 (M ϩ K).
74.2 (C-7), 71.6 (C-6), 68.7 (C-8), 62.3 (C-10), 52.9 (C-2), 52.3
(OMe), 28.3 (CMe3), 27.7 and 27.0 (C-3, C-4), 20.7, and 20.6
(MeCO); MALDI-TOF MS (547.6): m/z, 570.7 (M ϩ Na),
587.0 (M ϩ K).
Methyl 8,9,10,12-tetra-O-acetyl-7,11-anhydro-2,3,4,5,6-penta-
deoxy-1-O,2-N-isopropylidene-2-(tert-butoxycarbonylamino)-D-
erythro-L-galacto-dodeconate 6d Me ester
Methyl 8,12-anhydro-2,3,4,9,10,11,13-hepta-O-benzyl-6,7-
dideoxy-ꢀ-D-glycero-D-gulo-D-gluco-tridecopyranoside 8
To a warmed (85 ЊC), stirred solution of alkene 7 (590 mg, 0.60
mmol) and freshly recrystallized toluene-p-sulfonylhydrazide
(335 mg, 1.80 mmol) in 1,2-dimethoxyethane (12 cm3) was
added 1 M aq. sodium acetate (1.8 cm3) by a syringe-pump
apparatus during 4 h. After an additional 1 h at 85 ЊC the
Treatment of a solution of crude acid 6d in 1 : 1 Et2O–MeOH
with ethereal diazomethane at 0 ЊC for 5 min gave, after column
chromatography on silica gel (1.5 : 1 cyclohexane–AcOEt), 6d
Me ester as a syrup; [α]D Ϫ4.4 (c 1.0 in CHCl3) (Found: C,
2386
J. Chem. Soc., Perkin Trans. 1, 2001, 2380–2388

View Article Online
mixture was cooled to room temperature, diluted with water
(15 cm3), and extracted with CH2Cl2 (2 × 60 cm3). The com-
bined organic phases were dried (Na2SO4) and concentrated.
The residue was eluted from a column of silica gel with 5 : 1
cyclohexane–AcOEt to give 8 (538 mg, 91%) as a white solid;
mp 161–162 ЊC (from CH3CN); [α]D ϩ9.0 (c 1.0 in CHCl3)
(Found: C, 76.98; H, 7.11. Calc. for C63H68O10: C, 76.80; H,
6.96%); 1H NMR (CDCl3) selected data: δ 4.54 (d, 1 H, J1,2 3.6,
H-1), 3.96 (dd, 1 H, J2,3 9.6, J3,4 9.0, H-3), 3.52 (dd, 1 H, H-2),
3.31 (s, 3 H, OCH3), 3.18 (dd, 1 H, J4,5 9.5, H-4), 2.17–2.06 (m,
2 H, 2 × H-7), 1.50–1.40 (m, 2 H, 2 × H-6); MALDI-TOF MS
(985.2): m/z, 1007.5 (M ϩ Na), 1024.0 (M ϩ K).
7,8,9,14,15,16,18-Hepta-O-acetyl-6,10:13,17-dianhydro-2,3,4,
5,11,12-hexadeoxy-1-O,2-N-isopropylidene-2-(tert-butoxy-
carbonylamino)-D-arabino-D-allo-L-gulo-octadecitol 12
Hydrogenation and acetylation of 11 (179 mg, 0.15 mmol) as
described for the preparation of 5a afforded, after column
chromatography with 1.5 : 1 cyclohexane–AcOEt, 12 (97 mg,
75%) as a syrup; [α]D ϩ36.2 (c 0.8 in CHCl3) (Found: C, 56.07;
H, 7.21; N, 1.88. Calc. for C40H61NO19: C, 55.87; H, 7.15; N,
1
1.63%); H NMR (DMSO-d6; 140 ЊC): δ 5.17 (dd, 1 H, J7,8
9.0, J8,9 8.6, H-8), 5.16 (dd, 1 H, J14,15 = J15,16 = 9.4, H-15), 4.92
(dd, 1 H, J6,7 5.6, H-7), 4.87 (dd, 1 H, J16,17 9.8, H-16), 4.72
(dd, 1 H, J13,14 9.7, H-14), 4.68 (dd, 1 H, J9,10 9.0, H-9), 4.14
(dd, 1 H, J17,18a 5.3, J18a,18b 12.0, H-18a), 4.07 (dd, 1 H, J17,18b
3.0, H-18b), 4.05–3.99 (m, 1 H, H-6), 3.95 (dd, 1 H, J1a,2
6.0, J1a,1b 9.0, H-1a), 3.86–3.78 (m, 1 H, H-2), 3.81 (ddd, 1 H,
H-17), 3.68 (dd, 1 H, J1b,2 2.0, H-1b), 3.67–3.55 (m, 2 H, H-10,
H-13), 2.02, 2.01, 2.00, 1.99, 1.97, and 1.94 (6 s, 21 H, 7 × Ac),
1.85–1.26 (m, 10 H, 2 × H-3, 2 × H-4, 2 × H-5, 2 × H-11,
2 × H-12), 1.52 and 1.46 (2 s, 6 H, 2 × CH3), 1.48 (s, 9 H,
t-Bu); MALDI-TOF MS (859.9): m/z, 883.6 (M ϩ Na), 900.0
(M ϩ K).
1-O-Acetyl-8,12-anhydro-2,3,4,9,10,11,13-hepta-O-benzyl-6,7-
dideoxy-ꢀ,ꢁ-D-glycero-D-gulo-D-gluco-tridecopyranose 9
To a warmed (100 ЊC), stirred solution of 8 (591 mg, 0.60
mmol) in acetic acid (24 cm3) was added dropwise 1 M aq.
H2SO4 (2.4 cm3). The solution was stirred at 100 ЊC for an
additional 75 min, then cooled to room temperature, diluted
with CH2Cl2 (100 cm3), and washed with saturated aq. Na2CO3
(5 × 20 cm3). The combined organic phases were dried
(Na2SO4) and concentrated. A solution of the crude hemiacetal
in pyridine (5 cm3) and acetic anhydride (5 cm3) was kept at
room temperature for 3 h, then concentrated. The residue was
eluted from a column of silica gel with 6 : 1 cyclohexane–
AcOEt to give 9 (425 mg, 70%) as an amorphous solid (Found:
C, 75.59; H, 6.89. Calc. for C64H68O11: C, 75.86; H, 6.76%); 1H
NMR (CDCl3) selected data: δ 6.30 (d, 0.5 H, J1,2 3.5, H-1α),
5.59 (d, 0.5 H, J1,2 8.2, H-1β), 2.14 and 2.02 (2 s, 3 H, Ac);
MALDI-TOF MS (1013.2): m/z, 1036.7 (M ϩ Na), 1052.5
(M ϩ K).
7,8,9,14,15,16,18-Hepta-O-acetyl-6,10:13,17-dianhydro-2,3,4,5,
11,12-hexadeoxy-2-(tert-butoxycarbonylamino)-D-arabino-D-
allo-L-gulo-octadeconic acid 13
Treatment of the oxazolidine derivative 12 (86 mg, 0.10 mmol)
as described for the preparation of 6a gave 13 (75 mg, ca. 90%)
as a syrup ca. 95% pure by 1H NMR analysis. 1H NMR
(CDCl3) selected data: δ 5.30–5.26 (m, 1 H, NH), 5.26 (dd, 1 H,
J7,8 9.9, J8,9 9.0, H-8), 5.20 (dd, 1 H, J14,15 = J15,16 = 9.4, H-15),
5.03 (dd, 1 H, J16,17 9.1, H-16), 5.02 (dd, 1 H, J6,7 6.0, H-7), 4.90
(dd, 1 H, J13,14 9.9, H-14), 4.76 (dd, 1 H, J9,10 9.5, H-9), 4.47–
4.40 (m, 1 H, H-2), 4.22 (dd, 1 H, J17,18a 5.1, J18a,18b 12.4, H-18a),
3.61 (ddd, 1 H, J17,18b 2.0, H-17), 3.51–3.44 (m, 1 H, H-10),
3.36–3.29 (m, 1 H, H-13), 1.46 (s, 9 H, t-Bu).
4,8:11,15-Dianhydro-5,6,7,12,13,14,16-hepta-O-benzyl-1,2,3,9,
10-pentadeoxy-D-erythro-L-talo-D-ido-hexadec-1-enitol 10
A mixture of acetate 9 (811 mg, 0.8 mmol), allyltrimethylsilane
3 (0.38 cm3, 2.4 mmol), activated 4 Å powdered molecular
sieves (0.8 g), and anhydrous CH2Cl2 (8 cm3) was stirred at
room temperature for 15 min, then trimethylsilyl triflate (0.29
cm3, 1.6 mmol) was added dropwise. The suspension was stirred
at room temperature for 1 h, then treated with an excess of
Et3N, diluted with CH2Cl2, filtered through Celite, and concen-
trated. The residue was eluted from a column of silica gel with
8 : 1 cyclohexane–AcOEt (containing 5% of CH2Cl2) to give 10
(637 mg, 80%) as a white solid; mp 147–148 ЊC (from cyclo-
hexane); [α]D ϩ19.0 (c 1.0 in CHCl3) (Found: C, 78.29; H, 7.01.
Methyl 7,8,9,14,15,16,18-hepta-O-acetyl-6,10:13,17-dianhydro-
2,3,4,5,11,12-hexadeoxy-2-(tert-butoxycarbonylamino)-D-
arabino-D-allo-L-gulo-octadeconate 13 Me ester
Treatment of a solution of crude acid 13 in 1 : 1 Et2O–MeOH
with ethereal diazomethane at 0 ЊC for 5 min gave, after column
chromatography on silica gel (1 : 1 cyclohexane–AcOEt), 13 Me
ester as a syrup; [α]D ϩ29.8 (c 0.9 in CHCl3) (Found: C, 54.11;
H, 7.00; N, 1.51. Calc. for C38H57NO20: C, 53.83; H, 6.78; N,
1
1.65%); H NMR (CDCl3): δ 5.28 (dd, 1 H, J7,8 9.9, J8,9 9.0,
1
Calc. for C65H70O9: C, 78.44; H, 7.09%); H NMR (CDCl3)
H-8), 5.18 (dd, 1 H, J14,15 = J15,16 = 9.4, H-15), 5.17 (d, 1 H, J2,NH
8.0, NH), 5.04 (dd, 1 H, J16,17 9.1, H-16), 5.02 (dd, 1 H, J6,7 6.0,
H-7), 4.88 (dd, 1 H, J13,14 9.9, H-14), 4.79 (dd, 1 H, J9,10 9.5,
H-9), 4.37–4.30 (m, 1 H, H-2), 4.25 (dd, 1 H, J17,18a 5.1, J18a,18b
12.4, H-18a), 4.09 (dd, 1 H, J17,18b 2.3, H-18b), 4.09–4.04 (m,
1 H, H-6), 3.78 (s, 3 H, OCH3), 3.62 (ddd, 1 H, H-17), 3.54–
3.48 (m, 1 H, H-10), 3.42–3.36 (m, 1 H, H-13), 2.11, 2.07, 2.04,
2.03, and 2.01 (5 s, 21 H, 7 × Ac), 1.88–1.70 (m, 6 H, 2 × H-3,
2 × H-4, 2 × H-5), 1.53–1.32 (m, 4 H, 2 × H-11, 2 × H-12), 1.46
(s, 9 H, t-Bu); 13C NMR (CDCl3): δC 173.0, 170.6, 170.3, 170.2,
selected data: δ 5.76 (dddd, 1 H, J 6.5, 6.5, 10.2, 17.0, H-2), 5.10
(dddd, 1 H, J 1.7, 1.7, 2.0, 17.0, H-1a), 4.99 (dddd, 1 H, J 1.3,
1.3, 2.0, 10.2, H-1b), 4.93 and 4.81 (2 d, 2 H, J 10.8, PhCH2),
4.90 (s, 2 H, PhCH2), 4.87 and 4.63 (2 d, 2 H, J 10.8, PhCH2),
4.84 and 4.62 (2 d, 2 H, J 10.7, PhCH2), 4.84 and 4.59 (2 d, 2 H,
J 11.0, PhCH2), 4.72 and 4.65 (2 d, 2 H, J 11.8, PhCH2), 4.62
and 4.52 (2 d, 2 H, J 12.2, PhCH2); MALDI-TOF MS (995.3):
m/z, 1018.2 (M ϩ Na), 1034.4 (M ϩ K).
6,10:13,17-Dianhydro-7,8,9,14,15,16,18-hepta-O-benzyl-2,3,4,5,
11,12-hexadeoxy-1-O,2-N-isopropylidene-2-(tert-butoxy-
carbonylamino)-D-arabino-D-allo-L-gulo-octadec-3-enitol 11
169.5, and 155.3 (C᎐O), 79.8 (CMe ), 77.7 (C-13), 75.7 (C-17),
᎐
3
74.2 (C-15), 72.5 (C-6, C-9), 71.6 (C-14), 70.7 (C-7), 70.5 (C-8),
69.7 (C-10), 68.7 (C-16), 62.3 (C-18), 53.0 (C-2), 52.3 (OMe),
32.3, 27.1, 24.6, and 21.0 (C-3, C-4, C-5, C-11, C-12), 28.3
(CMe3), 20.7 (MeCO); MALDI-TOF MS (847.9): m/z, 870.6
(M ϩ Na), 886.6 (M ϩ K).
Cross-metathesis of allyl α-C-glycoside 10 (298 mg, 0.30 mmol)
with the vinyloxazolidine 1 (136 mg, 0.60 mmol) as described
for the preparation of 4a afforded, after column chromato-
graphy with cyclohexane–AcOEt (from 7 : 1 to 4 : 1), 11 (143
mg, 40%) as a ca. 5 : 1 E : Z mixture (Found: C, 75.15; H, 7.51;
N, 1.38. Calc. for C75H87NO12: C, 75.41; H, 7.34; N, 1.17%); 1H
NMR (CDCl3) selected data: δ 5.63–5.40 (m, 2 H, H-3, H-4),
2.47–2.32 (m, 2 H, 2 × H-5), 1.58 and 1.46 (2 s, 6 H, 2 × CH3),
1.46 (s, 9 H, t-Bu); MALDI-TOF MS (1194.5): m/z, 1217.7 (M
ϩ Na), 1233.2 (M ϩ K).
Acknowledgements
We thank Mr P. Formaglio (University of Ferrara) for NMR
measurements. This research was financially supported by
MURST, COFIN-2000 (Italy). We are grateful to Ajinomoto
Co., Inc. (Tokyo, Japan) for an unrestricted grant.
J. Chem. Soc., Perkin Trans. 1, 2001, 2380–2388
2387

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12 O. R. Martin, S. P. Rao, K. G. Kurz and H. A. El-Shenawy,
J. Am. Chem. Soc., 1988, 110, 8698.
13 A. D. Campbell, D. E. Paterson, T. M. Raynham and R. J. K. Taylor,
Chem. Commun., 1999, 1599.
14 E. Wellner, T. Gustafsson, J. Bäcklund, R. Holmdahl and J.
Kihlberg, ChemBioChem, 2000, 1, 272.
15 (a) H. Kunz, Pure Appl. Chem., 1993, 65, 1223; (b) M. Meldal and
K. Bock, Glycoconjugate J., 1994, 11, 59.
16 (a) H. G. Bossler and D. Seebach, Helv. Chim. Acta, 1994, 77,
1124; (b) S. Kalbag, D. Narindray and D. Slavazza, Proceedings
of the Twenty-Fifth European Peptide Symposium, Budapest, 1998,
p. 102.
17 A. Dondoni, H. M. Zuurmond and A. Boscarato, J. Org. Chem.,
1997, 62, 8114.
References
1 (a) A. Varki, Glycobiology, 1993, 3, 97; (b) R. A. Dwek, Chem. Rev.,
1996, 96, 683; (c) B. Imperiali, Acc. Chem. Res., 1997, 30, 452; (d )
Essentials of Glycobiology, ed. A. Varki, R. Cummings, J. Esko,
H. Freeze, G. Hart and J. Marth, Cold Spring Harbor Laboratory
Press, New York, 1999.
2 Selected recent papers with leading references: (a) L. A. Marcaurelle
and C. R. Bertozzi, Chem. Eur. J., 1999, 5, 1384; (b) K. Peilstöcker
and H. Kunz, Synlett, 2000, 820; K. Peilstöcker and H. Kunz,
Synlett, 2000, 823; (c) J. R. Allen, C. R. Harris and S. J. Danishefsky,
J. Am. Chem. Soc., 2001, 123, 1890; (d ) L. A. Marcaurelle, L. S.
Mizoue, J. Wilken, L. Oldham, S. B. H. Kent, T. M. Handel and
C. R. Bertozzi, Chem. Eur. J., 2001, 7, 1129.
3 A. Dondoni and A. Marra, Chem. Rev., 2000, 100, 4395.
4 (a) A. Dondoni, A. Marra and A. Massi, Tetrahedron, 1998, 54,
2827; (b) A. Dondoni, A. Marra and A. Massi, Chem. Commun.,
1998, 1741; (c) A. Dondoni, A. Massi and A. Marra, Tetrahedron
Lett., 1998, 39, 6601; (d ) A. Dondoni, A. Marra and A. Massi,
J. Org. Chem., 1999, 64, 933; (e) A. Dondoni, G. Mariotti and
A. Marra, Tetrahedron Lett., 2000, 41, 3483.
5 A. McKillop, R. J. K. Taylor, R. J. Watson and N. Lewis, Synthesis,
1994, 31.
6 Based on the same concept, other α-amino acid equivalents
constituted by the N-Boc-2,2-dimethyloxazolidine ring bearing a
reactive functional group are O-silyl enol, formyl (ref. 4) and ethynyl
derivatives (unpublished from our laboratory).
18 T. Takeda, M. Sawaki, Y. Ogihara and S. Shibata, Chem. Pharm.
Bull., 1989, 37, 54.
19 For the total synthesis of the natural N-glycosyl amino acid core and
the whole glycopeptide, see (a) A. J. Ratcliffe, P. Konradsson and
B. Fraser-Reid, J. Am. Chem. Soc., 1990, 112, 5665; (b) M. Sasaki,
K. Tachibana and H. Nakanishi, Tetrahedron Lett., 1991, 32, 6873;
(c) T. Teshima, K. Nakajima, M. Takahashi and T. Shiba,
Tetrahedron Lett., 1992, 33, 363; (d ) H. Zhang, Y. Wang,
R. Thürmer, K. Parvez, I. Choudhary, A. Rahman and W. Voelter,
Z. Naturforsch., Teil B, 1999, 54, 692.
20 W. L. F. Armarego and D. D. Perrin, Purification of Laboratory
Chemicals, 4th edn., Butterworth–Heinemann, Oxford, 1996.
21 W. C. Still, M. Kahn and A. Mitra, J. Org. Chem., 1978, 43,
2923.
7 R. Dominique, B. Liu, S. K. Das and R. Roy, Synthesis, 2000, 862.
8 (a) M. E. Maier, Angew. Chem., Int. Ed., 2000, 39, 2073; (b) L. Yet,
Chem. Rev., 2000, 100, 2963.
22 M. D. Lewis, J. K. Cha and Y. Kishi, J. Am. Chem. Soc., 1982, 104,
4976.
9 (a) T. N. Trnka and R. H. Grubbs, Acc. Chem. Res., 2001, 34, 18;
(b) J. Louie and R. H. Grubbs, Angew. Chem., Int. Ed., 2001, 40, 247.
10 (a) A. Fürstner, Angew. Chem., Int. Ed., 2000, 39, 3012; (b) R. Roy
and S. K. Das, Chem. Commun., 2000, 519; (c) A. H. Hoveyda and
R. R. Schrock, Chem. Eur. J., 2001, 7, 945.
11 M. Scholl, S. Ding, C. W. Lee and R. H. Grubbs, Org. Lett., 1999, 1,
953.
23 L. Cipolla, F. Nicotra, E. Vismara and M. Guerrini, Tetrahedron,
1997, 53, 6163.
24 W. M. Best, V. Ferro, J. Harle, R. V. Stick and D. M. Tilbrook,
Aust. J. Chem., 1997, 50, 463.
25 W. Zheng, J. A. DeMattei, J.-P. Wu, J. J.-W. Duan, L. R. Cook,
H. Oinuma and Y. Kishi, J. Am. Chem. Soc., 1996, 118, 7946.
26 G. A. Kraus and M. T. Molina, J. Org. Chem., 1988, 53, 752.
2388
J. Chem. Soc., Perkin Trans. 1, 2001, 2380–2388