Synthesis of new aza-C-disaccharides linking 4-deoxy-4-amino-β-L- erythrofuranose to C-2 of D-glucose and D-allose

Article abstract of DOI:10.1002/ejoc.200600199

The cross-aldol condensation of N-benzyl-2,5-dideoxy-2,5-imino-3,4-O- isopropylidene-L-ribose with 4,6-O-benzylidene-2-deoxy-α-D-erythro- hexopyranosid-3-ulose (potassium enolate + HMPA) gave an aldol as the major product. DAST-induced water elimination g

Full text of DOI:10.1002/ejoc.200600199

FULL PAPER
DOI: 10.1002/ejoc.200600199
Synthesis of New Aza-C-disaccharides Linking 4-Deoxy-4-amino-β-
L
-erythro-
furanose to C-2 of -Glucose and -Allose
D
D
Eliazar Rodríguez García,[a] Margaret A. Brimble,[b] and Pierre Vogel*[a]
Keywords: Aldol reactions / Aza-C-disaccharides / Enones / Iminoalditols / C-Glycosides / Hexopyranosid-3-ulose
The cross-aldol condensation of N-benzyl-2,5-dideoxy-2,5-
imino-3,4-O-isopropylidene- -ribose with 4,6-O-benzyl-
idene-2-deoxy-α- -erythro-hexopyranosid-3-ulose (potas-
pyranoside] and (+)-5 (the α-D-allopyranoside analogue). Re-
duction of the aldol and deprotection provided aza-C-di-
saccharide (+)-3 {methyl 2-deoxy-2-[(1R or 1S)-2,5-dideoxy-
L
D
sium enolate + HMPA) gave an aldol as the major product.
DAST-induced water elimination gave two enones that were
converted into the aza-C-disaccharides (+)-4 [methyl 2-de-
2,5-imino-
droxymethano linker.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
L
-ribitol-1C-yl]-α-
D
-allopyranoside} with
a
hy-
oxy-2-(1,2,5-trideoxy-2,5-imino-L-ribitol-1C-yl)-α-D-gluco-
in 1994. Since then several groups have proposed ingenious
and efficient syntheses of all kinds of aza-C-disaccharides
and their analogues.[23,24] Because we have found that
(2R,3R,4S)-3,4-dihydroxypyrrolidin-2-yl derivatives can be
selective and potent α-mannosidase inhibitors[25] with anti-
tumour activity[20] we have searched for methods to gener-
ate aza-C-disaccharides that link the (2R,3R,4S)-3,4-dihy-
droxypyrrolidin-2-yl moiety to various positions of several
hexoses through hydroxymethano linkers [e.g., ( )-1,[26] (+)-
Introduction
The cell-surface oligosaccharides are the “words” used
by cells to communicate with the outside world.[1–4] They
guide social behaviour such as cell–cell and cell–invader in-
teractions.[5] Carbohydrate mimetics such as C-disaccha-
rides and aza-C-disaccharides are potential tools with
which to study the mechanisms of cellular interactions, the
biosynthesis of glycoproteins, the catabolism of glycoconju-
gates[6,7] and the mechanisms of digestion.[8,9] Glycomimet-
ics can also be glycosidase inhibitors. They have focused
applications as therapeutic agents to treat type-II diabetes
(e.g., miglitol,[10] acarbose[11]) and obesity,[12] lysosomal dis-
eases such as Gaucher’s disease,[13] or influenza[14] [e.g., zan-
amivir (Relenza®),[15] oseltamivir phosphate (Tamiflu®)[16]].
Inhibitors of α--glucosidase and α--fucosidase are poten-
tial antiviral agents,[17] including anti-HIV agents.[5,18] In-
hibitors of α-mannosidases are potential anticancer
drugs.[19,20]
2
[27]].
Aza-C-linked-disaccharides have more recognition sites
In this report we disclose a very efficient approach to the
than their corresponding monosaccharide analogues and synthesis of the new aza-C-disaccharides (+)-3, (+)-4 and
are resistant to acid- and glycosidase-catalyzed hydrolysis. (+)-5.
They are expected to become more specific inhibitors of
glycosidases than monosaccharide mimetics such as polyhy-
droxypyrrolidine and piperidine derivatives.[21] The first ex-
ample of an aza-C-disaccharide (1,5-dideoxy-1,5-imino--
mannitol linked to the C-6 position of -galactose through
a CH2 linker) was prepared by Johnson and co-workers[22]
[a] Laboratoire de glycochimie et de synthèse asymétrique, ISIC,
Ecole Polytechnique Fédérale de Lausanne (EPFL),
BCH, 1015 Lausanne, Switzerland
Fax: +41-216-939-375,
E-mail: pierre.vogel@epfl.ch
Results and Discussion
Methyl 4,6-O-benzylidene-2-deoxy-α--erythro-hexopyr-
anosid-3-ulose [(+)-6] is readily available from -man-
[b] Department of Chemistry, University of Auckland,
23 Symonds Street, Auckland 1000, New Zealand
Supporting information for this article is available on the
WWW under http://www.eurojoc.org or from the author.
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E. Rodriguez García, M. A. Brimble, P. Vogel
FULL PAPER
nose.[28] The groups of Fraser-Reid[29] and Chapleur[30] have
established that β-elimination of a methoxide anion from
enolates of 6 is a relatively slow reaction permitting the con-
densation of the latter with various electrophiles, without
subsequent elimination. We thus envisaged a synthetic ap-
proach to the aza-C-disaccharides 8, such as (+)-3, (+)-4
and (+)-5, by cross-aldol condensation of ketone 6 with ad-
equately protected 2,5-dideoxy-2,5-imino--ribose deriva-
tives 7 (Scheme 1).
Scheme 1. Retrosynthesis plan to aza-C-disaccharides 8.
We chose first the known aldehyde (–)-9 derived from
1,4-(benzylimino)-1,4-dideoxy-2,3-O-isopropylidene--alli-
tol (10)[31] for cross-aldol condensation with (+)-6. As re-
lated Boc-protected pyrrolidine-2-carbaldehyde derivatives
could be coupled successfully with isolevoglucosenone-de-
rived ketones via their dichlorozinc enolates,[32] we applied
the same method to the reaction of (+)-6 and (–)-9 [(+)-6
+ KHMDS, then + ZnCl2/THF, then + (–)-9]. However,
none of our attempts met with success. We thus explored
all kinds of other conditions [Et3N/(c-C6H11)2BCl/Et2O;
iPr2NH/TiCl4, CH2Cl2, KHMDS alone/THF], but without
better results as aldehyde (–)-9 decomposed too readily
(Scheme 2).
As the carbamate moiety of (–)-9 is electrophilic and can
compete with the aldehyde in reactions with the various
enolates of (+)-6, we prepared the N-benzyl derivative (+)-
11. Various conditions [Pb(OAc)4/CH2Cl2, NaIO4/H2O/
EtOH] for the oxidative cleavage of diol 10 were applied
leading to low yields of impure aldehyde (+)-11. We finally
found that pure (+)-11 could be obtained in 90% yield
when the oxidation with NaIO4 involved a two-phase sys-
tem with silica gel/H2O and CH2Cl2. The aldehyde so-ob-
tained, an unstable compound at room temperature and in
the presence of light, underwent smooth cross-aldol con-
densation with (+)-6. The potassium enolate of (+)-6 was
prepared at –40 °C in THF by reaction with KHMDS. Af-
ter cooling to –85 °C, HMPA (30% with respect to THF)
was added and freshly obtained (+)-11 was mixed with this
Scheme 2. Synthesis of aza-C-disaccharide (+)-3. Reagents and
conditions: (a) SiO2/CH2Cl2 + NaIO4/H2O, 10/CH2Cl2 (90%); (b)
0.5  KHMDS in toluene added to (+)-6 in THF at –40 °C, 30 min,
then addition of HMPA, –85 °C, addition of (+)-11/THF, –85 °C/
15 h (81%); (c) NaBH4/EtOH, 0 °C (68%); (d) H2, PtO2·H2O (cata-
lyst), H2SO4 (cat.)/MeOH, 20 °C, 24 h (60%).
pyranoside moiety of (+)-12 was suggested by the 3J(1-H,2-
H) = 3.4 Hz coupling constant and was confirmed by the
transformation described below. The absolute configuration
of the hydroxymethano linker has not been determined. As-
suming the validity of the Zimmerman–Traxler model[33]
(steric factors and cyclic structure) for the cross-aldol reac-
tion between (+)-6 and (+)-11, it is expected to be (1ЈS)
(Figure 1).
Figure 1. Hypothetical transition state of the aldol reaction: K
enolate of (+)-6 + (+)-11 Ǟ (+)-12.
solution. After 15 h at –85 °C, 95% conversion of (+)-6 was
Reduction of (+)-12 with NaBH4 in EtOH furnished -
1
observed by H NMR spectroscopy. After aqueous work allopyranoside (+)-13 (68%), the structure of which was
up, aldol (+)-12 was obtained as the major product and confirmed by its 1H NMR spectrum [3J(2-H,3-H) = 3.4 Hz]
isolated (purification by flash chromatography on silica gel) and by the observation of an NOE between 3-OH and 5-
1
in 81% yield. Without HMPA the yield of (+)-12 never sur- H and between 2-H and 4-H in its 2D NOESY H NMR
passed 35%. No aldol was formed by using KHMDS and spectrum. Hydrogenolysis of (+)-13 in the presence of Ad-
ZnCl2 (–78 to –40 °C), LiHMDS or LDA. 1H NMR analy- ams’ catalyst and H2SO4 gave (+)-3 in 60% yield. Its struc-
sis of the crude reaction mixture before chromatographic ture (except for the absolute configuration of C-1Ј) was con-
purification showed the presence of 2–4% of a dia- firmed by its 1H and 13C NMR spectra and by its 2D
1
stereomeric aldol. The -ribo configuration of the methyl COSY-45, H NMR and HMQC (13C/1H) spectra.
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Synthesis of New Aza-C-disaccharides
FULL PAPER
Attempts to convert aldol (+)-12 into the corresponding petes, the latter type of elimination being favoured at higher
enones via the corresponding methanesulfonic acid or ace- concentrations of DAST. We have observed that (+)-(E)-15
tic esters all failed. Treatment of (+)-12 with Ac2O/pyridine and (+)-(Z)-15 do not equilibrate on prolonged standing in
with or without DMAP catalyst led to complex mixtures the reaction mixture, but that both are destroyed. Alterna-
containing less than 10% of the desired enones. Similarly, tively, competition of an E1 mechanism (formation of cat-
attempts to promote water elimination from (+)-12 by treat- ionic species by ionization of 17 assisted by the ben-
ment with I2/Ph3P,[34] CuSO4/SiO2 (20 °C, 2 Torr),[35] zylamino moiety) cannot be rejected. DAST-induced elimi-
BF3·Et2O,[36] camphorsulfonic acid/toluene (heating) or nations from alcohols have been reported.[39]
with HF/pyridine did not meet with success. We finally
Attempts to hydrogenate enone (+)-(E)-15 with H2/
found that treatment of aldol (+)-12 with DAST (Et2NSF3) PtO2·H2O or Pd/charcoal led to complex mixtures of prod-
under suitable conditions (3 equiv. of DAST, CH2Cl2, –78 ucts. Under Luche and Gemal’s conditions,[40] (+)-(E)-15
to +20 °C in 4 h, quenching with H2O and neutralization was reduced stereoselectively into the allylic alcohol (–)-(Z)-
1
with NaHCO3) provided a mixture of enones from which 18 in 87% yield (Scheme 5). The H NMR spectrum of the
(+)-(E)-15 and (+)-(Z)-15 could be separated by flash crude reaction mixture did not show any other product in
chromatography on silica gel in 34 and 49% yields, respec- addition to (–)-(Z)-18. Its structure was identified by the
tively. By using a larger excess of DAST and longer reaction observation of an NOE between 3-H and 5-H in its 2D
1
times at lower temperatures (–90 °C) lower yields of enones NOESY H NMR spectrum.
(+)-(E)-15 and (+)-(Z)-15 were obtained and the retro-aldol
The high diastereoselectivity of the reduction (+)-(E)-15
reaction competed generating ketone (+)-6, which was par- Ǟ (–)-(Z)-18 can be interpreted in terms of the favoured
tially converted (Scheme 3) into difluoro derivative (+)-16, boat conformation of the enone, rendering attack on the α-
a known compound.[37]
face highly preferred. Treatment of (–)-(Z)-18 with H2
The proportion of (E)-15/(Z)-15 decreased from 34:49 to (1 atm) and 10% palladium on charcoal in EtOAc gave a
10:34 (44% yield) on reducing the excess of DAST to mixture of two products from which pure debenzylated
2 equiv. A possible mechanism for the smooth DAST-pro- amine (+)-19 was isolated in 82% yield. Under these condi-
moted β-elimination reaction (+)-12 Ǟ (+)-(E)-15 + (+)- tions, removal of the benzylidene group was a very slow
(Z)-15 involves the intermediate 17, which is expected to process. This latter hydrogenolysis reaction required H2
undergo fast syn elimination (Scheme 4).[38]
with PtO2·H2O as catalyst in methanol and (+)-20 was ob-
If this mechanism was unique, it would generate either tained in 76% yield. Selective hydrolysis of the acetonide
(+)-(E)-15 or (+)-(Z)-15 since aldol (+)-12 is a single com- (+)-20 with aqueous CF3COOH provided the targeted aza-
pound. As the selectivity varies with the excess (concentra- C-disaccharide (+)-4 in 89% yield. The spectroscopic data
tion) of DAST, we propose that anti elimination also com- of (+)-19 and (+)-20 (see Exp. Sect.) proved their structures.
Scheme 3. DAST-promoted β-elimination. Reagents and conditions: (a) 3 equiv. of DAST/CH2Cl2, –78 to 25 °C (83%).
Scheme 4. Possible mechanism for the nonstereoselective β-elimination reaction (+)-12 Ǟ (+)-(E)-15 + (+)-(Z)-15.
Eur. J. Org. Chem. 2006, 3845–3855
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E. Rodriguez García, M. A. Brimble, P. Vogel
FULL PAPER
On treatment of (+)-22 with H2 (1 atm) in the presence
of PtO2·H2O as catalyst, smooth and selective hydro-
genolysis of the benzylidene moiety occurred, leaving the
thioether and the benzylamine intact. The triol (+)-23 so-
obtained was then hydrogenolysed with Raney nickel in
methanol giving (+)-24 in 71% yield. Selective hydrolysis of
the acetonide moiety of (+)-24 with aqueous CF3COOH
provided the aza-C-disaccharide (+)-5 in 95% yield. The
relative allo configuration of (+)-24 and (+)-5 was con-
firmed by their 1H NMR and 2D 1H NMR spectra.
Attempts to carry out the hydrogenolysis of (+)-23 with H2
and Pd/charcoal gave mixtures of several products from
which (+)-25 was isolated in low yield in addition to (+)-24
(Յ 29% yield).
Scheme 5. Preparation of aza-C-disaccharide (+)-4. Reagents and
conditions: (a) NaBH4/CeCl3/MeOH, 20 °C (87%); (b) H2 (1 atm),
10% Pd/charcoal/EtOAc, 20 °C, 6 h (82%); (c) H2, PtO2·H2O (cata-
lyst), H2SO4 (cat.), MeOH, 20 °C, 3 h (76%); (d) CF3COOH/H2O
(4:1), 20 °C, 1 h (89%).
Conclusions
Aldol condensation of N-benzyl-2,5-dideoxy-2,5-imino-
3,4-O-isopropylidene--ribose with methyl 4,6-O-benzyl-
idene-2-deoxy-α--erythro-hexopyranosid-3-ulose gives an
aldol as the major product which has been converted into
three aza-C-disaccharides linking 4-deoxy-4-amino-β--
erythro-furanose to C-2 of methyl α--glucopyranoside
[(+)-4], to C-2 of α--allopyranoside [(+)-5] through a
methano linker and to C-2 of α--allopyranoside [(+)-3]
through a hydroxymethano linker. Exploration of the bio-
logical activities of these aza-C-disaccharides is in progress
and will be reported in due course.
The high β-face hydrogenation of alkene (–)-(Z)-18 and the
preferred chair conformation adopted by the pyranoside
moiety of this compound can be attributed to steric factors.
Under Luche and Gemal’s conditions (NaBH4/CeCl3),
reduction of enone (+)-(Z)-15 gave the corresponding al-
lylic alcohol (+)-(E)-18 in low yield (Ͻ 20%). Steric hin-
drance to attack at the α-face of the ketone moiety of (+)-
(Z)-15 is probably the origin of this sluggish reaction. We
thus explored another route to convert this enone into an
aza-C-disaccharide. Conjugate addition of thiophenol[41] to
(+)-(Z)-15 in the presence of a catalytic amount of Et3N
furnished a single adduct (+)-21 in 91% yield (Scheme 6).
Then, reduction of ketone (+)-21 with NaBH4 in MeOH
gave a single alcohol (+)-22 in 95% yield. The absolute con-
figuration of C-1Ј in (+)-21 and (+)-22 has not been estab-
lished. The relative allo configuration of the pyranoside
Experimental Section
General: Commercial reagents (Fluka, Aldrich) were used without
further purification. Solvents were distilled prior to use: MeOH
from Mg and I2, DMF from P2O5 and CH2Cl2 from CaH2. Light
petroleum ether used refers to the fraction boiling at 40–60 °C.
Solutions after reactions and extractions were concentrated in a
rotary evaporator under reduced pressure. Liquid/solid flash
chromatography (FC): columns of silica gel (0.040–0.63 mm,
Merck No. 9385 silica gel 60, 240–400 mesh). TLC for reaction
monitoring: Merck silica gel 60F254 plates; detection by UV light;
Pancaldi reagent [(NH4)6MoO4, Ce(SO4)2, H2SO4, H2O], vanillin
or KMnO4. IR: Perkin–Elmer 1420 spectrometer. 1H NMR:
Bruker ARX 400 spectrometer (400 MHz); δ(H) in ppm relative to
1
moiety of (+)-22 was deduced from its H NMR spectrum
3
3
[typical J(2-H,3-H) = 3.0 Hz, J(3-H,4-H) = 2.6 Hz].
1
the solvent’s residual H signal (CDCl3: δ = 7.27 ppm; CD3OD: δ
= 3.34 ppm) as internal reference; coupling constants J in Hz; all
1H assignments were confirmed by 2D COSY-45 and 2D NOESY
spectra. 13C NMR: same instrument as above (100.6 MHz); δ(C)
in ppm relative to the solvent’s residual 13C signal (CDCl3: δ =
77.0 ppm; CD3OD: δ = 48.5 ppm) as internal reference; coupling
constants J in Hz. MS: chemical ionization (NH3), fast atom bom-
bardment (FAB) or electronic ionization (EI) mode; m/z (amu) (%
relative to the base peak). MALDI-TOF mass spectra were ob-
tained either from the Swiss Institute of Technology or from the
University of Auckland Mass Spectral Facility. Elemental analyses:
Ilse Beetz, 96301 Kronach, Germany. NMR spectra of the com-
pounds described below are given in the Supporting Information.
Scheme 6. Synthesis of aza-C-disaccharide (+)-5. Reagents and
conditions: (a) PhSH/CH2Cl2/Et3N, 0 °C, 1 h (91%); (b) NaBH4/
EtOH, 0 °C, 1 h (95%); (c) H2 (1 atm), 10% PtO2·H2O, H2SO4
(cat.), MeOH, 20 °C, 15 h (80%); (d) Raney Ni (excess)/MeOH,
20 °C, 75 min (71%); (e) CF3COOH/H2O (4:1), 20 °C, 30 min
(95%); (f) H2 (1 atm), 10% Pd/charcoal, EtOAc, 20 °C, 6 h [54%
of (+)-23, 29% of (+)-24, 4% of (+)-25].
N-Benzyl-2,5-dideoxy-2,5-imino-3,4-O-isopropylidene-L-ribose [(+)-
11]: A solution of NaIO4 (94 mg, 0.44 mmol) in H2O (0.68 mL)
was added dropwise to a vigorously stirred suspension of chroma-
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Synthesis of New Aza-C-disaccharides
FULL PAPER
1
1
tographic grade silica gel (0.68 g) in CH2Cl2 (6 mL) in an Erlen-
meyer flask and a flaky suspension was formed. Diol 10[31]
(100 mg, 0.34 mmol) in CH2Cl2 (0.68 mL) was then added. The
reaction was monitored by TLC until disappearance of the starting
material (10 min). The mixture was filtered under vacuum and the
silica gel was washed with CH2Cl2. Evaporation of the solvent af-
151 Hz, C-1Ј), 58.8 (t, JC,H = 142 Hz, C-5Ј), 57.0 (t, JC,H
=
=
=
1
1
136 Hz, CH2Ph), 55.5 (d, JC,H = 140 Hz, C-2), 55.4 (q, JC,H
1
1
143 Hz, OCH3), 27.4 (q, JC,H = 127 Hz, CH3), 25.5 (q, JC,H
126 Hz, CH3) ppm. UV (MeCN): λmax (ε) = 267 (3000), 214 nm
(8200 dm3 mol–1 cm–1). MS (FAB): m/z (%) = 526 (5) [M]+, 494 (12),
390 (2), 262 (4), 233 (15), 232 (100), 174 (4), 149 (6), 91 (100).
HRMS (FAB): calcd. for C29H36NO8 526.24409 [M + H]+; found
526.24319.
forded the unstable product (+)-11 (80 mg, 90%) as a colourless
20
oil. [α]
= +83 (c = 0.45, CHCl ). IR (NaCl): ν = 3060, 3030,
˜
3
589
2985, 2935, 2830, 2720, 2360, 1940, 1870, 1790, 1730, 1605, 1495,
Methyl 4,6-O-Benzylidene-2-deoxy-2-[(1R or 1S)-2,5-(benzylimino)-
2,5-dideoxy-3,4-O-isopropylidene-L-ribitol-1C-yl]-α-D-allopyran-
1455, 1375, 1210, 1150, 1080, 1050, 860, 740 cm–1. 1H NMR
3
(400 MHz, CDCl3, 25 °C): δ = 9.53 (d, JH,H = 2.4 Hz, 1 H, 1-H),
oside [(+)-13]: NaBH4 (5 mg, 0.14 mmol) was added to a solution
of crude (+)-12 (75 mg, ca. 0.14 mmol) in EtOH (3 mL) at 0 °C.
The mixture was stirred for 10 min and then quenched by addition
of an aq. satd. solution of NH4Cl (3 mL). The EtOH was evapo-
rated and the residue extracted with EtOAc. The organic layer was
dried with MgSO4 and the solvent evaporated. FC (EtOAc/light
petroleum ether, 1:1) yielded (+)-13 (50 mg, 68%) as a white foam.
3
3
7.34–7.30 (m, 5 H, ArH), 4.79 (dd, JH,H = 5.9, JH,H = 2.4 Hz, 1
3
3
H, 3-H), 4.72 (dt, JH,H = 5.9, JH,H = 2.8 Hz, 1 H, 4-H), 4.01 (d,
2JH,H = 13.1 Hz, 1 H, CH2Ph), 3.88 (d, JH,H = 13.1 Hz, 1 H,
2
CH2Ph), 3.44 (t, 3JH,H = 2.4 Hz, 1 H, 2-H), 3.17 (dd, 2JH,H = 11.2,
3JH,H = 5.9 Hz, 1 H, 5-H), 2.84 (dd, JH,H = 11.2, JH,H = 2.8 Hz,
2
3
1 H, 5-H), 1.57 (s, 3 H, CH3), 1.34 (s, 3 H, CH3) ppm. 13C NMR
1
(100.6 MHz, CDCl3, 25 °C): δ = 201.0 (d, JC,H = 175 Hz, C-1),
138.0, 128.8, 128.4, 127.4 (ArC), 113.1 [s, C(CH3)2], 80.5 (d, JC,H
[α]20 = +6 (c = 0.11, CHCl ). IR (NaCl): ν = 3495, 3065, 3030,
˜
589
3
1
2935, 2860, 2245, 1735, 1605, 1495, 1455, 1380, 1285, 1250, 1210,
1
1
= 154 Hz, C-4), 79.6 (d, JC,H = 158 Hz, C-3), 76.1 (d, JC,H
=
1
1120, 1100, 1055, 1005, 910 cm–1. H NMR (400 MHz, CDCl3,
155 Hz, C-2), 58.5 (t, 1JC,H = 145 Hz, C-5), 58.1 (t, 1JC,H = 135 Hz,
25 °C): δ = 7.56–7.26 (m, 10 H, ArH), 5.67 (s, 1 H, PhCH), 5.03
1
1
CH2Ph), 27.0 (q, JC,H = 126 Hz, CH3), 24.7 (q, JC,H = 126 Hz,
CH3) ppm. UV (MeCN): λmax (ε) = 217 nm (2200 dm3 mol–1 cm–1).
HRMS (MALDI-TOF): calcd. for C15H20NO3 262.1443 [M +
H]+; found 262.1467.
3
3
3
(d, JH,H = 3.4 Hz, 1 H, 1-H), 4.65 (dd, JH,H = 6.5, J = 5.0 Hz,
3
2
1 H, 3Ј-H), 4.53 (q, JH,H = 6.5 Hz, 1 H, 4Ј-H), 4.38 (dd, JH,H
10.0, J = 4.9 Hz, 1 H, 6-H), 4.36–4.33 (m, 2 H, 1Ј-H, 3-H), 4.20
(dt, JH,H = 10.0, JH,H = 4.9 Hz, 1 H, 5-H), 4.05 (d, JH,H
=
3
3
3
2
=
2
13.2 Hz, 1 H, CH2Ph), 3.83 (t, JH,H
=
3JH,H = 10.0 Hz, 1 H, 6-
Methyl 4,6-O-Benzylidene-2-deoxy-2-[(1R or 1S)-2,5-(benzylimino)-
2,5-dideoxy-3,4-O-isopropylidene-L-ribitol-1C-yl]-α-D-ribo-hexopyr-
H), 3.62 (dd, 3JH,H = 10.0, JH,H = 2.9 Hz, 1 H, 4-H), 3.49 (s, 3 H,
3
2
3
OCH3), 3.43 (d, JH,H = 13.2 Hz, 1 H, CH2Ph), 3.43 (d, JH,H
1.0 Hz, 1 H, 1Ј-OH), 3.30 (dd, JH,H = 10.0, JH,H = 6.5 Hz, 1 H,
=
anosid-3-ulose [(+)-12]: KHMDS (0.5  in toluene, 3.93 mL,
1.96 mmol) was added to a solution of ketone (+)-6[28] (400 mg,
1.51 mmol) in THF (8 mL) at –40 °C and the solution was stirred
for 30 min. After cooling to –85 °C, HMPA (2.4 mL) was added.
The mixture was allowed to settle for 1 h and then a solution of
freshly synthesised aldehyde (+)-11 (512 mg, 1.96 mmol) in THF
(2 mL) was added. The resulting mixture was stirred at –85 °C over-
night. Quenching was carried out at –85 °C by addition of an aq.
satd. solution of NH4Cl (5 mL). The mixture was extracted with
EtOAc (10 mL, 3 times), the combined organic layers were dried
with MgSO4 and the solvent was evaporated. FC (hexane/EtOAc,
1:1) yielded the unstable adduct (+)-12 (640 mg, 81%) as a white
2
3
3
3
5Ј-H), 3.02 (dd, JH,H = 4.7, JH,H = 2.0 Hz, 1 H, 2Ј-H), 2.92 (d,
3JH,H = 7.8 Hz, 1 H, 3-OH), 2.49 (dd, 2JH,H = 10.0, 3JH,H = 6.5 Hz,
3
3
1 H, 5Ј-H), 2.15 (dt, JH,H = 10.4, JH,H = 3.4 Hz, 1 H, 2-H), 1.47
(s, 3 H, CH3), 1.31 (s, 3 H, CH3) ppm. 13C NMR (100.6 MHz,
CDCl3, 25 °C): δ = 137.4, 129.1, 128.9, 128.4, 128.2, 127.3, 126.3
1
(ArC), 113.5 [s, C(CH3)2], 102.0 (d, JC,H = 163 Hz, PhCH), 99.8
1
1
(d, JC,H = 170 Hz, C-1), 79.6 (d, JC,H = 146 Hz, C-4), 78.9 (d,
1JC,H = 156 Hz, C-3Ј), 77.2 (d, 1JC,H = 155 Hz, C-4Ј), 69.4 (d, 1JC,H
1
1
= 137 Hz, C-2Ј), 69.4 (t, JC,H = 148 Hz, C-6), 66.5 (d, JC,H
152 Hz, C-3), 64.4 (d, JC,H = 150 Hz, C-1Ј), 59.0 (t, JC,H
140 Hz, C-5Ј), 58.1 (d, JC,H = 149 Hz, C-5), 56.9 (t, JC,H
143 Hz, CH2Ph), 55.9 (q, JC,H = 143 Hz, OCH3), 45.6 (d, JC,H
=
=
=
=
=
1
1
1
1
solid, m.p. 81–82 °C. [α]20 = +7 (c = 3.4, CHCl ). IR (NaCl): ν =
˜
589
3
1
1
3460, 3065, 2985, 2935, 2860, 1955, 1895, 1820, 1740, 1695, 1615,
1495, 1455, 1410, 1380, 1310, 1265, 1210, 1175, 1155, 1140, 1085,
1
1
127 Hz, C-2), 27.4 (q, JC,H = 127 Hz, CH3), 25.4 (q, JC,H
126 Hz, CH3) ppm. UV (MeCN): λmax (ε) = 203 (11600), 196 nm
(13300 dm3 mol–1 cm–1). MS (CI): m/z (%) = 528 (4) [M + H]+, 495
(5), 417 (3), 318 (7), 265 (38), 262 (30), 235 (85), 233 (54), 174
(53), 158 (40), 105 (59), 91 (100), 78 (31). HRMS (CI): calcd. for
C29H38NO8 528.25974 [M + H]+; found 528.26062.
1
1075, 1020, 970, 915 cm–1. H NMR (400 MHz, CDCl3, 25 °C): δ
= 7.55–7.28 (m, 10 H, ArH), 5.61 (s, 1 H, PhCH), 5.32 (d, 3JH,H
=
3
3
3.4 Hz, 1 H, 1-H), 4.60 (dd, JH,H = 6.7, JH,H = 5.0 Hz, 1 H, 3-
3
H), 4.51 (m, 1 H, 4Ј-H), 4.40 (d, JH,H = 10.0 Hz, 1 H, 4-H), 4.39
3
3
2
(dd, JH,H = 10.2, JH,H = 2.6 Hz, 1 H, 1Ј-H), 4.33 (dd, JH,H
=
3
10.2, JH,H = 1.1 Hz, 1 H, 6-H), 4.19–4.08 (m, 1 H, 5-H), 4.10 (d,
Methyl 4,6-O-Benzylidene-2-deoxy-2-[(1R or 1S)-1-O-acetyl-2,5-
benzylimino-2,5-dideoxy-3,4-O-isopropylidene-L-ribitol-1C-yl]-α-D-
2JH,H = 13.2 Hz, 1 H, CH2Ph), 3.97 (t, JH,H = JH,H = 10.2 Hz, 1
2
3
2
H, 6-H), 3.46 (d, JH,H = 13.2 Hz, 1 H, CH2Ph), 3.44 (s, 3 H, ribo-hexopyranosid-3-ulose [(+)-14]: Ac2O (19.4 mg, 0.19 mmol)
OCH3), 3.25 (dd, JH,H = 10.0, JH,H = 5.8 Hz, 1 H, 5Ј-H), 3.13 was added to a solution of (+)-12 (50 mg, 0.095 mmol) in pyridine
2
3
3
3
3
(br. dd, JH,H = 10.2, JH,H = 3.4 Hz, 1 H, 2-H), 3.06 (dd, JH,H
=
=
C
(2 mL) at 20 °C . The resulting mixture was stirred for 45 min. Pyri-
dine was evaporated and the residue was diluted in EtOAc (10 mL)
and in an aq. satd. solution of NaHCO3 (10 mL) and extracted.
3
2
3
5.0, JH,H = 2.6 Hz, 1 H, 2Ј-H), 2.50 (dd, JH,H = 10.0, JH,H
4.7 Hz, 1 H, 5Ј-H), 1.40 (s, 3 H, CH3), 1.29 (s, 3 H, CH3) ppm. 13
NMR (100.6 MHz, CDCl3, 25 °C): δ = 197.4 (s, C-3), 138.9 (s, The organic phase was dried with MgSO4 and the solvent was evap-
1
ArC), 138.5 (s, ArC), 136.6 (s, ArC), 129.3 (d, JC,H = 161 Hz,
orated. FC (light petroleum ether/EtOAc, gradient from 8:2 to 1:1)
gave (+)-14 (7.0 mg, 13%) and (+)-(E)-15 (2.7 mg, 5%) as yellow
solids. Data for (+)-(E)-15: see below. Data for (+)-14: M.p. 80–
1
1
ArC), 128.6 (d, JC,H = 160 Hz, ArC), 128.3 (d, JC,H = 160 Hz,
1
1
ArC), 128.2 (d, JC,H = 160 Hz, ArC), 126.9 (d, JC,H = 162 Hz,
ArC), 126.4 (d, 1JC,H = 157 Hz, ArC), 113.3 [s, C(CH3)2], 102.7 (d,
81 °C. [α]20 = +20 (c = 0.66, CHCl ). IR (NaCl): ν = 2930, 2850,
˜
589
3
1JC,H = 174 Hz, C-1), 101.7 (d, JC,H = 163 Hz, PhCH), 83.2 (d,
1730, 1605, 1495, 1455, 1405, 1370, 1220, 1130, 1090, 1050, 1030,
1
1JC,H = 134 Hz, C-4), 79.5 (d, JC,H = 154 Hz, C-3Ј), 77.3 (d, 1JC,H 910, 850 cm–1. H NMR (400 MHz, CDCl3, 25 °C): δ = 7.57–7.55
1
1
1
1
= 157 Hz, C-4Ј), 69.8 (t, JC,H = 140 Hz, C-6), 69.2 (d, JC,H
143 Hz, C-2Ј), 66.7 (d, JC,H = 142 Hz, C-5), 62.9 (d, JC,H
=
=
(m, 2 H, ArH), 7.41–7.40 (m, 3 H, ArH), 7.34–7.32 (m, 5 H, ArH),
1
1
3
3
5.95 (dd, JH,H = 7.9, JH,H = 5.5 Hz, 1 H, 1Ј-H), 5.65 (s, 1 H,
Eur. J. Org. Chem. 2006, 3845–3855
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3849

E. Rodriguez García, M. A. Brimble, P. Vogel
FULL PAPER
PhCH), 5.55 (s, 1 H, 1-H), 4.89 (dd, 3JH,H = 6.3, J = 4.8 Hz, 1 H,
3
CH2Cl2 (20 mL, 3 times) and after drying the collected organic
fractions with MgSO4, the solvent was evaporated. FC (light petro-
leum ether/EtOAc, 7:3) gave (+)-(E)-15 (210 mg, 34%) and (+)-(Z)-
15 (303 mg, 49%), both as yellow solids. Data for (+)-(E)-15: M.p.
3
3
3Ј-H), 4.62 (d, JH,H = 10.0 Hz, 1 H, 4-H), 4.59 (dd, JH,H = 6.3,
3JH,H = 5.1 Hz, 1 H, 4Ј-H), 4.42 (dd, 2JH,H = 10.0, JH,H = 4.5 Hz,
3
2
3
1 H, 6-H), 4.30 (d, JH,H = 13.4 Hz, 1 H, CH2Ph), 4.19 (dt, JH,H
= 10.0, 3JH,H = 4.5 Hz, 1 H, 5-H), 3.88 (t, 2JH,H = 3JH,H = 10.0 Hz,
1 H, 6-H), 3.61 (d, 3JH,H = 5.5 Hz, 1 H, 2-H), 3.41 (s, 3 H, OCH3),
58–59 °C. [α]20 = +58 (c = 2.5, CHCl ). IR (NaCl): ν = 2985, 2930,
˜
589
3
2830, 1715, 1630, 1495, 1455, 1400, 1380, 1255, 1210, 1150, 1120,
1
2
2
1085, 1050, 1030, 1010, 915 cm–1. H NMR (400 MHz, CDCl3,
3.15 (d, JH,H = 13.4 Hz, 1 H, CH2Ph), 3.06 (d, JH,H = 11.5 Hz,
3
3
25 °C): δ = 7.53–7.28 (m, 10 H, ArH), 6.75 (br. d, 3JH,H = 10.2 Hz,
1 H, 1Ј-H), 5.59 (s, 1 H, PhCH), 5.22 (br. s, 1 H, 1-H), 4.72 (dt,
3JH,H = 6.0, 3JH,H = 3.3 Hz, 1 H, 4Ј-H), 4.46 (dd, 3JH,H = 6.0, 3JH,H
1 H, 5Ј-H), 2.49 (dd, JH,H = 7.9, JH,H = 4.8 Hz, 1 H, 2Ј-H), 2.09
2
3
(dd, JH,H = 11.5, JH,H = 5.1 Hz, 1 H, 5Ј-H), 2.08 (s, 3 H, OC-
OCH3), 1.57 (s, 3 H, CH3), 1.34 (s, 3 H, CH3) ppm. 13C NMR
(100.6 MHz, CDCl3, 25 °C): δ = 199.4 (s, C-3), 169.8 (s, OCOCH3),
138.6, 136.5, 129.4, 128.4, 128.3, 128.2, 127.0, 126.4 (ArC), 111.5
2
3
= 3.4 Hz, 1 H, 3Ј-H), 4.41 (dd, JH,H = 10.0, JH,H = 5.0 Hz, 1 H,
3
3
6-H), 4.30 (dt, JH,H = 10.0, JH,H = 5.0 Hz, 1 H, 5-H), 4.18 (d,
2
3
1
1
3JH,H = 10.0 Hz, 1 H, 4-H), 3.85 (t, JH,H = JH,H = 10.0 Hz, 1 H,
[s, C(CH3)2], 102.4 (d, JC,H = 162 Hz, PhCH), 102.2 (d, JC,H
=
=
=
=
=
=
=
=
2
2
1
1
6-H), 3.77 (d, JH,H = 13.1 Hz, 1 H, CH2Ph), 3.45 (d, JH,H
=
174 Hz, C-1), 82.8 (d, JC,H = 145 Hz, C-4), 80.4 (d, JC,H
1
1
13.1 Hz, 1 H, CH2Ph), 3.43–3.40 (m, 1 H, 2Ј-H), 3.40 (s, 3 H,
155 Hz, C-3Ј), 77.4 (d, JC,H = 156 Hz, C-4Ј), 71.4, (d, JC,H
2
3
1
1
OCH3), 3.21 (dd, JH,H = 10.6, JH,H = 6.0 Hz, 1 H, 5Ј-H), 2.69
154 Hz, C-1Ј), 69.9 (t, JC,H = 145 Hz, C-6), 67.7 (d, JC,H
2
3
1
1
(dd, JH,H = 10.6, JH,H = 3.3 Hz, 1 H, 5Ј-H), 1.57 (s, 3 H, CH3),
142 Hz, C-2Ј), 64.7 (d, JC,H = 152 Hz, C-5), 60.2 (t, JC,H
1
1
1.32 (s, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CDCl3, 25 °C): δ
135 Hz, C-5Ј), 58.9 (t, JC,H = 132 Hz, CH2Ph), 58.8 (d, JC,H
1
1
1
= 189.6 (s, C-3), 142.6 (d, JC,H = 158 Hz, C-1Ј), 138.0 (s, ArC),
136 Hz, C-2), 54.8 (q, JC,H = 143 Hz, OCH3), 26.3 (q, JC,H
1
1
136.6 (s, C-2), 136.5 (s, ArC), 129.3 (d, 1JC,H = 159 Hz, ArC), 128.5
126 Hz, CH3), 25.0 (q, JC,H = 127 Hz, CH3), 21.4 (q, JC,H
1
1
(d, JC,H = 159 Hz, ArC), 128.3 (d, JC,H = 160 Hz, ArC), 128.2
130 Hz, OCOCH3) ppm. UV (MeCN): λmax (ε) = 241 nm
(1800 dm3 mol–1 cm–1). MS (FAB): m/z (%) = 568 (13) [M]+, 508
(7), 308 (6), 232 (9), 219 (4), 154 (100), 136 (66), 120 (13), 91 (22),
89 (16). HRMS (FAB): calcd. for C31H38NO9 568.25466 [M +
H]+; found 568.25489.
1
1
(d, JC,H = 160 Hz, ArC), 127.3 (d, JC,H = 160 Hz, ArC), 126.4
1
1
(d, JC,H = 161 Hz, ArC), 113.0 [s, C(CH3)2], 102.4 (d, JC,H
=
=
=
=
=
=
=
1
1
163 Hz, PhCH), 98.2 (d, JC,H = 170 Hz, C-1), 84.4 (d, JC,H
1
1
158 Hz, C-3Ј), 81.8 (d, JC,H = 140 Hz, C-4), 78.5 (d, JC,H
1
1
156 Hz, C-4Ј), 69.2 (t, JC,H = 147 Hz, C-6), 66.4 (d, JC,H
Methyl 2-Deoxy-2-[(1R or 1S)-2,5-dideoxy-2,5-imino-
L-ribitol-1C-
1
1
139 Hz, C-2Ј), 62.2 (d, JC,H = 152 Hz, C-5), 58.1 (t, JC,H
yl]-α- -allopyranoside [(+)-3]: A degassed mixture of (+)-13 (40 mg,
D
1
1
140 Hz, C-5Ј), 57.0 (t, JC,H = 130 Hz, CH2Ph), 54.9 (q, JC,H
0.076 mmol), PtO2·H2O (2 mg, 10 mol%), one drop of H2SO4 and
MeOH (2 mL) was stirred under H2 (1 atm) at 20 °C for 24 h. After
evaporation of the solvent, FC (MeCN/NH4OH, 4:1) gave (+)-3
1
1
143 Hz, OCH3), 27.2 (q, JC,H = 127 Hz, CH3), 25.0 (q, JC,H
1 2 6 H z , C H 3 ) p p m . U V ( M e C N ) : λ m a x ( ε ) = 2 4 5 n m
(8600 dm3 mol–1 cm–1). MS (EI): m/z (%) = 507 (8) [M]+, 476 (11),
475 (10), 404 (8), 372 (4), 264 (3), 232 (28), 105 (23), 91 (100), 77
(13), 43 (14). HRMS (EI): calcd. for C29H33NO7 507.22570 [M]+;
25
25
25
(14 mg, 60%) as a yellowish oil. [α] = +41, [α] = +43, [α] =
589
577
435
+52 (c = 0.4, MeOH). IR (NaCl): ν = 3350, 2930, 2360, 1590, 1410,
˜
1115, 1045 cm–1. 1H NMR (400 MHz, CD3OD, 25 °C): δ = 4.90
found 507.22624. C29H33NO7 (507.57): calcd. C 68.62, H 6.55;
3
(d, JH,H = 3.2 Hz, 1 H, 1-H), 4.14–4.09 (m, 1 H, 1Ј-H), 4.10 (br.
20
found C 68.57, H 6.56. Data for (+)-(Z)-15: M.p. 64–65 °C. [α]
589
3
3
s, 1 H, 3-H), 3.98 (q, JH,H = 5.5 Hz, 1 H, 3Ј-H), 3.93 (q, JH,H
=
= +93 (c = 0.3, CHCl ). IR (NaCl): ν = 2980, 2925, 2855, 1955,
˜
3
2
3
5.5 Hz, 1 H, 4Ј-H), 3.80 (dd, JH,H = 9.6, JH,H = 4.7 Hz, 1 H, 6-
H), 3.72–3.64 (m, 2 H, 5-H, 6-H), 3.37 (s, 3 H, OCH3), 3.37–3.35
1720, 1660, 1605, 1495, 1455, 1405, 1380, 1300, 1265, 1210, 1155,
1
1120, 1085, 1045, 1030, 1010, 970, 920 cm–1. H NMR (300 MHz,
3
3
(m, 1 H, 4-H) 3.20 (dd, JH,H = 5.5, JH,H = 2.2 Hz, 1 H, 2Ј-H),
CDCl3, 25 °C): δ = 7.55–7.27 (m, 10 H, ArH), 5.85 (d, 3J = 9.7 Hz,
2
3
2
3.14 (dd, JH,H = 12.0, JH,H = 5.5 Hz, 1 H, 5Ј-H), 2.71 (dd, JH,H
3
1 H, 1Ј-H), 5.58 (s, 1 H, PhCH), 5.21 (s, 1 H, 1-H), 4.65 (dt, JH,H
3
2
3
= 12.0, JH,H = 5.5 Hz, 1 H, 5Ј-H), 2.04 (dt, JH,H = 10.6, JH,H
=
3
2
3
= 6.4, JH,H = 4.4 Hz, 1 H, 4Ј-H), 4.40 (dd, JH,H = 10.0, JH,H
=
3.2 Hz, 1 H, 2-H) ppm. 13C NMR (100.6 MHz, CD3OD, 25 °C): δ
3
4.6 Hz, 1 H, 6-H), 4.36–4.29 (m, 2 H, 3Ј-H, 4-H), 4.26 (dt, JH,H
1
1
= 100.5 (d, JC,H = 168 Hz, C-1), 73.6 (d, JC,H = 149 Hz, C-3Ј),
71.8 (d, JC,H = 145 Hz, C-4Ј), 69.7 (d, JC,H = 148 Hz, C-3), 69.3
3
2
= 10.0, JH,H = 4.6 Hz, 1 H, 5-H), 3.93 (d, JH,H = 13.5 Hz, 1 H,
1
1
2
CH2Ph), 3.92–3.85 (m, 2 H, 6-H, 2Ј-H), 3.51 (d, JH,H = 13.5 Hz,
1
1
(d, JC,H = 145 Hz, C-5), 69.0 (d, JC,H = 144 Hz, C-1Ј), 68.8 (d,
1 H, CH2Ph), 3.40 (s, 3 H, OCH3), 3.23 (dd, 2JH,H = 10.2, JH,H
=
3
1JC,H = 142 Hz, C-4), 64.7 (d, JC,H = 140 Hz, C-2Ј), 63.1 (t, JC,H
1
1
6.4 Hz, 1 H, 5Ј-H), 2.43 (dd, 2JH,H = 10.2, 3JH,H = 4.4 Hz, 1 H, 5Ј-
1
1
= 143 Hz, C-6), 55.8 (q, JC,H = 142 Hz, OCH3), 52.7 (t, JC,H
=
H), 1.48 (s, 3 H, CH3), 1.29 (s, 3 H, CH3) ppm. 13C NMR
1
139 Hz, C-5Ј), 47.4 (d, JC,H = 125 Hz, C-2) ppm. UV (MeOH):
λmax (ε) = 207 nm (1000 dm3 mol–1 cm–1). MS (FAB): m/z (%) = 310
(6) [M + H]+, 309 (2) [M]+, 308 (3), 273 (2), 219 (5), 176 (18), 152
(9), 124 (10), 120 (12), 89 (24). HRMS (FAB): calcd. for
C12H24NO8 310.15019 [M + H]+; found 310.14969. C12H23NO8·
3/2H2O (322.16): calcd. C 42.85, H 7.79; found C 43.21, H 7.46.
1
(100.6 MHz, CDCl3, 25 °C): δ = 192.0 (s, C-3), 141.4 (d, JC,H
=
154 Hz, C-1Ј), 138.9 (s, ArC), 138.5 (s, ArC), 136.6 (s, C-2), 129.3
1
1
(d, JC,H = 161 Hz, ArC), 128.6 (d, JC,H = 160 Hz, ArC), 128.3
1
1
(d, JC,H = 160 Hz, ArC), 128.2 (d, JC,H = 160 Hz, ArC), 126.9
(d, 1JC,H = 162 Hz, ArC), 126.4 (d, 1JC,H = 157 Hz, ArC), 113.8 [s,
C(CH3)2], 104.0 (d, 1JC,H = 170 Hz, C-1), 102.0 (d, 1JC,H = 163 Hz,
PhCH), 85.5 (d, 1JC,H = 157 Hz, C-3Ј), 83.8 (d, 1JC,H = 144 Hz, C-
Methyl 4,6-O-Benzylidene-2-deoxy-2-[(1E)-2,5-(benzylimino)-1,2,5-
trideoxy-3,4-O-isopropylidene-L-ribitol-1C-ylidene]-α-D-erythro-
hexopyranosid-3-ulose [(+)-(E)-15] and Methyl 4,6-O-Benzylidene-2-
deoxy-2-[(1Z)-2,5-(benzylimino)-1,2,5-trideoxy-3,4-O-isopropyl-
idene-L-ribitol-1C-ylidene]-α-D-erythro-hexopyranosid-3-ulose [(+)-
(Z)-15]: Compound (+)-12 (640 mg, 1.22 mmol) in CH2Cl2 (8 mL)
was added to a solution of Et2NSF3 (DAST, 480 µL, 3.66 mmol)
in CH2Cl2 (2 mL) at –78 °C. The resulting mixture was warmed to
25 °C over a period of 4 h. Quenching was carried out by addition
of H2O (4 mL) and then dropwise addition of an aq. satd. solution
of NaHCO3 (6 mL). The resulting mixture was extracted with
1
1
4), 78.1 (d, C-4Ј), 69.4 (t, JC,H = 140 Hz, C-6), 66.5 (d, JC,H
=
=
=
=
1
1
142 Hz, C-2Ј), 64.0 (d, JC,H = 151 Hz, C-5), 58.2 (t, JC,H
142 Hz, C-5Ј), 57.7 (t, JC,H = 136 Hz, CH2Ph), 54.8 (q, JC,H
143 Hz, OCH3), 27.3 (q, JC,H = 128 Hz, CH3), 25.5 (q, JC,H
1 2 7 H z , C H ) p p m . U V ( M e C N ) : λ
1
1
1
1
( ε ) =
3
m a x
243 nm(6800 dm3 mol–1 cm–1). MS (EI): m/z (%) = 507 (7) [M]+,
475 (33), 430 (3), 398 (4), 340 (5), 245 (7), 232 (20), 105 (22), 91
(100), 77 (16), 57 (22), 43 (23). HRMS (EI): calcd. for C29H33NO7
507.22570 [M]+; found 507.22559. C29H33NO7 (507.57): calcd. C
68.62, H 6.55; found C 68.44, H 6.58.
3850
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3845–3855

Synthesis of New Aza-C-disaccharides
FULL PAPER
1
1
Methyl 4,6-O-Benzylidene-2-deoxy-2-[(1Z)-2,5-(benzylimino)-1,2,5-
159 Hz, ArC), 128.2 (d, JC,H = 159 Hz, ArC), 127.5 (d, JC,H
=
1
trideoxy-3,4-O-isopropylidene-
L-ribitol-1C-ylidene]-α-D-arabino- 152 Hz, C-1Ј), 126.4 (d, JC,H = 159 Hz, ArC), 114.0 [s, C(CH3)2],
1
1
hexopyranoside [(–)-(Z)-18]: NaBH4 (1.0 mg, 0.027 mmol) was 105.3 (d, JC,H = 170 Hz, C-1), 102.1 (d, JC,H = 160 Hz, PhCH),
1
1
added to a solution of CeCl3 (6.7 mg, 0.027 mmol) and (+)-(E)-15
(14 mg, 0.027 mmol) in MeOH (0.75 mL). After 10 min, the reac-
tion was quenched with an aq. satd. solution of NH4Cl (10 mL)
and the resulting mixture extracted with Et2O (10 mL, 3 times).
The organic phases were dried with MgSO4 and the solvents evapo-
85.9 (d, JC,H = 157 Hz, C-3Ј), 84.7 (d, JC,H = 146 Hz, C-4), 77.2
1
1
(C-3), 70.6 (d, JC,H = 150 Hz, C-4Ј), 69.1 (t, JC,H = 147 Hz, C-
1
1
6), 66.8 (d, JC,H = 139 Hz, C-2Ј), 64.0 (d, JC,H = 149 Hz, C-5),
1
1
57.9 (t, JC,H = 140 Hz, C-5Ј), 57.5 (t, JC,H = 135 Hz, CH2Ph),
1
1
54.8 (q, JC,H = 145 Hz, OCH3), 27.1 (q, JC,H = 128 Hz, CH3),
1
rated. FC (light petroleum ether/EtOAc, 1:1) gave (–)-(Z)-18
25.2 (q, JC,H = 127 Hz, CH3) ppm. UV (MeCN): λmax (ε) = 257
(12 mg, 87%) as a colourless oil. [α] = –19 (c = 0.21, CHCl3).
(1300), 241 nm (1800 dm3 mol–1 cm–1). MS (FAB): m/z (%) = 510
20
589
IR (NaCl): ν = 3435, 2985, 2930, 2860, 1640, 1495, 1455, 1375, (80) [M + H]+, 509 (14) [M]+, 508 (15), 494 (3), 478 (12), 391 (13),
˜
1255, 1210, 1160, 1105, 1090, 1060, 1035, 970 cm–1 1H NMR 360 (3), 232 (12), 219 (5), 120 (16), 167 (9), 149 (28), 120 (20), 91
.
(400 MHz, CDCl3, 25 °C): δ = 7.53–7.30 (m, 10 H, ArH), 5.85 (dd,
(100). HRMS (FAB): calcd. for C29H36NO7 510.24918 [M + H]+;
found 510.24884.
4
3JH,H = 9.5, JH,H = 1.8 Hz, 1 H, 1Ј-H), 5.56 (s, 1 H, PhCH), 5.39
4
(d, JH,H = 1.8 Hz, 1 H, 1-H), 4.70–4.61 (m, 2 H, 4Ј-H, 3-H), 4.37
Methyl 4,6-O-Benzylidene-2-deoxy-2-(1,2,5-trideoxy-2,5-imino-3,4-
O-isopropylidene-L-ribitol-1C-yl)-α-D-glucopyranoside [(+)-19]: A
degassed suspension of (–)-(Z)-18 (75 mg, 0.15 mmol), 10% Pd on
charcoal (156 mg) and EtOAc (15 mL) was stirred under H2 (1 atm)
at 20 °C for 6 h. The mixture was filtered through Celite and the
solvent evaporated. FC (EtOAc) gave (+)-19 (51 mg, 82%) as a
(dd, 3JH,H = 7.0, 3JH,H = 4.8 Hz, 1 H, 3Ј-H), 4.31 (dd, 3JH,H = 10.2,
3
3
3J = 4.8 Hz, 1 H, 6-H), 4.02 (dt, JH,H = 10.2, JH,H = 4.8 Hz, 1
2
2
H, 5-H), 3.87 (d, JH,H = 13.2 Hz, 1 H, CH2Ph), 3.75 (t, JH,H
=
3JH,H = 10.2 Hz, 1 H, 6-H), 3.47–3.40 (m, 2 H, 2Ј-H, 4-H), 3.42 (s,
2
3 H, OCH3), 3.35 (d, 1 H, JH,H = 13.2 Hz, CH2Ph), 3.20 (dd,
3
2
2JH,H = 10.3, JH,H = 6.2 Hz, 1 H, 5Ј-H), 2.48 (dd, JH,H = 10.3,
3JH,H = 4.0 Hz, 1 H, 5Ј-H), 1.54 (s, 3 H, CH3), 1.31 (s, 3 H, CH3)
ppm. 13C NMR (100.6 MHz, CDCl3, 25 °C): δ = 138.3 (s, ArC),
137.5 (s, C-2), 137.2 (s, ArC), 129.8 (d, 1JC,H = 161 Hz, ArC), 128.8
25
25
25
white solid, m.p. 76–77 °C. [α]
= +5, [α]
= +5, [α]
= +9,
589
577
435
[α]25 = +11 (c = 1.35, MeOH). IR (NaCl): ν = 3415, 2930, 2360,
˜
405
1640, 1375, 1060 cm–1. 1H NMR (400 MHz, CDCl3, 25 °C): δ =
7.48–7.46 (m, 2 H, ArH), 7.31–7.29 (m, 3 H, ArH), 5.56 (s, 1 H,
PhCH), 4.71 (t, 3JH,H = 5.0 Hz, 1 H, 4Ј-H), 4.66 (d, 3JH,H = 3.5 Hz,
1
1
(d, JC,H = 162 Hz, ArC), 128.4 (d, JC,H = 159 Hz, ArC), 128.2
1
1
(d, JC,H = 159 Hz, ArC), 127.1 (d, JC,H = 159 Hz, ArC), 126.2
3
2
1 H, 1-H), 4.38 (br. d, JH,H = 5.0 Hz, 1 H, 3Ј-H), 4.16 (dd, JH,H
(d, 1JC,H = 161 Hz, ArC), 124.9 (d, 1JC,H = 140 Hz, C-1Ј), 113.0 [s,
3
= 10.2, JH,H = 4.8 Hz, 1 H, 6-H), 3.76–3.63 (m, 3 H, 5-H, 6-H, 3-
H), 3.43 (t, JH,H = 9.0 Hz, 1 H, 4-H), 3.43 (s, 3 H, OCH3), 3.14
1
1
C(CH3)2], 101.9 (d, JC,H = 158 Hz, PhCH), 97.7 (d, JC,H
169 Hz, C-1), 85.0 (d, JC,H = 155 Hz, C-3Ј), 84.1 (d, JC,H
=
=
3
1
1
3
3
2
(dd, JH,H = 12.0, JH,H = 4.0 Hz, 1 H, 2Ј-H), 2.97 (br. d, JH,H
=
1
145 Hz, C-4), 77.9 (C-3), 69.4 (d, JC,H = 149 Hz, C-4Ј), 69.0 (t,
2
3
13.3 Hz, 1 H, 5Ј-H), 2.93 (dd, JH,H = 13.3, JH,H = 5.0 Hz, 1 H,
1JC,H = 145 Hz, C-6), 66.3 (d, JC,H = 135 Hz, C-2Ј), 62.9 (d, 1JC,H
1
2
3
5Ј-H), 1.83 (m, 1 H, 2-H), 1.61 (ddd, JH,H = 14.8, JH,H = 12.0,
1
1
= 147 Hz, C-5), 58.0 (t, JC,H = 137 Hz, C-5Ј), 56.9 (t, JC,H
135 Hz, CH2Ph), 54.7 (q, JC,H = 143 Hz, OCH3), 27.3 (q, JC,H
=
=
3JH,H = 7.0 Hz, 1 H, 1Ј-H), 1.47 (dt, JH,H = 14.8, JH,H = 4.0 Hz,
2
3
1
1
1 H, 1Ј-H), 1.40 (s, 3 H, CH3), 1.25 (s, 3 H, CH3) ppm. 13C NMR
1
127 Hz, CH3), 25.3 (q, JC,H = 126 Hz, CH3) ppm. UV (MeCN):
λmax (ε) = 206 nm (23000 dm3 mol–1 cm–1). MS (FAB): m/z (%) =
510 (77) [M + H]+, 509 (18) [M]+, 508 (20), 494 (17), 478 (33), 391
(13), 360 (5), 232 (10), 120 (16), 91 (100). HRMS (FAB): calcd. for
C29H36NO7 510.24918 [M + H]+; found 510.24725.
1
(100.6 MHz, CDCl3, 25 °C): δ = 139.4 (s, ArC), 129.9 (d, JC,H
=
=
1
1
160 Hz, ArC), 129.1 (d, JC,H = 160 Hz, ArC), 127.6 (d, JC,H
162 Hz, ArC), 112.3 [s, C(CH3)2], 103.2 (d, 1JC,H = 163 Hz, PhCH),
102.8 (d, 1JC,H = 170 Hz, C-1), 87.7 (d, 1JC,H = 154 Hz, C-3Ј), 84.8
1
1
(d, JC,H = 142 Hz, C-4), 82.8 (d, JC,H = 158 Hz, C-4Ј), 71.2 (d,
1
1
1JC,H = 142 Hz, C-3), 70.2 (t, JC,H = 145 Hz, C-6), 64.9 (d, JC,H
Methyl 4,6-O-Benzylidene-2-deoxy-2-[(1E)-2,5-(benzylimino)-1,2,5-
trideoxy-3,4-O-isopropylidene-L-ribitol-1C-ylidene]-α-D-arabino-
1
1
= 143 Hz, C-2Ј), 63.9 (d, JC,H = 148 Hz, C-5), 55.5 (q, JC,H
=
=
=
1
1
142 Hz, OCH3), 51.4 (t, JC,H = 140 Hz, C-5Ј), 47.4 (d, JC,H
hexopyranoside [(+)-(E)-18]: NaBH4 (0.5 mg, 0.013 mmol) was
added to a solution of CeCl3 (3.2 mg, 0.013 mmol) and (+)-(Z)-15
(6.7 mg, 0.013 mmol) in MeOH (0.5 mL). After 10 min, the reac-
tion was quenched with an aq. satd. solution of NH4Cl (10 mL)
and the resulting mixture extracted with Et2O (10 mL, 3 times).
The organic phases were dried with MgSO4 and the solvents evapo-
1
1
128 Hz, C-2), 31.2 (t, JC,H = 126 Hz, C-1Ј), 26.5 (q, JC,H
1
127 Hz, CH3), 24.2 (q, JC,H = 126 Hz, CH3) ppm. UV (MeCN):
λmax (ε) = 204 (3600), 194 nm (3800 dm3 mol–1 cm–1). HRMS
(MALDI-TOF): calcd. for C22H31NNaO7 444.1998 [M + Na]+;
found 444.1947.
rated. FC (light petroleum ether/EtOAc, 1:1) gave (+)-(E)-18
Methyl 2-Deoxy-2-(1,2,5-trideoxy-2,5-imino-3,4-O-isopropylidene-
L-ribitol-1C-yl)-α-D-glucopyranoside [(+)-20]: A degassed mixture
20
(1.5 mg, 20%) as a colourless oil. [α] = +22 (c = 0.15, CHCl3).
589
IR (NaCl): ν = 3435, 2925, 2850, 1725, 1650, 1495, 1455, 1375, of (+)-19 (20 mg, 0.047 mmol), PtO2·H2O (2 mg, 15 mol%) and
˜
1335, 1260, 1210, 1175, 1155, 1125, 1090, 1060, 970 cm–1. 1H NMR
MeOH (3 mL) was stirred under H2 (1 atm) at 20 °C for 3 h. The
resulting suspension was filtered through Celite and the solution
evaporated. FC (MeCN/NH4OH, 9:1) gave (+)-20 (12 mg, 76%) as
(300 MHz, CDCl3, 25 °C): δ = 7.56–7.26 (m, 10 H, ArH), 5.80 (dd,
4
3JH,H = 8.0, JH,H = 1.8 Hz, 1 H, 1Ј-H), 5.53 (s, 1 H, PhCH), 4.90
(s, 1 H, 1-H), 4.76–4.70 (m, 2 H, 4Ј-H, 3-H), 4.64 (dd, 3JH,H = 6.9,
a white solid, m.p. 71–72 °C. [α]
= +26, [α]
= +27, [α]
=
25
25
25
589
577
435
3
25
3JH,H = 5.5 Hz, 1 H, 3Ј-H), 4.29 (dd, 3JH,H = 10.1, JH,H = 4.8 Hz,
+48, [α]
= +58 (c = 0.5, MeOH). IR (NaCl): ν = 3400, 3110,
˜
405
2
3
1 H, 6-H), 4.04 (d, JH,H = 13.2 Hz, 1 H, CH2Ph), 3.98 (dt, JH,H 3040, 2360, 1405, 1055 cm–1. 1H NMR (400 MHz, CD3OD, 25 °C):
= 10.1, 3JH,H = 4.8 Hz, 1 H, 5-H), 3.72 (t, 2JH,H = 3JH,H = 10.1 Hz,
δ = 4.96 (br. t, JH,H = 6.0 Hz, 1 H, 4Ј-H), 4.67 (br. s, 1 H, 1-H),
3
3
3
3
3
1 H, 6-H), 3.51 (dd, JH,H = 8.0, JH,H = 5.5 Hz, 1 H, 2Ј-H), 3.46
4.66 (br. d, JH,H = 6.0 Hz, 1 H, 3Ј-H), 3.87 (br. dd, JH,H = 9.5,
(t, JH,H = 10.1 Hz, 1 H, 4-H), 3.40 (s, 3 H, OCH3), 3.39 (d, JH,H 3JH,H = 6.0 Hz, 1 H, 3-H), 3.79 (dd, JH,H = 11.0, JH,H = 2.2 Hz,
3
2
2
3
2
3
2
3
= 13.2 Hz, 1 H, CH2Ph), 3.25 (dd, JH,H = 10.3, JH,H = 6.2 Hz, 1
1 H, 6-H), 3.67 (dd, JH,H = 11.0, JH,H = 5.4 Hz, 1 H, 6-H), 3.57
2
3
3
H, 5Ј-H), 2.38 (dd, JH,H = 10.3, JH,H = 4.9 Hz, 1 H, 5Ј-H), 1.51 (br. t, JH,H = 9.5 Hz, 1 H, 2Ј-H), 3.52–3.40 (m, 3 H, 5Ј-H, 5Ј-H,
(s, 3 H, CH3), 1.30 (s, 3 H, CH3) ppm. 13C NMR (75.5 MHz,
5-H), 3.23 (s, 3 H, OCH3), 3.24 (dd, JH,H = 11.0, JH,H = 6.0 Hz,
1 H, 4-H), 1.80–1.76 (m, 3 H, 2-H, 1Ј-H, 1Ј-H), 1.49 (s, 3 H, CH3),
1.30 (s, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CD3OD, 25 °C):
3
3
1
CDCl3, 25 °C): δ = 141.7 (s, ArC), 136.9 (s, C-2), 129.0 (d, JC,H
161 Hz, ArC), 128.8 (d, JC,H = 162 Hz, ArC), 128.5 (d, JC,H
=
=
1
1
Eur. J. Org. Chem. 2006, 3845–3855
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3851

E. Rodriguez García, M. A. Brimble, P. Vogel
FULL PAPER
1
1
1
δ = 113.2 [s, C(CH3)2], 102.2 (d, JC,H = 170 Hz, C-1), 84.7 (d,
83.7 (d, JC,H = 149 Hz, C-4), 82.7 (d, JC,H = 157 Hz, C-3Ј), 78.8
1
1
1JC,H = 161 Hz, C-3Ј), 79.2 (d, 1JC,H = 161 Hz, C-4Ј), 74.8 (d, 1JC,H
(d, JC,H = 157 Hz, C-4Ј), 72.1, (d, JC,H = 137 Hz, C-2), 69.7 (t,
1
1
1
1
= 140 Hz, C-3), 73.7 (d, JC,H = 139 Hz, C-5), 72.7 (d, JC,H
=
=
=
=
=
1JC,H = 145 Hz, C-6), 67.5 (d, JC,H = 146 Hz, C-5), 58.6 (t, JC,H
1
1
1
1
143 Hz, C-4), 66.2 (d, JC,H = 147 Hz, C-2Ј), 62.6 (t, JC,H
= 141 Hz, CH2Ph), 58.3 (t, JC,H = 137 Hz, C-5Ј), 56.2 (q, JC,H
143 Hz, OCH3), 54.7 (d, JC,H = 142 Hz, C-2Ј), 46.2 (d, JC,H
145 Hz, C-1Ј), 27.4 (q, JC,H = 127 Hz, CH3), 25.3 (q, JC,H
=
=
=
1
1
1
1
144 Hz, C-6), 55.4 (q, JC,H = 141 Hz, OCH3), 50.2 (t, JC,H
1
1
1
1
149 Hz, C-5Ј), 45.6 (d, JC,H = 127 Hz, C-2), 29.8 (t, JC,H
1
1
133 Hz, C-1Ј), 26.1 (q, JC,H = 128 Hz, CH3), 24.0 (q, JC,H
126 Hz, CH3) ppm. UV (MeCN): λmax (ε) = 257 (12500), 207
(32800), 202 nm (30300 dm3 mol–1 cm–1). HRMS (MALDI-TOF):
calcd. for C35H40NO7S 618.2525 [M + H]+; found 618.2589.
1 2 7 H z , C H 3 ) p p m . U V ( M e C N ) : λ m a x ( ε ) = 1 9 7 n m
(1400 dm3 mol–1 cm–1). HRMS (MALDI-TOF): calcd. for
C15H28NO7 334.1866 [M + H]+; found 334.1864.
C
35H39NO7S·3/2H2O: calcd. C 65.20, H 6.57, N 2.17; found C
65.10, H 6.37, N 1.93.
Methyl 2-Deoxy-2-(1,2,5-trideoxy-2,5-imino-L-ribitol-1C-yl)-α-D-
glucopyranoside [(+)-4]: Acetonide (+)-20 (10 mg, 0.033 mmol) was
dissolved in CF3COOH/H2O (4:1, 9.0 mL) at 20 °C. The reaction
was monitored by TLC and after 1 h, the solvent was evaporated.
Methyl 4,6-O-Benzylidene-2-deoxy-2-[(1R or 1S)-2,5-(benzylimino)-
1,2,5-trideoxy-3,4-O-isopropylidene-1-(phenylthio)-L-ribitol-1C-yl]-
α-D-allopyranoside [(+)-22]: NaBH4 (15 mg, 0.40 mmol) was added
FC (MeCN/NH4OH, 4:1) yielded (+)-4 (8.6 mg, 89%) as a white portionwise to a solution of (+)-21 (125 mg, 0.20 mmol) in EtOH
250
25
25
solid, m.p. 65–66 °C. [α]
= +48, [α]
= +53, [α] = +96,
˜
(5 mL) at 0 °C. After 1 h at 0 °C, an aq. satd. solution of NH4Cl
(10 mL) was added and the resulting mixture was extracted with
CH2Cl2 (15 mL, 3 times). The organic phases were combined, dried
with MgSO4 and the solvent was evaporated. FC (pentane/EtOAc,
589
577
435
[α]25 = +117 (c = 0.21, MeOH). IR (NaCl): ν = 3150, 2360, 1405,
405
1055 cm–1. 1H NMR (400 MHz, CD3OD, 25 °C): δ = 4.69 (d, 3JH,H
3
3
= 3.2 Hz, 1 H, 1-H), 4.20 (br. dd, JH,H = 4.8, JH,H = 3.9 Hz, 1
H, 4Ј-H), 3.84 (dd, JH,H = 8.2, JH,H = 3.9 Hz, 1 H, 3Ј-H), 3.79 8:2) gave (+)-22 (119 mg, 95%) as a white solid, m.p. 98–99 °C. [α]
(dd, JH,H = 11.8, JH,H = 2.2 Hz, 1 H, 6-H), 3.68 (dd, JH,H
3
3
2
3
2
25
25
25
25
=
= +49, [α]
= +53, [α]
= +112, [α]
= +142 (c = 0.55,
589
577
435
405
3
3
3
11.8, JH,H = 5.4 Hz, 1 H, 6-H), 3.54 (br. dd, JH,H = 10.0, JH,H
= 9.2 Hz, 1 H, 3-H), 3.51–3.41 (m, 3 H, 5-H, 5Ј-H, 2Ј-H), 3.34 (s,
CHCl ). IR (NaCl): ν = 3455, 3060, 2930, 1950, 1010, 1735, 1580,
˜
3
1450, 1375, 1210, 1100, 865 cm–1. H NMR (400 MHz, CDCl3,
1
3 H, OCH3), 3.25 (t, 3JH,H = 10.0 Hz, 1 H, 4-H), 3.20 (br. d, JH,H
25 °C): δ = 7.53 (dd, JH,H = 7.9, J = 2.8 Hz, 2 H, ArH), 7.51 (br.
2
3
2
2
3
3
3
= 11.8 Hz, 1 H, 5Ј-H), 2.01 (ddd, JH,H = 15.1, JH,H = 5.5, JH,H d, JH,H = 8.2 Hz, 2 H, ArH), 7.41–7.38 (m, 3 H, ArH), 7.29–7.26
3
= 3.2 Hz, 1 H, 1Ј-H), 1.90–1.82 (m, 1 H, 1Ј-H), 1.78 (dq, JH,H
=
(m, 2 H, ArH), 7.21–7.16 (m, 4 H, ArH), 6.90–6.87 (m, 2 H, ArH),
9.2, JH,H = 3.2 Hz, 1 H, 2-H) ppm. 13C NMR (100.6 MHz,
5.67 (s, 1 H, PhCH), 5.37 (d, JH,H = 3.0 Hz, 1 H, 1-H), 4.69 (q,
3
3
1
1
3
3
CD3OD, 25 °C): δ = 101.5 (d, JC,H = 167 Hz, C-1), 77.4 (d, JC,H
3JH,H = 6.1 Hz, 1 H, 4Ј-H), 4.62 (dd, JH,H = 6.1, JH,H = 3.5 Hz,
1
1
2
3
= 143 Hz, C-3Ј), 74.3 (d, JC,H = 139 Hz, C-3), 73.8 (d, JC,H
=
=
=
=
=
1 H, 3Ј-H), 4.53 (br. s, 1 H, 3-H), 4.39 (dd, JH,H = 10.0, JH,H =
5.0 Hz, 1 H, 6-H), 4.20 (dt, JH,H = 10.0, J = 5.0 Hz, 1 H, 5-H),
4.06 (dd, JH,H = 11.9, JH,H = 2.1 Hz, 1 H, 1Ј-H), 3.94 (d, JH,H
= 13.1 Hz, 1 H, CH2Ph), 3.83 (t, JH,H = JH,H = 10.0 Hz, 1 H, 6-
H), 3.65 (dd, JH,H = 2.6, JH,H = 10.0 Hz, 1 H, 4-H), 3.41 (br. s,
1 H, 2Ј-H), 3.30 (d, JH,H = 13.2 Hz, 1 H, CH2Ph), 3.21 (s, 3 H,
OCH3), 3.19 (dd, JH,H = 10.0, JH,H = 6.1 Hz, 1 H, 5Ј-H), 2.93
(d, JH,H = 7.6 Hz, 1 H, 3-OH), 2.34 (dd, JH,H = 10.0, JH,H
6.1 Hz, 1 H, 5Ј-H), 2.25 (dt, JH,H = 11.9, JH,H = 3.0 Hz, 1 H, 2-
H), 1.48 (s, 3 H, CH3), 1.34 (s, 3 H, CH3) ppm. 13C NMR
(100.6 MHz, CDCl3, 25 °C): δ = 138.3, 137.4, 137.3, 130.3, 129.2,
129.0, 128.6, 128.3, 128.0, 126.7, 126.3 (ArC), 113.1 [s, C(CH3)2],
102.1 (d, 1J = 165 Hz, PhCH), 100.3 (d, 1JC,H = 174 Hz, C-1), 82.1
1
1
3
3
138 Hz, C-5), 72.9 (d, JC,H = 141 Hz, C-4), 70.8 (d, JC,H
1
1
3
3
2
153 Hz, C-4Ј), 62.7 (t, JC,H = 145 Hz, C-6), 61.4 (d, JC,H
1
1
2
3
140 Hz, C-2Ј), 55.4 (q, JC,H = 142 Hz, OCH3), 50.5 (t, JC,H
1
1
3
3
146 Hz, C-5Ј), 45.5 (d, JC,H = 124 Hz, C-2), 30.9 (t, JC,H
2
1 2 9 H z , C - 1 Ј ) p p m . U V ( M e O H ) : λ m a x ( ε ) = 2 0 5 n m
(900 dm3 mol–1 cm–1). HRMS (MALDI-TOF): calcd. for
C12H23NNaO7 316.1372 [M + Na]+; found 316.1381.
2
3
3
2
3
=
3
3
Methyl 4,6-O-Benzylidene-2-deoxy-2-[(1R or 1S)-2,5-(benzylimino)-
1,2,5-trideoxy-3,4-O-isopropylidene-1-(phenylthio)-
α- -ribo-hexopyranosid-3-ulose [(+)-21]: Et3N (14 µL, 0.10 mmol)
L-ribitol-1C-yl]-
D
was added to a solution of (+)-(Z)-15 (115 mg, 0.23 mmol) and
thiophenol (30 µL, 0.29 mmol) in CH2Cl2 (5 mL) at 0 °C and the
resulting solution was stirred at 0 °C for 1 h. The reaction was
quenched by addition of an aq. satd. solution of NH4Cl (10 mL)
and extracted with CH2Cl2 (10 mL, 3 times). The combined organic
layers were dried with MgSO4 and after evaporation FC (light pe-
troleum ether/EtOAc, 8:2) gave (+)-21 (127 mg, 91%) as a white
1
1
(d, JC,H = 153 Hz, C-3Ј), 79.6 (d, JC,H = 138 Hz, C-4), 78.6 (d,
1JC,H = 156 Hz, C-4Ј), 69.8 (d, 1JC,H = 137 Hz, C-2Ј) 69.4 (t, JC,H
1
1
1
= 143 Hz, C-6), 66.4 (d, JC,H = 152 Hz, C-3), 58.5 (t, JC,H
138 Hz, C-5Ј), 58.3 (t, JC,H = 139 Hz, CH2Ph), 58.1 (d, JC,H
146 Hz, C-5), 55.3 (q, JC,H = 143 Hz, OCH3), 48.9 (d, JC,H
143 Hz, C-1Ј), 46.2 (d, JC,H = 127 Hz, C-2), 27.6 (q, JC,H
127 Hz, CH3), 25.5 (q, JC,H = 126 Hz, CH3) ppm. UV (MeOH):
λmax (ε) = 260 (5100), 212 nm (8800 dm3 mol–1 cm–1). HRMS
(MALDI-TOF): calcd. for C35H42NO7S 620.2682 [M + H]+; found
620.2645.
=
=
=
=
1
1
1
1
1
1
25
25
25
solid, m.p. 92–93 °C. [α] = +74, [α] = +78, [α] = +158 (c =
589
577
435
1
1.56, CHCl ). IR (NaCl): ν = 2935, 2870, 1740, 1580, 1450, 1375,
˜
3
1255, 1210, 1110, 1075, 1030, 965, 865 cm–1.1H NMR (400 MHz,
3
CDCl3, 25 °C): δ = 7.56–7.54 (m, 2 H, ArH), 7.50 (br. d, JH,H
7.5 Hz, 2 H, ArH), 7.40–7.38 (m, 3 H, ArH), 7.30–7.18 (m, 6 H,
=
3
3
ArH), 6.97 (br. t, JH,H = 3.4 Hz, 2 H, ArH), 5.62 (br. d, JH,H
=
Methyl 2-Deoxy-2-[(1R or 1S)-2,5-(benzylimino)-1,2,5-trideoxy-3,4-
4.3 Hz, 1 H, 1-H), 5.61 (br. s, 1 H, PhCH), 4.66 (q, 3JH,H = 4.5 Hz,
O-isopropylidene-1-(phenylthio)-L-ribitol-1C-yl]-α-D-allopyranoside
3
3
1 H, 4Ј-H), 4.58 (dd, JH,H = 6.5, JH,H = 4.5 Hz, 1 H, 3Ј-H), 4.39 [(+)-23]: PtO2·H2O (5 mg, 10 mol%) and a drop of H2SO4 were
(dd, JH,H = 10.0, JH,H = 4.4 Hz, 1 H, 6-H), 4.34 (d, JH,H
2
3
3
=
added to a solution of (+)-22 (100 mg, 0.19 mmol) in MeOH
9.5 Hz, 1 H, 4-H), 4.14–4.00 (m, 3 H, 1Ј-H, 5-H, CH2Ph), 3.99 (t,
(10 mL). The resulting suspension was stirred under H2 (1 atm) at
2JH,H = 3JH,H = 10.0 Hz, 1 H, 6-H), 3.44 (d, 3JH,H = 13.3 Hz, 1 H, 20 °C overnight. The catalyst was filtered off (Celite) and the solu-
CH2Ph), 3.20–3.10 (m, 3 H, 2-H, 5Ј-H, 2Ј-H), 3.09 (s, 3 H, OCH3), tion concentrated. FC (EtOAc) gave (+)-23 (69 mg, 80%) as a white
2
3
25
25
25
2.37 (dd, JH,H = 10.4, JH,H = 4.5 Hz, 1 H, 5Ј-H), 1.45 (s, 3 H, solid, m.p. 79–80 °C. [α]
= +50, [α]
= +60, [α]
= +118,
589
577
435
CH3), 1.32 (s, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CDCl3,
[α]25 = +145 (c = 0.15, MeOH). IR (NaCl): ν = 3455, 3060, 2925,
˜
405
25 °C): δ = 197.8 (s, C-3), 138.9, 136.9, 136.5, 129.8, 129.3, 129.0, 2855, 1645, 1580, 1450, 1375, 1250, 1210, 1150, 1110, 1045, 980,
128.5, 128.3, 128.0, 126.7, 126.4, 126.3 (ArC), 112.8 [s, C(CH3)2],
104.1 (d, JC,H = 176 Hz, C-1), 101.9 (d, JC,H = 162 Hz, PhCH),
860 cm–1. 1H NMR (400 MHz, CD3OD, 25 °C): δ = 7.49 (br. d,
1
1
3
3JH,H = 7.5 Hz, 2 H, ArH), 7.24 (t, JH,H = 7.5 Hz, 2 H, ArH),
3852
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 3845–3855

Synthesis of New Aza-C-disaccharides
7.15 (m, 1 H, ArH), 7.09–7.07 (m, 3 H, ArH), 6.78 (dd, JH,H
FULL PAPER
1 H, 2Ј-H), 2.89 (br. d, JH,H = 12.0 Hz, 1 H, 5Ј-H), 2.00 (ddd, J
3
3
3
=
4
3
3
3
6.3, JH,H = 2.6 Hz, 2 H, ArH), 5.27 (d, JH,H = 3.0 Hz, 1 H, 1- = 13.6, JH,H = 7.0, JH,H = 3.1 Hz, 1 H, 2-H), 1.97–1.91 (m, 1 H,
3
2
3
H), 4.62–4.60 (m, 2 H, 3Ј-H, 4Ј-H), 4.25 (br. t, JH,H = 3.0 Hz, 1
1Ј-H), 1.69 (dt, JH,H = 14.7, JH,H = 7.0 Hz, 1 H, 1Ј-H) ppm. 13C
3
3
1
H, 3-H), 4.03 (dd, JH,H = 11.8, JH,H = 3.0 Hz, 1 H, 1Ј-H), 3.86–
NMR (100.6 MHz, CD3OD, 25 °C): δ = 101.5 (d, JC,H = 168 Hz,
3
3
1
1
3.69 (m, 4 H, 5-H, 6-H, CH2Ph), 3.43 (dd, JH,H = 10.0, JH,H
3.0 Hz, 1 H, 4-H), 3.32 (t, 3JH,H = 3.0 Hz, 1 H, 2Ј-H), 3.19 (s, 3 H,
OCH3), 3.18 (d, 2JH,H = 13.2 Hz, 1 H, CH2Ph), 3.07–3.03 (m, 1 H, 69.0 (d, JC,H = 143 Hz, C-4), 63.0 (t, JC,H = 142 Hz, C-6), 60.2
=
C-1), 78.7 (d, JC,H = 145 Hz, C-3Ј), 72.1 (d, JC,H = 148 Hz, C-
1
1
4Ј), 71.8 (d, JC,H = 147 Hz, C-3), 69.4 (d, JC,H = 144 Hz, C-5),
1
1
2
3
1
5Ј-H), 2.24 (dd, JH,H = 9.7, JH,H = 4.6 Hz, 1 H, 5Ј-H), 2.07 (dt,
(d, 1JC,H = 140 Hz, C-2Ј), 55.8 (q, JC,H = 142 Hz, OCH3), 52.0 (t,
3JH,H = 11.8, JH,H = 3.0 Hz, 1 H, 2-H), 1.47 (s, 3 H, CH3), 1.27
1JC,H = 142 Hz, C-5Ј), 41.7 (d, JC,H = 124 Hz, C-2), 32.0 (t, JC,H
3
1
1
(s, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CD3OD, 25 °C): δ = = 125 Hz, C-1Ј) ppm. UV (MeOH): λm a x (ε) = 206 nm
139.6, 139.2, 131.4, 130.1, 129.8, 129.0, 127.9, 127.3 (ArC), 114.4
(600 dm3 mol–1 cm–1). HRMS (MALDI-TOF): calcd. for
C
1 2 H 2 4 N O 7 [ M + H ] + 2 9 4 . 1 5 5 3 ; f o u n d 2 9 4 . 1 5 6 2 .
C12H23NO7·2H2O: calcd. C 43.76, H 8.26; found C 43.28, H 8.00.
1
1
[s, C(CH3)2], 100.9 (d, JC,H = 169 Hz, C-1), 83.4 (d, JC,H
=
=
=
1
1
154 Hz, C-3Ј), 79.7 (d, JC,H = 157 Hz, C-4Ј), 71.2 (d, JC,H
1
1
132 Hz, C-2Ј), 69.9 (d, JC,H = 145 Hz, C-3), 69.3 (d, JC,H
Methyl 2-Deoxy-2-[(1R or 1S)-1,2,5-trideoxy-2,5-imino-3,4-O-iso-
propylidene-1-(phenylthio)-L-ribitol-1C-yl]-α-D-allopyranoside [(+)-
138 Hz, C-5), 69.0 (d, 1JC,H = 140 Hz, C-4), 63.0 (t, 1JC,H = 142 Hz,
1
1
C-6), 59.7 (t, JC,H = 139 Hz, C-5Ј), 59.2 (t, JC,H = 130 Hz,
25]: A degassed mixture of (+)-23 (60 mg, 0.11 mmol), Pd on char-
coal (100 mg) and EtOAc was stirred under H2 (1 atm) at 20 °C.
The reaction was monitored by TLC and after 6 h, only starting
material was observed. More Pd on charcoal (300 mg) was added
and the suspension was left at 20 °C overnight. The catalyst was
filtered off (Celite) and the solvent evaporated. FC (MeCN/
NH4OH, 10:1) yielded (+)-23 (32.4 mg, 54%), (+)-25 (1.9 mg, 4%)
and (+)-24 (11 mg, 29%). Data for (+)-25: White solid, m.p. 64–
1
1
CH2Ph), 55.5 (q, JC,H = 143 Hz, OCH3), 49.8 (d, JC,H = 144 Hz,
C-1Ј), 47.1 (d, 1JC,H = 126 Hz, C-2), 27.9 (q, 1JC,H = 127 Hz, CH3),
1
25.6 (q, JC,H = 126 Hz, CH3) ppm. UV (MeOH): λmax (ε) = 260
(13800), 212 nm (20900 dm3 mol–1 cm–1). HRMS (MALDI-TOF):
calcd. for C28H37NNaO7S 554.2188 [M + Na]+; found 554.2190.
Methyl 2-Deoxy-2-(1,2,5-trideoxy-2,5-imino-3,4-O-isopropylidene-
L
-ribitol-1C-yl)-α-D-allopyranoside [(+)-24]: A solution of (+)-23
65 °C. [α]25 = +41, [α]25 = +50 (c = 0.07, MeOH). IR (NaCl): ν
(17 mg, 0.032 mmol) in MeOH (3 mL) was treated with Raney Ni
(200 mg) and stirred at 20 °C for 75 min. The resulting suspension
was filtered through Celite and the solid was washed with MeOH.
The solvent was evaporated. FC (MeCN/NH4OH, 9:1) gave (+)-24
˜
589
577
= 3385, 2925, 2360, 1450, 1410, 1210, 1045, 980 cm–1. 1H NMR
(400 MHz, CD3OD, 25 °C): δ = 7.48 (br. d, 3J = 7.5 Hz, 2 H, ArH),
3
3
7.30 (br. t, JH,H = 7.5 Hz, 2 H, ArH), 7.20 (br. t, JH,H = 7.5 Hz,
25
25
3
3
(7.5 mg, 71%) as a white solid, m.p. 69–70 °C. [α] = +20, [α]
1 H, ArH), 5.12 (d, JH,H = 3.0 Hz, 1 H, 1-H), 4.67 (dt, JH,H
=
=
589
577
= +22, [α]25 = +40, [α]25 = +48 (c = 0.6, MeOH). IR (NaCl): ν
3
3
3
˜
6.1, JH,H = 3.5 Hz, 1 H, 4Ј-H), 4.59 (dd, JH,H = 6.1, JH,H
435
405
= 3140, 3040, 2360, 1405, 1050, 980 cm–1. 1H NMR (400 MHz,
3
3.5 Hz, 1 H, 3Ј-H), 4.21 (br. t, JH,H = 3.0 Hz, 1 H, 3-H), 3.82–
3.77 (m, 2 H, 1Ј-H, 6-H), 3.70–3.68 (m, 2 H, 5-H, 6-H), 3.63 (t,
3
CD3OD, 25 °C): δ = 4.97 (br. t, JH,H = 5.0 Hz, 1 H, 4Ј-H), 4.69
(br. d, JH,H = 5.0 Hz, 1 H, 3Ј-H), 4.63 (d, JH,H = 3.4 Hz, 1 H, 1-
3
3
3
3
3JH,H = 3.5 Hz, 1 H, 2Ј-H), 3.40 (dd, JH,H = 9.6, J = 3.0 Hz, 1
3
2
3
H), 3.90 (br. t, JH,H = 2.5 Hz, 1 H, 3-H), 3.85–3.81 (m, 2 H, 2Ј-
H, 4-H), 3.34 (dd, JH,H = 12.5, J = 6.1 Hz, 1 H, 5Ј-H), 2.95 (s, 3
2
3
H, OCH3), 2.86 (dd, 2JH,H = 12.5, 3JH,H = 3.5 Hz, 1 H, 5Ј-H), 2.07
H, 6-H), 3.76–3.69 (m, 2 H, 5-H, 6-H), 3.52 (dd, JH,H = 13.3, J
3
3
3
= 5.0 Hz, 1 H, 5Ј-H), 3.49 (br. d, JH,H = 10.0 Hz, 1 H, 4-H), 3.45
(dt, JH,H = 11.5, JH,H = 3.0 Hz, 1 H, 2-H), 1.46 (s, 3 H, CH3),
1.29 (s, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CD3OD, 25 °C):
(br. d, 2JH,H = 13.3 Hz, 1 H, 5Ј-H), 3.37 (s, 3 H, OCH3), 2.07–2.01
2
1
1
(m, 1 H, 2-H), 1.98–1.90 (m, 1 H, 1Ј-H), 1.80 (ddd, JH,H = 14.4,
δ = 137.6 (s, ArC), 131.5 (d, JC,H = 163 Hz, ArC), 130.3 (d, JC,H
3JH,H = 9.8, JH,H = 6.0 Hz, 1 H, 1Ј-H), 1.50 (s, 3 H, CH3), 1.31
3
1
= 162 Hz, ArC), 128.0 (d, JC,H = 162 Hz, ArC), 115.2 [s,
(s, 3 H, CH3) ppm. 13C NMR (100.6 MHz, CD3OD, 25 °C): δ =
1
1
C(CH3)2], 100.7 (d, JC,H = 170 Hz, C-1), 84.3 (d, JC,H = 155 Hz,
113.6 [s, C(CH3)2], 101.3 (d, 1JC,H = 169 Hz, C-1), 83.8 (d, JC,H
=
=
=
=
=
=
=
1
1
1
C-3Ј), 83.2 (d, JC,H = 152 Hz, C-4Ј), 69.5 (d, JC,H = 150 Hz, C-
1
1
1
1
161 Hz, C-3Ј), 79.4 (d, JC,H = 160 Hz, C-4Ј), 70.0 (d, JC,H
147 Hz, C-3), 69.3 (d, JC,H = 148 Hz, C-5), 68.8 (d, JC,H
142 Hz, C-4), 63.9 (d, JC,H = 149 Hz, C-2Ј), 62.9 (t, JC,H
141 Hz, C-6), 55.8 (q, JC,H = 142 Hz, OCH3), 50.5 (t, JC,H
141 Hz, C-5Ј), 40.9 (d, JC,H = 126 Hz, C-2), 26.8 (t, JC,H
128 Hz, C-1Ј), 26.2 (q, JC,H = 127 Hz, CH3), 24.1 (q, JC,H
3), 69.3 (d, JC,H = 142 Hz, C-5), 68.8 (d, JC,H = 140 Hz, C-4),
1
1
1
1
66.2 (d, JC,H = 140 Hz, C-2Ј), 63.0 (t, JC,H = 157 Hz, C-6), 55.2
1
1
(q, 1JC,H = 143 Hz, OCH3), 53.1 (t, 1JC,H = 143 Hz, C-5Ј), 51.8 (d,
1
1
1
1JC,H = 140 Hz, C-1Ј), 48.5 (C-2), 27.4 (q, JC,H = 126 Hz, CH3),
1
1
1
25.1 (q, JC,H = 127 Hz, CH3) ppm. UV (MeOH): λmax (ε) =
1
1
255 (11400), 207 nm (15100 dm3 mol–1 cm–1). HRMS (MALDI-
TOF): calcd. for C21H31NNaO7S 464.1719 [M + Na]+; found
464.1700.
1 2 6 H z , C H 3 ) p p m . U V ( M e O H ) : λ m a x ( ε ) = 2 0 5 n m
(1000 dm3 mol–1 cm–1). HRMS (MALDI-TOF): calcd. for
C15H28NO7 334.1866 [M + H]+; found 334.1848.
Supporting Information (see footnote on the first page of the arti-
cle): 1H NMR (400 MHz) spectra of (+)-11, (+)-12, (+)-13, (+)-14,
(+)-(Z)-15, (+)-(E)-15, (–)-(Z)-18, (+)-(E)-18, (+)-19, (+)-20, (+)-
21, (+)-22, (+)-23, (+)-24, (+)-25, (+)-3, (+)-4, (+)-5; 13C NMR
(100.6 MHz) spectra of (+)-3, (+)-4, (+)-5, (+)-25, (+)-13, (+)-14,
(+)-(Z)-18, (–)-(E)-18, (+)-19, (+)-20, (+)-22, (+)-23, (+)-24.
Methyl 2-Deoxy-2-(2,5-imino-1,2,5-trideoxy-L-ribitol-1C-yl)-α-D-al-
lopyranoside [(+)-(5)]: Compound (+)-24 (13 mg, 0.039 mmol) was
dissolved in CF3COOH/H2O (4:1, 10.0 mL) and the solution was
stirred at 20 °C for 30 min. The solvent was evaporated. FC
(MeCN/NH4OH, 4:1) gave (+)-5 (10.8 mg, 95%) as a white solid,
25
25
25
25
m.p. 58–59 °C. [α] = +23, [α] = +24, [α] = +45, [α] = +55
589
577
435
405
(c = 0.5, MeOH). IR (NaCl): ν = 3355, 2925, 2360, 1665, 1420,
˜
1130, 1045 cm–1. 1H NMR (400 MHz, CD3OD, 25 °C): δ = 4.68
Acknowledgments
(d, 3JH,H = 3.1 Hz, 1 H, 1-H), 4.07 (dd, 3JH,H = 6.5, 3JH,H = 5.0 Hz,
This work was supported by the Swiss National Science Founda-
3
2
1 H, 4Ј-H), 3.85 (br. t, JH,H = 2.7 Hz, 1 H, 3-H), 3.82 (dd, JH,H
tion (Grant No. 200020-108103) and by the Secrétariat d’Etat à
3
= 10.0, JH,H = 5.2 Hz, 1 H, 6-H), 3.72–3.67 (m, 2 H, 5-H, 6-H), l’Education et à la Recherche (SER) (European FG TRIoH pro-
3.63 (dd, JH,H = 7.0, JH,H = 5.0 Hz, 1 H, 3Ј-H), 3.43 (dd, JH,H
3
3
3
ject, No. 03.07380FES). We thank Mr. Michael Walker, Mr. Mar-
tial Rey, Mr. Francisco Sepúlveda and Dr. Srinivas Reddy Dub-
baka for their technical help.
3
= 9.4, JH,H = 2.7 Hz, 1 H, 4-H), 3.36 (s, 3 H, OCH3), 3.24 (dd,
2JH,H = 12.0, JH,H = 6.5 Hz, 1 H, 5Ј-H), 3.09 (q, JH,H = 7.0 Hz,
3
3
Eur. J. Org. Chem. 2006, 3845–3855
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3853

E. Rodriguez García, M. A. Brimble, P. Vogel
FULL PAPER
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