Improved synthesis of the Kijanimicin oligodeoxytetrasaccharide

Article abstract of DOI:10.1016/j.carres.2018.10.014

By sequential synthesis the four 2,6-dideoxy saccharide moieties of the kijanimicin tetrasaccharide could be stereoselectively assembled. For formation of all required 2-deoxy α-glycoside linkages various S-(hexopyranosyl)-phosphorodithioates as donor str

Full text of DOI:10.1016/j.carres.2018.10.014

CarbohydrateResearch471(2019)19–27
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Improved synthesis of the Kijanimicin oligodeoxytetrasaccharide
Joachim Thiem∗, Henry Sajus
University of Hamburg, Faculty of Science, Department of Chemistry, Martin-Luther-King-Platz 6, D-20146, Hamburg, Germany
A R T I C L E I N F O
A B S T R A C T
Keywords:
By sequential synthesis the four 2,6-dideoxy saccharide moieties of the kijanimicin tetrasaccharide could be
stereoselectively assembled. For formation of all required 2-deoxy α-glycoside linkages various S-(hexopyr-
anosyl)-phosphorodithioates as donor structures could be convincingly employed. The terminal 2-deoxy β-gly-
coside linkage was stereoselectively formed following the dibromomethyl methyl ether approach. The target
octadeoxy-tetrasaccha-ride could be obtained via nine subsequent steps in 5% overall yield.
Oligodeoxy-oligosaccharides
S-hexopyranosyl phosphorodithioates
Stereoselective α- and β-glycosylations
2,6-Dideoxy sugars
1. Introduction
2. Results and discussion
From Kenian soil Actinomadura kijanata was isolated and shown to
form the macrolide antibiotic Kijanimicin (1, Fig. 1) [1,2], the structure
of which was nicely elucidated by Mallams et al. [3] In addition to
antitumor activity 1 was observed to be effective against anaerobic
bacteria as well as malaria [4,5]. The stereo-chemically rather complex
macrolide is glycosylated at the 17-OH group with a methyl-branched
dideoxy nitro-amino sugar E, named D-kijanose [6,7]. Further, at po-
sition 9 Kijanimicin is decorated with a tetrasaccharide moiety con-
taining exclusively four L-digitoxose units A – D. The A, B, and C L-ribo
moieties are interglycosidically linked via α,1–3 linkages, however, the
4-O-methylated terminal unit D is attached via a β,1–3 interglycosidic
bond.
2.1. Synthesis of the B-A disaccharide precursor
Starting with L-rhamnal (2) [16] simple benzoylation using ben-
zoylchloride at room temperature led to the mixture of 3-Oe (3), 4-Oe
(4), and 3,4-di-O-benzoyl-L-rhamnal (5) in 95% yield and a ratio 19: 1:
3, which could be facile separated by chromatography. Thus, the de-
sired compound 3 could be obtained in about 80% yield, which com-
petes convincingly with previous more elaborate approaches for re-
gioselective acylations of
2
employing dibutyl-stannylidene
intermediates [17]. As reported before [15] treatment of 3 with O,O-
diethyl S-hydrogen phosphorodithioate led to the raw S-(2-deoxy-α,β-L-
arabino-hexopyranosyl)-phosphorodithioate (6), which could be di-
rectly used for glycosylation.
In previous studies the trisaccharide moity A-C could be nicely
synthesized [8] employing the NIS reaction [9]. However, the attach-
ment of the terminal D unit employing the approach reported by
Wiesner et al. [10,11] could be just realized in moderate yields. Thus,
substantial improvements toward formation of the decisive b,1–4
linkage and hence the tetrasaccharide would be desirable.
The acceptor formation started with 2-deoxy-L-rhamnose (7) [18]
which gave both anomeric benzyl glycosides, from which the pure β-
component 8 was separated. Inversion by Mitsunobu conditions [19,20]
could be employed to give the monoinverted 3-O-benzoate 9, and by
alkaline treatment the L-ribo derivative 10 resulted in 75% yield via
two steps. Benzylation with sodium hydride and benzylbromide in an-
hydrous dimethylformamide at room temperature gave 3-Oe (11), 4-
Oe (12), and 3,4-di-O-benzyl-L-ribo-hexo-pyranoside (13) in 75% yield
and a ratio of 4: 10: 1, which were separated by chromatography.
The rhamno-configured dithiophosphate 6 with its weakly nucleo-
philic (“disarmed”) 4-OH group represents an ideal donor molecule.
Earlier studies demonstrated the dibromomethyl methyl ether
(DBE) [12] method to be efficiently employed for rather difficult β-
glycosylations in the 2-deoxy sugar series [13,14]. Other accesses to α-
glycosidically linked 2-deoxy sugars were developed by iodonium-
promoted transformations employing S-(2-deoxy-glycosyl) phosphor-
odithioates obtained easily from glycals as donors [15].
∗ Corresponding author.
E-mail address: thiem@chemie.uni-hamburg.de (J. Thiem).
https://doi.org/10.1016/j.carres.2018.10.014
Received 12 October 2018; Received in revised form 29 October 2018; Accepted 29 October 2018
Availableonline01November2018
0008-6215/©2018ElsevierLtd.Allrightsreserved.

J. Thiem, H. Sajus
CarbohydrateResearch471(2019)19–27
Fig. 1. Kijanimicin (1).
Scheme 2. Synthesis of the A-B-D- Trisaccharide Precursor. Reaction conditions:
a) AgOTf, nitromethane/toluene; b) nBu3SnH, AIBN, toluene, 70 °C; c) NaOH,
MeOH.
separation of the anomers at this stage was inefficient, as next step the
radical debromination with tri-n-butyl stannane was performed to give
the anomeric mixture 17 in 95% yield, separation of which was not
feasible as above. Thus, the alkaline deacylation was done with the
anomeric mixture to give the trisaccharides 18 and 19 in 90% yield.
These could be successfully separated resulting in the desired β,1´´-3´´-
linked trisaccharide 18 (78%) and in addition 12% of the α,1´´-3´´-
linked trisaccharide species 19 (Scheme 2).
Scheme 1. Synthesis of the A-B Disaccharide Precursor. Reaction conditions:(a)
Benzoyl chloride, pyridine; (b) benzyl bromide, NaH, DMF; (c) O,O-diethyl S-
hydrogen phosphorodithioate; (d) P(Ph)3, BzOH, diethylazodicarboxylate; e)
NaOH, MeOH; f) I(Coll)2C1O4, MeCN.
2.3. Synthesis of the D-B-A trisaccharide
Thus, for glycosylation the mixture of the crystalline acceptor 12 and
the raw material 6 were treated with iodonium bis-collidine perchlorate
[I(Coll)2ClO4] as promotor at room temperature under exclusion of
light in benzene/acetonitrile to give the α,1-3-glycosidically linked A-B
disaccharide precursor 14 in 62% yield (Scheme 1).
Employing trisaccharide 18 in a Mitsunobu reaction was expected to
result in inversion of both hydroxyl groups at 3′- as well as 3´´-posi-
tions. However, as a favorable outcome, apparently due to considerable
steric shielding from the upper side of unit B, there was exclusively
observed inversion at 3´´-position to give the crystalline component 20
in 85% yield. Thus, in deviation from the original planning, another
method for inversion at 3′-position e.g. by an oxidation/reduction se-
quence had to be engaged. Use of pyridinium dichromate in di-
chloromethane with acetic acid catalysis [21] was the method of choice
to result in formation of the crystalline 3′-ulose 21 in 90% yield. Indeed
its reduction with sodium borohydride went extraordinarily well to give
the desired trisaccharide 22 with an axial 3′-hydroxy group crystalline
in 99% yield. As previously reported in other cases [22,23] axially
glycosylated 3-keto derivatives allow an exclusive hydride attack from
below. Since the A-B disaccharide moieties are α,1-3-glycosidically
2.2. Synthesis of the D-B-A trisaccharide precursor
En route to the trisaccharide precursor A-BeC the next stage was the
introduction of the 4-O-methylated moiety C employing a stereo-
selective β-glycosylation with the glycosyl bromide precursor 15 [13].
As acceptor the above described disaccharide unit 14 with an un-
blocked 4′eOH position was employed. Indeed, the silver triflate
mediated reaction resulted in formation of the trisaccharide 16 as
anomeric mixture in 81% yield with a ratio α: β = 2: 13. Since
20

J. Thiem, H. Sajus
CarbohydrateResearch471(2019)19–27
Scheme 4. Synthesis of the A-BeC-D-Tetrasaccharide Precursor. Reaction condi-
tions: a) O,O-diethyl S-hydrogen phosphorodithioate; b) P(Ph)3, BzOH, die-
thylazodicarboxylate; c) l(Coll)2CIO4, MeCN.
exclusion of light in acetonitrile the A-BeC-D tetrasaccharides 25 and
26 precursors were obtained in 20% yield with a ratio of 25: 26 = 3:
1.1H NMR clearly allowed to identify compound 25 having a β,1´´-3´-
(H-1´´ with J1´´,2´´ax = 8.2, J1´´,2´´eq = 2.0 Hz) and the desired 26 an
α,1´´-3′- interglycosidic linkage (H-1´´ with
J1´´,2´´ax = 3.6,
J
1´´,2´´eq = 0.8 Hz). Even though the complete tetrasaccharide structure
resulted, these yields in the range of previous approaches [8] were not
convincing, which required an alternative approach (Scheme 4).
2.5. Synthesis of an alternative glycosylation precursor
The results of the above findings clearly required a rather plain
donor showing stereoselectivity for α-glycosylations. It seemed to be
attractive to develop an ulose type hexopyranosyl-phosphorodithioate,
even though it remains uncertain whether or not the keto function
would survive the glycosylation conditions. Allylic oxidation of L-
rhamnal (2) [16] with manganese oxide led to ulose 27 [24], which
after benzoylation to 28 on treatment with O,O-diethyl S-hydrogen
phosphoro-dithioate gave the glycosylation donor 29 (Scheme 5).
Scheme 3. Synthesis of the D-B-A-Trisaccharide. Reaction conditions: a) P(Ph)3,
BzOH, diethylazodicarboxylate; b) pyridinium dichromate, HOAc; c) NaBH4,
MeOH.
linked, this conception could be effectively employed here as well
(Scheme 3).
2.6. Final synthesis of the A-BeC-D-tetrasaccharide
Based on previous glycosylation approaches with corresponding
2.4. Synthesis of the A-BeC-D tetrasaccharide precursor
Even though a stereoselective glycosylation was not necessarily to
be expected employing an S-(2,6-dideoxy-α,β-L-ribo-hexopyranosyl)-
phosphorodithioate [15] it was to be tested as expedient approach.
Thus, 4-O-benzoyl-L-rhamnal (4) was reacted with O,O-diethyl S-hy-
drogen phosphorodithioate to give quantitatively the raw of S-(2,6-di-
deoxy-α,β-L-arabino-hexopyranosyl)-phosphorodithioate (23). Inver-
sion of the 3-hydroxy group by Mitsunobu reaction led to the L-ribo
derivative 24, which could be directly used for glycosylation at 3′-po-
sition of the trisaccharide 22. By catalysis with iodonium bis-collidine
perchlorate [I(Coll)2ClO4] as promotor at room temperature under
Scheme 5. Synthesis of the Glycosylation Precursor. Reaction conditions:.a) BzCI,
pyridine; b) O,O-diethyl S-hydrogen phosphorodithioate.
21

J. Thiem, H. Sajus
CarbohydrateResearch471(2019)19–27
4. Experimental
4.1. General methods
All reactions were monitored by thin layer chromatography on silica
gel foils GF254 (Merck). Detection was by UV or spraying with 10%
ethanolic sulfuric acid and subsequent heating. Column chromato-
graphy was done on silica gel 60 (40–63 μm, Merck) by flash mode with
the solvent mixture recorded. 1H NMR (250 or 400 MHz) and 13C NMR
spectra (62.89 or 100.67 MHz) were done on Bruker AC-250 or AMX-
400. Signal assignment was by 1H,1HeCOSYe, HSQC- and HMBC ex-
periments. Melting points are uncorrected and were taken on a Reichert
heating microscope. Optical rotations were measured with Perkin-
Elmer polarimeter 243 using sodium D line (589 nm), cuvette length
10 cm, and temperature 20 °C.
4.2. General procedures
4.2.1. DBE method (GP1)
The sugar (1.0 mmol) dissolved in dichloromethane (4 mL) was re-
acted with zinc bromide (45 mg) and dibromomethyl methyl ether
(350 μL) at room temperature overnight. Following addition of di-
chloromethane (20 mL) the solution was washed twice with aqueous
hydrochloric acid (4 M), the organic phase dried over MgSO4, filtered
and evaporated at room temperature. The raw material was directly
used for glycosylation.
4.2.2. Glycosylation employing silver triflate (GP2)
Under nitrogen cover a solution of the acceptor (1.0 mmol) in ni-
tromethane (7 mL) and toluene (23 mL) was stirred with activated
molecular sieves (4 A, small rods). Silver triflate (2.2 eq) and sym-
collidine (5 drops) were added and the solution cooled to −78 °C. Then
a pre-dried solution of the glycosyl bromide (GP1, 2.2 eq) in anhydrous
toluene (2 mL) was added, and the reaction stirred under nitrogen and
exclusion of light for 24–48 h, thereby gradually warming to room
temperature. For work up the solution was diluted with ethyl acetate,
washed with aqueous sodium thiosulfate and aqueous sodium hydrogen
carbonate, filtered over celite, dried over MgSO4 and evaporated. The
raw material was purified by flash chromatography.
Scheme 6. Synthesis of A-B-C-D- Tetrasaccharide.
donor components [15] compound 29 was used for glycosylation of the
trisaccharide acceptor 22 under catalysis of iodonium bis-collidine
perchlorate [I(Coll)2ClO4] as promotor, room temperature and exclu-
sion of light. There was detected almost no solvent influence on the α: β
ratio: in anhydrous dichloromethane the total yield amounted to 60%
and a ratio α: β = 1.1: 2, whereas in anhydrous acetonitrile 55% were
obtained with α: β = 1: 2.1H NMR data clearly confirmed the anomeric
assignment and also show a conservation of the keto unit C. Following
this approach the desired tetrasaccharide 31 could be obtained in 33%
and the anomeric counterpart 30 in 27% yield. The terminal step re-
quired a sodium borohydride reduction. As discussed above there is an
exclusive hydride attack in both compounds at the 3´´-keto function
from underneath to result in the required α-L-ribo-hexopyranosyl unit
C. In addition to the syrupy isomer 32 (45%) the α,1´´-3′-anomer 33
was isolated as a crystalline material in 50% yield. This concluded the
synthesis of the genuine kijanimicin tetrasaccharide, the correct inter-
glycosidic linkages of which were clearly shown by extended NMR as-
signments (Scheme 6).
4.2.3. Debromination with tri-n-butyl stannane (GP3)
Under nitrogen a solution of the bromo component (1.0 eq) in to-
luene (3 mL) was treated with tri-n-butyl stannic hydride (1.1 eq).
Following addition of a catalytic amount of α,α′-azobis-isobutyronitrile
as radical starter the mixture was heated to 70 °C and stirred for 3 h.
The solvent was evaporated and the raw mixture directly purified by
chromatography.
4.2.4. Benzoylation (GP4)
The saccharide (1 eq) dissolved in anhydrous pyridine (4 mL) was
cooled to 0 °C and treated dropwise with benzoyl chloride (1 eq per
hydroxyl function). After 1–12 h the mixture was warmed to room
temperature, evaporated and purified by chromatography.
4.2.5. Benzylation (GP5)
The saccharide (1 mmol) dissolved in anhydrous N,N-dimethyl-for-
mamide (DMF, 10 mL) was stirred with sodium hydride (1.2 eq per
hydroxyl group) for 20 min. After cooling to 0 °C a solution of benzyl
bromide (1 eq per hydroxyl group) in anhydrous DMF (2 mL) was added
dropwise, and stirring continued for 2 h while gradually warming to
room temperature. Then methanol (4 mL per mmol benzyl bromide)
was added and stirred for another 20 min. The mixture was evaporated
and the raw material purified by chromatography.
3. Conclusion
Essentially by use of the four monosaccharide building units 3, 12,
15, and 28 the sequential synthesis of the kijanimicin octadeoxy-tet-
rasaccharide 33 could be achieved. This target compound having the
required α,1′-3-, α,1´´-3´-, and β,1´´´-4′-interglycosidic linkages was
obtained in nine steps and overall 5% yield.
4.2.6. Deacylation (GP6)
The acylated material (1 mmol) dissolved in methanol (20 mL) was
22

J. Thiem, H. Sajus
CarbohydrateResearch471(2019)19–27
treated with sodium hydroxide (2 eq per acyl function) and stirred at
room temperatures until complete saponification. The mixture was
dissolved in water (20 mL) and neutralized with aqueous hydrochloric
acid (4 M), then extracted with dichloromethane, dried over MgSO4,
filtered, evaporated and purified by chromatography.
7.40–7.60 (m, 5-H, aryl-H). Compound 12: colourless solid, mp 53 °C,
[α]D = + 16.4 (c = 1.0, CH2Cl2); 1H NMR (250 MHz, CDCl3):
20
δ = 4.92 (dd, 1H, J1,2ax 9.6, J1,2eq 2.4 Hz, H-1), 1.70 (dd, 1H, J1,2ax 9.6,
J
2ax,2eq 14.0, J2ax,3 2.8 Hz, H-2ax), 2.20 (dd, 1H, J1,2eq 2.4, J2ax,2eq 14.0,
J2eq,3 3.6 Hz, H-2eq), 4.20 (m, 1H, H-3), 3.16 (dd, 1H, J3,4 3.2, J4,5
9.6 Hz, H-4), 3.82 (dq, 1H, J4,5 9.6, J5,6 6.4 Hz, H-5), 1.32 (d, 3H, J5,6
6.4 Hz, CH3-6), 4.52, 4.54, 4.62 and 4.86 (each d, each 1H, JCH2Bn
12.0 Hz, CH2Bn), 7.40–7.60 (m, 5-H, aryl-H). Calcd. for C20H24O4
(328.3): C, 73.14; H, 7.36. Found: C, 73.20; H, 7.36. Compound 13:
colourless syrup, [α]D20 = - 18.4 (c = 1.0, CH2Cl2); 1H NMR (250 MHz,
CDCl3): δ = 4.94 (dd, 1H, J1,2ax 9.6, J1,2eq 2.4 Hz, H-1), 1.60 (dd, 1H,
J1,2ax 9.6, J2ax,2eq 14.0, J2ax,3 2.8 Hz, H-2ax), 2.22 (dd, 1H, J1,2eq 2.4,
4.3. Syntheses
4.3.1. 3-O-Benzoyl-L-rhamnal (3), 4-O-Benzoyl-L-rhamnal (4) and 3,4-
Di-O-benzoyl-L-rhamnal (5)
L-Rhamnal (2, 900 mg, 6.92 mmol) [16] was treated with benzoyl
chloride (1eq/OH) according to GP4. The raw material was separated
by column chroma-tography (toluene/ethyl acetate 8: 1) to give com-
pounds 3 (1.27 g, 78%), 4 (67 mg, 4.1%), and 5290 mg, 12.3%) as
colourless solids. 1H-NMR-data, melting points and optical rotations
were in accord with the literature data [17].
J
2ax,2eq 14.0, J2eq,3 3.6 Hz, H-2eq), 3.92 (m, 1H, H-3), 3.16 (dd, 1H, J3,4
3.2, J4,5 9.6 Hz, H-4), 4.04 (dq, 1H, J4,5 9.6, J5,6 6.4 Hz, H-5), 1.32 (d,
3H, J5,6 6.4 Hz, CH3-6), 4.42, 4.52, 4.56, 4.62, 4.64 and 4.82 (each d,
each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.40–7.60 (m, 5-H, aryl-H).
4.3.2. Benzyl 2,6-dideoxy-β-L-arabino-hexopyranoside (8)
4.3.6. Benzyl 3-O-(3-O-benzoyl-2,6-dideoxy-α-L-arabino-hexopyranosyl)-
4-O-benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside (14)
According to GP5 2-deoxy-L-rhamnose [18] (7, 1.2 g, 8.1 mmol) was
treated with benzyl bromide (1 eq). The raw material was purified by
flash chromatography (toluene/ethyl acetate 2: 1) to give 1.35 g (70%)
yellow syrup (anomeric mixture α: β = 1:4). Further separation gave
the pure β-anomer 8, the 1H NMR data of which are in accord with
those of the D-isomer [25].
A solution of compound 3 (1.1 g, 4.7 mmol) in benzene (15 mL) was
stirred with an equimolar amount of O,O-diethyl S-hydrogen phos-
phoro-dithioate (800 μL) for 12 h at room temperature. The solvent was
evaporated and the raw of S-(2-deoxy-α,β-L-arabino-hexo-pyranosyl)-
phosphorodithioate (6) used directly for glycosylation with compound
12 (4.0 g, 12.1 mmol, 2.5 eq) dissolved in anhydrous acetonitrile
(20 mL). After stirring with molecular sieves (3A) for 20 min as pro-
motor iodonium bis-collidine perchlorate [I(Coll)2ClO4, 3.0 g, 1.5 eq]
was added and stirring continued at room temperature under exclusion
of light for another hour. The mixture was dissolved with di-
chloromethane (100 mL), washed with sodium thiosulfate (10% aqu-
eous solution), dried over MgSO4, filtered and evaporated. By chro-
matographic purification (petroleum ether/ether 7: 2) 1.58 g (62%) of
compound 14 resulted as colourless syrup; [α]D20 = - 95.2 (c = 1.0,
CH2Cl2). 1H NMR (250 MHz, CDCl3): δ = 4.92 (dd, 1H, J1,2ax 9.6, J1,2eq
2.0 Hz, H-1), 1.62 (dd, 1H, J1,2ax 9.6, J2ax,2eq 14.0, J2ax,3 2.4 Hz, H-2ax),
2.12 (dd, 1H, J1,2eq 2.0, J2ax,2eq 14.0, J2eq,3 4.0 Hz, H-2eq), 4.31 (m, 1H,
H-3), 3.16 (dd, 1H, J3,4 2.8, J4,5 9.2 Hz, H-4), 4.06 (dq, 1H, J4,5 9.2, J5,6
6.4 Hz, H-5), 1.32 (d, 3H, J5,6 6.4 Hz, CH3-6), 5.03 (dd, 1H, J1′,2′ax 3.6,
J1′,2′eq 0.4 Hz, H-1′), 1.91 (dt, 1H, J1′,2′ax 3.6, J2′ax,2′eq 12.4, J2′ax,3′
12.0 Hz, H-2′ax), 2.22 (dd, 1H, J1′,2′eq 0.4, J2′ax,2′eq 12.4, J2′eq,3′ 5.2 Hz,
H-2′eq), 5.38 (m, 1H, H-3′), 3.34 (t, 1H, J3′,4′ 9.2, J4′,5′ 9.2 Hz, H-4′),
4.06 (dq, 1H, J4′,5′ 9.2, J5′,6′ 6.2 Hz, H-5′), 1.18 (d, 3H, J5′,6′ 6.2 Hz, CH3-
6′), 4.50, 4.53, 4.71 and 4.91 (each d, each 1H, JCH2Bn 12.0 Hz, CH2Bn),
7.40–7.80 (m, 15-H, aryl-H). Calcd. for C33H37O8 (561.6): C, 70.44; H,
6.80. Found: C, 69.98; H, 6.80.
4.3.3. Benzyl 3-O-benzoyl-2,6-dideoxy-β-L-ribo-hexopyranoside (9)
A solution of compound 8 (7.7 g, 32.0 mmol) and triphenylpho-
sphine (11.0 g, 48.0 mmol) in tetrahydrofuran (100 mL) were stirred for
20 min. Then benzoic acid (5.0 g, 48 mmol) and a solution of diethy-
lazodicarboxylate (6.4 mL, 48 mmol) in tetra-hydrofuran (60 mL) were
added and stirring continued for another 30 min. The mixture was
evaporated and the raw material purified by column chroma-tography
(toluene/ethyl acetate 15: 1) to give 9 (8.2 g, 75%) as amorphous solid.
1H NMR (250 MHz, CDCl3): δ = 4.94 (dd, 1H, J1,2ax 9.6, J1,2eq 2.4 Hz,H-
1), 1.95 (dd, 1H, J1,2ax 9.6, J2ax,2eq 14.0, J2ax,3 2.8 Hz, H-2ax), 2.26 (dd,
1H, J1,2eq 2.4, J2ax,2eq 14.0, J2eq,3 3.6 Hz, H-2eq), 5.52 (m, 1H, H-3),
3.54 (dd, 1H, J3,4 3.2, J4,5 9.6 Hz, H-4), 3.88 (dq, 1H, J4,5 9.6, J5,6
6.4 Hz, H-5), 1.36 (d, 3H, J5,6 6.4 Hz, CH3-6), 4.60 and 4.93 (each d,
each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.40–8.10 (m, 5-H, aryl-H).
4.3.4. Benzyl 2,6-dideoxy-β-L-ribo-hexopyranoside (10)
According to GP6 compound 9 (8.2 g, 24.0 mmol) were saponified
for 30 min. After filtration over silica gel (toluene/ethyl acetate 1: 1)
the pure product 10 (5.7 g, quantitative yield) was obtained as col-
20
ourless syrup, [α]D = + 32.1 (c = 1.0, CH2Cl2). 1H NMR (250 MHz,
CDCl3): δ = 4.90 (dd, 1H, J1,2ax 9.6, J1,2eq 2.4 Hz, H-1), 1.75 (dd, 1H,
J1,2ax 9.6, J2ax,2eq 14.0, J2ax,3 2.8 Hz, H-2ax), 2.12 (dd, 1H, J1,2eq 2.4,
4.3.7. Benzyl 3-O-[3-O-benzoyl-4-O-(2-bromo-2,6-dideoxy-3-O-formyl-4-
O-methyl-α/β-L-glucopyranosyl)-2,6-dideoxy-α-L-arabino-hexopyranosyl]-
4-O-benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside (16)
J
2ax,2eq 14.0, J2eq,3 3.6 Hz, H-2eq), 4.06 (m, 1H, H-3), 3.30 (dd, 1H, J3,4
3.2, J4,5 9.6 Hz, H-4), 3.72 (dq, 1H, J4,5 9.6, J5,6 6.4 Hz, H-5), 1.34 (d,
3H, J5,6 6.4 Hz, CH3-6), 4.58 and 4.82 (each d, each 1H, JCH2Bn 12.0 Hz,
CH2Bn), 7.40–7.60 (m, 5-H, aryl-H). Calcd. for C13H18O4 (238.2): C,
65.52; H, 7.61. Found: C, 65.34; H, 7.59.
The raw material 15 [13] obtained from methyl 6-deoxy-2,3-O-
isopropylidene-4-O-methyl-α-L-mannopyranoside (300 mg, 1.29 mmol)
following GP1 and the disaccharide 14 (195 mg, 0.34 mmol) were re-
acted for 12 h and worked up according to GP2. By chromatographic
purification (petroleum ether/ether 5: 1) 224 mg (81%) of compound
16 resulted as colourless syrup. Anomeric mixture α: β = 2: 13.16β: 1H
NMR (400 MHz, CDCl3): δ = 4.94 (dd, 1H, J1,2ax 9.6, J1,2eq 2.0 Hz, H-1),
1.58 (dd, 1H, J1,2ax 9.6, J2ax,2eq 13.6, J2ax,3 2.4 Hz, H-2ax), 2.10 (dd, 1H,
J1,2eq 2.0, J2ax,2eq 13.6, J2eq,3 3.6 Hz, H-2eq), 4.30 (m, 1H, H-3), 3.14
(dd, 1H, J3,4 2.8, J4,5 9.6 Hz, H-4), 4.23 (dq, 1H, J4,5 9.6, J5,6 6.4 Hz, H-
5), 1.20 (d, 3H, J5,6 6.4 Hz, CH3-6), 4.99 (dd, 1H, J1′,2′ax 2.8, J1′,2′eq
0.8 Hz, H-1′), 1.84 (dd, 1H, J1′,2′ax 2.8, J2′ax,2′eq 12.4, J2′ax,3′ 11.2 Hz, H-
2′ax), 2.24 (dd, 1H, J1′,2′eq 0.8, J2′ax,2′eq 12.4, J2′eq,3′ 5.6 Hz, H-2′eq),
5.57 (dd, 1H, J2′ax,3′ 11.2, J2′eq,3′ 5.6, J3′,4′ 9.2 Hz, H-3′), 3.58 (t, 1H,
J3′,4′ 9.2, J4′,5′ 9.2 Hz, H-4′), 4.08 (dq, 1H, J4′,5′ 9.2, J5′,6′ 6.4 Hz, H-5′),
0.92 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 4.64 (d, 1H, J1´´,2´´ 8.4 Hz, H-1´´),
3.64 (dd, 1H, J1´´,2´´ 8.4, J2´´,3´´ 10.8 Hz, H-2´´), 5.09 (t, 1H, J2´´,3´´ 10.8.
4.3.5. Benzyl
3-O-benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside
(11),
Benzyl 4-O-benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside (12) and Benzyl
3,4-di-O-benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside (13)
According to GP5 compound 10 (7.44 g, 31.0 mmol) was benzylated
regioselectively. After workup chromatographic separation (petroleum
ether/ether 3:1) gave 640 mg (5%) of 13, 5.1 g (50%) of 12, and 2.08 g
20
(20%) of 11. Compound 11: colourless syrup, [α]D = + 24.3
(c = 1.0, CH2Cl2); 1H NMR (250 MHz, CDCl3): δ = 4.94 (dd, 1H, J1,2ax
9.6, J1,2eq 2.4 Hz, H-1), 1.60 (dd, 1H, J1,2ax 9.6, J2ax,2eq 14.0, J2ax,3
2.8 Hz, H-2ax), 2.20 (dd, 1H, J1,2eq 2.4, J2ax,2eq 14.0, J2eq,3 3.6 Hz, H-
2eq), 3.98 (m, 1H, H-3), 3.28 (dd, 1H, J3,4 3.2, J4,5 9.6 Hz, H-4), 3.72
(dq, 1H, J4,5 9.6, J5,6 6.4 Hz, H-5), 1.32 (d, 3H, J5,6 6.4 Hz, CH3-6), 4.42,
4.52, 4.64 and 4.88 (each d, each 1H, JCH2Bn 12.0 Hz, CH2Bn),
23

J. Thiem, H. Sajus
CarbohydrateResearch471(2019)19–27
J3´´,4´´ 9.6, H-3´´), 2.74 (t, 1H, J3´´,4´´ 9.6, J4´´,5´´ 9.6 Hz, H-4´´), 3.01 (dq,
1H, J4´´,5´´ 9.6, J5´´,6´´ 6.4 Hz, H-5´´), 1.32 (d, 3H, J5´´,6´´ 6.4 Hz, CH3-
6´´), 3.32 (s, 3H, OCH3), 4.46, 4.51, 4.71 and 4.91 (each d, each 1H,
J3′,4′ 9.2, J4′,5′ 9.2 Hz, H-4′), 3.96 (dq, 1H, J4′,5′ 9.2, J5′,6′ 6.4 Hz, H-5′),
1.10 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 5.29 (dd, 1H, J1´´,2´´ax4.0, J1´´,2´´eq
1.2 Hz, H-1´´), 1.68 (dd, 1H, J1´´,2´´ax 4.0, J2´´ax,2´´eq 12.4, J2´´ax,3´´
11.2 Hz, H-2´´ax), 2.08 (dd, 1H, J1´´,2´´eq 1.2, J2´´ax,2´´eq 12.4, J2´´eq,3´´
5.2 Hz, H-2´´eq), 3.88 (m, 1H, H-3´´), 2.68 (t, 1H, J3´´,4´´ 9.2, J4´´,5´´
9.2 Hz, H-4´´), 3.65 (dq, 1H, J4´´,5´´ 9.2, J5´´,6´´ 6.4 Hz, H-5´´), 1.28 (d,
3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 3.56 (s, 3H, OCH3), 4.45, 4.52, 4.66 and
4.89 (each d, each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.20 (m, 10-H, aryl-H).
J
CH2Bn 12.0 Hz, CH2Bn), 8.18 (s, 1H, OCHO), 7.20–8.00 (m, 15-H, aryl-
H). Calcd. for C41H48BrO12(812.6): C, 60.51; H, 6.06; Br, 9.82. Found:
C, 59.95; H, 6.07; Br, 9.70.
4.3.8. Benzyl 3-O-[3-O-benzoyl-4-O-(2,6-dideoxy-3-O-formyl-4-O-methyl-
α/β-L-arabino-hexopyranosyl)-2,6-dideoxy-α-L-arabino-hexopyranosyl]-4-
O-benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside (17)
4.3.10. Benzyl 3-O-[4-O-(3-O-benzoyl-2,6-dideoxy-4-O-methyl-β-L-ribo-
hexopyran-osyl)-2,6-dideoxy-α-L-arabino-hexopyranosyl]-4-O-benzyl-2,6-
dideoxy-β-L-ribo-hexopyranoside (20)
The trisaccharide 16 (1.0 g, 1.23 mmol) was reacted according to
GP3. Chromatographic purification (petroleum ether/ether 2: 1) gave
885 mg (95%) of the anomeric mixture 17 as amorphous solid. 17β: 1H
NMR (400 MHz, CDCl3): δ = 4.93 (dd, 1H, J1,2ax 9.6, J1,2eq 2.0 Hz, H-1),
1.50 (dd, 1H, J1,2ax 9.6, J2ax,2eq 13.6, J2ax,3 2.4 Hz, H-2ax), 1.95 (dd, 1H,
J1,2eq 2.0, J2ax,2eq 13.6, J2eq,3 3.6 Hz, H-2eq), 4.28 (m, 1H, H-3), 3.12
(dd, 1H, J3,4 2.8, J4,5 9.6 Hz, H-4), 4.16 (dq, 1H, J4,5 9.6, J5,6 6.4 Hz, H-
5), 1.05 (d, 3H, J5,6 6.4 Hz, CH3-6), 4.98 (dd, 1H, J1′,2′ax 3.2, J1′,2′eq
0.8 Hz, H-1′), 1.91 (dd, 1H, J1′,2′ax 3.2, J2′ax,2′eq 12.4, J2′ax,3′ 11.2 Hz, H-
2′ax), 2.30 (dd, 1H, J1′,2′eq 0.8, J2′ax,2′eq 12.4, J2′eq,3′ 5.2 Hz, H-2′eq),
5.53 (dd, 1H, J2′ax,3′ 11.2, J2′eq,3′ 5.2, J3′,4′ 9.2 Hz, H-3′), 3.43 (t, 1H,
J3′,4′ 9.2, J4′,5′ 9.2 Hz, H-4′), 4.05 (dq, 1H, J4′,5′ 9.2, J5′,6′ 6.4 Hz, H-5′),
0.90 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 4.50 (dd, 1H, J1´´,2´´ax 9.6, J1´´,2´´eq
2.0 Hz, H-1´´), 1.50 (dd, 1H, J1´´,2´´ax 9.6, J2´´ax,2´´eq 12.4, J2´´ax,3´´
12.0 Hz, H-2´´ax), 2.18 (dd, 1H, J1′,2´´´eq 2.0, J2´´ax,2´´eq 12.4, J2´´eq,3´´
5.2 Hz, H-2´´eq), 4.85 (dd, 1H, J2´´ax,3´´ 12.0, J2´´eq,3´´ 5.2, J3´´,4´´ 9.2 Hz,
H-3´´), 2.72 (t, 1H, J3´´,4´´ 9.2, J4´´,5´´ 9.2 Hz, H-4´´), 3.03 (dq, 1H, J4´´,5´´
9.2, J5´´,6´´ 6.4 Hz, H-5´´), 1.30 (d, 3H, J5´´,6´´ 6.2 Hz, CH3-6´´), 3.38 (s,
3H, OCH3), 4.48, 4.52, 4.69 and 4.91 (each d, each 1H, JCH2Bn 12.0 Hz,
CH2Bn), 8.12 (s, 1H, OCHO), 7.20–8.00 (m, 15-H, aryl-H).
A solution of trisaccharide 18 (580 mg, 0.96 mmol) in anhydrous
tetrahydrofuran (30 mL) was stirred with triphenylphosphine (3.1 g,
13.64 mmol) for 30 min and cooled to 0 °C. Then a solution of benzoic
acid (1.56 g, 12.8 mmol) and diethylazodicarboxylate (1.8 mL,
11.5 mmol) in anhydrous tetrahydrofuran (15 mL) was added and
stirring continued for 1 h at room temperature. The solvent was eva-
porated and the residue purified by column chromatography (petro-
leum ether/ether 7: 2) to give 595 mg (85%) of 20 as colourless crys-
tals; mp 65–66 °C, [α]D20 = - 73.7 (c = 1.0, CH2Cl2). 1H NMR
(400 MHz, CDCl3): δ = 4.88 (dd, 1H, J1,2ax 9.2, J1,2eq 2.0 Hz, H-1), 1.59
(dd, 1H, J1,2ax 9.2, J2ax,2eq 13.2, J2ax,3 2.4 Hz, H-2ax), 2.11 (dd, 1H,
J1,2eq 2.0, J2ax,2eq 13.2, J2eq,3 3.6 Hz, H-2eq), 4.26 (m, 1H, H-3), 3.11
(dd, 1H, J3,4 2.8, J4,5 9.2 Hz, H-4), 3.97 (dq, 1H, J4,5 9.2, J5,6 6.4 Hz, H-
5), 1.28 (d, 3H, J5,6 6.4 Hz, CH3-6), 4.96 (dd, 1H, J1′,2′ax 3.2, J1′,2′eq
0.8 Hz, H-1′), 1.66 (dd, 1H, J1′,2′ax 3.2, J2′ax,2′eq 13.2, J2′ax,3′ 11.6 Hz, H-
2′ax), 2.11 (dd, 1H, J1′,2′eq 0.8, J2′ax,2′eq 13.2, J2′eq,3′ 5.2 Hz, H-2′eq),
3.97 (m, 1H, H-3′), 2.98 (t, 1H, J3′,4′ 9.2, J4′,5′ 9.2 Hz, H-4′), 4.04 (dq,
1H, J4′,5′ 9.2, J5′,6′ 6.4 Hz, H-5′), 0.98 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 4.84
(dd, 1H, J1´´,2´´ax 9.6, J1´´,2´´eq 2.0 Hz, H-1´´), 1.90 (dd, 1H, J1´´,2´´ax 9.6,
J2´´ax,2´´eq 14.4, J2´´ax,3´´ = 2.8 Hz, H-2´´ax), 2.20 (dd, 1H,
J1´´,2´´´eq = 2.0, J2´´ax,2´´eq = 14.4, J2´´eq,3´´ = 3.6 Hz, H-2´´eq), 5.80 (q,
1H, J2´´ax,3´´ 2.8, J2´´eq,3´´ 3.6, J3´´,4´´ 2.8 H, H-3´´), 3.05 (dd, 1H, J3´´,4´´
2.8, J4´´,5´´ 9.6 Hz, H-4´´), 3.07 (dq, 1H, J4´´,5´´ = 9.6, J5´´,6´´ 6.4 Hz, H-
5´´), 1.32 (d, 3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 3.38 (s, 3H, OCH3), 4.45, 4.52,
4.67 and 4.89 (each d, each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.30–8.00 (m,
15-H, aryl-H). Calcd. for C40H50O11(706.8): C, 67.96; H, 7.13. Found: C,
67.36; H, 7.15.
4.3.9. Benzyl 3-O-[4-O-(2,6-dideoxy-4-O-methyl-β-L-arabino-hexopyranosyl)-
2,6-dideoxy-α-L-arabino-hexopyranosyl]-4-O-benzyl-2,6-dideoxy-β-L-ribo-
hexopyranoside (18) and Benzyl 3-O-[4-O-(2,6-dideoxy-4-O-methyl-α-L-
arabino-hexopyranosyl)-2,6-dideoxy-α-L-arabino-hexopyranosyl]-4-O-benzyl-
2,6-dideoxy-β-L-ribo-hexopyranoside (19)
The anomeric mixture 17 (800 mg, 1.09 mmol) was completely
deacylated according to GP6. By chromatographic separation (toluene/
ethyl acetate 2: 1) 510 mg (78%) of 18 were obtained as colourless
crystals, mp 103–105 °C, [α]D20 = - 56.6 (c = 1.0, CH2Cl2). 1H NMR
(400 MHz, CDCl3): δ = 4.87 (dd, 1H, J1,2ax 9.6, J1,2eq 2.0 Hz, H-1), 1.60
(dd, 1H, J1,2ax 9.6, J2ax,2eq 12.0, J2ax,3 2.4 Hz, H-2ax), 2.11 (dd, 1H,
J1,2eq 2.0, J2ax,2eq 12.0, J2eq,3 3.6 Hz, H-2eq), 4.26 (m, 1H, H-3), 3.12
(dd, 1H, J3,4 2.8, J4,5 9.2 Hz, H-4), 3.98 (dq, 1H, J4,5 9.2, J5,6 6.4 Hz, H-
5), 1.28 (d, 3H, J5,6 6.4 Hz, CH3-6), 4.95 (dd, 1H, J1′,2′ax 3.2, J1′,2′eq
0.8 Hz, H-1′), 1.60 (dd, 1H, J1′,2′ax 3.2, J2′ax,2′eq 12.4, J2′ax,3′ 11.2 Hz, H-
2′ax), 2.11 (dd, 1H, J1′,2′eq 0.8, J2′ax,2′eq = 12.4, J2′eq,3′ 5.2 Hz, H-2′eq),
3.97 (m, 1H, H-3′), 2.91 (t, 1H, J3′,4′ 9.2, J4′,5′ 9.2 Hz, H-4′), 3.96 (dq,
1H, J4′,5′ 9.2, J5′,6′ 6.4 Hz, H-5′), 1.02 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 4.44
(dd, 1H, J1´´,2´´ax 9.6, J1´´,2´´eq 2.0 Hz, H-1´´), 1.67 (dd, 1H, J1´´,2´´ax 9.6,
J2´´ax,2´´eq 12.4, J2´´ax,3´´ 12.0 Hz, H-2´´ax), 2.18 (dd, 1H, J1´´,2´´eq 2.0,
J2´´ax,2´´eq 12.8, J2´´eq,3´´ 5.2 Hz, H-2´´eq), 3.63 (m, 1H, H-3´´), 2.74 (t,
1H, J3´´,4´´ 9.2, J4´´,5´´ 9.2 Hz, H-4´´), 3.34 (dq, 1H, J4´´,5´´ 9.2,
4.3.11. Benzyl 3-O-[4-O-(3-O-benzoyl-2,6-dideoxy-4-O-methyl-β-L-ribo-
hexopyranosyl)-2,6-dideoxy-3-ulose-α-L-erythro-hexopyranosyl]-4-O-
benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside (21)
A solution of trisaccharide 20 (300 mg, 0.42 mmol) in anhydrous
dichloromethane (12 mL) was stirred with molecular sieves (4 A), a
drop of acetic acid and pyridinium dichromate (376 mg, 1.0 mmol) for
4 h at room temperature. The solvent was evaporated and the residue
purified by column chromatography (toluene/ethyl acetate 2: 1) to give
270 mg (90%) of 21 as colourless crystals; mp 70–72 °C, [α]D20 = -
117.6 (c = 1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 4.86 (dd, 1H,
J1,2ax 9.6, J1,2eq 2.0 Hz, H-1), 1.60 (dd, 1H, J1,2ax 9.6, J2ax,2eq 13.6, J2ax,3
2.4 Hz, H-2ax), 2.05 (dd, 1H, J1,2eq 2.0, J2ax,2eq 13.6, J2eq,3 4.0 Hz, H-
2eq), 4.26 (m, 1H, H-3), 3.08 (dd, 1H, J3,4 2.8, J4,5 9.2 Hz, H-4), 3.92
(dq, 1H, J4,5 9.2, J5,6 6.4 Hz, H-5), 1.22 (d, 3H, J5,6 6.4 Hz, CH3-6), 5.24
(dd, 1H, J1′,2′ax 4.0, J1′,2′eq 0.8 Hz, H-1′), 2.77 (dd, 1H, J1′,2′ax 4.0,
J2′ax,2′eq 13.6, J2′ax,4′ 0.8 Hz, H-2′ax), 2.56 (dd, 1H, J1′,2′eq 0.8, J2′ax,2′eq
13.6 Hz, H-2′eq), 3.90 (dd, 1H, J2′ax,4′ 0.8, J4′,5′ 9.6 Hz, H-4′), 4.43 (dq,
1H, J4′,5′ 9.6, J5′,6′ 6.4 Hz, H-5′), 1.10 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 4.90
(dd, 1H, J1´´,2´´ax 9.6, J1´´,2´´eq 2.0 Hz, H-1´´), 1.96 (dd, 1H, J1´´,2´´ax 9.6,
J2´´ax,2´´eq 14.4, J2´´ax,3´´ 2.8 Hz, H-2´´ax), 2.25 (dd, 1H, J1´´,2´´eq 2.0,
J2´´ax,2´´eq 14.4, J2´´eq,3´´ 3.6 Hz, H-2´´eq), 5.79 (q, 1H, J2´´ax,3´´ 2.8,
J2´´eq,3´´ 3.6, J3´´,4´´ 2.8 Hz, H-3´´), 3.05 (dd, 1H, J3´´,4´´ 2.8, J4´´,5´´
9.6 Hz, H-4´´), 3.87 (dq, 1H, J4´´,5´´ = 9.6, J5´´,6´´ 6.4 Hz, H-5´´), 1.28 (d,
3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 3.32 (s, 3H, OCH3), 4.45, 4.49, 4.64 and
4.88 (each d, each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.30–8.00 (m, 15-H,
aryl-H). Calcd. for C40H48O11(704.7): C, 68.16; H, 6.86. Found: C,
J
5´´,6´´ = 6.4 Hz, H-5´´), 1.37 (d, 3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 3.58 (s, 3H,
OCH3), 4.46, 4.52, 4.68 and 4.89 (each d, each 1H, JCH2Bn 12.0 Hz,
CH2Bn), 7.20 (m, 10-H, aryl-H). Calcd. for C33H46O10(602.7): C, 65.75;
H, 7.96. Found: C, 65.81; H, 7.69.
Further 80 mg (12%) of 19 were isolated, colourless syrup,
[α]D20 = - 96.4 (c = 1.0, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 4.85
(dd, 1H, J1,2ax 9.6, J1,2eq 2.0 Hz, H-1), 1.59 (dd, 1H, J1,2ax 9.6, J2ax,2eq
13.2, J2ax,3 2.4 Hz, H-2ax), 2.12 (dd, 1H, J1,2eq 2.0, J2ax,2eq 12.0, J2eq,3
3.6 Hz, H-2eq), 4.28 (m, 1H, H-3), 3.14 (dd, 1H, J3,4 2.8, J4,5 9.2 Hz, H-
4), 3.87 (dq, 1H, J4,5 9.2, J5,6 6.4 Hz, H-5), 1.30 (d, 3H, J5,6 6.4 Hz, CH3-
6), 4.94 (dd, 1H, J1′,2′ax 3.2, J1′,2′eq 0.8 Hz, H-1′), 1.65 (dd, 1H, J1′,2′ax
3.2, J2′ax,2′eq 12.4, J2′ax,3′ 11.2 Hz, H-2′ax), 1.97 (dd, 1H, J1′,2′eq 0.8,
J2′ax,2′eq 12.4, J2′eq,3′ 5.2 Hz, H-2′eq), 4.07 (m, 1H, H-3′), 3.11 (t, 1H,
24

J. Thiem, H. Sajus
CarbohydrateResearch471(2019)19–27
67.55; H, 6.97.
6.2 Hz, CH3-6), 7.40–8.00 (m, 10H, aryl-H), 4.20 (m, 4H, 2x CH2), 1.40
(m, 6H, 2x CH3).
4.3.12. Benzyl 3-O-[4-O-(3-O-benzoyl-2,6-dideoxy-4-O-methyl-β-L-ribo-
hexopyranosyl)-2,6-dideoxy-α-L-ribo-hexopyranosyl]-4-O-benzyl-2,6-
dideoxy-β-L-ribo-hexopyranoside (22)
4.3.15. Benzyl 3-O-[4-O-(3-O-benzoyl-2,6-dideoxy-4-O-methyl-β-L-ribo-
hexopyranosyl)-3-O-(3,4-di-O-benzoyl-2,6-dideoxy-β-L-ribo-
A solution of trisaccharide 21 (230 mg, 0.32 mmol) in anhydrous
methanol (5 mL) was cooled to 0 °C and treated with sodium borohy-
dride (50 mg, 1.32 mmol). After stirring for 10 min at room temperature
the mixture was neutralized with hydrochloric acid (4 M), diluted with
water, extracted with dichloromethane, the organic phase dried
(MgSO4), filtered, evaporated and the raw material purified by column
chromatography (toluene/ethyl acetate 10: 1) to give 230 mg (99%) of
22 as colourless crystals; mp 63–65 °C, [α]D20 = - 103.5 (c = 1.0,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 4.86 (dd, 1H, J1,2ax 9.6, J1,2eq
2.0 Hz, H-1), 1.57 (dd, 1H, J1,2ax 9.6, J2ax,2eq 13.6, J2ax,3 2.8 Hz, H-2ax),
2.17 (dd, 1H, J1,2eq 2.0, J2ax,2eq 13.6, J2eq,3 3.6 Hz, H-2eq), 4.29 (m, 1H,
H-3), 3.13 (dd, 1H, J3,4 2.8, J4,5 9.2 Hz, H-4), 3.91 (dq, 1H, J4,5 9.2, J5,6
6.4 Hz, H-5), 1.24 (d, 3H, J5,6 6.4 Hz, CH3-6), 5.00 (dd, 1H, J1′,2′ax 3.2,
J1′,2′eq 0.8 Hz, H-1′), 1.94 (dt, 1H, J1′,2′ax 3.2, J2′ax,2′eq 13.6,
J2′ax,3´ = 3.2 Hz, H-2′ax), 2.08 (dd, 1H, J1′,2′eq 0.8, J2′ax,2′eq 13.6, J2′eq,3′
3.6 Hz, H-2′eq), 4.23 (m, 1H, H-3′), 3.24 (dd, 1H, J3′,4′ 2.8, J4′,5′
10.0 Hz, H-4′), 4.23 (dq, 1H, J4′,5′ 10.0, J5′,6′ 6.4 Hz, H-5′), 1.08 (d, 3H,
J5′,6′ 6.4 Hz, CH3-6′), 4.91 (dd, 1H, J1´´,2´´ax 9.6, J1´´,2´´eq 2.0 Hz, H-1´´),
1.99 (dd, 1H, J1´´,2´´ax 9.6, J2´´ax,2´´eq 13.2, J2´´ax,3´´ 2.8 Hz, H-2´´ax), 2.15
(dd, 1H, J1´´,2´´eq 2.0, J2´´ax,2´´eq 13.2, J2´´eq,3´´ 3.6 Hz, H-2´´eq), 5.78 (q,
1H, J2´´ax,3´´ 2.8, J2´´eq,3´´ 3.6, J3´´,4´´ 2.8 Hz H-3´´), 3.03 (dd, 1H, J3´´,4´´
2.8, J4´´,5´´ 9.2 Hz, H-4´´), 3.91 (dq, 1H, J4´´,5´´ 9.2, J5´´,6´´ 6.4 Hz, H-5´´),
1.28 (d, 3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 3.32 (s, 3H, OCH3), 4.49, 4.50,
4.69 and 4.88 (each d, each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.30–8.00 (m,
15-H, aryl-H). Calcd. for C40H50O11(706.8): C, 67.96; H, 7.13. Found: C,
67.92; H, 7.35.
hexopyranosyl)-2,6-dideoxy-α-L-ribo-hexopyranosyl]-4-O-benzyl-2,6-
dideoxy-β-L-ribo-hexopyranoside (25) and Benzyl 3-O-[4-O-(3-O-benzoyl-
2,6-dideoxy-4-O-methyl-β-L-ribo-hexopyranosyl)-3-O-(3,4-di-O-benzoyl-
2,6-dideoxy-α-L-ribo-hexopyranosyl)-2,6-dideoxy-α-L-ribo-
hexopyranosyl]-4-O-benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside (26)
A solution of compound 24 (75 mg, 0.14 mmol) and the acceptor 22
(20 mg, 0.028 mmol) in anhydrous acetonitrile (0.2 mL) were stirred
with activated molecular sieves (3 A) for 20 min. Then under light ex-
clusion as promotor iodonium bis-collidine perchlorate (100 mg,
0.21 mmol) was added and stirred for 30 min at room temperature. The
mixture was diluted with dichloro-methane (10 mL) washed with aqu-
eous sodium thiosulfate(10%, 20 mL), dried over MgSO4,filtered, eva-
porated and purified by chromatography (toluene/ethyl acetate 10: 1)
to give 6 mg (20%) of the anomeric mixture 25 + 26; anomeric ratio β:
α = 3: 1. β-anomer 25: 1H NMR (400 MHz, CDCl3): δ = 4.99 (dd, 1H,
J1,2ax 9.6, J1,2eq 2.0 Hz, H-1), 1.58 (dd, 1H, J1,2ax 9.6, J2ax,2eq = 13.6,
J
2ax,3 = 2.8 Hz, H-2ax), 2.16 (dd, 1H, J1,2eq 2.0, J2ax,2eq 13.6, J2eq,3
3.6 Hz, H-2eq), 4.38 (m, 1H, H-3), 3.24 (dd, 1H, J3,4 2.8, J4,5 9.6 Hz, H-
4), 4.35 (dq, 1H, J4,5 9.6, J5,6 6.4 Hz, H-5), 0.92 (d, 3H, J5,6 6.4 Hz, CH3-
6), 4.87 (dd, 1H, J1′,2′ax 3.6, J1′,2′eq 0.8 Hz, H-1′), 1.35 (dt, 1H, J1′,2′ax
3.6, J2′ax,2′eq 13.6, J2′ax,3′ 3.2 Hz, H-2′ax), 1.96 (dd, 1H, J1′,2′eq 0.8,
J2′ax,2′eq 13.6, J2′eq,3′ 3.6 Hz, H-2′eq), 4.26 (m, 1H, H-3′), 3.12 (dd, 1H,
J3′,4′ 2.8, J4′,5′ 8.8 Hz, H-4′), 4.13 (dq, 1H, J4′,5′ 8.8, J5′,6′ 6.4 Hz, H-5′),
1.32 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 5.38 (dd, 1H, J1´´,2´´ax 8.2, J1´´,2´´eq
2.0 Hz, H-1´´), 1.93 (dd, 1H, J1´´,2´´ax 8.2, J2´´ax,2´´eq 14.0, J2´´ax,3´´
2.8 Hz, H-2´´ax), 2.38 (dd, 1H, J1´´,2´´eq 2.0, J2´´ax,2´´eq 14.0, J2´´eq,3´´
3.6 Hz, H-2´´eq), 5.71 (m, 1H, H-3´´), 5.01 (dd, 1H, J3´´,4´´ 2.8, J4´´,5´´
9.2 Hz, H-4´´), 4.23 (dq, 1H, J4´´,5´´ 9.2, J5´´,6´´ 6.4 Hz, H-5´´), 1.34 (d,
3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 4.82 (dd, 1H, J1´´´,2´´´ax 10.0, J1´´´,2´´´eq
2.0 Hz, H-1´´´), 1.45 (dd, 1H, J1´´´,2´´´ax 10.0, J2´´´ax,2´´´eq 13.2, J2´´´ax,3´´´
2.8 Hz, H-2´´´ax), 1.98 (dd, 1H, J1´´´,2´´´eq 2.0, J2´´´ax,2´´´eq 13.2, J2´´´eq,3´´´
3.6 Hz, H-2´´´eq), 5.43 (m, 1H, H-3´´´), 2.65 (dd, 1H, J3´´´,4´´´ 2.8,
J4´´´,5´´´ 9.2 Hz, H-4´´´), 3.83 (dq, 1H, J4´´´,5´´´ 9.2, J5´´´,6´´´ 6.4 Hz, H-5´´´),
1.24 (d, 3H, J5´´´,6´´´ 6.4 Hz, CH3-6´´´), 3.28 (s, 3H, OCH3), 4.48, 4.56,
4.74 and 4.94 (each d, each 1H, JCH2Bn = 12.0 Hz, CH2Bn), 7.40–8.00
(m, 25-H, aryl-H). α-anomer 26: 1H NMR (400 MHz, CDCl3): δ = 4.99
(dd, 1H, J1,2ax 9.6, J1,2eq 2.0 Hz, H-1), 1.48 (dd, 1H, J1,2ax 9.6, J2ax,2eq
13.6, J2ax,3 2.8 Hz, H-2ax), 2.24 (dd, 1H, J1,2eq 2.0, J2ax,2eq 13.6, J2eq,3
3.6 Hz, H-2eq), 4.40 (m, 1H, H-3), 3.35 (dd, 1H, J3,4 2.8, J4,5 9.6 Hz, H-
4), 4.40 (dq, 1H, J4,5 9.6, J5,6 6.4 Hz, H-5), 1.10 (d, 3H, J5,6 6.4 Hz, CH3-
6), 4.87 (dd, 1H, J1′,2′ax 3.6, J1′,2′eq 0.8 Hz, H-1′), 1.78 (dt, 1H, J1′,2′ax
3.6, J2′ax,2′eq 13.6, J2′ax,3´ = 3.2 Hz, H-2′ax), 2.00 (dd, 1H, J1′,2′eq = 0.8,
4.3.13. S-[O,O-Diethyl-(4-O-benzoyl-2,6-dideoxy-α/β-L-arabino-
hexopyranosyl)]-dithiophosphate (23)
A solution of 4-O-benzoyl-L-rhamnal (4, 100 mg, 0.42 mmol) in
anhydrous benzene (2 mL) was stirred with O,O-diethyl S-hydrogen
phosphorodithioate (70 μL, 1.42 mmol) for 16 h at room temperature.
Following evaporation the remaining syrup was purified by column
chromatography (petroleum ether/ether 1: 1) to give 175 mg (quant.)
of 23 as greenish syrup; α: β ratio = 11: 1. α-anomer: 1H NMR
(250 MHz, CDCl3): δ = 5.90 (dd, 1H, J1,2ax 5.0, J1,2eq 1.0, J1,P 10.0 Hz,
H-1), 2.20–2.60 (m, 2H, H-2ax,-2eq), 4.20 (m, 1H, H-3), 4.80 (dd, 1H,
J3,4 9.2, J4,5 9.6 Hz, H-4), 4.20 (m, 1H, H-5), 1.25 (d, 3H, J5,6 6.4 Hz,
CH3-6), 7.40–8.00 (m, 5H, aryl-H), 4.20 (m, 4H, 2x CH2), 1.22 (m, 6H,
2x CH3). β-anomer: 1H NMR (250 MHz, CDCl3): δ = 5.00 (t, 1H, J1,2ax
9.6, J1,P 10.0 Hz, H-1), 2.20–2.60 (m, 2H, H-2ax,-2eq), 4.20 (m, 1H, H-
3), 4.75 (t, 1H, J3,4 9.2, J4,5 9.6 Hz, H-4), 4.20 (m, 1H, H-5), 1.28 (d, 3H,
J5,6 6.4 Hz, CH3-6), 7.40–8.00 (m, 5H, aryl-H), 4.20 (m, 4H, 2x CH2),
1.22 (m, 6H, 2x CH3).
J
2′ax,2′eq = 13.6, J2′eq,3´ = 3.6 Hz, H-2′eq), 4.09 (m, 1H, H-3′), 2.86 (dd,
1H, J3′,4´ = 2.8, J4′,5´ = 8.8 Hz, H-4′), 3.74 (dq, 1H, J4′,5′ 8.8, J5′,6′
6.4 Hz, H-5′), 1.10 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 5.71 (dd, 1H, J1´´,2´´ax
3.6, J1´´,2´´eq 0.8 Hz, H-1´´), 2.08 (dd, 1H, J1´´,2´´ax 3.6, J2´´ax,2´´eq 14.0,
J2´´ax,3´´ 2.8 Hz, H-2´´ax), 2.34 (dd, 1H, J1´´,2´´eq 0.8, J2´´ax,2´´eq 14.0,
J2´´eq,3´´ 3.6 Hz, H-2´´eq), 5.71 (m, 1H, H-3´´), 5.06 (dd, 1H, J3´´,4´´ 2.8,
4.3.14. S-[O,O-Diethyl-(3,4-di-O-benzoyl-2,6-dideoxy-α/β-L-ribo-
hexopyranosyl)]-dithiophosphate (24)
A solution of 23 (150 mg, 0.35 mmol) in anhydrous tetrahydrofuran
(2 mL) was stirred with triphenylphosphine (130 mg, 0.82 mmol) for
30 min and cooled to 0 °C. Then a solution of benzoic acid (130 mg,
1.1 mmol) and diethyl azodicarboxylate (150 μL, 0.96 mmol) in anhy-
drous tetrahydrofuran (2 mL) was added and stirring continued for
1 h at room temperature. The solvent was evaporated and the residue
purified by column chromatography (petroleum ether/ether 8: 1) to
give 75 mg (40%) of 24 as light green syrup; α: β ratio = 1: 9. β-
anomer: 1H NMR (250 MHz, CDCl3): δ = 5.50 (dt, 1H, J1,2ax 9.6, J1,2eq
2.2, J1,P 9.6 Hz, H-1), 2.40 (m, 2H, H-2ax,-2eq), 5.80 (m, 1H, H-3), 4.95
(dd, 1H, J3,4 3.6, J4,5 9.6 Hz, H-4), 4.20 (m, 1H, H-5), 1.30 (d, 3H, J5,6
J
4´´,5´´ 9.2 Hz, H-4´´), 4.23 (dq, 1H, J4´´,5´´ 9.2, J5´´,6´´ 6.4 Hz, H-5´´), 1.30
(d, 3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 5.05 (dd, 1H, J1´´´,2´´´ax 10.6, J1´´´,2´´´eq
2.0 Hz, H-1´´´), 1.84 (dd, 1H, J1´´´,2´´´ax 10.6, J2´´´ax,2´´´eq 13.2, J2´´´ax,3´´´
2.8 Hz, H-2´´´ax), 2.27 (dd, 1H, J1´´´,2´´´eq 2.0, J2´´´ax,2´´´eq 13.2, J2´´´eq,3´´´
3.6 Hz, H-2´´´eq), 5.77 (m, 1H, H-3´´´), 2.90 (dd, 1H, J3´´´,4´´´ 2.8,
J
4´´´,5´´´ 9.2 Hz, H-4´´´), 3.94 (dq, 1H, J4´´´,5´´´ 9.2, J5´´´,6´´´ 6.4 Hz, H-5´´´),
1.30 (d, 3H, J5´´´,6´´´ 6.4 Hz, CH3-6´´´), 3.32 (s, 3H, OCH3), 4.48, 4.56,
4.74 and 4.94 (each d, each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.40–8.00 (m,
25-H, aryl-H).
25

J. Thiem, H. Sajus
CarbohydrateResearch471(2019)19–27
4.3.16. Benzyl 3-O-[4-O-(3-O-benzoyl-2,6-dideoxy-4-O-methyl-β-L-ribo-
hexopyranosyl)-3-O-(4-O-benzoyl-2,6-dideoxy-3-ulose-β-L-erythro-hexo-
pyranosyl)-2,6-dideoxy-α-L-ribo-hexopyranosyl]-4-O-benzyl-2,6-dideoxy-
β-L-ribo-hexopyranoside (30) and Benzyl 3-O-[4-O-(3-O-benzoyl-2,6-
dideoxy-4-O-methyl-β-L-ribo-hexopyrano-syl)-3-O-(4-O-benzoyl-2,6-
dideoxy-3-ulose-α-L-erythro-hexopyranosyl)-2,6-dideoxy-α-L-ribo-
2´´eq), 5.20 (d, 1H, J4´´,5´´ 10.0 Hz, H-4´´), 4.74 (dq, 1H, J4´´,5´´ 10.0,
J
5´´,6´´ 6.4 Hz, H-5´´), 1.40 (d, 3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 4.90 (dd, 1H,
J1´´´,2´´´ax 0.6, J1´´´,2´´´eq 2.0 Hz, H-1´´´), 1.84 (dd, 1H, J1´´´,2´´´ax 9.6,
J
J
2´´´ax,2´´´eq 13.2, J2´´´ax,3´´´ 2.8 Hz, H-2´´´ax), 2.21 (dd, 1H, J1´´´,2´´´eq 2.0,
2´´´ax,2´´´eq 13.2, J2´´´eq,3´´´ 3.6 Hz, H-2´´´eq), 5.79 (dt, 1H, J2´´´ ax,3´´´ 2.8,
J2´´´ eq,3´´´ 3.6, J3´´´,4´´´ 2.8 Hz, H-3´´´), 2.90 (dd, 1H, J3´´´,4´´´ 2.8, J4´´´,5´´´
9.2 Hz, H-4´´´), 3.86 (dq, 1H, J4´´´,5´´´ 9.2, J5´´´,6´´´ 6.4 Hz, H-5´´´), 1.30
(d, 3H, J5´´´,6´´´ 6.4 Hz, CH3-6´´´), 3.34 (s, 3H, OCH3), 4.45, 4.54, 4.72
and 4.87 (each d, each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.40–8.00 (m, 25-
H, aryl-H). Calcd. for C53H62O15(939.0): C, 67.78; H, 6.65. Found: C,
67.71; H, 6.70.
hexopyranosyl]-4-O-benzyl-2,6-dideoxy-β-L-ribo-hexopyranoside (31)
a) Compound 28 (65 mg, 0.28 mmol) and O,O-diethyl S-hydrogen
phosphorodithioate (70 μL, 1.01 mmol) dissolved in benzene (1 mL)
were stirred overnight at room temperature. The solvent was evapo-
rated and the raw anomeric material 29 directly used for glycosylation.
Dissolved in anhydrous dichloromethane (1.5 mL) it was mixed with
the acceptor 22 (90 mg, 0.12 mmol) and stirred with molecular sieves
(3 A) for 20 min. Then the promotor iodine bis-collidinium perchlorate
(195 mg, 0.41 mmol) was added under light exclusion and stirred for
1 h at room temperature. The mixture was diluted with di-
chloromethane (20 mL), washed with aqueous sodium thiosulfate(10%,
40 mL), dried over MgSO4, filtered, evaporated and purified by chro-
matography (petroleum ether/ether 2: 1) to give 71 mg (60%) of the
anomeric mixture 30 + 31; anomeric ratio α: β = 1.1: 1.
4.3.17. Benzyl 3-O-[4-O-(3-O-benzoyl-2,6-dideoxy-4-O-methyl-β-L-ribo-
hexopy-ranosyl)-3-O-(4-O-benzoyl-2,6-dideoxy-β-L-ribo-hexopyranosyl)-
2,6-dideoxy-α-L-ribo-hexopyranosyl]-4-O-benzyl-2,6-dideoxy-β-L-ribo-
hexopyranoside (32) and Benzyl 3-O-[4-O-(3-O-benzoyl-2,6-dideoxy-4-O-
methyl-β-L-ribo-hexopyranosyl)-3-O-(4-O-benzoyl-2,6-dideoxy-α-L-ribo-
hexopyranosyl)-2,6-dideoxy-α-L-ribo-hexopyranosyl]-4-O-benzyl-2,6-
dideoxy-β-L-ribo-hexopyranoside (33)
A solution of the anomeric mixture of tetrasaccharides 30 + 31
(40 mg, 0.043 mmol) in anhydrous methanol (2 mL) was cooled to 0 °C
and treated with sodium borohydride (20 mg, 0.52 mmol). After stirring
for 10 min at room temperature the mixture was neutralized with hy-
drochloric acid (4 M), diluted with water, extracted with di-
chloromethane (10 mL), the organic phase dried (MgSO4), filtered,
evaporated and the raw material purified and separated by column
chromatography (toluene/ethyl acetate 6: 1) to give 38 mg (95%) of
32 + 33.
b) Compound 28 (22 mg, 0.09 mmol) and O,O-diethyl S-hydrogen
phosphorodithioate (25 μL, 0.34 mmol) dissolved in benzene (1 mL)
were stirred overnight at room temperature. The solvent was evapo-
rated and the raw anomeric material 29 directly used for glycosylation.
Dissolved in anhydrous acetonitrile (0.5 mL) it was mixed with the
acceptor 22 (30 mg, 0.04 mmol) and stirred with molecular sieves (3 A)
for 20 min. Then the promotor iodonium bis-collidine perchlorate
(195 mg, 0.41 mmol) was added under light exclusion and stirred for
1 h at room temperature. The mixture was diluted with di-
chloromethane (10 mL) washed with aqueous sodium thiosulfate(10%,
20 mL), dried over MgSO4,filtered, evaporated and purified by chro-
matography (petroleum ether/ether 2: 1) to give 22 mg (55%) of the
anomeric mixture 30 + 31; anomeric ratio α: β = 1: 2. Part of the β-
anomer 30 was obtained as colourless crystals, mp 163–165 °C;
[α]D20 = - 73.4 (c = 1.0, CH2Cl2); β-anomer 30: 1H NMR (400 MHz,
CDCl3): δ = 4.99 (dd, 1H, J1,2ax 9.2, J1,2eq 2.0 Hz, H-1), 1.60 (dd, 1H,
J1,2ax 9.2, J2ax,2eq 13.2, J2ax,3 2.8 Hz, H-2ax), 2.13 (dd, 1H, J1,2eq 2.0,
β-anomer 32: 18 mg (45%) as colourless syrup; [α]D20 = - 84.2
(c = 1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ = 5.01 (dd, 1H, J1,2ax
8.8, J1,2eq 2.0 Hz, H-1), 1.58 (dd, 1H, J1,2ax 8.8, J2ax,2eq 13.6, J2ax,3
2.8 Hz, H-2ax), 2.13 (dd, 1H, J1,2eq 2.0, J2ax,2eq 13.6, J2eq,3 3.6 Hz, H-
2eq), 4.27 (m, 1H, H-3), 3.12 (dd, 1H, J3,4 2.8, J4,5 8.8 Hz, H-4), 4.14
(dq, 1H, J4,5 8.8, J5,6 6.4 Hz, H-5), 1.28 (d, 3H, J5,6 6.4 Hz, CH3-6), 4.89
(dd, 1H, J1′,2′ax 4.0, J1′,2′eq 0.8 Hz, H-1′), 1.95 (dd, 1H, J1′,2′ax 4.0,
J2′ax,2′eq 14.4, J2′ax,3′ 4.4 Hz, H-2′ax), 2.21 (dd, 1H, J1′,2′eq 0.8, J2′ax,2′eq
14.4, J2′eq,3′ 3.6 Hz, H-2′eq), 4.34 (m, 1H, H-3′), 3.29 (dd, 1H, J3′,4′ 2.8,
J4′,5′ 9.6 Hz, H-4′), 4.36 (dq, 1H, J4′,5′ 9.6, J5′,6′ 6.4 Hz, H-5′), 1.00 (d,
3H, J5′,6′ 6.4 Hz, CH3-6′), 5.04 (dd, 1H, J1´´,2´´ax 8.4, J1´´,2´´eq 2.0 Hz, H-
1´´), 1.76 (dd, 1H, J1´´,2´´ax 8.4, J2´´ax,2´´eq 12.8, J2´´ax,3´´ 9.6 Hz, H-2´´ax),
2.36 (dd, 1H, J1´´,2´´eq 2.0, J2´´ax,2´´eq 12.8, J2´´eq,3´´ 5.6 Hz, H-2´´eq),
3.89 (m, 1H, H-3´´), 4.84 (t, 1H, J3´´,4´´ 8.8, J4´´,5´´ 8.8 Hz, H-4´´), 3.58
(dq, 1H, J4´´,5´´ 8.8, J5´´,6´´ 6.4 Hz, H-5´´), 1.30 (d, 3H, J5´´,6´´ 6.4 Hz,
CH3-6´´), 4.90 (dd, 1H, J1´´´,2´´´ax 9.6, J1´´´,2´´´eq 2.0 Hz, H-1´´´), 1.82 (dd,
1H, J1´´´,2´´´ax 9.6, J2´´´ax,2´´´eq 13.2, J2´´´ax,3´´´ 2.8 Hz, H-2´´´ax), 2.24 (dd,
1H, J1´´´,2´´´eq 2.0, J2´´´ax,2´´´eq 14.4, J2´´´eq,3´´´3.6 Hz, H-2´´´eq), 5.80 (dt,
1H, J2´´´ ax,3´´´ 2.8, J2´´´ eq,3´´´ 3.6, J3´´´,4´´´ 2.8 Hz, H-3´´´), 3.00 (dd, 1H,
J3´´´,4´´´ 2.8, J4´´´,5´´´ 9.2 Hz, H-4´´´), 3.93 (dq, 1H, J4´´´,5´´´ 9.2, J5´´´,6´´´
6.4 Hz, H-5´´´), 1.30 (d, 3H, J5´´´,6´´´ 6.4 Hz, CH3-6´´´), 3.38 (s, 3H,
OCH3), 4.40, 4.57, 4.75 and 4.93 (each d, each 1H, JCH2Bn 12.0 Hz,
CH2Bn), 7.40–8.00 (m, 25-H, aryl-H).
J
2ax,2eq 13.2, J2eq,3 3.6 Hz, H-2eq), 4.27 (m, 1H, H-3), 3.13 (dd, 1H, J3,4
2.4, J4,5 8.4 Hz, H-4), 4.09 (dq, 1H, J4,5 8.4, J5,6 6.4 Hz, H-5), 1.32 (d,
3H, J5,6 6.4 Hz, CH3-6), 4.90 (dd, 1H, J1′,2′ax 4.0, J1′,2′eq = 0.8 Hz, H-1′),
1.97 (dt, 1H, J1′,2′ax 4.0, J2′ax,2′eq 14.4, J2′ax,3′ 4.0 Hz, H-2′ax), 2.27 (dd,
1H, J1′,2′eq 0.8, J2′ax,2′eq 14.4, J2′eq,3′ 3.6 Hz, H-2′eq), 4.42 (m, 1H, H-3′),
3.26 (dd, 1H, J3′,4′ 2.8, J4′,5′ 9.6 Hz, H-4′), 4.35 (dq, 1H, J4′,5′ 9.6, J5′,6′
6.4 Hz, H-5′), 0.96 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 5.22 (dd, 1H, J1´´,2´´ax
9.2, J1´´,2´´eq 2.4 Hz, H-1´´), 2.67 (dd, 1H, J1´´,2´´ax 9.2, J2´´ax,2´´eq
14.4 Hz, H-2´´ax), 2.86 (dd, 1H, J1´´,2´´eq 2.4, J2´´ax,2´´eq 14.4 Hz, H-
2´´eq), 5.12 (d, 1H, J4´´,5´´ 10.0 Hz, H-4´´), 3.80 (dq, 1H, J4´´,5´´ 10.0,
J
5´´,6´´ 6.4 Hz, H-5´´), 1.44 (d, 3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 4.88 (dd, 1H,
J1´´´,2´´´ax 9.6, J1´´´,2´´´eq 2.0 Hz, H-1´´´), 1.77 (dd, 1H, J1´´´,2´´´ax 9.6,
J
2´´´ax,2´´´eq 14.0, J2´´´ax,3´´´ 2.8 Hz, H-2´´´ax), 2.14 (dd, 1H, J1´´´,2´´´eq 2.0,
J2´´´ax,2´´´eq 14.0, J2´´´eq,3´´´ 3.6 Hz, H-2´´´eq), 5.78 (m, 1H, H-3´´´), 2.99
(dd, 1H, J3´´´,4´´´ 2.8, J4´´´,5´´´ 9.2 Hz, H-4´´´), 3.92 (dq, 1H, J4´´´,5´´´ 9.2,
J5´´´,6´´´ 6.4 Hz, H-5´´´), 1.30 (d, 3H, J5´´´,6´´´ 6.4 Hz, CH3-6´´´), 3.38 (s,
3H, OCH3), 4.48, 4.55, 4.74 and 4.93 (each d, each 1H, JCH2Bn 12.0 Hz,
CH2Bn), 7.40–8.00 (m, 25-H, aryl-H). α-anomer 31: 1H NMR (400 MHz,
CDCl3): δ = 4.76 (dd, 1H, J1,2ax 9.6, J1,2eq 2.0 Hz, H-1), 1.75 (dd, 1H,
J1,2ax 9.6, J2ax,2eq 13.6, J2ax,3 2.8 Hz, H-2ax), 2.09 (dd, 1H, J1,2eq 2.0,
α-anomer 33: 20 mg (50%) as colourless crystals; mp 78–80 °C,
[α]D20 = - 131.2 (c = 1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3):
δ = 4.78 (dd, 1H, J1,2ax 9.6, J1,2eq 2.0 Hz, H-1), 1.57 (dd, 1H, J1,2ax 9.6,
J
2ax,2eq 13.6, J2ax,3 2.8 Hz, H-2ax), 2.10 (dd, 1H, J1,2eq 2.0, J2ax,2eq 13.6,
J2eq,3 3.6 Hz, H-2eq), 4.28 (m, 1H, H-3), 3.10 (dd, 1H, J3,4 2.8, J4,5
9.2 Hz, H-4), 3.85 (dq, 1H, J4,5 9.2, J5,6 6.4 Hz, H-5), 1.26 (d, 3H, J5,6
6.4 Hz, CH3-6), 4.87 (dd, 1H, J1′,2′ax 4.0, J1′,2′eq 0.8 Hz, H-1′), 1.76 (dd,
1H, J1′,2′ax 4.0, J2′ax,2′eq 14.8, J2′ax,3′ 3.2 Hz, H-2′ax), 2.20 (dd, 1H,
J1′,2′eq 0.8, J2′ax,2′eq 14.8, J2′eq,3′ 3.6 Hz, H-2′eq), 4.32 (m, 1H, H-3′),
3.35 (dd, 1H, J3′,4′ 3.2, J4′,5′ 9.6 Hz, H-4′), 4.33 (dq, 1H, J4′,5′ 9.6, J5′,6′
6.4 Hz, H-5′), 0.94 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 5.23 (dd, 1H, J1´´,2´´ax
2.8, J1´´,2´´eq 0.4 Hz, H-1´´), 1.93 (dt, 1H, J1´´,2´´ax = 2.8, J2´´ax,2´´eq 14.4,
J2´´ax,3´´ 3.2 Hz, H-2´´ax), 2.22 (dd, 1H, J1´´,2´´eq 0.4, J2´´ax,2´´eq 14.4,
J2´´eq,3´´ 3.6 Hz, H-2´´eq), 4.23 (m, 1H, H-3´´), 4.78 (dd, 1H, J3´´,4´´ 3.2,
J4´´,5´´ 10.4 Hz, H-4´´), 4.57 (dq, 1H, J4´´,5´´ 10.4, J5´´,6´´ 6.4 Hz, H-5´´),
J
2ax,2eq 13.6, J2eq,3 3.6 Hz, H-2eq), 4.25 (m, 1H, H-3), 3.06 (dd, 1H, J3,4
2.8, J4,5 9.2 Hz, H-4), 3.90 (dq, 1H, J4,5 9.2, J5,6 6.4 Hz, H-5), 1.30 (d,
3H, J5,6 6.4 Hz, CH3-6), 4.87 (dd, 1H, J1′,2′ax 4.4, J1′,2′eq 0.8 Hz, H-1′),
1.78 (dd, 1H, J1′,2′ax 4.4, J2′ax,2′eq 13.6, J2′ax,3′ 3.2 Hz, H-2′ax), 2.09 (dd,
1H, J1′,2′eq 0.8, J2′ax,2′eq 13.6, J2′eq,3′ 3.6 Hz, H-2′eq), 4.25 (m, 1H, H-3′),
3.28 (dd, 1H, J3′,4′ 3.2, J4′,5′ 10.0 Hz, H-4′), 4.33 (dq, 1H, J4′,5′ 10.0, J5′,6′
6.4 Hz, H-5′), 0.94 (d, 3H, J5′,6′ 6.4 Hz, CH3-6′), 5.34 (dd, 1H, J1´´,2´´ax
4.0, J1´´,2´´eq 0.8 Hz, H-1´´), 2.72 (dd, 1H, J1´´,2´´ax 4.0, J2´´ax,2´´eq
14.0 Hz, H-2´´ax), 2.80 (dd, 1H, J1´´,2´´eq 0.8, J2´´ax,2´´eq 14.0 Hz, H-
26

J. Thiem, H. Sajus
CarbohydrateResearch471(2019)19–27
1.29 (d, 3H, J5´´,6´´ 6.4 Hz, CH3-6´´), 4.96 (dd, 1H, J1´´´,2´´´ax 9.6,
J1´´´,2´´´eq 2.0 Hz, H-1´´´), 2.07 (dd, 1H, J1´´´,2´´´ax 9.6, J2´´´ax,2´´´eq 13.2,
[6] K. Funaki, K. Takeda, E. Yoshii, Chem. Pharm. Bull. 30 (1982) 4031–4036.
[7] N. Hirayama, M. Kasai, K. Shirata, Y. Ottashi, Y. Sasada, Bull. Chem. Soc. Jpn. 56
(1983) 2112–2115.
J
J
J
2´´´ax,3´´´ 2.8 Hz, H-2´´´ax), 2.24 (dd, 1H, J1´´´,2´´´eq 2.0, J2´´´ax,2´´´eq 13.2,
2´´´eq,3´´´ 3.6 Hz, H-2´´´eq), 5.82 (dt, 1H, J2´´´ ax,3´´´ 2.8, J2´´´ eq,3´´´ = 3.6,
3´´´,4´´´ 2.8 Hz, H-3´´´), 2.99 (dd, 1H, J3´´´,4´´´ 2.8, J4´´´,5´´´ 9.2 Hz, H-4´´´),
[8] J. Thiem, S. Köpper, Tetrahedron 46 (1990) 113–138.
[9] J. Thiem, H. Karl, J. Schwentner, Synthesis (1978) 696–698.
[10] H. Jin, T.Y.R. Tsai, K. Wiesner, Can. J. Chem. 61 (1983) 2442–2444.
[11] K. Wiesner, T.Y.R. Tsai, H. Jin, Helv. Chim. Acta 68 (1985) 300–314.
[12] H. Gross, U. Karsch, J. Prakt. Chem. 29 (1965) 315–318.
[13] H. Sajus, J. Thiem, Liebigs Ann. Chem. (1993) 211–213.
[14] K. Bock, C. Pedersen, Thiem, J. Carbohydr. Res 73 (1979) 85–91.
[15] L. Laupichler, H. Sajus, J. Thiem, Synthesis (1992) 1133–1136.
[16] M. Bergmann, H. Schotte, Ber. Dtsch. Chem. Ges. 54B (1921) 440–455.
[17] H.B. Mereyala, V.R. Kulkani, Carbohydr. Res. 187 (1989) 154–158.
[18] B. Iselin, T. Reichstein, Helv. Chim. Acta 28 (1944) 1146–1149.
[19] O. Mitsunobu, Synthesis (1981) 1–28.
3.95 (dq, 1H, J4´´´,5´´´ 9.2, J5´´´,6´´´ 6.4 Hz, H-5´´´),1.33 (d, 3H, J5´´´,6´´´
6.4 Hz, CH3-6´´´), 3.32 (s, 3H, OCH3), 4.46, 4.52, 4.71 and 4.89 (each d,
each 1H, JCH2Bn 12.0 Hz, CH2Bn), 7.40–8.00 (m, 25-H, aryl-H). Calcd.
for C53H64O15(941.0): C, 67.64; H, 6.85. Found: C, 67.54; H, 6.90.
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