Formation of aureolic acid oligodeoxy mono-, di-, and trisaccharides employing the dibromomethyl methyl ether reaction

Article abstract of DOI:10.1080/07328303.2017.1397682

2,3-Isopropylidene D-rhamnopyranoside 2 obtained from mannose was treated with dibromomethyl methyl ether to give 2,6-dideoxy-2-bromo-glucopyranosyl bromide 5. Correspondingly, the D-talo precursor 3 led to the epimeric galacto-pyranosyl bromide 4. Both g

Full text of DOI:10.1080/07328303.2017.1397682

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
Formation of aureolic acid oligodeoxy mono-, di-,
and trisaccharides employing the dibromomethyl
methyl ether reaction
Joachim Thiem & Bernhard Schöttmer
To cite this article: Joachim Thiem & Bernhard Schöttmer (2017) Formation of aureolic acid
oligodeoxy mono-, di-, and trisaccharides employing the dibromomethyl methyl ether reaction,
Journal of Carbohydrate Chemistry, 36:7, 279-293, DOI: 10.1080/07328303.2017.1397682
To link to this article: https://doi.org/10.1080/07328303.2017.1397682
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Date: 05 December 2017, At: 00:44

JOURNAL OF CARBOHYDRATE CHEMISTRY
, VOL. , NO. , –
https://doi.org/./..
Formation of aureolic acid oligodeoxy mono-, di-, and
trisaccharides employing the dibromomethyl methyl ether
reaction
Joachim Thiem and Bernhard Schöttmer
University of Hamburg, Faculty of Science, Department of Chemistry, Martin-Luther-King-Platz ,
Hamburg, Germany
ABSTRACT
ARTICLE HISTORY
Received  August 
Accepted  October 
2,3-Isopropylidene D-rhamnopyranoside
2
obtained from
mannose was treated with dibromomethyl methyl ether to give
2,6-dideoxy-2-bromo-glucopyranosyl bromide 5. Correspond-
ingly, the D-talo precursor 3 led to the epimeric galacto-pyranosyl
bromide 4. Both glycopyranosyl bromides were glycosylated
selectively to give exclusively β,1-3-linked glycopyranosides
by silver triflate catalysis. The 3-exo-methylene component
was epoxidized with mCPBA to give after reductive oxirane
opening the 3-C-methyl-β-D-ribo-hexopyranoside structure 17.
A corresponding build up led to the trisaccharide structure 21.
Formation of the exo-methylene derivative 25, its epoxidation to
26 and reductive opening gave stereoselectively the all-β-linked
methyl-branched trisaccharide 27, representing the mithramycin
E-D-C- trisaccharide.
KEYWORDS
Aureolic acids;
Oligodeoxyoligosaccharides;
Mithramycin;
Dibromomethyl methyl ether
method; β-Glycosylation for
-Deoxysaccharides
GRAPHICAL ABSTRACT
CONTACT Prof. Dr. Joachim Thiem
thiem@chemie.uni-hamburg.de
Department of Chemistry, Martin- Luther-King-Platz , D- Hamburg, Germany.
University of Hamburg, Faculty of Science,
©  Taylor & Francis Group, LLC

280
J. THIEM AND B. SCHÖTTMER
Introduction
Syntheses of oligosaccharides or glycoconjugates by glycosylation of normal sac-
charides has achieved a status generally accepted as solved, although often individ-
ual problems may require modified approaches, often rather particular solutions.[1]
For instance, stereospecific glycosylations of 2-deoxy sugars were extensively stud-
ied and resulted in many unusual and modified approaches. One of the particularly
effective methods in formation of 2-deoxy-α-glycosides is the N-iodosuccinimide
(NIS) method.[2,3] More recently some interesting alternative procedures were
suggested.[4,5] For formation of 2-deoxy-β-glycosides the dibromomethyl methyl
ether (DBE) pathway showed to be an ideally suited access.[2,3] Recently also some
other approaches were proposed.[6–8] Among the plethora of glycosylated natu-
ral products[9] the ubiquitous deoxy saccharides represent dominant structural
components,[10] thus, effective preparative accesses are of utmost importance.
Anthracycline antitumor antibiotics are well studied in the past decades.[11,12]
The most important members of the aureolic acid group are the cytostatics
chromomycin A3, olivomycin A, and the extremely effective yet rather toxic
mithramycin (Figure 1), whose constitution could be finally secured.[13,14] Attached
to the tetrahydroanthraquinone nucleus at the phenolic 6-OH is the B-A disaccha-
ride having D-arabino and D-lyxo configuration. At the 2-OH position the E-D-C
trisaccharide moiety with D-ribo and twice D-arabino configuration is found. The
saccharides are linked throughout via anomeric β-configurations. Since all sugars
display 2, 6-dideoxy structures it was of special attraction to employ the DBE
method[15] for the formation of these mithramycin oligodeoxyoligosaccharides.
Results and discussion
Synthesis of the mithramycin B-A disaccharide unit
As a follow-up to previous synthetic approaches for the B-A entity of
mithramycin,[13] the present approach was to employ the DBE method
throughout.[16] Isopropylidenation of methyl α-D-rhamnopyranoside[17] led to
compound 1, which was further benzoylated to give crystalline 2.[18] Derivative
1 was oxidized by pyridinium dichromate in dichloromethane at room temper-
ature to give the corresponding 4-ulose (L-configuration[19]). By reduction with
LiAlH4 the talo compound was obtained,[19] the benzoylation of which resulted in
the formation of crystalline compound 3. Treatment of 3 with zinc bromide and
dibromomethyl methyl ether in anhydrous dichloromethane at room temperature
gave the 2-bromo-galactopyranosyl bromide 4 in a good yield. By glycosylation
with benzyl alcohol in the presence of silver carbonate the crystalline glycoside 6
was obtained in a moderate yield. This in turn could be deformylated with acid
methanol to give in a good yield compound 7, which was used as the acceptor
structure in the glycosylation to follow.
As donor molecule for the glycosylation reaction, compound 5 was obtained by
DBE reaction of 2.[18] In a solvent mixture of toluene and nitromethane (4:1) the

JOURNAL OF CARBOHYDRATE CHEMISTRY
281
Figure . Mithramycin.
components were treated with silver triflate at −78°C to give the α-1,3- (8α) and
the β-1,3-interglycosidically linked derivative 8β in about a 60% yield and a ratio
of α:β = 1:3, which were separated by HPLC. Zemplén deacylation cleaved both
the formate and the benzoate functionalities in the non-reducing terminal ring,
but for unknown reasons the benzoate in the reducing moiety remained intact,
resulting in compound 9. Following radical reduction of 8β with tri-n-butyl stan-
nic hydride, the tetradeoxy component 10 was obtained in a good yield. As above
its Zemplén treatment led to the final derivative 11, which alternatively could be
obtained by radical reduction of compound 9. Both methods gave yields close to
80% (Scheme 1).

282
J. THIEM AND B. SCHÖTTMER
Reacꢀon condiꢀons: a) PDC, CH2Cl2 ; b) LiAlH4, dioxane; c) BzCl, pyridine ; d)
Br2CHOMe, ZnBr2, CH2Cl2, 0 °C; e) BnOH, Ag2CO3, 20 °C; f) MeOH, HCl, 20 °C; g)
AgOTf, toluene/nitromethane 4:1, 78°C; h) NaOMe/MeOH; i) Bu3SnH,toluene,
60°C,1h.
Scheme . Synthesis of the mithramycin B-A unit.
Synthesis of the mithramycin E unit
Starting with derivative 5 a four step preparation led to the crystalline 3-ulose
12,[20] which on treatment with methyl lithium gave a mixture of benzyl β-D-
olivomycoside and benzyl β-D-mycaroside in a ratio of arabino:ribo = 2:1, appar-
ently due to the missing of a directing axial anomeric functionality.[20] Therefore, an
alternative approach was devised to obtain the ribo component exclusively. Treat-
ment of 12 by Wittig reaction using methyltriphenyl phosphonium bromide and
n-butyl lithium[21] gave the exo-methylene derivative 13 cleanly, which was deben-
zoylated by Zemplén method to give compound 14.
In structure 14 the exo-methylene group together with the (S)-configured
hydroxy group at C-4 represented an ideal allylic alcohol system for employment of
Sharpless asymmetric epoxidation.[22] Considering the well-established and often
successfully reported requirements for a stereoselective Sharpless epoxidation,[22–25]

JOURNAL OF CARBOHYDRATE CHEMISTRY
283
Reacꢀon condiꢀons: a) Ph3PBr/n-BuLi ; b) NaOMe/MeOH; c) m-Cl-C6H4-CO3H; d)
LiAlH4, THF.
Scheme . Synthesis of the mithramycin E unit.
the oxidizing system for compound 14 using tert-butyl hydroperoxide and tetra
isopropyl ortho-titanate should contain (R,R)-diethyl-(+)-tartrate as directing
catalyst to give a (Re)-attack resulting in the desired (3R) – epoxide. Surprisingly,
under manifold varied conditions there was no evidence for the formation of
any epoxide. Even taking the “wrong” (S,S)-diethyl-(-)-tartrate no transformation
could be observed. Perhaps in this particular case limits for the utilization of the
Sharpless method became apparent.It could be discussed, whether the arrangement
of internal chirality in the sugar component may account for this result.
In this situation an application of the well-established m-chloroperbenzoic acid
for normal epoxidation (Prilezhaev reaction) was considered and applied to ben-
zoate 13. Gratifyingly, by reaction in dichloromethane at room temperature the
desired (3R)-configured spiro-epoxide 15 was obtained in an 83% yield with high
stereoselectivity. Evidently, the preferential attack to the exo-methylene sugar com-
ponent occurred from “underneath” and perhaps also influenced by the internal
chirality at carbons 1, 4, and 5, resulting in an unexpected high stereoselectivity for
the achiral reagent. A corresponding epoxidation of compound 14 under the above
conditions likewise resulted in a good yield (84%) and extraordinary high stereose-
lectivity to give the desired (3R)-epoxide 16. Finally, reductive opening of the epox-
ide with lithium aluminum hydride in tetrahydrofuran resulted in the β-glycoside
17 of mycarose[14,20] in a 75% yield (Scheme 2).
Synthesis of the mithramycin E-D-C trisaccharide unit
Based on previous studies,[20] the construction of the E-D-C-trisaccharide unit was
approached. First, the D-C-discacharide unit 19 having two β-1,3-linked gluco moi-
eties was synthesized under silver triflate catalysis at −78°C employing compound
5[18] and the benzyl glycoside 18.[26] The formate functionality was cleaved with

284
J. THIEM AND B. SCHÖTTMER
hydrochloric acid in methanol to give the crystalline compound 20.[21] Another
glycosylation with glycosyl bromide 5 under the above conditions led to the all-
β-1,3-linked trisaccharide 21 in a 70% yield. The α:β-ratio was determined to be
about 1:10.[20] The formate residue at the non-reducing terminus could be cleaved
as above to give the crystalline component 22. Under radical conditions employ-
ing tri-n-butyl stannic hydride all three bromo functions could be removed to give
compound 23, and this in turn was cleanly oxidized using pyridinium dichromate
in anhydrous dichloromethane to give the crystalline 3ꢀꢀ-ulose 24 in a 78% yield.[20]
In contrast to the successful employment of the Wittig reaction[27] en route for-
mation of the E monosaccharide unit, olefination in this trisaccharide case had
to be altered, since the basic reaction conditions led to considerable elimination
events with cleavage of the saccharide units. Also modification of the Wittig reaction
(Schlosser variation[28]), trimethylsulfonium iodide/sodium hydride (Corey)[29] or
[30]
the CH2I2-Zn-TiCl4 reagent system (Takai)
likewise led to eliminations or
low yields. Finally, even Peterson olefination[31] of compound 24 with freshly pre-
pared trimethylsilyl magnesium chloride in anhydrous tetrahydrofuran could also
result in some elimination, however, the exo-methylene trisaccharide component
25 could be obtained in a moderate yield of 22% after chromatographic purifica-
tion.
Further epoxidation of 25 could be nicely performed stereoselectively again
employing simply m-chloroperbenzoic acid as discussed above in the monosaccha-
ride case to give epoxy trisaccharide 26 in a 65% yield. As the final step, reduc-
tive opening of the epoxide with LiAlH4 in THF resulted in the formation of
target E-D-C-trisaccharide unit of mithramycin with all β-1,3-interglycosidically
linked 2,6-dideoxy saccharide moieties and the correct D-ribo structure
at the non-reducing terminus 27 in a 68% yield (Scheme 3).
Conclusion
Initially, the D-arabino-β,1-3-D-lyxo (B-A) disaccharide structure of mithramycin
was prepared selectively by the DBE reaction. The C-3-methyl-branched D-ribo
component (E) was obtained by use of a Prilezhaev epoxidation. Finally, the E-D-
C trisaccharide of mithramycin comprising the 3ꢀꢀ-metyl-branched D-ribo as well
as two subsequent D-arabino components, all β-1,3-interglycosidically linked, was
synthesized. Thus, the demanding formation of β-2,6-dideoxy oligosaccharides in
aureolic acid could be solved employing the DBE method throughout.
Experimental
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 chromatography was done on sil-
ica gel 60 (40–63 μm, Merck) by flash mode with the solvent mixture recorded.

JOURNAL OF CARBOHYDRATE CHEMISTRY
285
Reacꢀon condiꢀons: a) AgOTf, toluene and nitromethane 4:1, 78 °C; b) MeOH,
HCl, 20 °C; c) Bu3SnH, toluene, 60 °C, 1h; d) (C5H6N)2Cr2O7, HOAc, CH2Cl2; e)
(H3C)3SiCH2MgCl; f) m-Cl-C6H4-CO3H; g) LiAlH4, THF.
Scheme . Synthesis of the mithramycin E-D-C unit.
1H NMR (300 MHz) was done on Bruker WM-300 and signal assignment was by
1H,1H-COSY experiments. Mass spectra were recorded by the CI method on Varian
MAT 44S. Melting points are uncorrected and were taken with on Reichert heating
microscope. Optical rotations were measured with Perkin-Elmer polarimeters 241
using sodium D line (589 nm), cuvette length 10 cm, and temperature 20°C.
Methyl 4-O-benzoyl-6-deoxy-2,3-O-isopropylidene-α-D-talopyranoside (3).
Reaction of methyl 6-deoxy-2,3-O-isopropylidene-α-D-talopyranoside[19] (3.34 g,
15.3 mmol) dissolved in anhydrous pyridine (20 mL) was treated with benzoylchlo-
ride (8.0 mL, 0.07 mmol) at 0°C. After 24h at room temperature dichloromethane
(150 mL) was added, and the mixture was washed four times with diluted sulfuric

286
J. THIEM AND B. SCHÖTTMER
acid (1N) and water (two times), then dried over MgSO4 and purified on silica gel
with toluene/ethyl acetate 3:1. Crystallization was from methanol to give 3 as color-
20
less crystals. Yield 3.2 g (65%), mp 132°C, [α]D = +63.8 (c = 1.0, CH2Cl2). 1H-
NMR (300 MHz, CDCl3): δ = 7.46–7.15 (m, 5H, Aryl-H), 4.99 (d, 1H, J1,2 1.2 Hz,
H-1), 4.09 (dd, 1H, J1,2 1.2, J2,3 6.5 Hz, H-2), 4.44 (dd, 1H, J2,3 6.5, J3,4 5.4 Hz H-3),
5.30 (dd, 1H, J3,4 5.4, J4,5 2.0 Hz, H-4), 4.06 (dq, 1H, J4,5 2.0, J5,6 6.6 Hz H-5), 1.25 (d,
3H, J5,6 6.6 Hz, 6-CH3), 3.45 (s, 3H, OCH3), 1.19 and 1.28 (each s, each 3H, isoprop-
CH3). Calcd. for C17H22O6 (322.4): C, 63.34; H, 8.88. Found: C, 63.44; H, 6.87.
4-O-Benzoyl-2-bromo-2,6-dideoxy-3-O-formyl-α-D-galactopyranosyl
bromide (4). A solution of compound 3 (1.18 g, 3.66 mmol) in anhydrous
dichloromethane (25 mL) was treated at 0°C with dibromomethyl methyl ether
(1.25 mL, 7.6 mmol) and zinc bromide (187 mg, 0.83 mmol). Overnight the mix-
ture was stirred at room temperature. Then the reddish solution was cooled to 0°C
diluted with cold dichloromethane (20 mL) and washed with cold hydrochloric acid
(4N), dried over MgSO4 and quickly purified over silica gel by elution with cold
dichloromethane (100 mL). After evaporation 4 was obtained as colorless syrup;
20
yield 1.08 g (70%), [α]D = +297.6 (c = 0.13, CH2Cl2). The labile compound
can be kept as solution in anhydrous dichloromethane at −20°C for some time.
1H-NMR (300 MHz,CDCl3): δ = 7.43–8.06 (m, 5H, Aryl-H), 8.03 (d, 1H, J3,OCHO
0.9 Hz, OCHO), 6.59 (d, 1H, J1,2 3.5 Hz, H-1), 4.52 (dd, 1H, J1,2 3.5, J2,3 10.9 Hz,
H-2), 5.65 (ddd, 1H, J2,3 10.9, J3,4 3.5, J3,OCHO 0.9 Hz H-3), 5.30 (dd, 1H, J3,4 3.5,
J4,5 1.4 Hz, H-4), 4.06 (dq, 1H, J4,5 1.4, J5,6 6.6 Hz H-5), 1.26 (d, 3H, J5,6 6.6 Hz,
6-CH3).Calcd. for C14H14Br2O5 (422.1): C, 39.84; H, 3.34. Found: C, 38.54; H, 3.41.
Benzyl 4-O-benzoyl-2-bromo-2,6-dideoxy-3-O-formyl-β-D-galacto-pyrano-
side (6). A solution of compound 4 (95 mg, 0.22 mmol) in a mixture of anhy-
drous ether and dichloromethane (4 mL, 1:1) was treated at 0°C with benzyl alcohol
(0.1 mL, 0.96 mmol) and silver carbonate (220 mg, 11.3 mmol). Under exclusion
of light stirring was continued at room temperature overnight. After filtration via
Celite/active charcoal the mixture was evaporated and the remainder purified by
column chromatography on silica (dichloromethane/n-hexane 5:1). The syrup was
crystallized from ether/n-hexane to give 6 as colorless crystals. Yield 48 mg (48%),
20
1
mp 119°C, [α]D = +51.0 (c = 0.9, CH2Cl2). H-NMR (300 MHz,CDCl3): δ =
7.25–8.10 (m, 10H, Aryl-H), 8.01 (d, 1H, J3,OCHO 0.9 Hz, OCHO), 4.67 (d, 1H, J1,2
8.5 Hz, H-1), 4.12 (dd, 1H, J1,2 8.5, J2,3 11.0 Hz, H-2), 4.29 (ddd, 1H, J2,3 11.0, J3,4 3.3,
J3,OCHO 0.9 Hz H-3), 5.48 (dd, 1H, J3,4 3.3, J4,5 1.0 Hz, H-4), 4.70 and 4.97 (AB, 2H,
JAB = 11.8 Hz, CH2-C6H5), 3.82 (dq, 1H, J4,5 1.0, J5,6 6.5 Hz H-5), 1.31 (d, 3H, J5,6
6.5 Hz, 6-CH3). Calcd. for C21H21BrO6 (449.3): C, 56.14; H, 4.71. Found: C, 56.02;
H, 4.73.
Benzyl 4-O-benzoyl-2-bromo-2,6-dideoxy-β-D-galactopyranoside (7). A
solution of compound 6 (480 mg, 1.10 mmol) in methanol (60 mL) was treated
with 2 drops of concentrated HCl and kept overnight at room temperature. After
addition of sodium hydrogen carbonate and evaporation the residue was dissolved
in dichloromethane (50 mL), successively washed with aqueous sodium hydro-
gen carbonate and water, dried over MgSO4, filtered and evaporated to give 7 as

JOURNAL OF CARBOHYDRATE CHEMISTRY
287
20
colorless syrup. Yield 371 mg (80%), [α]D = +36.4 (c = 0.7, CH2Cl2). 1H-NMR
(300 MHz,CDCl3): δ=7.21-8.14 (m, 10H, Aryl-H), 4.60 (d, 1H, J1,2 8.4 Hz, H-1),
4.07 (dd, 1H, J1,2 8.4, J2,3 10.6 Hz, H-2), 3.97 (ddd, 1H, J2,3 10.6, J3,4 3.5, J3,3-OH
3.8 Hz H-3), 5.40 (dd, 1H, J3,4 3.5, J4,5 1.1 Hz, H-4), 4.71 and 4.98 (AB, 2H, JAB
=
12.0 Hz, CH2-C6H5), 3.85 (dq, 1H, J4,5 1.1, J5,6 6.4 Hz H-5), 2.55 (d, 1H, J3,3-OH
3.8 Hz, OH-3), 1.29 (d, 3H, J5,6 6.4 Hz, 6-CH3). Calcd. for C20H21BrO5 (421.3): C,
57.01; H, 5.02. Found: C, 57.10; H, 5.09.
Benzyl 4-O-benzoyl-3-O-(4-O-benzoyl-2-bromo-2,6-dideoxy-3-O-formyl-
α-D-glucopyranosyl)-2-bromo-2,6-dideoxy-β-D-galactopyranoside (8α) and
Benzyl 4-O-benzoyl-3-O-(4-O-benzoyl-2-bromo-2,6-dideoxy-3-O-formyl-β-D-
gluco-pyranosyl)-2-bromo-2,6-dideoxy-β-D-galactopyranoside (8β). A solution
of compound 7 (57 mg, 0.14 mmol) and compound 5[18] (70 mg, 0.17 mmol) in
a mixture of anhydrous nitromethane and toluene(5 mL, 1:4) was stirred with
activated molecular sieves (4 A, Merck) under nitrogen for 1 h. The mixture was
cooled to −78°C and silver triflate (57 mg, 0.21 mmol) added. Following stirring
for 30 h under nitrogen and exclusion of light the mixture was gradually warmed
to room temperature. After filtration purification by HPLC (dichloro-methane/n-
hexane/ethyl acetate 10:12:1) the mixture of 8α:8β (1:3) was obtained. Yield 58 mg
(56%).
20
Compound 8α: yield 12 mg (14%), colorless syrup [α]D = +42.6 (c = 0.45,
CH2Cl2). 1H-NMR (300 MHz,C6D6): δ = 7.06–8.14 (m, 15H, Aryl-H), 8.06 (d, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
J
3,OCHO 0.7 Hz, OCHO), 6.10 (dt, 1H, J2 ,3 11.2, J3 ,4 9.0, J3 ,OCHO 0.7 Hz H-3ꢀ), 5.36
(dd, 1H, J3,4 3.4, J4,5 0.8 Hz, H-4), 5.29 (d, 1H, J1 ,2 3.5 Hz, H-1ꢀ), 5.23 (t, 1H, J3 ,4
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9.0, J4 ,5 10.0 Hz, H-4 ), 4.88 (dq, 1H, J4 ,5 10.0, J5 ,6 6.4 Hz H-5 ), 4.58 and 4.82 (AB,
2H, JAB = 12.2 Hz, CH2-C6H5), 4.48 (dd, 1H, J1,2 8.6, J2,3 10.8 Hz, H-2), 4.38 (d,
ꢀ
ꢀ
1H, J1,2 8.6 Hz, H-1), 3.84 (dd, 1H, J2,3 10.8, J3,4 3.4 Hz H-3), 3.57 (dd, 1H, J1 ,2 3.5,
J2 ,3 11.2 Hz, H-2ꢀ), 2.82 (dq, 1H, J4,5 0.8, J5,6 6.2 Hz H-5), 1.29 (d, 3H, J5,6 6.4 Hz,
6ꢀ-CH3), 1.04 (d, 3H, J5,6 6.2 Hz, 6-CH3).
ꢀ
ꢀ
20
Compound 8β: yield 44 mg (42%), colorless syrup, [α]D = +38.5 (c = 0.85,
1
CH2Cl2). H-NMR (300 MHz,C6D6): δ = 7.02–8.14 (m, 15H, Aryl-H), 8.08 (d,
ꢀ
ꢀ
ꢀ
ꢀ
1H, J3,OCHO 0.8 Hz, OCHO), 5.59 (ddd, 1H, J2 ,3 10.8, J3 ,4 10.4, J3 ,OCHO 0.8 Hz
H-3ꢀ), 5.47 (dd, 1H, J3,4 3.4, J4,5 0.8 Hz, H-4), 4.92 (dd, 1H, J3 ,4 10.4, J4 ,5
ꢀ
ꢀ
ꢀ
ꢀ
9.8 Hz, H-4ꢀ), 4.69 (d, 1H, J1 ,2 8.6 Hz, H-1ꢀ), 4.65 and 4.90 (AB, 2H, JAB
=
ꢀ
ꢀ
12.2 Hz, CH2-C6H5), 4.57 (dd, 1H, J1,2 8.6, J2,3 10.4 Hz, H-2), 4.49 (d, 1H, J1,2
ꢀ
ꢀ
8.6 Hz, H-1), 3.75 (dd, 1H, J2,3 10.4, J3,4 3.4 Hz, H-3), 3.52 (dd, 1H, J1 ,2 8.6,
J2 ,3 10.8 Hz, H-2ꢀ), 3.19 (dq, 1H, J4 ,5 9.8, J5 ,6 6.2 Hz, H-5ꢀ), 3.10 (dq, 1H,
J4,5 0.8, J5,6 6.4 Hz, H-5), 1.18 (d, 3H, J5,6 6.2 Hz, 6ꢀ-CH3), 1.13 (d, 3H, J5,6
6.4 Hz, 6-CH3). Calcd. for C34H34Br2O10 (762.4): C, 53.56; H, 4.49. Found for 8α:
C, 53.65; H, 4.44; found for 8β: C, 53.68; H, 4.42.
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Benzyl
4-O-benzoyl-3-O-(2-bromo-2,6-dideoxy-β-D-glucopyranosyl)-2-
bromo-2,6-dideoxy-β-D-galactopyranoside (9). A solution of compound 8β
(36 mg, 0.054 mmol) in anhydrous methanol (5 mL) was treated with a catalytic
amount of sodium methylate for 6 h at room temperature. After neutralization with

288
J. THIEM AND B. SCHÖTTMER
Amberlite IR 120 H+ the residue was filtered, dissolved in ethyl acetate (10 mL)
20
filtered and evaporated to give 9 as colorless syrup. Yield 23 mg (78%), [α]D
=
1
+48.7 (c = 1.4, CH2Cl2). H-NMR (300 MHz,CDCl3): δ = 7.23–8.04 (m, 10H,
ꢀ
ꢀ
ꢀ
ꢀ
Aryl-H), 5.42 (dd, 1H, J3,4 3.5, J4,5 0.8 Hz, H-4), 3.15 (dd, 1H, J3 ,4 8.2, J4 ,5 9.2 Hz,
H-4ꢀ), 4.78 (d, 1H, J1 ,2 8.0 Hz, H-1ꢀ), 4.70 and 4.96 (AB, 2H, JAB = 11.8 Hz,
CH2-C6H5), 4.22 (dd, 1H, J1,2 8.5, J2,3 10.9 Hz, H-2), 4.59 (d, 1H, J1,2 8.5 Hz, H-1),
ꢀ
ꢀ
3.96 (dd, 1H, J2,3 10.9, J3,4 3.5 Hz H-3), 3.54 (m, 2H, H-2ꢀ, −3ꢀ), 3.37 (dq, 1H, J4 ,5
ꢀ
ꢀ
9.2, J5 ,6 6.2 Hz H-5ꢀ), 3.80 (dq, 1H, J4,5 0.8, J5,6 6.6 Hz H-5), 1.68 and 2.74 (bs, 2H,
OH),1.28 (d, 3H, J5,6 6.2 Hz, 6ꢀ-CH3), 1.26 (d, 3H, J5,6 6.6 Hz, 6-CH3). Calcd. for
C26H30Br2O8 (630.3): C, 49.54; H, 4.80. Found: C, 49.46; H, 4.72.
ꢀ
ꢀ
Benzyl
4-O-benzoyl-3-O-(4-O-benzoyl-2,6-dideoxy-3-O-formyl-β-D-ara-
bino-hexopyranosyl)-2,6-dideoxy-β-D-lyxo-hexopyranoside (10). A solution of
compound 8β (136 mg, 0.18 mmol) in anhydrous toluene (23 mL) was treated
under nitrogen with tri-n-butyl stannic hydride (290 μL, 1.0 mmol) and a catalytic
amount of α,αꢀ-azo-bis-isobutyronitrile and stirred for 3 h at 50°C. After evapo-
ration of the solvent the residue was purified by chromatography (toluene/ethyl
20
acetate 12:1) to give 10 as colorless syrup. Yield 92 mg (85%), [α]D = −4.3 (c =
1
1.1, CH2Cl2). H-NMR (300 MHz,CDCl3): δ=7.16–8.21 (m, 15H, Aryl-H), 8.07
(d, 1H, J3,OCHO 0.8 Hz, OCHO), 5.39 (bd, 1H, J3,4 3.0, J4,5 1.2 Hz, H-4), 5.19 (dddd,
1H, J2a ,3 9.8, J2e ,3 5.4, J3 ,4 9.4, J3 ,OCHO 0.8 Hz, H-3ꢀ), 4.97 (t, 1H, J3 ,4 9.4, J4 ,5
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
9.6 Hz, H-4ꢀ), 4.71 (dd, 1H, J1 ,2a 9.6, J1 ,2e 2.2 Hz, H-1ꢀ), 4.65 and 4.95 (AB, 2H,
JAB = 12.2 Hz, CH2-C6H5), 4.59 (dd, 1H, J1,2a 9.4, J1,2e 2.4 Hz, H-1), 4.03 (ddd, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
J
2a,3 8.2, J2e,3 4.8, J3,4 3.0 Hz, H-3), 3.69 (dq, 1H, J4,5 1.2, J5,6 6.4 Hz, H-5), 3.55 (dq,
1H, J4 ,5 9.6, J5 ,6 6.2 Hz, H-5ꢀ), 2.22 (ddd, 1H, J1 ,2e 2.2, J2a ,2e 10.6, J2a ,3 5.4 Hz,
H-2eꢀ), 2.08 (mc, 1H, J1,2e 2.4, J2a,2e 10.5, J2e,3 4.8 Hz, H-2e), 2.07 (mc, 1H, J1,2a 9.4,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J2a,2e 10.5, J2a,3 8.2 Hz, H-2a), 1.69 (ddd, 1H, J1 ,2a 9.6, J2a ,2e 10.6, J2a ,3 9.8 Hz,
H-2aꢀ), 1.27 (d, 3H, J5,6 6.4 Hz, 6-CH3), 1.22 (d, 3H, J5,6 6.2 Hz, 6ꢀ-CH3). Calcd. for
C34H36O10 (604.7): C, 67.54; H, 6.00. Found: C, 67.62; H, 6.06.
Benzyl
4-O-benzoyl-3-O-(2,6-dideoxy-3-O-formyl-β-D-arabino-hexo-
pyrano-syl)- 2,6-dideoxy-β-D-lyxo-hexopyranoside (11). a) A solution of com-
pound 10 (45 mg, 0.07 mmol) in anhydrous methanol (7 mL) was treated with a
catalytic amount of sodium methylate for 2 h at room temperature. After neutral-
ization with Amberlite IR 120 H+ the residue was filtered, dissolved in ethyl acetate
(10 mL) filtered and evaporated to give 78 as colorless syrup. Yield 26 mg (78%).
b) A solution of compound 9 (70 mg, 0.11 mmol) in anhydrous toluene (20
mL) was treated under nitrogen with tri-n-butyl stannic hydride (175 μL, 0.6
mmol) and a catalytic amount of α,αꢀ-azo-bis-isobutyronitrile and stirred for 1 h
at 60°C. After evaporation of the solvent the residue was purified by chromato-
graphy (toluene/ethyl acetate 12:1) to give 11 as colorless syrup. Yield 39 mg (75%),
20
[α]D = −7.4 (c = 1.3, CH2Cl2). 1H-NMR (300 MHz,CDCl3): δ = 7.16–8.21 (m,
ꢀ
ꢀ
ꢀ
ꢀ
10H, Aryl-H), 5.35 (bd, 1H, J3,4 3.0, J4,5 0.7 Hz, H-4), 4.97 (t, 1H, J3 ,4 8.0, J4 ,5
9.0 Hz, H-4ꢀ), 4.63 and 4.94 (AB, 2H, JAB = 12.2 Hz, CH2-C6H5), 4.56 (dd, 1H,
J1 ,2a 9.2, J1 ,2e 2.0 Hz, H-1ꢀ), 4.55 (dd, 1H, J1,2a 9.2, J1,2e 1.8 Hz, H-1), 4.01 (ddd,
ꢀ
ꢀ
ꢀ
ꢀ

JOURNAL OF CARBOHYDRATE CHEMISTRY
289
1H, J2a,3 8.2, J2e,3 4.8, J3,4 3.0 Hz, H-3), 3.68 (dq, 1H, J4,5 0.7, J5,6 6.4 Hz H-5), 3.46
(mc, 1H, J3 ,4 8.0 Hz, H-3ꢀ), 3.19 (dq, 1H, J4 ,5 9.0, J5 ,6 6.2 Hz H-5ꢀ), 2.10 (ddd, 1H,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J
1,2e 1.8, J2a,2e 11.6, J2e,3 4.8 Hz, H-2e), 2.02 (mc, 1H, J1,2a 9.2, J2a,2e 11.6, J2a,3 8.2 Hz,
H-2a), 2.01 (mc, 1H, J1 ,2e 2.0 Hz, H-2eꢀ), 1.60 (mc, 1H, J1 ,2a 9.2 Hz, H-2aꢀ), 1.31
(d, 3H, J5,6 6.4 Hz, 6-CH3), 1.33 (d, 3H, J5,6 6.2 Hz, 6ꢀ-CH3). Calcd. for C26H32O8
(472.5): C, 66.09; H, 6.83. Found: C, 65.98; H, 6.78.
ꢀ
ꢀ
ꢀ
ꢀ
Benzyl 4-O-benzoyl-3-C-methylen-2,3,6-trideoxy-β-D-erythro-hexopyrano-
side (13). A solution of methyl triphenyl phosphonium bromide (436 mg, 1.2 mmol)
in anhydrous THF (20 mL) was treated under nitrogen with n-butyl lithium in n-
hexane (436 μL, 1.0 mmol) at 0°C to give a yellow suspension. Under vigorous stir-
ring compound 12[18] (173 mg, 0.51 mmol) was added and stirred another 30 min at
room temperature. Diethyl ether (7 mL) was added, filtered and the remainder evap-
orated. Purification was by column chromato-graphy (toluene/ethyl acetate 20:1) to
20
give 13 as colorless syrup. Yield 110 mg (64%), [α]D = −70.6 (c = 1.0, CH2Cl2).
1H-NMR (300 MHz,CDCl3): δ = 7.32–8.12 (m, 10H, Aryl-H), 4.62 (dd, 1H, J1,2a
9.2, J1,2e 2.6 Hz, H-1), 4.92 and 5.28 (mc, 2H, CH2 = C), 4.92 (mc, 1H, J4,5 9.1 Hz,
H-4), 4.64 and 4.95 (AB, 2H, JAB = 11.9 Hz, CH2-C6H5), 3.60 (dq, 1H, J4,5 9.1, J5,6
6.2 Hz H-5), 2.70 (dd, 1H, J1,2e 2.6, J2a,2e 13.3 Hz, H-2e), 2.55 (dd, 1H, J1,2a 9.2, J2a,2e
13.3 Hz, H-2a), 1.37 (d, 3H, J5,6 6.2 Hz, 6-CH3). Calcd. for C21H22O4 (338.4): C,
74.54; H, 6.55. Found: C, 74.16; H, 6.47.
Benzyl 3-C-methylen-2,3,6-trideoxy-β-D-erythro-hexopyranoside (14). A
solution of compound 13 (107 mg, 0.32 mmol) in anhydrous methanol (10 mL) was
treated with a catalytic amount of sodium methylate for 24 h at room temperature.
After neutralization with Amberlite IR 120 H+ the residue was filtered, dissolved
in ethyl acetate (20 mL) filtered and evaporated to give 14 as colorless syrup. Yield
20
51 mg (66%), [α]D = −11.8 (c = 0.9, CH2Cl2). 1H-NMR (300 MHz, CDCl3): δ =
7.21–7.62 (m, 5H, Aryl-H), 4.90 and 5.05 (bs, 2H, CH2 = C), 4.57 and 4.88 (AB, 2H,
JAB = 11.8 Hz, CH2-C6H5), 4.48 (dd, 1H, J1,2a 9.0, J1,2e 2.4 Hz, H-1), 3.71 (mc, 1H,
J
4,5 8.8 Hz, H-4), 3.20 (dq, 1H, J4,5 8.8, J5,6 6.1 Hz H-5), 2.60 (dd, 1H, J1,2e 2.4, J2a,2e
13.2 Hz, H-2e), 2.38 (dd, 1H, J1,2a 9.0, J2a,2e 13.2 Hz, H-2a), 1.40 (d, 3H, J5,6 6.1 Hz,
6-CH3). Calcd. for C14H18O3 (234.3): C, 71.77; H, 7.74. Found: C, 71.69; H, 7.66.
Benzyl
3,3ꢀ-anhydro-4-O-benzoyl-2,6-dideoxy-3-C-hydroxymethyl-β-D-
ribo-hexopyranoside (15). A solution of compound 13 (250 mg, 0.74 mmol) in
1,2-dichloroethane (20 mL) was stirred with m-chloroperbenzoic acid (312 mg,
1.8 mmol) for 24 h at room temperature. The solution was washed with aqueous
sodium hydroxide (0.1 N) and trice with water, dried over MgSO4, filtered, and
evaporated. Purification by chromatography (toluene/ethyl acetate 4:1) gave 15 as
20
colorless syrup. Yield 215 mg (83%), [α]D = −33.7 (c = 0.7, CH2Cl2). 1H-NMR
(300 MHz,CDCl3): δ = 7.17–8.05 (m, 10H, Aryl-H), 5.15 (d, 1H, J4,5 9.3 Hz, H-4),
4.96 (dd, 1H, J1,2a 9.4, J1,2e 2.4 Hz, H-1), 4.62 and 4.93 (AB, 2H, JAB = 11.8 Hz,
CH2-C6H5), 4.00 (dq, 1H, J4,5 9.3, J5,6 6.2 Hz H-5), 2.61 and 2.72 (AB, 2H, JAB
=
4.2 Hz, H2C-epoxide), 2.32 (dd, 1H, J1,2e 2.4, J2a,2e 13.7 Hz, H-2e), 1.73 (dd, 1H,
1,2a 9.4, J2a,2e 13.7 Hz, H-2a), 1.32 (d, 3H, J5,6 6.2 Hz, 6-CH3). Calcd. for C21H22O5
(354.4): C, 71.17; H, 6.26. Found: C, 71.28; H, 6.31.
J

290
J. THIEM AND B. SCHÖTTMER
Benzyl
3,3ꢀ-anhydro-2,6-dideoxy-3-C-hydroxymethyl-β-D-ribo-hexo-
pyrano-side (16). A solution of compound 14 (70 mg, 0.30 mmol) in 1,2-dichloro-
ethane (10 mL) was stirred with m-chloroperbenzoic acid (139 mg, 0.80 mmol)
for 24 h at room temperature. The solution was washed with aqueous sodium
hydroxide (0.1 N) and trice with water, dried over MgSO4, filtered, and evaporated.
Purification by chromatography (toluene/ethyl acetate 4:1) gave 16 as colorless
20
1
syrup. Yield 60 mg (84%), [α]D = −15.8 (c = 0.6, CH2Cl2). H-NMR (300
MHz,CDCl3): δ = 7.17–8.05 (m, 5H, Aryl-H), 4.79 (dd, 1H, J1,2a 9.8, J1,2e 2.2 Hz,
H-1), 4.59 and 4.90 (AB, 2H, JAB = 11.8 Hz, CH2-C6H5), 3.46 (m, 2H, H-4, −5),
2.59 and 3.06 (AB, 2H, JAB = 4.4 Hz, H2C-epoxide), 2.28 (dd, 1H, J1,2e 2.2, J2a,2e
14.1 Hz, H-2e),1.68 (dd, 1H, J1,2a 9.8, J2a,2e 14.1 Hz, H-2a), 1.34 (d, 3H, J5,6 6.0 Hz,
6-CH3). Calcd. for C14H18O4 (250.3): C, 67.18; H, 7.25. Found: C, 67.22; H, 7.23.
Benzyl 2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranoside (17). A solution
of compound 16 (20 mg, 0.08 mmol) in anhydrous THF (3 mL) was stirred with
lithium aluminium hydride (5 mg, 0.13 mmol) for 24 h at room temperature. After
cautious addition of methanol the residue was filtered, taken up in ethyl acetate (10
mL), washed with water, dried over MgSO4 and evaporated to give 17 as colorless
20
20
syrup. Yield 15 mg (75%), [α]D = −40.9 (c = 0.7, CH2Cl2), lit.[17] [α]D
=
1
−44.1 (c = 0.42, CH2Cl2). The H-NMR (300 MHz, CDCl3) data corresponded
throughout.
Benzyl 4-O-benzoyl-3-O-[4-O-benzoyl-3-O-(3-C-methylen-2,3,6-trideoxy-
β-D-erythro-hexopyranosyl)-2,6-dideoxy-β-D-arabino-hexopyranosyl]-2,6-
dideoxy-β-D-arabino-hexopyranoside (25). Under nitrogen cover to magnesium
chips (15 mg, 0.6 mmol) in anhydrous THF (5 mL) was added trimethylsilyl methyl
chloride (71 mg, 0.6 mmol) and the reaction started by addition of some drops of
1,2-dibromo-ethane. After reflux for 1h and cooling to room temperature a solution
of compound 24 [20] (50 mg, 0.06 mmol) in warm anhydrous toluene (2 mL) and
stirred for another hour at 20°C. Following addition of aqueous ammonium sulfate
solution (20 mL), extraction with dichloromethane (3 times, each 10 mL) and dry-
ing over MgSO4, evaporation gave the raw material, which was purified by column
chromatography (toluene/ethyl acetate 4:1) to give compound 25 as colorless syrup.
20
Yield 10 mg (22%), [α]D = −53.7 (c = 0.8, CH2Cl2). 1H-NMR (300 MHz,CDCl3):
δ = 7.26–8.14 (m, 15H, Aryl-H), 4.91 (t, 1H, J3 ,4 9.5, J4 ,5 9.6 Hz, H-4ꢀ), 4.79 and
4.93 (bd, 2H, CH2 = C), 4.62 and 4.94 (AB, 2H, JAB = 12.0 Hz, CH2-C6H5), 4.66
ꢀ
ꢀ
ꢀ
ꢀ
(dd, 1H, J3,4 9.2, J4,5 9.3 Hz, H-4), 4.58 (dd, 1H, J1 ,2a 9.8, J1 ,2e 2.1 Hz, H-1ꢀ), 4.56
ꢀ
ꢀ
ꢀ
ꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
(dd, 1H, J1,2a 9.7, J1,2e 2.0 Hz, H-1), 4.32 (dd, 1H, J1 ,2a 9.2, J1 ,2e 2.6 Hz, H-1 ), 4.06
(ddd, 1H, J2a ,3 11.9, J2e ,3 5.3, J3 ,4 9.5 Hz, H-3ꢀ), 3.99 (ddd, 1H, J2a,3 12.0, J2e,3 5.2,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J3,4 9.2 Hz, H-3), 3.56 (dq, 1H, J4 ,5 9.6, J5 ,6 6.2 Hz, H-5ꢀ), 3.45 (dd, 1H, J4 ,5 9.0,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀꢀ ꢀꢀ
J4 ,4 -OH 7.0 Hz, H-4ꢀꢀ), 3.38 (dq, 1H, J4,5 9.3, J5,6 6.2 Hz, H-5), 2.96 (dq, 1H, J4 ,5
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
9.0, J5 ,6 6.2 Hz, H-5ꢀꢀ), 2.34 (dd, 1H, J1 ,2e 2.6, J2a ,2e 13.6 Hz, H-2eꢀꢀ), 2.32 (ddd,
ꢀꢀ ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1H, J1 ,2e 2.1, J2a ,2e 12.2, J2e ,3 5.3 Hz, H-2e ), 2.13 (ddd, 1H, J1,2e 2.0, J2a,2e 13.4, J2e,3
5.2 Hz, H-2e), 2.11 (dd, 1H, J1 ,2a 9.2, J2a ,2e 12.2, J2a ,3 13.6 Hz, H-2aꢀꢀ), 1.82 (ddd,
ꢀꢀ
ꢀꢀ
ꢀ
ꢀ
ꢀꢀ ꢀꢀ
1H, J1 ,2a 9.8, J2a ,2e 12.2, J2a ,3 11.9 Hz, H-2aꢀ), 1.58 (mc, 1H, J1,2a 9.7, J2a,2e 13.4,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ

JOURNAL OF CARBOHYDRATE CHEMISTRY
291
J2a,3 12.0 Hz, H-2a), 1.46 (d,1H, J4 ,4 -OH 7.0 Hz, 4ꢀꢀ-OH), 1.31 (d, 3H, J5 ,6 6.2 Hz,
ꢀꢀ ꢀꢀ
ꢀ
ꢀ
6ꢀ-CH3), 1.06 (d, 3H, J5 ,6 6.2 Hz, 6ꢀꢀ-CH3), 1.02 (d, 3H, J5,6 6.2 Hz, 6-CH3). Calcd.
ꢀꢀ ꢀꢀ
for C40H46O11 (702.8): CI with ammonia found (M+NH4)+ 721.
Benzyl 4-O-benzoyl-3-O-[4-O-benzoyl-3-O-(3,3ꢀ-anhydro-2,6-dideoxy-3-C-
hydroxymethyl-β-D-ribo-hexopyranosyl)-2,6-dideoxy-β-D-arabino-hexo-
pyranosyl]-2,6-dideoxy-β-D-arabino-hexopyranoside (26). A solution of com-
pound 25 (8 mg, 0.01 mmol) in 1,2-dichloroethane (3 mL) was stirred with
m-chloroperbenzoic acid (3.5 mg, 0.02 mmol) for 2 h at room temperature. The
solution was washed with aqueous sodium hydroxide (0.1 N) and trice with water,
dried over MgSO4, filtered, and evaporated. Purification by chromato-graphy
20
(toluene/ethyl acetate 4:1) gave 26 as colorless syrup. Yield 5 mg (65%), [α]D
=
1
−66.9 (c = 0.6, CH2Cl2). H-NMR (300 MHz,CDCl3): δ = 7.32–8.14 (m, 15H,
ꢀ
ꢀ
ꢀ
ꢀ
Aryl-H), 4.91 (dd, 1H, J3,4 9.4, J4,5 9.3 Hz, H-4), 4.65 (t, 1H, J3 ,4 9.0, J4 ,5 9.3 Hz,
H-4ꢀ), 4.64 (dd, 1H, J1 ,2a 10.0, J1 ,2e 2.0 Hz, H-1ꢀꢀ), 4.61 and 4.92 (AB, 2H, JAB
=
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀ
ꢀ
12.0 Hz, CH2-C6H5), 4.58 (dd, 1H, J1,2a 9.2, J1,2e 2.0 Hz, H-1), 4.57 (dd, 1H, J1 ,2a
ꢀ
ꢀ
ꢀ
9.7, J1 ,2e 1.8 Hz, H-1 ), 4.04 (ddd, 1H, J2a,3 12.0, J2e,3 5.1, J3,4 9.4 Hz, H-3), 3.93 (ddd,
1H, J2a ,3 11.8, J2e ,3 5.3, J3 ,4 9.0 Hz, H-3ꢀ), 3.56 (dq, 1H, J4,5 9.5, J5,6 6.4 Hz H-5),
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3.39 (dq, 1H, J4 ,5 9.3, J5 ,6 6.2 Hz, H-5ꢀ), 3.16 (mc, 2H, H-4ꢀꢀ,-5ꢀꢀ), 2.47 and 2.91
(AB, 2H, JAB = 4.5 Hz, CH2-epoxide), 2.32 (ddd, 1H, J1,2e 2.0, J2a,2e 12.2, J2e,3 5.1 Hz,
ꢀ
ꢀ
ꢀ
ꢀ
H-2e), 2.13 (ddd, 1H, J1 ,2e 1.8, J2a ,2e 12.4, J2e ,3 5.3 Hz, H-2eꢀ), 1.96 (dd, 1H, J1 ,2e
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀꢀ
ꢀꢀ
2.0, J2a ,2e 14.0 Hz, H-2eꢀꢀ), 1.81 (ddd, 1H, J1,2a 9.2, J2a,2e 12.2, J2a,3 12.0 Hz, H-2a),
ꢀꢀ
ꢀꢀ
1.54 (ddd, 1H, J1 ,2a 9.7, J2a ,2e 12.4, J2a ,3 11.8 Hz, H-2aꢀ), 1.43 (dd, 1H, J1 ,2a 10.0,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀꢀ
ꢀꢀ
ꢀꢀ
ꢀ
ꢀ
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
J2a ,2e 14.0, J2a ,3 11.8 Hz, H-2a ), 1.31 (d, 3H, J5,6 6.4 Hz, 6-CH3), 1.05 (d, 3H, J5 ,6
5.9 Hz, 6ꢀꢀ-CH3), 1.01 (d, 3H, J5 ,6 6.2 Hz, 6ꢀ-CH3). Calcd. for C40H46O12 (718.8):
ꢀ
ꢀ
CI with ammonia found (M+NH4)+ 737.
Benzyl
3-O-[3-O-(2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl)-2,6-
dideoxy-β-D-arabino-hexopyranosyl]-2,6-dideoxy-β-D-arabino-hexopyrano-
side (27). A solution of compound 26 (5 mg, 7 μmol) in anhydrous THF (2 mL)
was stirred with lithium aluminium hydride (2 mg, 0.05 mmol) for 24 h at room
temperature. After cautious addition of methanol the residue was filtered, taken up
in ethyl acetate (5 mL), washed with water, dried over MgSO4 and evaporated to
20
give 27 as colorless syrup. Yield 2.4 mg (68%), [α]D = – 58.3 (c = 0.15, CH2Cl2),
1H-NMR [300 MHz,(CD3)2CO]: δ=7.18-8.04 (m, 5H, Aryl-H), 4.83 (dd, 1H, J1 ,2a
ꢀꢀ
ꢀꢀ
9.4, J1 ,2e 2.2 Hz, H-1ꢀꢀ), 4.67 (dd, 1H, J1 ,2a 9.6, J1 ,2e 2.0 Hz, H-1ꢀ), 4.59 (dd, 1H,
ꢀꢀ
ꢀꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J
1,2a 9.8, J1,2e 2.0 Hz, H-1), 4.55 and 4.82 (AB, 2H, JAB = 12.0 Hz, CH2-C6H5), 3.97
(d, 1H, J4 ,4 -OH 7.8 Hz, 4ꢀꢀ-OH), 3.69 (dq, 1H, J4 ,5 9.4, J5 ,6 6.4 Hz, H-5ꢀꢀ), 3.59
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
(ddd, 1H, J2a ,3 10.8, J2e ,3 5.0, J3 ,4 9.0 Hz, H-3ꢀ), 3.57 (ddd, 1H, J2a,3 9.8, J2e,3 4.8,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
J3,4 9.2 Hz, H-3), 3.31 (dq, 1H, J4 ,5 9.8, J5 ,6 6.2 Hz, H-5ꢀ), 3.22 (dq, 1H, J4,5 9.3,
ꢀ
ꢀ
ꢀ
ꢀ
J5,6 6.0 Hz, H-5), 2.99 (dd, 1H, J4 ,5 9.4, J4 ,4 -OH 7.8 Hz, H-4ꢀꢀ), 2.93 (t, 1H, J3 ,4
ꢀꢀ ꢀꢀ
ꢀꢀ ꢀꢀ
ꢀ
ꢀ
9.0, J4 ,5 9.8 Hz, H-4ꢀ), 2.92 (1, 1H, J3,4 9.2, J4,5 9.3 Hz, H-4), 2.47 and 2.91 (AB, 2H,
ꢀ
ꢀ
JAB = 4.5 Hz, CH2-epoxide), 2.17 (mc, 2H, H-2e, −2eꢀ), 1.92 (dd, 1H, J1 ,2e 2.2,
ꢀꢀ
ꢀꢀ
J2a ,2e 13.4 Hz, H-2eꢀꢀ), 1.52 (mc, 3H, H-2a, −2aꢀ, −2aꢀꢀ), 1.28 (d, 3H, J5,6 6.0 Hz,
ꢀꢀ
ꢀꢀ
ꢀ
ꢀꢀ
ꢀ
ꢀ
ꢀꢀ ꢀꢀ
6-CH3), 1.26 (d, 3H, J5 ,6 6.2 Hz, 6 -CH3), 1.22 (d, 3H, J5 ,6 6.4 Hz, 6 -CH3), 1.21 (s,

292
J. THIEM AND B. SCHÖTTMER
3H, 3ꢀꢀ-CH3). Calcd. for C26H40O10 (512.6): CI with ammonia found (M+NH4)+
531.
Acknowledgements
Partial support of these studies by the Deutsche Forschungsgemeinschaft (DFG) is gratefully
acknowledged.
References
[1] Fraser-Reid, B.O.; Tatsuta, K.; Thiem, J. (Eds.) Synthesis of Oligo-saccharides, Chapter 5,
Glycoscience, 2nd Edition, Springer-Verlag, Berlin 2008.
[2] Thiem, J.; Klaffke, W. Syntheses of Deoxy Oligosaccharides, Top. Curr. Chem., 1990, 154,
284–332.
[3] Klaffke, W.; Thiem, J. Synthesis of 2-Deoxy Glycosides, Chaper 1.08, in Comprehensive Gly-
coscience (Eds. Kamerling, J.P. et al.), Elsevier, Amsterdam, 2007, pp 313–333.
[4] Zhu, D.; Adhikari, S.; Baryal, K.N.; Abdullah, B.N.; Zhu, J. Stereoselective Synthesis of
α-Digitoxosides and α-Boivinosides via Chelation-Controlled Anomeric O-Alkylation, J.
Carbohydr. Chem. 2014, 33, 438–451.
[5] Wang, H.; Tao, J.; Cai, X.; Chen, W.; Zhao, Y.; Xu, Y.; Yao, W.; Zeng, J.; Wan, Q. Stereoselective
Synthesis of α-Linked 2-Deoxy Glycosides Enabled by Visible-Light-Mediated Reductive
Deiodination, Chem. Eur. J. 2014, 20, 17319–17323.
[6] Baryal, K.N.; Adhikari, S.; Zhu, J. Catalytic Stereoselective Synthesis of β-Digitoxosides:
Direct Synthesis of Digitoxin and C1ꢀ-epi-Digitoxin, J. Org. Chem. 2013, 78, 12469–12476.
[7] Zhu, D.; Baryal, K.N.; Adhikari, S.; Zhu, J. Direct Synthesis of 2-Deoxy-β-Glycosides
via Anomeric O-Alkylation with Secondary Electrophiles, J. Am. Chem. Soc. 2014, 136,
3172–3175.
[8] Issa, J.P.; Bennett, C.S. A Reagent-Controlled SN2-Glycosylation for the Direct Synthesis of
β-Linked 2-Deoxy-Sugars, J. Am. Chem.Soc. 2014, 136, 5740–5744.
[9] Elshahawi, S.I.; Shaaban, K.A.; Kharel, M.K.; Thorson, J.S. A comprehensive review of gly-
cosylated bacterial natural products, Chem. Soc. Rev. 2015, 44, 7591–7697.
[10] de Lederkremer, R.M.; Marino, C. Deoxy sugars: occurrence and synthesis, Adv. Carbohydr.
Chem. Biochem. 2008, 61, 143–216.
[11] Remers, W.A. The Chemistry of Antitumor Antibiotics, Wiley, New York 1979.
[12] Lown, J.W. Discovery and development of anthracycline antitumour antibiotics, Chem. Soc.
Rev. 1993, 22, 165–76.
[13] Thiem, J.; Schneider, G. Structure determination and synthesis of disaccharide fragments
B-A of mithramycin, Angew. Chem. 1983, 95, 54–55.
[14] Thiem, J.; Schneider, G.; Sinnwell, V. Syntheses of olivosyloliosides and spectroscopic struc-
ture assignment of mithramycin, Liebigs Ann. Chem. 1986, 814–824.
[15] Bock, K.; Pedersen, C.; Thiem, J. Reaction of sugar derivatives with dibromomethyl methyl
ether: formation of bromodeoxy compounds, Carbohydr. Res. 1979, 73, 85–91.
[16] Thiem, J.; Schöttmer, B. ß-Glycosylierung bei 2-Desoxysacchariden: Konvergente Synthe-
sen der Oligosaccharide von Mithramycin, Angew. Chem. 1987, 99, 591–592; Angew. Chem.
Int. Ed. Engl. 1987, 26, 555–557.
[17] Evans, M.E.; Long, L.; Parrish, F.W. Reaction of carbohydrates with methylsulfonyl chlo-
ride in N,N-dimethylformamide. Preparation of some methyl 6-chloro-6-deoxyglycosides,
J. Org. Chem. 1968, 33, 1074–1076.

JOURNAL OF CARBOHYDRATE CHEMISTRY
293
[18] Thiem, J.; Gerken, M.; Bock, K. Synthesis of the tetradeoxydi-saccharide D-C of aureolic
acids, Liebigs Ann. Chem. 1983, 462–470.
[19] Defaye, J.; Gadelle, A.; Angyal, S.J. An efficient synthesis of L-fucose and L-(4-2H)fucose,
Carbohydr. Res. 1984, 126, 165–169.
[20] Thiem, J.; Gerken, M.; Schöttmer, B.; Weigand, J. Neue Synthesen von Aureolsäuretrisac-
chariden, Carbohydr. Res. 1987, 164, 327–341.
[21] Yoshimura, J.; Sato, K.; Funabashi, M. Branched-chain sugars XVII. Stereoselectivity
in the oxidation of several methyl 4,6-O-benzylidene-2-C- or −3-C-methylene-α- and
−β-D-hexopyranosides with m-chloroperbenzoic acid, Bull. Chem. Soc. Japan 1979, 52,
2630–2634.
[22] Katsuki, T.; Sharpless, K.B. The first practical method for asymmetric epoxidation, J. Am.
Chem. Soc. 1980, 102, 5974–5976.
[23] Seebach, D.; Prelog, V. Specification of the steric course of asymmetric syntheses, Angew.
Chem. 1982, 94, 696–702.
[24] Sharpless, K.B.; Woodard, S.S.; Finn, M.G. On the mechanism of titanium-tartrate catalyzed
asymmetric epoxidation, Pure Appl. Chem. 1983, 55, 1823–1836.
[25] Finn, M.G.; Sharpless, K.B. On the mechanism of asymmetric epoxidation with titanium-
tartrate catalysts, Asymmetric Synth. 1985, 5, 247–308.
[26] Thiem, J.; Gerken, M. Synthesis of β-D-olivosyl(1 → 3)-D-olivosides from mithramycin,
J. Carbohydr. Chem. 1983, 1, 229–249.
[27] Sato, K.; Yoshimura, J. Branched-chain sugars. XII. The stereoselec-tivities in the reaction
of methyl 4,6-O-benzylidene-α- and −β-D-hexopyranosid-3-uloses with diazomethane,
Bull. Chem. Soc. Japan 1978, 51, 2116–2121.
[28] Schlosser, M.; Schaub, B. Instant ylide: a storable and ready-to-use Wittig reagent, Chimia,
1982, 36, 396–397.
[29] Corey, E.J.; Chaykovsky, M.J. Dimethyloxosulfonium methylide and dimethylsulfonium
methylide. Formation and application to organic synthesis, J. Am. Chem. Soc. 1965, 87,
1353–1364.
[30] Hibino, J.; Okazoe, T.; Takai, K.; Nozaki, H. Carbonyl methylenation of easily enolizable
ketones, Tetrahedron Lett. 1985, 26, 5579–5580.
[31] Peterson, D.J. Carbonyl olefination reaction using silyl-substituted organometallic com-
pounds, J. Org. Chem. 1968, 33, 780–784.