Synthesis of carbohydrate-based azamacrocycles by Richman-Atkins cyclisation

C. R. Chimie 14 (2011) 286–300

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´

Full paper/Memoire

Synthesis of carbohydrate-based azamacrocycles by Richman–Atkins

cyclisation

*

Andreas Rathjens, Joachim Thiem

Department of Chemistry, Faculty of Science, University, of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany

A R T I C L E I N F O

A B S T R A C T

Article history:

Symmetrical nitrogen containing ring structures with two or four glucose units were easily

obtained from accessible monosaccharide building units. Various tetherings via 4,4’- and

6,6’-positions lead to a variety of precursors which were transformed successively

employing different bridging units by Richman–Atkins cyclisation to result in deﬁned

glycophane coronands.

Received 4 February 2010

Accepted after revision 29 March 2010

Available online 8 June 2010

Keywords:

Aza-macrocycles

Tethered disaccharides

Carbohydrates

Cyclisations

1. Introduction

suggested by Wilcox et al. to be termed ‘‘glycophanes’’ [11].

Previously, several groups were involved in the synthesis

Chiral macrocyclic receptors are presently under

intense study. Particularly suitable structures for construc-

tion of such moities are saccharide units. Due to their

polyfunctional character leaving excessive room for all

types of derivatives, their pronounced and broadly variable

chirality, as well as their immanent ethylenoxy units, the

ubiquitously accessible carbohydrate derivatives contain

the primary structural elements as crown ethers.

The advantage of such starting materials, in contrast to

other structures, was previously noted and used by Stoddart

et al. who could obtain monosaccharide coronands from D-

mannitol [1,2]. According to their studies carbohydrate

precursors are suitable for construction of enzyme models

[3–5]. Also Penades et al. could employ disaccharide crown

ethers as chiral catalysts [6–8], and later reported on the

complexation capacity of water-soluble carbohydrate-

based macrocyles for neutral molecules [9–10]. The

distinctive feature of these host molecules resides in the

linkage of cyclophane and saccharide building units. Such

hybrids of glycosides and aromatic building elements were

and characterisation of carbohydrate-based macrocycles

[12–26], and some further examples were also reported on

hetereoatom-substituted azacycles and bicyclic cryptandes

[18,19,27–32].

2. Results and discussion

In this contribution a general synthetic approach for the

selective construction of azamacrocycles from monosac-

charide derivatives will be proposed. As a constraint, ring

systems were required to contain at least two saccharide

fragments. Thus, deﬁned and adequately functionalised

tethered monosaccharide precursors had to be synthe-

sised. The most important reaction step in these sequences

is the Richman–Atkins cyclisation [33,34]. Generally, in

this method, alkali (preferred cesium) metal salts of

sulfonamides are employed as excellent nucleophiles to

react with good electrophiles in polar aprotic media such

as dimethyl formamide. The conditions, applicability and

scope of this condensation were broadly studied by various

groups [35–42]. In comparison to the high dilution method

[43,44] or template-mediated ring closing procedures

[45,46], the Richman–Atkins approach is preparatively

facile and advantageous. Even though the many polar

* Corresponding author.

E-mail address: thiem@chemie.uni-hamburg.de (J. Thiem).

doi:10.1016/j.crci.2010.03.032

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

287

Scheme 1. Synthesis of 4,4’-tetherod glucopyranosides: (a) (for 3)

50% NaOH, Bu,NBr. Tol, 60–808C. (c)

,

50% NaOH. Bu₄nBr, Tol, 40X, (b) (for 6/9)

˚

, 50% NaOH. Bu₄NBr. Tol. 60C; (d) (for 12) TsNH₂

Cs₂CO₃DMF. 508C; (e) Pd/C (5%). Hj MeOH, Et₃N; f) TsCI. Py, -208C.

functions in saccharide units may present problems for the

required preorganisation of cycles, this approach seemed

to be attractive and the preferred pathway.

tosylation led to the corresponding bis 6-tosylamides 5, 8,

11 and 14 via three steps in about 50% yield from 1.

Further, cyclisation of the 4,4’-tethered derivatives 5

and 14 via their 6,6’-bis tosylamide functions was made by

Richman–Atkins cyclisation employing various alkyl tosy-

lates {ethylene glycol ditosylate, diethylene glycol ditosy-

late, diethanol amine tritosylate [50,51], and 1,8-bis-p-

toluene sulfonyloxy-3,6-dithia-octane (15)} as well as

As a suitable monosaccharide building unit the base

stable derivative 1 [47] was identiﬁed. This carries benzyl

ether protecting groups, the unblocked 4-OH position and

the azido as a masked amino function. For construction of

the 4,4’-tethered disaccharide mimetics the phase-transfer

catalysed ether formation [48] employing various alkyl-

ation reagents was applied (Scheme 1). By using the two-

phase system toluene and concentrated aqueous sodium

hydroxide the 3-oxapentylene-bridged compound 3 was

obtained with diethylene glycol ditosylate. Correspond-

a,a’-dibromo-p-xylene to give compounds 16–31 in good

yields (Scheme 2). Treatment of the precursors 5 and 14

with 1,8-ditosyloxy-3,5-dithia-octane 15 as electrophilic

partner could be performed at room temperature to give in

somewhat reduced yields yet without elimination the

carbohydrate coronands 19 and 31. The macrocyclic

system 19 comprises a doubly tethered disaccharide

component with a 23-membered ring, and 31 represents

ingly, use of

a,a’-dibromo p- and m-xylene resulted in

formation of the p- and m-xylene-bridged compounds 6

and 9. Treatment of 1 with bis (2-chloroethyl)-ether gave 2

in high yields, which in turn with stoichoimetric amounts

of p-toluene sulphonamide and cesium carbonate, led to

formation of compound 12 bridged by a 3,9-oxa-6-N-tosyl-

aza-undecane chain. Subsequently the azido functions

were catalytically hydrogenated [49] to give the corre-

sponding bis 6-amino derivatives 4, 7, 10 and 13 with

palladium/charcoal in the presence of trietylamine to

preserve the benzyloxy functions. Finally, low temperature

a

novel class of carbohydrate coronands containing

oxygen, nitrogen and sulphur donors within 29-

a

membered ring system. In all ring closing reactions

dimethyl formamide as solvent and cesium carbonate as

base were used advantageously exploiting the cesium

effect [36–38,52,53]. Thus rings systems 16–31 containing

two carbohydrate units and 17 to 29 chain links could be

obtained in remarkable average yields above 50%.

288

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

Scheme 2. Richman- Atkins cydization via 6,6’-positions of 4,4-telhered glucopyranosides: (a) (for 16–18, 20–21, 23–25, 27–29)

.

˚

C82CO3 DMF. 20–90’C. (b) (for 22, 26, 30)

. Cs₂CO, DMF. 20–90’C: (c) (for 19. 31)

(15) CS₂CO₃. DMF. 20C.

It was of interest to achieve the synthesis of ring

systems containing four saccharide fragments. Attempts to

this endeavour via a [2+2] cyclisation could not be realised.

Thus, by starting with the previously described 4,4’-

tethered structures 5, 11 and 14 activated 6,6’-extended

precursors had to be prepared (Scheme 3). By reaction of 5

or 11 with 2-(2-chloroethoxy)-tetrahydropyran [54] in

excess and subsequent acid cleavage of the ether deriva-

tive gave compounds 32 and 34, respectively. By further

low temperature tosylation the 6,6’-extended 4,4’-teth-

ered glucopyranosides 33 and 35 could be obtained easily.

Using a corresponding approach the precursors 5 and

14 were transformed into other 6,6’-extended derivatives.

The mono-silylated reagent 36 was obtained from

diethanolamine by reaction with two equivalents of tosyl

chloride at 0 8C and low temperature workup to give N-

tosyl-diethanolamine [55] followed by selective silylation.

After Cs₂CO₃-mediated reaction with compounds 11 and

14 the silylether groups were cleaved with tetrabutylam-

monium ﬂuoride to give compounds 37 and 39, respec-

tively. These in turn underwent monotosylations to give

the ﬁnal derivatives 38 and 40. Thus, in overall yields

between 40–70% these readily available components are

ideally suited for further reactions to function as electro-

philic components in Richman–Atkins cyclisations

(Scheme 3).

The ﬁnal cyclisation towards the tetrasaccharide

coronands 41–43 could be realised in around 50% yield.

As previously mentioned [56] combinations of long-chain

electrophiles and short nucleophiles would be preferred

for condensations, in contrast to the opposite arrangement.

However, in the present case the reactions of the 4,4’

tethered substrates 5 and 11 with the 6,6’-extended

derivatives 33, 35 and 38 went as straight forward as in the

previously described formation of the disaccharide ana-

logs. These novel macrocycles with 34 to 40 ring atoms are

novel representatives of [2+2]-glycophanes. Initially,

smaller glycophanes made from trehalose in lower yields

´

were reported by Penades et al. [7,9,10]. In the present case

the excellent operation of the Richman-Atkins approach

allowed quite pleasing yields and very large components

(Scheme 4).

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

289

˚

Scheme 3. Preparation of 6,6’-extended 4.4’-tethered giucopyranosides (a)

CS₂CO₃DMF. 100C; (b) cone. HCI/MeOH, CH₂CI₂20C; (c)

TsCI, Py. –208C; (d)

(36), CS₂CO₃DMF, 708C; (e) Bu₄NBr, THF, 208C.

Generally difﬁcult is the analysis of these coronands.

Both by NMR and combustion analyses it remains

ambiguous whether the products were obtained by a

[1+1] or a [2+2] condensation due to the molecular

symmetry. However, by Maldi-Tof an unequivocal struc-

tural assignment was at hand.

In conclusion, it was demonstrated that the Richman–

Atkins cyclisation could be used advantageously to

synthesize a number of structurally quite diverse aza-

carbohydrate coronands in high yields. Based on single

starting materials the present approach should be accept-

ed as the preferred method for formation of ﬂexibly

variable glyophanes. Experiments are under way to

address the de-blocking of these coronands. Further

studies will be concerned with the properties such as

stability of the cavities as well as their complexation

capability for various metal ions.

ethanol and further heating to 200 8C. Column chromatog-

raphy was done on silica gel 60 (230–400 mesh, Merck) by

the ﬂash mode with the solvent mixture recorded. ¹H NMR

(400 MHz) and ¹³C NMR spectra (100 and 62 MHz) were

done on Bruker AMX-400 and AC-250. Signal assignment

was by ¹H,¹H- and ¹H,¹³C-COSY measurements. CDCl₃

77.0 for ¹³C) and TMS ( 0.0 for ¹H) were used as internal

(d

d

standards. FAB mass spectra were recorded on double

focussing mass spectrometer VG 70-250 S (VG Analytical)

with m-nitrobenzyl alcohol as matrix material and xenon as

ionisation gas. Maldi-Tof mass spectra were done on Bruker

Biﬂex with nitrogen laser 337 nm, puls width 5 ms and 4-

hydroxy-a-cinnamic acid as matrix. Melting points and

glass temperatures are uncorrected and were taken with a

Leitz heating microscope or with an Olympus BH polarising

microscope and Mettler FP82 heating table. Optical rota-

tions were measured with Perkin-Elmer polarimeters 241

and243usingsodiumDline(589 nm), cuvettelength10 cm,

and temperature 20 8C. Elemental analysis was performed

by the Microanalytical Section of the Department of

Chemistry.

3. Experimental part

3.1. General

All reactions were monitored by thin layer chromatog-

raphy on silica gel foils GF₂₅₄(Merck). Detection was by UV

or spraying with 20% ethanolic sulfuric acid and subsequent

heating. Amines were detected with 10% ninhydrin in

3.1.1. General procedure 1

3.1.1.1. Alkylation by phase transfer catalysis (GP1). The

saccharide derivative was dissolved in the given solvent

290

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

Scheme 4. Synthesis of highly symmetric tetrasaccharide coronands: (a) Cs₂CO₃DMF, 70–80X.

and alkylation reagent (0.55 eq) and phase transfer catalyst

(1.5 eq) were added. Under vigorous stirring 20–50%

aqueous sodium hydroxide was added and the reaction

performed as recorded. For workup the aqueous phase was

thoroughly extracted by an organic solvent, combined with

the organic phase, dried over sodium sulfate, and after

evaporation the residue puriﬁed or separated by chroma-

tography.

3.1.4. General procedure 4

3.1.4.1. Richman-Atkins cyclisation (GP4). The ditosylate or

dichloride (0.5–1.0 mmol) and the nucleophilic component

(0.5–1.0 mmol) were dissolved in anhydrous dimethyl

formamide (10 mL). After addition of base (3–5 eq of

Na₂CO₃, K₂CO₃of Cs₂CO₃) the reaction was kept as 60–

80 8C for several days. Workup was by ﬁltration over silica

gel and evaporation. The remainder was dissolved in

toluene/ethyl acetate and treated by ultra soniﬁcation for

5 min followed by ﬁltration over silica gel, evaporation and

puriﬁcation of the raw material by chromatography.

3.1.2. General procedure 2

3.1.2.1. Hydrogenation of azides without cleavage of benzyl

ethers (GP2). The diazido derivatives (3–5 mmol) were

dissolved in methanol (50–100 mL), triethylamine (2 mL)

and 5% palladium on charcoal (500 mg) added. Hydro-

genation was done at normal pressure for about 24 h,

and workup was by ﬁltration over celite and evapora-

tion.

4. Methyl 6-azido-2,3-di-O-benzyl-4-O-(5-chloro-3-

oxapentyl)-6-deoxy-a-D-glucopyranoside (2)

The synthesis followed GP1 employing 1 (5.7 g,14.27

mmol), bis(2-chloro-ethyl)-ether (40.8 g, 33 mL, 285

mmol), (4.5 g, 14.2 mmol) tetrabutylammonium bromide,

toluene (150 mL), 50% aqueous sodium hydroxide (60 mL),

60 8C, 3 h. Puriﬁcation was by ﬂash chromatography

(dichloromethane/acetone 50:1). Yield 6.4 g (88%), colour-

3.1.3. General procedure 3

3.1.3.1. Tosylation of amines and alcohols (GP3). The start-

ing material was dissolved in anhydrous pyridine (5–

15 mL per hydroxyl or amino group) and cooled to –20 8C.

Under stirring tosyl chloride (1.15 equ per hydroxyl or

amino group) added. After termination of the reaction (1–

5d) the solvent was evaporated in vacuo (temperature

below 50 8C) and several times coevaporated with toluene.

The raw material was puriﬁed by chromatography.

less syrup; [

CDCl₃): 7.36–7.28 (m, 10 H, Ph), 4.60 (d, H-1), 3.49 (dd, H-

a]

D

+ 52.4 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

d

2), 3.90 (dd, H-3), 3.27 (dd, H-4), 3.75 (ddd, H-5), 3.56 (dd,

H-6a), 3.48 (dd, H-6b), 3.40 (s, 3 H, OCH₃), 4.95 (d,

OCH_ABn), 4.79 (d, OCH_ABn), 4.77 (d, OCH_BBn), 4.65 (d,

OCH_BBn), 4.01–3.95 (m, 1 H, OCH_A), 3.73–3.63 (m, 3 H,

OCH₂), 3.58 (dd, 2 H, CH₂Cl), 3.56 (dd, 2 H, OCH₂); J_1,2= 3.5,

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

291

J_2,3= 9.5, J_3,4= 9.5, J₄,₅= 9.5, J_5,6a= 3.0, J_5,6b= 5.0,

²J_6a,6b= 12.0, J_CH,CH= 4.5 and 6.0,²J_Bn= 10.5 and 12.0 Hz.;

mmol), pyridine (250 mL), À20 8C, 48 h. Puriﬁcation was

by ﬂash chromatography (dichloromethane/acetone 17:1).

¹³C NMR (100 MHz, CDCl₃):

d

98.06 (C-1), 79.87 (C-2),

Yield 8.4 g (74%); glass temperature: 51 8C; [

a] + 38.7 (c

D

81.59 (C-3), 79.10 (C-4), 69.97 (C-5), 51.27 (C-6), 55.34

(OCH₃), 75.62, 73.41 (2 C, OCH₂Ph), 72.31, 71.27, 70.69

(3 C, OCH₂), 42.73 (CH₂C1), 138.73, 138.06 (2 C, q, Ph),

128.49–127.64 (10C, Ph).

1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.72–7.24 (m, 28

H, Ph), 4.39 (d, 2 H, H-1,1’), 3.34 (dd, 2 H, H-2,2’), 3.79 (dd, 2

H, H-3,3’), 3.25–3.15 (m, 6 H, H-4,4’, H-6a,6a’, H-6b,b’),

3.60–3.45 (m, 6 H, H-5,5’, OCH₂), 3.20 (s, 6 H, OCH₃, OCH₃’),

5.25 (dd, 2 H, NHTs), 4.89 (d, 2 H, OCH_ABn, Bn’), 4.72 (d, 2 H,

OCH_ABn, Bn’), 4.70 (d, 2 H, OCH_BBn, Bn’), 4.56 (d, 2 H, OCH_B

Bn, Bn’), 3.97–3.90 (m, 2 H, OCH_A), 3.78–3.71 (m, 2 H,

OCH_A), 2.38 (s, 6 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5,

4.1. Bis-1,5-[methyl-6-azido-2,3-di-O-benzyl-6-deoxy-4-

yloxy-a-D-glucopyranoside]-(3-oxapentane) (3)

2

The synthesis followed GP1 employing 1 (8.3 g, 20.8

mmol), diethylene glycol ditosylate (4.74 g, 11.4 mmol),

tetrabutylammonium bromide (3.3 g, 10.4 mmol), toluene

(100 mL), 50% aqueous sodium hydroxide (70 mL), 40 8C, 3

d. Puriﬁcation was by ﬂash chromatography (dichloro-

methane/acetone 60:1). Yield 5.1 g (57%); glass tempera-

J₆,_NH= 6.0, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR (100 MHz,

CDCl₃):

d 98.05 (C-1,1’), 79.82 (C-2,2’), 81.59 (C-3,3’), 80.59

(C-4,4’), 68.52 (C-5,5’), 44.69 (C-6,6’), 55.28 (OCH₃, OCH₃’),

75.42, 73.47 (4 C, OCH₂Ph), 72.31, 70.93 (4 C, OCH₂), 21.55

(2 C, CH₃Ts), 143.24–137.44 (8 C, q, Ph), 129.71–127.18

(28 C, Ph); Anal. calcd. for C₆₀H₇₂N₂O₁₅S₂(1125.4): C 64.04,

H 6.45, N 2.49, S 5.70. Found: C 63.58, H 6.50, N 2.38, S 5.71.

ture 83–87 8C; [

a

]

D

+ 55.3 (c 1.0, CHCl₃); ¹H NMR

(400 MHz, CDCl₃):

d

7.34–7.25 (m, 20 H, Ph), 4.60 (d, 2

H, H-1,1’), 3.46 (dd, 2 H, H-2,2’), 3.87 (dd, 2 H, H-3,3’), 3.24

(dd, 2 H, H-4.4’), 3.73 (ddd, 2 H, H-5,5’), 3.48 (dd, 2 H, H-

6a,6a’), 3.45 (dd, 2 H, H-6b,6b’), 3.39 (s, 6 H, OCH₃, OCH₃’),

4.92 (d, 2 H, OCH_ABn, Bn’), 4.76 (d, 2 H, OCH_ABn, Bn’), 4.75

(d, 2 H, OCH_BBn, Bn’), 4.73 (d, 2 H, OCH_BBn, Bn’), 3.95–3.90

(m, 2 H, OCH_A), 3.70–3.64 (m, 2 H, OCH_A), 3.47 (s, 4 H,

OCH₂); J_1,2= 3.5, J₂,₃= 9.0, J_3,4= 9.5, J₄,₅= 9.5, J₅,_6a= 2.5,

4.4. Bis[methyl-6-azido-2,3-di-O-benzyl-6-deoxy-4-yloxy-

a-D-glucopyranoside]-p-xylene (6)

The formation followed GP1 employing 1 (4.5 g, 11.3

mmol), ’-dibromo-p-xylene (1.6 g, 6.2 mmol), tetra-

a,a

butylammonium bromide (3.6 g, 11.1 mmol), toluene

(50 mL), 50% aqueous sodium hydroxide (40 mL), 80 8C,

24 h. Puriﬁcation was by ﬂash chromatography (dichlor-

omethane/acetone 40:1). Yield 3.37 g (66%), colourless

2

J₅,_6b= 5.5, J_{6a 6b}

,

= 13.2, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR

(100 MHz, CDCl₃):

d

98.03 (C-1,1’), 79.86 (C-2,2’), 81.62 (C-

3,3’), 79.05 (C-4,4’), 70.04 (C-5,5’), 51.23 (C-6,6’), 55.32

(OCH₃, OCH₃’), 75.56, 73.40 (4 C, OCH₂Ph), 72.26, 70.60

(4 C, OCH₂), 138.79, 138.12 (4 C, q, Ph), 128.50–127.65

(20 C, Ph).

syrup; [

a

]

+ 47.1 (c 1.0, CHCI₃); ¹H NMR (400 MHz,

D

CDCl₃):

d

7.37–7.20 (m, 24 H, Ph), 4.61 (d, 2 H, H-1,1’), 3.53

(dd, 2 H, H-2,2’), 3.96 (dd, 2 H, H-3,3’), 3.42 (dd, 2 H, H-4,4’),

3.76 (ddd, 2 H, H-5,5’), 3.43 (dd, 2 H, H-6a,6a’), 3.32 (dd, 2

H, H-6b,b’), 3.39 (s, 6 H, OCH₃, OCH₃’), 4.98 (d, 2 H, OCH_ABn,

Bn’), 4.79 (d, 2 H, OCH_ABn, Bn’), 4.88 (d, 2 H, OCH_BBn, Bn’),

4.55 (d, 2 H, OCH_BBn, Bn’), 4.78 (d, 2 H, OCHcBn, Bn’’), 4.66

4.2. Bis-1,5-[methyl-6-amino-2,3-di-O-benzyI-6-deoxy-4-

yloxy-a-D-glucopyranoside]-(3-oxapentane) (4)

(d, 2 H, OCHc Bn, Bn’); J_1,2= 3.5, J₂,₃= 9.5, J_3,4= 9.5, J₄,₅= 9.5,

2

The synthesis followed GP2 using 3 (6.4 g, 7.36 mmol),

Pd/C (5%, 1 g), triethylamine (4 mL), methanol (150 mL),

J₅,_6a= 2.5, J₅,_6b= 5.5,2 J_{6a 6b}

,

= 13.0, J_Bn= 10.5, 11.0 and

12.0 Hz; ¹³C-NMR (100 MHz, CDCl₃):

d

98.06 (C-1,1’), 80.01

24 h. Yield 5.7 g (94%); colourless syrup; [

a

]

_D+38.7 (c 1.0,

(C-2,2’), 81.84 (C-3,3’), 78.37 (C-4,4’), 69.93 (C-5,5’), 51.40

(C-6,6’), 55.38 (OCH₃, OCH₃’), 75.73, 74.76, 73.42 (6 C,

OCH₂Ph), 138.63–137.69 (6 C, q, Ph), 128.50–127.67 (24 C,

Ph); Anal. calcd. for C₅₀H₅₆N₆O₁₀(901.0): C 66.65, H 6.26, N

9.33. Found: C 66.59, H 6.29, N 9.22.

in CHCl₃);¹H NMR (400 MHz, CDCl₃):

d

7.35–7.25 (m, 20 H,

Ph), 4.54 (d, 2 H, H-1,1’), 3.43 (dd, 2 H, H-2,2’), 3.88 (dd, 2 H,

H-3,3’), 3.19 (dd, 2 H, H-4,4’), 3.52 (ddd, 2 H, H-5,5’), 3.01

(dd, 2 H, H-6a,6a’), 2.78 (dd, 2 H, H-6b,6b’), 3.36 (s, 6 H,

OCH₃, OCH3’), 4.92 (d, 2 H, OCH_ABn, Bn’), 4.77 (d, 2 H,

OCH_ABn, Bn’), 4.75 (d, 2 H, OCH_BBn, Bn’), 4.62 (d, 2 H, OCH_B

Bn, Bn’), 3.94–3.86 (m, 2 H, OCH_A), 3.75–3.68 (m, 2 H,

OCH_A), 3.55–3.45 (m, 4 H, OCH₂), 1.72 (b, 4H,NH₂);

J_1,2= 3.5, J_2,3= 9.5, J₃,₄= 9.5, J_4,5= 9.5, J₅,_6a= 3.0,

4.5. Bis[methyl-6-amino-2,3-di-O-benzyl-6-deoxy-4-yloxy-

a

-D

-glucopyranoside]-p-xylene (7)

The synthesis followed GP2 using 6 (3.1 g, 3.44 mmol),

2

J₅,_6b= 6.5, J_6a,6b= 13.0, J_Bn= 11.0 and 12.0 Hz. ¹³C NMR

Pd/C (5%, 500 mg), triethylamine (2 mL), methanol (50 mL),

ethyl acetate (30 mL), 24 h. Yield 2.73 g (94%); colourless

(100 MHz, CDCI₃): 97.94 (C-1,1’), 80.03 (C-2,2’), 81.91 (C-

d

3,3’), 79.90 (C-4,4’), 71.62 (C-5,5’), 42.78 (C-6,6’), 55.05

syrup; [

a

]

D

+ 34.6 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

’

(OCH₃, OCH₃), 75.51, 73.34 (4 C, OCH₂Ph), 72.23, 70.95

CDCl₃): d 7.37–7.25 (m, 24 H, Ph), 4.56 (d, 2 H, H-1,1), 3.49

(4 C, OCH₂), 138.80, 138.13 (4 C, q, Ph), 128.43–127.55

(20 C, Ph).

(dd, 2 H, H-2,2’), 3.98 (dd, 2 H, H-3,3’), 3.33 (dd, 2 H, H-4,4’),

3.56 (ddd, 2 H, H-5,5’), 2.97 (dd, 2 H, H-6a,6a’), 2.70 (dd, 2

H, H-6b,b’), 3.37 (s, 6 H, OCH₃, OCH₃’), 4.98 (d, 2 H, OCH_ABn,

Bn’), 4.80 (d, 2 H, OCH_ABn, Bn’), 4.86 (d, 2 H, OCH_BBn, Bn’),

4.59 (d, 2 H, OCH_BBn, Bn’), 4.78 (d, 2 H, OCH_CBn, Bn’), 4.66

(d, 2 H, OCH_CBn, Bn’), 1.49 (b, 4 H, NH₂); J_1,2= 3.5, J_2,3= 9.5,

J_3,4= 9.5, J_4,5= 9.5, J₅,_6a= 2.5, J₅,_6b= 6.5, J_6a,6b= 13.0,

²J_Bn= 10.5, 11.0 and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d

97.94 (C-1,1), 80.17 (C-2,2’), 82.13 (C-3,3’), 78.77 (C-4,4’),

4.3. Bis-1,5-[methyl-2,3-di-O-benzyl-6-deoxy-6-

tosylamino-4-yloxy-a-D-glucopyranoside]-(3-oxapentane)

(5)

2

The preparation followed GP3 employing 4 (8.25 g, 10.1

mmol), p-toluene sulfonic acid chloride (4.43 g, 23.2

292

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

71.69 (C-5,5’), 42.86 (C-6,6’), 55.08 (OCH₃, OCH₃’), 75.69,

74.61, 73.35 (6 C, OCH₂Ph), 138.79–137.83 (6 C, q, Ph),

128.46–127.60 (24 C, Ph).

Ph), 4.54 (d, 2 H, H-1,1’), 3.47 (dd, 2 H, H-2,2’), 3.96 (dd, 2 H,

H-3,3’), 3.31 (dd, 2 H, H-4,4’), 3.53 (ddd, 2 H, H-5,5’), 2.94

(dd, 2 H, H-6a,6a’), 2.68 (dd, 2 H, H-6b,6b’), 3.35 (s, 6 H,

OCH₃, OCH₃’), 4.95 (d, 2 H, OCH_ABn, Bn’), 4.77 (d, 2 H,

OCH_ABn, Bn’), 4.84 (d, 2 H, OCH_BBn, Bn’), 4.56 (d, 2 H, OCH_B

Bn, Bn’), 4.76 (d, 2 H, OCH_CBn, Bn’), 4.63 (d, 2 H, OCH_CBn,

Bn’), 1.39 (b, 4 H, NH₂); J_1,2= 3.5, J₂,₃= 9.5, J₃,₄= 9.5,

4.6. Bis[methyl-2,3-di-O-benzyl-6-deoxy-6-tosylamino-4-

yloxy-a-D-glucopyranoside]-p-xylene (8)

The synthesis followed GP3 using 7 (2.73 g, 3.22 mmol),

p-toluene sulfonic acid chloride (1.42 g, 7.4 mmol),

pyridine (75 mL), À20 8C, 48 h. Puriﬁcation was by ﬂash

chromatography (toluene/ethyl acetate 1:1). Yield 3.14 g

J

_4,5= 9.5, J_5,6a= 2.5, J₅,_6b= 6.5, ²J_{6a 6b}

,

= 13.0, ²J_Bn= 11.0, 11.0

97.94 (C-1,1’),

and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d

80.17 (C-2,2’), 82.11 (C-3,3’), 78.89 (C-4,4’), 71.82 (C-5,5’),

42.86 (C-6,6’), 55.08 (OCH₃, OCH₃’), 75.66, 74.78, 73.34

(6 C, OCH₂Ph), 138.79-138.19 (6 C, q, Ph), 128.46-127.27

(24 C, Ph).

(84%); glass temperature 71–78 8C; [

a

]

À 3.2 (c 1.0,

D

CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.68–7.23 (m, 32 H,

Ph), 4.43 (d, 2 H, H-1,1’), 3.42 (dd, 2 H, H-2,2’), 3.93 (dd, 2 H,

H-3,3’), 3.41 (dd, 2 H, H-4,4’), 3.63 (ddd, 2 H, H-5,5’), 3.15–

3.07 (m, 4 H, H-6a,6a’, H-6b,b’), 3.26 (s, 6 H, OCH₃, OCH₃’),

4.96 (d, 2 H, OCH_ABn, Bn’), 4.76 (d, 2 H, OCH_ABn, Bn’), 4.84

(d, 2 H, OCH_BBn, Bn’), 4.58 (d, 2 H, OCH_BBn, Bn’), 4.80 (d, 2

H, OCH_CBn, Bn’), 4.61 (d, 2 H, OCH_CBn, Bn’), 4.63 (dd, 2 H,

NHTs), 2.38 (s, 6 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5,

4.9. Bis[methyl-2,3-di-O-benzyl-6-deoxy-6-tosylamino-4-

yloxy-a-D-glucopyranoside]-m-xylene (11)

The preparation followed GP3 employing 10 (13.9 g,

16.4 mmol), p-toluene suIfonic acid chloride (7.2 g, 37.7

mmol), pyridine (350 mL), –20 8C, 4 d. Puriﬁcation was by

ﬂash chromatography (dichloromethane/acetone 20:1).

2

J_4,5= 9.5, J_5,6= 4.0 and 5.0, J_6,NH= 6.0 and 6.5, J_Bn= 10.5,

11.5 and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d

98.15 (C-

Yield 14.4 g (76%); glass temperature: 58-60 8C; [

a] +9.9

D

1,1’), 81.76, 79.82, 78.06 (C-2,2’, C-3,3’, C-4,4’), 68.91 (C-

5,5’), 43.58 (C-6,6’), 55.37 (OCH₃, OCH₃’), 75.70, 74.69,

73.51 (6 C, OCH₂Ph), 21.50 (2 C, CH₃Ts), 143.52–136.73

(10 C, q, Ph), 129.76–127.14 (32 C, Ph); Anal. calcd. for

(c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.65–7.20 (m,

32 H, Ph), 4.42 (d, 2 H, H-1,1’), 3.41 (dd, 2 H, H-2,2’), 3.92

(dd, 2 H, H-3,3’), 3.40 (dd, 2 H, H-4,4’), 3.63 (ddd, 2 H, H-

5,5’), 3.12-3.07 (m, 4 H, H-6a,6a’, H-6b, 6b’), 3.25 (s, 6 H,

OCH₃, OCH₃’), 4.93 (d, 2 H, OCH_ABn, Bn’), 4.78 (d, 2 H, OCH_A

Bn, Bn’), 4.84 (d, 2 H, OCH_BBn, Bn’), 4.62 (d, 2 H, OCH_BBn,

Bn’), 4.74 (d, 2 H, OCH_CBn, Bn’), 4.59 (d, 2 H, OCHc Bn, Bn’),

4.60 (dd, 2 H, NHTs), 2.36 (s, 6 H, CH₃Ts); J_1,2= 3.5, J₂,₃= 9.5,

J_3,4= 9.5, J_4,5= 9.5, J_5,6= 4.5 and 5.0, J_6NH= 6.0 and 6.0,

C₆₄H₇₂N₂O₁₄S₂(1157.4): C 66.42, H 6.27, N 2.42, S 5.54.

Found: C 66.13, H 6.33, N 2.41, S 5.55.

4.7. Bis[methyl-6-azido-2,3-di-O-benzyl-6-deoxy-4-yloxy-

a-D-glucopyranoside]-m-xylene (9)

²J_Bn= 10.5, 11.5 and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d

The preparation followed GP1 using 1 (16.2 g, 40.5

mmol), ’-dibromo-m-xylene (5.88 g, 22.3 mmol), tetra-

98.09 (C-1,1’), 78.26 (C-2,2’), 81.63 (C-3,3’), 79.82 (C-4,4’),

68.91 (C-5,5’), 43.69 (C-6,6’), 55.34 (OCH₃, OCH₃’), 75.65,

74.77, 73.46 (6 C, OCH₂Ph), 21.49 (2 C, CH₃Ts), 143.42-

136.67 (10 C, q, Ph), 129.71–127.10 (32 C, Ph); Anal. calcd.

for C₆₄H₇₂N₂O₄S₂(1157.4): C 66.42, H 6.27, N 2.42, S 5.54.

Found: C 65.80, H 6.29, N 2.32, S 5.88.

a,a

butylammonium bromide (6.4 g, 20 mmol), toluene

(250 mL), 50% aqueous sodium hydroxide (100 mL),

60 8C, 24 h. Puriﬁcation was by ﬂash chromatography

(dichloromethane/acetone 40:1). Yield 15.6 g (86%); col-

ourless syrup; [

CHCI₃): 7.38–7.18 (m, 24 H, Ph), 4.63 (d, 2 H, H-1,1’), 3.55

a

]_D+ 53.8 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

d

4.10. Bis-1,11-[methyl-6-azido-2,3-di-O-benzyl-6-deoxy-4-

(dd, 2 H, H-2,2’), 3.98 (dd, 2 H, H-3,3’), 3.43 (dd, 2 H, H-4,4’),

3.78 (ddd, 2 H, H-5,5’), 3.42 (dd, 2 H, H-6a,6a’), 3.22 (dd, 2

H, H-6b,b’), 3.41 (s, 6 H, OCH₃, OCH₃’), 4.99 (d, 2 H, OCH_ABn,

Bn’), 4.80 (d, 2 H, OCH_ABn, Bn’), 4.90 (d, 2 H, OCH_BBn, Bn’),

4.56 (d, 2 H, OCH_BBn, Bn’), 4.79 (d, 2 H, OCH₂Bn, Bn’), 4.67

(d, 2 H, OCH_CBn, Bn’); J_1,2= 3.5, J₂,₃= 9.5, J₃,₄= 9.5, J₄,₅= 9.5,

yloxy-a-D-glucopyranoside]-(6-tosyl-3,9-dioxa-6-aza-

undecane) (12)

The formation followed GP4 employing 2 (7.66 g, 15.1

mmol), p-toluene sulphonamide (1.43 g, 8.33 mmol),

cesium carbonate (10 g, 30.7 mmol), DMF (150 mL),

80 8C, 3 d. Puriﬁcation was by ﬂash chromatography

(dichloromethane/acetone 30:1). Yield 7.09 g (85%); col-

J_5,6a= 2.5, J₅,_6b= 5.5,²J_{6a 6b}

,

= 13.0,²J_Bn= 10.5, 11.0 and

98.05 (C-1,1’), 80.01

12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d

(C-2,2’), 81.80 (C-3,3’), 78.46 (C-4,4’), 69.92 (C-5,5’), 51.39

(C-6,6’), 55.38 (OCH₃, OCH₃’), 75.69, 74.90, 73.41 (6 C,

OCH₂Ph), 138.61-138.04 (6 C, q, Ph), 129.04-127.08 (24 C,

Ph); Anal. calcd. for C₅₀H₅₆N₆O₁₀(901.0): C 66.65, H 6.26, N

9.33. Found: C 66.48, H 6.28, N 9.21.

ourless syrup; [

CDCl₃): 7.66–7.24 (m, 24 H, Ph), 4.60 (d, 2 H, H-1,1’), 3.47

a

]_D+ 46.1 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

d

(dd, 2 H, H-2,2’), 3.88 (dd, 2 H, H-3,3’), 3.23 (dd, 2 H, H-4,4),

3.73 (ddd, 2 H, H-5,5’), 3.42 (dd, 2 H, H-6a,6a), 3.40 (dd, 2 H,

H-6b,b), 3.39 (s, 6 H, OCH₃, OCH₃), 4.92 (d, 2 H, OCH_ABn,

Bn’), 4.77 (d, 2 H, OCH_ABn, Bn’), 4.77 (d, 2 H, OCH_BBn, Bn’),

4.64 (d, 2 H, OCH_BBn, Bn’), 3.93–3.89 (m, 2 H, OCH_A), 3.66–

3.60 (m, 2 H, OCH_A), 3.55-3.40 (m, 8 H, OCH₂), 3.30 (dd, 4 H,

4.8. Bis[methyl-6-amino-2,3-di-O-benzyl-6-deoxy-4-yloxy-

a-

D-glucopyranoside]-m-xylene (10)

CH₂NTs), 2.39 (s, 3 H, CH,Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.0,

2

The synthesis followed GP2 using 9 (15.4 g, 17.1 mmol),

J_4,5= 9.5, J₅,_6a= 5.5, J₅,_6b= 2.5, J_{6a 6b}

,

= 12.0, J_CH,CH= 6.0,

Pd/C (5%, 1.5 g), triethylamine (5 mL), methanol (300 mL),

5 d. Yield 14.0 g (96%); colourless syrup [a]_D+ 35.3 (c 1.0,

²J_Bn= 11.0 and 12.0 Hz; 13C NMR (100 MHz, CDC13):

d

98.05 (C-1,1’), 81.57, 79.87, 79.01 (C-2,2’, C-3,3’, C-4,4’),

70.46 (C-5,5’), 48.80 (C-6,6’), 55.35 (OCH₃, OCH₃’), 75.58,

CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d 7.35-7.17 (m, 24 H,

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

293

73.40, 72.24, 70.46, 70.00 (10 C, OCH₂, OCH₂Ph), 48.80 (2 C,

CH₂NTs), 21.48 (CH₃Ts), 138.70–138.06 (6 C, q, Ph),

129.64–127.18 (24 C, Ph).

acid (300 mL) and ice water (300 mL), dried over Na₂SO₄

and evaporated to give 29. Yield 28.6 g (71%), mp 71 8C; ¹H

NMR (400 MHz, CDCl₃):

d 7.78 (m, 4 H, Ph), 7.36 (m, 4 H,

Ph), 4.14 (dd, 4 H, CH₂OTs), 2.79 (dd, 4 H, CH₂CH₂OTs), 2.67

(s, 6 H, CH₂S), 2.45 (s, 6 H, CH₃Ts); J_CH,CH= 7.0 Hz; Anal.

calcd. for C₂₀H₂₆O₆(490.7): C 48.96, H 5.34, S 26.14. Found:

C 48.76, H 5.38, S 26.21.

4.11. Bis-1,11-[methyl-6-amino-2,3-di-O-benzyl-6-deoxy-4-

yloxy-a-D-glucopyranoside]-(6-tosyl-3,9-dioxa-6-aza-

undecane) (13)

The synthesis followed GP2 using 12 (6.95 g, 6.26

4.14. Cyclo-(N,N’)-1,2- {bis-1,5-(methyl-2,3-di-O-benzyl-6-

mmol), Pd/C (5%, 1.0 g), triethylamine (3 mL), methanol

deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside]-(3-

(120 mL), 3 d. Yield 6.22 g (94%); colourless syrup; [a]_D

+

oxapentane)}-ethane (16)

36.4 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.67-7.23

(m, 24 H, Ph), 4.55 (d, 2 H, H-1,1’), 3.44 (dd, 2 H, H-2,2’),

3.88 (dd, 2 H, H-3,3’), 3.18 (dd, 2 H, H-4,4’), 3.53 (ddd, 2 H,

H-5,5’), 3.01 (dd, 2 H, H-6a,6a’), 2.77 (dd, 2 H, H-6b,b’), 3.36

(s, 6 H, OCH₃, OCH₃’), 4.92 (d, 2 H, OCH_ABn, Bn’), 4.77 (d, 2

H, OCH_ABn, Bn’), 4.75 (d, 2 H, OCH_BBn, Bn’), 4.63 (d, 2 H,

OCH_BBn, Bn’), 3.93-3.86 (m, 2 H, OCH_A), 3.70-3.63 (m, 2 H,

OCH_A), 3.55-3.40 (m, 8 H, OCH₂), 3.30 (dd, 4 H, CH₂NTs),

The preparation followed GP4 using 5 (495 mg, 0.44

mmol), ethylene glycol ditosylate (163 mg, 0.44 mmol),

cesium carbonate (717 mg, 2.2 mmol), DMF (10 mL), 80 8C,

24 h. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 4:1). Yield 362 mg (71%); mp 145 8C; [

a] +

D

5.0 (c 0.5, CHCl₃); ¹HMR (400 MHz, CDCl₃):

d

7.73–7.19 (m,

28 H, Ph), 4.24 (d, 2 H, H-1,1’), 3.42 (dd, 2 H, H-2,2’), 3.83

(dd, 2 H, H-3,3’), 3.09 (dd, 2 H, H-4,4’), 3.85–3.60 (m, 8 H, H-

5,5’, H-6a,6a’, OCH₂), 3.23 (dd, 2 H, H-6b,6b’), 2.75 (s, 6 H,

OCH₃, OCH₃’), 4.91 (d, 2 H, OCH_ABn, Bn’), 4.72 (d, 2 H,

OCH_ABn, Bn’), 4.74 (d, 2 H, OCH_BBn, Bn’), 4.58 (d, 2 H, OCH_B

Bn, Bn’), 3.54–3.36 (m, 8 H, OCH₂, CH₂NTs), 2.40 (s, 6 H,

CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5, J_4,5= 9.5, J_5,6b= 9.0,

2.39 (s, 3 H, CH₃Ts), 1.88 (b, 4 H, NH₂); J₁,₂= 3.5, J_2,3= 9.0,

2

J₃,₄= 9.0, J₄,₅= 9.5, J₅,_6a= 3.0, J_5,6b= 6.0, J_{6a 6b}

,

= 13.0,

J_CH,CH= 6.5, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR (100 MHz,

CDCl₃): 97.92 (C-1,1’), 80.03 (C-2,2’), 81.86 (C-3,3’), 79.91

2

d

(C-4,4’), 71.09 (C-5,5’), 42.80 (C-6,6’), 55.12 (OCH₃, OCH₃’),

75.52, 73.32 (4 C, OCH₂Ph), 71.57, 70.66, 69.92 (6 C, OCH₂),

48.85 (2 C, CH₂NTs), 21.48 (CH₃Ts), 138.80-136.66 (6 C, q,

Ph), 129.66-126.96 (24 C, Ph).

2

²J_6a,6b= 15.0, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR (100 MHz,

CDCl₃):

d 97.16 (C-1,1’), 80.18 (C-2,2’), 82.00 (C-3,3’), 79.88

(C-4,4’), 68.38 (C-5,5’), 49.79 (C-6,6’), 54.48 (OCH₃OCH₃’)

75.57, 73.49 (4 C, OCH₂Ph), 71.67, 71.16 (4 C, OCH₂), 46.21

(2 C, CH₂NTs), 21.47 (2 C, CH₃Ts), 142.85–137.65 (8 C, q,

Ph), 129.17–127.51 (28 C, Ph); Anal. calcd. for

4.12. Bis-1,11-[methyl-2,3-di-O-benzyl-6-deoxy-6-

tosyIamino-4-yloxy-a-D-glucopyranoside]-(6-tosyl-3,9-

dioxa-6-aza-undecane) (14)

C₆₂H₇₄N₂O₁₅S₂(1151.4): C 64.68, H 6.48, N 2.43, S 5.57.

The preparation followed GP3 employing 13 (6.22 g,

5.88 mmol), p-toluene sulfonic acid chloride (2.58 g, 13.5

mmol), pyridine (200 mL), À20 8C, 24 h. Puriﬁcation was by

ﬂash-chromatography (dichloromethane/acetone 14:1).

Found: C 63.89, H 6.44, N 2.39, S 5.66. FAB-MS: m/z

(%) = 1174 (90) [M+Na⁺], 996 (100) [M⁺-CH₃C₆H₄SO₂].

4.15. Cyclo-(N,N’)-1,5-{bis-1,5-[methyl-2,3-di-O-benzyl-6-

Yield 4.28 g (53%); glass temperature 46-49 8C; [

a

]

+

deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside]-(3-

oxapentane)}-(3-oxapentane) (17)

D

12.1 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.75–7.23

(m, 32 H, Ph), 4.40 (d, 2 H, H-1,1’), 3.33 (dd, 2 H, H-2,2’),

3.79 (dd, 2 H, H-3,3’), 3.14 (dd, 2 H, H-4,4’), 3.70-3.30 (m, 16

H, H-5,5’, H-6a,6a’, H-6b,b’, OCH₂), 3.21 (s, 6 H, OCH₃,

OCH₃’), 5.33 (dd, 2 H, NHTs), 4.88 (d, 2 H, OCH_ABn, Bn’),

4.72 (d, 2 H, OCH_ABn, Bn’), 4.71 (d, 2 H, OCH_BBn, Bn’), 4.57

(d, 2 H, OCH_BBn, Bn’), 3.93–3.87 (m, 2 H, OCH₂), 3.23–3.10

(m, 4 H, CH₂NTs), 2.37, 2.36 (s, 9 H, CH₃Ts); J_1,2= 3.5,

The synthesis followed GP4 using 5 (680 mg, 0.61

mmol), diethylene glycol ditosylate (252 mg, 0.61 mmol),

cesium carbonate (977 mg, 3.0 mmol), DMF (10 mL), 80 8C,

3 d. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 4:1). Yield 392 mg (54%); glass temperature

68–70 8C; [

a]

+ 9.9 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

D

J

_2,3= 9.0, J_3,4= 9.0, J_4,5= 9.5, J_6,NH= 6.0 and 6.5, ²J_Bn= 11.5

and 12.0 Hz. ¹³C NMR (100 MHz, CDCl₃):

98.03 (C-1,1’),

CDCl₃): 7.73–7.22 (m, 28 H, Ph), 4.36 (d, 2 H, H-1,1’), 3.40

d

(dd, 2 H, H-2,2’), 3.66 (dd, 2 H, H-3,3’), 3.06 (dd, 2 H, H-4,4’),

3.73–3.44 (m, 16 H, H-5,5’, H-6a,6a’ H-6b,6b’, OCH₂,

CH₂NTs), 2.88 (s, 6 H, OCH₃, OCH₃’), 4.88 (d, 2 H, OCH_ABn,

Bn’), 4.68 (d, 2 H, OCH_ABn, Bn’), 4.72 (d, 2 H, OCH_BBn, Bn’),

4.55 (d, 2 H, OCH_BBn, Bn’), 4.00–3.89 (m, 4 H, OCH₂), 4.40–

4.33 (m, 2 H, CH₂NTs), 2.37 (s, 6 H, CH₃Ts); J_1,2= 3.5,

79.77 (C-2,2’), 81.46 (C-3,3’), 80.64 (C-4,4’), 68.34 (C-5,5’),

44.71 (C-6,6’), 55.24 (OCH₃, OCH₃’), 75.44, 73.40 (4 C,

OCH₂Ph), 72.27, 70.49, 69.81 (6 C, OCH₂), 48.58 (2 C,

CH₂NTs), 21.49 (3 C, CH₃Ts), 138.65–137.10 (10 C, q, Ph),

129.69–127.13 (32 C, Ph).

2

J_2,3= 9.0, J_3,4= 9.0, J_4,5= 9.0, J_Bn= 11.0 and 12.0 Hz; ¹³C

4.13. 1,8-Bis-p-toluenesulfonyloxy-3,6-dithia-octane (15)

NMR (100 MHz, CDCl₃): d 97.72 (C-1,1’), 79.75 (C-2,2’),

82.04 (C-3,3’), 80.53 (C-4,4’), 70.84 (C-5,5’), 54.77 (OCH₃,

OCH₃’), 75.24, 73.39 (4 C, OCH₂Ph), 73.16, 70.94, 70.08 (6 C,

OCH₂), 47.94, 47.68 (4 C, C-6,6’, CH₂NTs), 21.46 (2 C,

CH₃Ts), 142.79–138.18 (8 C, q, Ph), 129.48–127.36 (28 C,

Ph); Anal. calcd. for C₆₄H₇₈N₂O₁₆S₂(1195.5): C 64.30, H

6.58, N 2.34, S 5.36. Found: C 64.06, H 6.59, N 2.26, S 5.44.

FAB-MS: m/z (%) =1218 (100) [M+Na⁺].

1,8-Dihydroxy-3,6-dithia-octane (15 g, 82 mmol) were

dissolved in pyridine (200 mL) cooled to À20 8C and p-

toluene sulfonic acid chloride (34.5 g, 181 mmol) added in

portions. After 4 h the solution was poured onto iced water

(300 mL) and diethylether (300 mL). The combined organic

phases were extracted twice with cold 2 N hydrochloric

294

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

4.16. Cyclo-(N,N’)-1,5-{bis-1,5-[methyl-2,3-di-O-benzyl-6-

deoxy-6-tosylamino-4-yloxy- -glucopyranoside]-(3-

cesium carbonate (750 mg, 2.3 mmol), DMF (10 mL), 70 8C,

24 h. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 1:1). Yield 382 mg (72%); glass temperature

a

-D

oxapentane)}-(3-tosyl-3-azapentane) (18)

105 8C; [

a

]

D

+ 49.4 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

This preparation was by GP4 employing 5 (450 mg, 0.40

mmol), diethanol amine tritosylate (228 mg, 0.40 mmol),

cesium carbonate (652 mg, 2.0 mmol), DMF (10 mL), 80 8C,

3 d. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 5:1). Yield 390 mg (73%); glass temperature

CDCl₃): d 7.69–7.22 (m, 32 H, Ph), 4.41 (d, 2 H, H-1,1’), 3.46

(dd, 2 H, H-2,2’), 3.88 (dd, 2 H, H-3,3’), 3.05 (dd, 2 H, H-4,4’),

3.52–3.41 (m, 6 H, H-5,5’, OCH₂), 3.39 (ddꢀd, 2 H, H-

6a,6a’), 2.92 (dd, 2 H, H-6b,6b’), 2.95 (s, 6 H, OCH₃, OCH₃’),

5.01 (d, 2 H, OCH_ABn, Bn’), 4.84 (d, 2 H, OCH_ABn, Bn’), 4.87

(d, 2 H, OCH_BBn, Bn’), 4.52 (d, 2 H, OCH_BBn, Bn’), 4.73 (d, 2

H, OCH_CBn, Bn’), 4.60 (d, 2 H, OCH_CBn, Bn’), 3.33–3.25 (m, 4

H, CH₂NTs), 2.41 (s, 6 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5,

85–86 8C; [

CDCl₃): 7.75–7.16 (m, 32 H, Ph), 4.35 (d, 2 H, H-1,1’), 3.48

a]

D

= + 34.2 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

d

(dd, 2 H, H-2,2’), 3.78 (dd, 2 H, H-3,3’), 3.20 (dd, 2 H, H-4,4’),

3.60 (dddꢀdd, 2 H, H-5,5’), 3.76–3.27 (m, 18 H, H-6a,6a’, H-

6b,6b’, OCH₂, CH₂NTs), 2.84 (s, 6 H, OCH₃, OCH₃’), 4.88 (d, 2

H, OCH_ABn, Bn’), 4.78 (d, 2 H, OCH_ABn, Bn’), 4.70 (d, 2 H,

OCH_BBn, Bn’), 4.55 (d, 2 H, OCH_BBn, Bn’), 3.93–3.86 (m, 2 H,

OCH₂), 2.44, 2.43 (s, 9 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.0,

J

_4,5= 9.5, J_5,6aꢀ 0, J_5,6b= 10.0, ²J_6a,6b= 15.5, ²J_Bn= 11.0, 11.5

and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d 97.48 (C-1,1’),

77.53 (C-2,2’), 79.76 (C-3,3’), 82.43 (C-4,4’), 69.74 (C-5,5’),

48.50 (C-6,6’), 54.84 (OCH₃, OCH₃’), 75.67, 74.14, 73.36

(6 C, OCH₂Ph), 69.68 (2 C, OCH₂), 46.40 (2 C, CH₂NTs), 21.50

(2 C, CH₃Ts), 142.94–137.54 (10 C, q. Ph), 129.52–127.41

(32 C, Ph); Anal. calcd. for C₆₈H₇₈N₂O₁₅S₂(1227.5): C 66.54,

H 6.40, N 2.28, S 5.22. Found: C 65.89, H 6.45, N 2.25, 5.24.

2

J_3,4= 9.0, J_4,5= 9.5, J_5,6= 9.5, J_Bn= 11.0 and 12.0 Hz; ¹³C

NMR (100 MHz, CDCl₃):

d 97.65 (C-1,1’), 80.36 (C-2,2’),

82.21 (C-3,3’), 79.60 (C-4,4’), 68.55 (C-5,5’), 54.98 (OCH₃,

OCH₃’), 75.43, 73.50 (4 C, OCH₂Ph), 71.54, 71.13 (4 C,

OCH₂), 50.17, 49.74, 47.84 (6 C, C-6,6’, CH₂NTs), 21.47 (3 C,

CH₃Ts), 143.11–137.18 (10 C, q, Ph), 129.83–127.38 (32 C,

Ph); Anal. calcd. for C₇₁H₈₅N₃O₇S₃(1348.7): C 63.23, H

6.35, N 3.12, S 7.13: Found: C 63.12, H 6.44, N 3.12, S 7.01.

FAB-MS: m/z (%) = 1370 (100) [M+Na⁺], 1193 (75) [M⁺-

CH₃C₆H₃SO₂].

4.19. Cyclo-(N,N’)-15-{bis[methyl-2,3-di-O-benzyl-6-deoxy-

6-tosylamino-4-yloxy-a-D-glucopyranoside]-p-xylene}-(3-

tosyl-3-aza-pentane) (21)

The synthesis followed GP4 using 8 (512 mg, 0.44

mmol), diethanol amine tritosylate (290 mg, 0.51 mmol),

cesium carbonate (750 mg, 2.3 mmol), DMF (10 mL), 70 8C,

24 h. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 2:1). Yield 445 mg (73%); glass temperature

4.17. Cyclo-(N,N’)-1,8-{bis-1,5-[methyl-2,3-di-O-benzyI-6-

deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside]-(3-

oxapentane)}-(3,6-dithia-octane) (19)

85–87 8C; [

CDCl₃): 7.73–7.10 (m, 36 H, Ph), 4.39 (d, 2 H, H-1,1’), 3.42

a]

D

+ 46.3 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

d

The synthesis was done by GP4 employing 5 (310 mg,

0.28 mmol), 1,8-bis-p-toluene sulfonyloxy-3,6-dithia-oc-

tane (15, 135 mg, 0.28 mmol), cesium carbonate (450 mg,

1.38 mmol), DMF (10 mL), 20 8C, 5 d. Puriﬁcation was by

ﬂash chromatography (toluene/ethyl acetate 4:1). Yield

(dd, 2 H, H-2,2’), 3.92 (dd, 2 H, H-3,3’), 2.94 (dd, 2 H, H-4,4’),

3.62 (ddd, 2 H, H-5,5’), 3.36 (dd, 2 H, H-6a,6a’), 2.53 (dd, 2

H, H-6b,6b’), 2.96 (s, 6 H, OCH₃, OCH₃’), 5.04 (d, 2 H,

OCH_ABn, Bn’), 4.88 (d, 2 H, OCH_ABn, Bn’), 4.84 (d, 2 H,

OCH_BBn, Bn’), 4.50 (d, 2 H, OCH_BBn, Bn’), 4.74 (d, 2 H,

OCH_CBn, Bn’), 4.63 (d, 2 H, OCHcBn, Bn’), 3.40–3.32 (m, 4 H,

CH₂NTs), 3.23–3.08 (m, 4 H, CH₂NTs), 2.43, 2.40 (s, 9 H,

CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.0, J_4,5= 9.5, J_5,6a= 2.5,

132 mg (38%); glass temperature 59–62 8C; [

a] + 12.5 (c

D

1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.71–7.19 (m, 28

H, Ph), 4.32 (d, 2 H, H-1,1’), 3.37 (dd, 2 H, H-2,2’), 3.73 (dd, 2

H, H-3,3’), 2.99 (dd, 2 H, H-4,4’), 3.74–3.34 (m, 16 H, H-5,5’,

H-6a,6a’, H-6b,6b’, OCH₂, CH₂NTs), 2.93 (s, 6 H, OCH₃,

OCH₃’), 4.89 (d, 2 H, OCH_ABn, Bn’), 4.71 (d, 2 H, OCH_ABn,

Bn’), 4.70 (d, 2 H, OCH_BBn, Bn’), 4.55 (d, 2 H, OCH_BBn, Bn’),

3.93–3.85 (m, 2 H, OCH₂), 2.86–2.72 (m, 8 H, CH₂S), 2.36 (s,

6 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.0, J_4,5= 9.5, ²J_Bn= 11.0

2

J_5,6b= 9.0, J_6a,6b= 15.0, J_Bn=11.0, 12.0 and 12.0 Hz; ¹³C

NMR (100 MHz, CDCl₃): 97.38 (C-1,1’), 79.67 (C-2,2’),

d

82.25 (C-3,3’), 78.44 (C-4,4’), 68.19 (C-5,5’), 50.98 (C-6,6’),

54.95 (OCH₃, OCH₃’), 75.74, 74.21, 73.20 (6 C, OCH₂Ph),

49.08, 47.58 (4 C, CH₂NTs), 21.56, 21.53 (3 C, CH₃Ts),

143.35–135.84 (12 C, q, Ph), 129.72–127.64 (36 C, Ph);

Anal. calcd. for C₇₅H₈₅N₃O₁₆S₃(1380.7): C 65.24, H 6.21, N

3.04, S 6.97. Found: C 64.85, H 6.32, N 3.00, S 7.08. FAB-MS:

and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d 97.59 (C-1,1’),

79.70 (C-2,2’), 81.83 (C-3,3’), 80.42 (C-4,4’), 68.90 (C-5,5’),

54.98 (OCH₃, OCH₃’), 75.48, 73.46 (4 C, OCH₂Ph), 72.41,

70.83 (4 C, OCH₂), 48.74, 47.57 (4 C, C-6,6’, CH₂NTs), 32.50,

30.83 (4 C, CH₂S), 21.46 (2 C, CH₃Ts), 143.03–137.82 (8 C, q,

Ph), 129.38–127.53 (28 C, Ph); C₆₆H₈₂N₂O₁₅S₄(1271.7);

m/z (%)

CH₃C₆H₄SO₂].

=

1402 (100) [M+Na⁺], 1225 (75) [M⁺-

4.20. Cyclo-(N,N’)-{bis[methyl-2,3-di-O-benzyl-6-deoxy-6-

FAB-MS: m/z (%) = 1293 (100) [M+Na⁺], 1240 (80) [M⁺

OCH₃].

-

tosylamino-4-yloxy-a-D-glucopyranoside)-p-xylene}-p-

xylene (22)

4.18. Cyclo-(N,N’)-1,5-{bis[methyl-2,3-di-O-benzyI-6-

The synthesis followed GP4 using 8 (450 mg, 0.39

mmol), ’-dibromo-p-xylene (113 mg, 0.43 mmol),

deoxy-6-tosylamino-4-yloxy-

a

-D-glucopyranoside]-p-

a,a

xylene}-(3-oxapentane) (20)

cesium carbonate (650 mg, 2.0 mmol), DMF (10 mL),

70 8C, 24 h. Puriﬁcation was by ﬂash chromatography

(toluene/ethyl acetate 3:1). Yield 325 mg (67%); mp

The preparation followed GP4 using 8 (500 mg, 0.43

mmol), diethylene glycol ditosylate (210 mg, 0.5 mmol),

100 8C; [

a

]

D

– 1.5 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

295

CDCl₃):

d

7.68–6.96 (m, 36 H, Ph), 4.24 (d, 2 H, H-1,1’), 3.41

4.97 (d, 2 H, OCH_ABn, Bn’), 4.80 (d, 2 H, OCH_ABn, Bn’), 4.89

(d, 2 H, OCH_BBn, Bn’) 4.66 (d, 2 H, OCH_BBn, Bn’), 4.72 (d, 2

H, OCH_CBn, Bn’), 4.59 (d, 2 H, OCH_CBn, Bn’), 3.16–3.10 (m, 2

H, CH₂NTs), 2.36 (s, 6 H, CH₃Ts); J_1,2= 3.5, J_1,3= 9.5, J_3,4= 9.5,

(dd, 2 H, H-2,2’), 3.89 (dd, 2 H, H-3,3’), 3.02 (dd, 2 H, H-4,4’),

3.74 (ddd, 2 H, H-5,5’), 3.42 (dd, 2 H, H-6a,6a’), 3.33 (dd, 2

H, H-6b,6b’), 2.91 (s, 6 H, OCH₃, OCH₃’), 4.97 (d, 2 H,

OCH_ABn, Bn’), 4.78 (d, 2 H, OCH_ABn, Bn’), 4.82 (d, 2 H,

OCH_BBn, Bn’), 4.36 (d, 2 H, OCH_BBn, Bn’), 4.78 (d, 2 H,

OCH_CBn, Bn’), 4.60 (d, 2 H, OCH_CBn, Bn’), 4.59 (d, 2 H,

NCH_ABn, Bn’), 4.21 (d, 2 H, NCH_ABn, Bn’), 2.41 (s, 6 H,

CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.0, J_4,5= 9.0, J_5,6b= 2.0,

J

_4,5= 9.5, J_5,6a= 0, J_5,6b= 9.5, ²J_6a,6b= 15.5, ²J_Bn= 11.0, 11.5

and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

97.56 (C-1,1’),

d

79.71 (C-2,2’), 82.37 (C-3,3’), 79.16 (C-4,4’), 69.81 (C-5,5’),

48.37 (C-6,6’), 54.72 (OCH₃, OCH₃’), 75.49, 74.92, 73.40

(6 C, OCH₂Ph), 70.02 (2 C, OCH₂), 46.98 (2 C, CH₂NTs), 21.47

(2 C, CH₃Ts), 142.89–138.10 (10 C, q, Ph), 129.43–127.26

(32 C, Ph); Anal. calcd. for C₆₈H₇₈N₂O₁₅S₂(1227.5): C 66.54,

H 6.40, N 2.28, S 5.22. Found: C 66.37, H 6.44, N 2.22, S 5.39.

FAB-MS: m/z (%) = 1250 (100) [M+Na⁺].

2

J_5,6b= 9.5, J_6a,6b= 15.0, J_NBn= 15.0, J_Bn= 10.5, 11.5 and

12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

97.45 (C-1,1’), 80.06

d

(C-2,2’), 81.98 (C-3,3’), 78.83 (C-4,4’), 67.54 (C-5,5’), 46.52

(C-6,6’), 54.90 (OCH₃, OCH₃’), 75.70, 74.33, 73.51 (6 C,

OCH₂Ph), 49.10 (2 C, NCH₂Ph), 21.49 (2 C, CH₃Ts), 142.78–

135.07 (12 C, q, Ph), 129.13–127.61 (36 C, Ph); Anal. calcd.

for C₇₂H₇₈N₂O₁₄S₂(1259.5): C 68.66, H 6.24, N 2.22, S 5.09.

Found: C 68.32, H 6.35, N 2.23, S 5.13. FAB-MS: m/z

(%) = 1282 (100) [M+Na⁺], 1103 (30) [M⁺-CH₃C₆H₄SC₂].

4.23. Cyclo-(N,N’)-1,5-{bis[methyl-2,3-di-O-benzyl-6-

deoxy-6-tosyIamino-4-yloxy-a-D-glucopyranoside]-m-

xylol}-(3-tosyl-3-azapentane) (25)

The synthesis followed GP4 using 11 (1.0 g, 0.89 mmol),

diethanolamine tritosylate (539 mg, 0.95 mmol), cesium

carbonate (1.36 g, 4.2 mmol), DMF (20 mL), 70 8C, 24 h.

Puriﬁcation was by ﬂash chromatography (toluene/ethyl

acetate 3:1). Yield 498 mg (41%); glass temperature 87–

4.21. Cyclo-(N,N’)-1,2-{bis[methyl-2,3-di-O-benzyl-6-

deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside]-m-

xylene}-ethane (23)

The preparation followed GP4 using 11 (1.09 mg, 0.94

mmol), ethylene glycol ditosylate (348 mg, 0.94 mmol),

cesium carbonate (1.63 mg, 5.0 mmol), DMF (20 mL), 80 8C,

48 h. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 5:1). Yield 604 mg (54%); glass temperature

90 8C; [

7.68–7.03 (m, 36 H, Ph), 4.36 (d, 2 H, H-1,1’), 3.46 (dd, 2 H,

a]

_D+ 20.2 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

H-2,2’), 3.94 (dd, 2 H, H-3,3’), 3.17 (dd, 2 H, H-4,4’), 3.67

(ddd, 2 H, H-5,5’), 3.48–3.03 (m, 12 H, H-6a,6a’, H-6b,6b’,

NCH₂Ts), 2.94 (s, 6 H, OCH₃, OCH₃’), 4.99 (d, 2 H, OCH_ABn,

Bn’), 4.81 (d, 2 H, OCH_ABn, Bn’), 4.86 (d, 2 H, OCH_BBn, Bn’),

4.52 (d, 2 H, OCH_DBn, Bn’), 4.74 (d, 2 H, OCH_CBn, Bn’), 4.53

(d, 2 H, OCHc Bn, Bn’’), 2.43, 2.41 (s, 9 H, CH₃Ts); J_1,2= 3.5,

91–96 8C; [

CDCl₃): 7.71–6.93 (m, 32 H, Ph), 4.13 (d, 2 H, H-1,1’), 3.42

a]

D

– 17.3 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

d

(dd, 2 H, H-2,2’), 3.89 (dd, 2 H, H-3,3’), 3.08 (dd, 2 H, H-4,4’),

3

3.62–3.58 (m, 4 H, H 5,5’, H-6a,6a’), 3.33 (ddꢀd, 2 H, H-

J_2,3= 9.5, J_3,4= 9.5, J_4,5= 9.5, J_4,6= 2.5 and 9.5, J_Bn= 10.5,

’

6b,6b’), 2.62 (s, 6 H, OCH₃, OCH₃), 4.96 (d, 2 H, OCH_ABn,

11.0 and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d 97.58 (C-

Bn’), 4.72 (d, 2 H, OCH_ABn, Bn’), 4.90 (d, 2 H, OCH_BBn, Bn’),

4.46 (d, 2 H, OCH_BBn, Bn’), 4.79 (d, 2 H, OCH_CBn, Bn’), 4.60

(d, 2 H, OCH_CBn, Bn’), 3.84–3.77 (m, 2 H, CH₂NTs), 3.15–

1,1’), 79.83 (C-2,2’), 82.06 (C-3,3’), 79.62 (C-4,4’), 67.86 (C-

5,5’), 54.72 (OCH₃, OCH₃’), 75.73, 74.58, 73.37 (6 C,

OCH₃Ph), 50.86, 49.08, 47.81 (6 C, C-6,6’, CH₃NTs), 21.56,

21.50 (3 C, CH₃Ts), 143.18–136.73 (12 C, q, Ph), 129.78–

127.50(36 C, Ph); Anal. calcd. for C₇₅H₈₅N₃O₁₆S₃(1380.7):

C 65.24, H 6.21, N 3.04, S 6.97. Found: C 64.51, H 6.21, N

2.97, S 7.04. FAB-MS: m/z (%) = 1403 (100) [M+Na⁺], 1225

(40) [M⁺-CH₃C₆H₄SO₂].

3.06 (m, 2 H, CH₂NTs), 2.39 (s, 6 H, CH₃Ts); J_1,2= 3.5, J_2,3

=

2

9.5, J_3,4= 9.0, J_4,5= 9.0, J_5,6bꢀ 0, J_6a,6b= 14.0, J_Bn= 11.0,

11.5 and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d

96.94 (C-

1,1’), 80.03 (C-2,2’), 81.94 (C-3,3’), 79.54 (C-4,4’), 67.95 (C-

5,5’), 46.32 (C-6,6’), 54.33 (OCH₃, OCH_3’), 75.69, 74.57,

73.53 (6 C, OCH₂Ph), 50.38 (2 C, CH₂NTs), 21.45 (2 C,

CH₃Ts), 142.81–137.54 (10 C, q, Ph), 129.04–126.00 (32 C,

Ph); Anal. calcd. for C₆₆H₇₄N₂O₁₄S₂(1183.5): C 66.98, H

6.30, N 2.37, S 5.42. Found: C 66.97, H 6.33, N 2.29, S 5.60.

FAB-MS: m/z (%) = 1205 (100) [M+Na⁺].

4.24. Cyclo-(N,N’)-{bis[methyl-2,3-di-O-benzyl-6-deoxy-6-

tosylamino-4-yloxy-a-D-glucopyranoside]-m-xylene}-p-

xylene (26)

The preparation followed GP4 using 11 (1.0 g, 0.89

mmol), ’-dibromo-p-xylene (250 mg, 0.95 mmol),

4.22. Cyclo-(N,N’)-1,5-{bis[methyl-2,3-di-O-benzyl-6-

a,a

deoxy-6-tosylamino-4-yloxy-

a

-

D

-glucopyranoside]-m-

cesium carbonate (1.36 g, 4.2 mmol), DMF (20 mL),

70 8C, 24 h. Puriﬁcation was by ﬂash chromatography

(toluene/ ethyl acetate 7:1). Yield 553 mg (49%); glass

xylene}-(3-oxapentane) (24)

The synthesis followed GP4 using 11 (1.0 g, 0.89 mmol),

diethylene glycol ditosylate (393 mg, 0.95 mmol), cesium

carbonate (1.36 g, 4.2 mmol), DMF (20 mL), 70 8C, 24 h.

Puriﬁcation was by ﬂash chromatography (toluene/ethyl

acetate 3:1). Yield 626 mg (57%); glass temperature 79–

temperature 89–91 8C; [

(400 MHz, CDCl₃): 7.68–7.01 (m, 36 H, Ph), 4.26 (d, 2 H,

a]

D

– 1.0 (c 1.0, CHCl₃); ¹H NMR

d

H-1,1’), 3.40 (dd, 2 H, H-2,2’), 3.85 (dd, 2 H, H-3,3’), 3.02

(dd, 2 H, H-4,4’), 3.67 (ddd, 2 H, H-5,5’), 3.28–3.17 (m, 4 H,

H-6a,6a’, H-6b,6b’), 3.00 (s, 6 H, OCH₃, OCH₃’), 4.94 (d, 2 H,

OCH_ABn, Bn’), 4.72 (d, 2 H, OCH_ABn, Bn’), 4.76 (d, 2 H,

OCH_BBn, Bn’), 4.59 (d, 2 H, OCH_BBn, Bn’), 4.65 (d, 2 H,

OCH_CBn, Bn’), 4.34 (d, 2 H, OCH_CBn, Bn’), 4.54 (d, 2 H,

NCH_ABn, Bn’), 4.16 (d, 2 H, NCH_ABn, Bn’), 2.41 (s, 6 H,

CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5, J_4,5= 9.5, J_5,6= 2.5 and

81 8C; [

7.60–7.16 (m, 32 H, Ph), 4.39 (d, 2 H, H-1,1’), 3.49 (dd, 2 H,

a]

_D+ 40.6 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

H-2,2’), 3.80 (dd, 2 H, H-3,3’), 3.21 (dd, 2 H, H-4,4’), 3.65–

3.44 (m, 8 H, H-5,5’, OCH₂, NCH₂Ts), 3.91 (ddꢀd, 2 H, H-

6a,6a), 3.25 (dd, 2 H, H-6b,6b’), 2.90 (s, 6 H, OCH₃, OCH₃’),

296

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

2

9.5, J_NBn=15.0, J_Bn= 11.0, 11.5 and 12.0 Hz; ¹³C NMR

2.92, S 6.69. Found: C 62.69, H 6.60, N 2.84, S 6.6. FAB-MS:

m/z (%)

1458 (100) [M+Na⁺], 1280 (35) [M⁺-

CH₃C₆H₄SO₂].

(100 MHz, CDCl₃): 97.46 (C-1,1’), 80.07 (C-2,2’), 81.81 (C-

d

=

3,3’), 79.17 (C-4,4’), 67.17 (C-5,5’), 46.64 (C-6,6’), 55.13

(OCH₃, OCH₃’), 75.70, 74.47, 73.43 (6 C, OCH₂Ph), 49.66

(2 C, NCH₂Ph), 21.50 (2 C, CH₃Ts), 142.76–134.82 (12 C, q,

Ph), 129.11–125.30 (36 C,Ph); Anal. calcd. for

4.27. Cyclo-(N,N’)-1,5-{bis-1,11-[methyl-2,3-di-O-benzyl-6-

deoxy-6-tosylamino-4-yloxy- -glucopyranoside-(6-tosyl-

a

-D

C₇₂H₇₈N₂O₁₄S₂(1259.5): C 68.66, H 6.24, N 2.22, S 5.09.

3,9-dioxa-6-aza-undecane)}-(3-tosyl-3-azapentane) (29)

Found: C 68.15, H 6.27, N 2.20, S 4.97. FAB-MS: m/z

(%) = 1281 (100) [M+Na⁺], 1103 (40) [M⁺-CH₃C₆H₄SO₂].

The synthesis followed GP4 employing 14 (290 mg, 0.21

mmol), diethanol amine tritosylate (120 mg, 0.21 mmol),

cesium carbonate (325 mg, 1.0 mmol), DMF (10 mL), 80 8C,

3 d. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 3:1). Yield 204 mg (60%); glass temperature

4.25. Cyclo-(N,N’)-1,2-{bis-1,11-[methyl-2,3-di-O-benzyl-6-

deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside]-(6-tosyl-

3,9-dioxa-6-aza-undecane)}-ethane (27)

93 8C; [

d 7.72–7.20 (m, 36 H, Ph), 4.39 (d, 2 H, H-1,1’), 3.42 (dd, 2 H,

a]

_D+ 20.7 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

The preparation followed GP4 using 14 (432 mg, 0.32

mmol), ethylene glycol ditosylate (117 mg, 0.32 mmol),

cesium carbonate (488 mg, 1.5 mmol), DMF (10 mL), 80 ⁸C,

2 d. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 4:1). Yield 202 mg (45%); glass temperature

H-2,2’), 3.74 (dd, 2 H, H-3,3’), 2.94 (dd, 2 H, H-4,4’), 3.94–

3.25 (m, 30 H, H-5,5’, H-6a,6a’ H-6b,6b’, OCH₂, CH₂NTs),

2.84 (s, 6 H, OCH₃, OCH₃’), 4.90 (d, 2 H, OCH_ABn, Bn’), 4.72

(d, 2 H, OCH_ABn, Bn’), 4.70 (d, 2 H, OCH_BBn, Bn’), 4.58 (d, 2

H, OCH_BBn, Bn’), 2.44, 2.41, 2.39 (s, 12 H, CH₃Ts); J_1,2= 3.5,

74–77 8C; [

CDCl₃): 7.72–7.22 (m, 32 H, Ph), 4.53 (d, 2 H, H-1,1’), 3.46

a]

+ 28.0 (c 1.0, CHC1₃); ¹H NMR (400 MHz,

D

2

d

J_2,3= 9.5, J_3,4= 9.0, J_4,5= 9.5, J_Bn= 11.0 and 12.0 Hz; ¹³C

(dd, 2 H, H-2,2’), 3.76 (dd, 2 H, H-3,3’), 2.94 (dd, 2 H, H-4,4’),

3.66–3.62 (m, 2 H, H-5,5’), 3.58–3.17 (m, 22 H, H-6a,6a’, H-

6b,6b’, OCH₂, CH₂NTs), 3.02 (s, 6 H, OCH₃, OCH₃’), 4.92 (d, 2

H, OCH_ABn, Bn’), 4.70 (d, 2 H, OCH_ABn, Bn’), 4.69 (d, 2 H,

OCH_BBn, Bn’), 4.60 (d, 2 H, OCH_BBn, Bn’), 3.95–3.87 (m, 2 H,

OCH₂), 2.40, 2.39 (s, 9 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.0,

NMR (100 MHz, CDCl₃): d 97.54 (C-1,1’), 79.88 (C-2,2’),

81.86 (C-3,3’), 80.27 (C-4,4’), 69.22 (C-5,5’), 54.87 (OCH₃,

OCH₃’), 75.52, 73.33 (4 C, OCH₂Ph), 72.29, 70.63, 69.75 (6 C,

OCHj), 49.85, 49.22, 48.71, 47.73 (8 C, C-6,6’, CH₂NTs),

21.50 (4 C, CH₃Ts), 143.20–138.17 (12 C, q, Ph), 129.78–

127.10 (36 C, Ph); Anal. calcd. for C₈₂H₁₀₀N₄O₂₀S₄(1590.0):

C 61.95, H 6.34, N 3.52, S 8.07. Found: C 61.68, H 6.43, N

3.59, S 8.27. FAB-MS: m/z (%) = 1612 (100) [M+Na⁺].

1

J_3,4= 9.0, J_4,5= 9.5, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR

(100 MHz, CDCl₃):

d 97.50 (C-1,1’), 80.49 (C-2,2’), 82.05 (C-

3,3’), 80.23 (C-4,4’), 69.24 (C-5,5’), 55.00 (OCH₃, OCH₃’),

75.52, 73.22 (4 C, OCH₂Ph), 72.45, 70.98, 70.55 (6 C, OCH₂),

50.21, 49.97, 47.73 (6 C, C-6,6’, CH₂NTs), 21.49 (3 C, CH₃Ts),

143.18–136.90 (10 C, q, Ph), 129.71–126.98 (32 C, Ph);

Anal. calcd. for C₃H₈₉N₃O₁₈S₃(1392.7): C 62.96, H 6.44, N

3.02, S 6.9. Found: C 62.43, H 6.45, N 3.08, S 7.17. FAB-MS:

4.28. Cyclo-(N,N’)-{bis-1,11-[methyl-2,3-di-O-benzyl-6-

deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside]-(6-tosyl-

3,9-dioxa-6-aza-undecane)}-p-xylene (30)

The synthesis followed GP4 using 14 (479 mg, 0.35

mmol), a,a’-dibromo-p-xylene (93 mg, 0.35 mmol), cesi-

m/z(%)

=

1414 (95) [M+Na⁺], 1237 (100) [M⁺

-

CH₃C₆H₄SO₂].

um carbonate (488 mg, 1.5 mmol), DMF (10 mL), 80 8C, 3 d.

Puriﬁcation was by ﬂash chromatography (toluene/ethyl

acetate 4:1). Yield 278 mg (54%); glass temperature 75–

]_D+ 3.6 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

82 8C; [a d

4.26. Cyclo-(N,N’)-1,5-{bis-1,11-(methyl-2,3-di-O-benzyl-6-

deoxy-6-tosylamino-4-yloxy- -gIucopyranoside]-(6-tosyl-

a

-D

3,9-dioxa-6-aza-undecane)}-(3-oxapentane) (28)

7.74–7.21 (m, 36 H, Ph), 4.27 (d, 2 H, H-1,1’), 3.36 (dd, 2 H,

H-2,2’), 3.70 (dd, 2 H, H-3,3’), 3.87–3.22 (m, 24 H, H-4,4’, H-

5,5’, H-6a,6a’, H-6b,6b’, OCH₂, CH₂NTs), 2.88 (s, 6 H, OCH₃,

OCH₃’), 4.90 (d, 2 H, OCH_ABn, Bn’), 4.69 (d, 2 H, OCH_ABn,

Bn’), 4.72 (d, 2 H, OCH_BBn, Bn’), 4.56 (d, 2 H, OCH_BBn, Bn’),

4.50 (d, 2 H, NCH_ABn, Bn’), 4.35 (d, 2 H, NCH_ABn, Bn’), 2.41,

2.38 (s, 9 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5, ²J_NBn= 15.0,

The preparation followed GP4 using 14 (480 mg, 0.35

mmol), diethylene glycol ditosylate (146 mg, 0.35 mmol),

cesium carbonate (570 mg, 1.8 mmol), DMF (10 mL), 80 8C,

2 d. Puriﬁcation was by ﬂash chromatography (toluene/

ethyl acetate 3:1). Yield 304 mg (61%); glass temperature

62–65 8C; [

a

]

D

+ 16.9 (c 1.0, CHCl₃); ¹H NMR (400 MHz,

²J_Bn= 11.0 and 12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d 97.57

CDCl₃): 7.71–7.16 (m, 32 H, Ph), 4.39 (d, 2 H, H-1,1’), 3.40

d

(C-1,1’), 79.82 (C-2,2’), 81.91 (C-3,3’), 80.94 (C-4,4’), 68.29

(C-5,5’), 54.97 (OCH₃, OCH₃’), 75.47, 73.43 (4 C, OCH₂Ph),

72.50, 70.88, 70.11 (6 C, OCH₂), 50.11 (2 C, NCH₂Bn), 49.42,

46.74 (4 C, C-6,6’, CH₂NTs), 21.49 (3 C, CH₃Ts), 142.87–

135.66 (12 C, q, Ph), 129.80–127.27 (36 C, Ph).

(dd, 2 H, H-2,2’), 3.75 (dd, 2 H, H-3,3’), 3.95–3.28 (m, 32 H,

H-4,4’, H-5,5’, H-6a,6a’ H-6b,6b’, OCH₂, CH₂NTs), 2.94 (s, 6

H, OCH₃, OCH₃’), 4.90 (d, 2 H, OCH_ABn, Bn’), 4.72 (d, 2 H,

OCH_ABn, Bn’), 4.69 (d, 2 H, OCH_BBn, Bn’), 4.56 (d, 2 H, OCH_B

Bn, Bn’), 2.38, 2.35 (s, 9 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5,

2

J_3,4= 9.5, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR (100 MHz,

4.29. Cyclo-(N,N’)-1,8-{bis-1,11-[methyl-2,3-di-O-benzyl-6-

CDCl₃):

d

97.60 (C-1,1’), 81.84, 80.47, 79.78 (6 C, C-2,2’, C-

deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside]-(6-tosyl-

3,3’, C-4,4’), 69.62 (C-5,5’), 54.93 (OCH₃, OCH₃’), 75.54,

73.34 (4 C, OCH₂Ph), 72.24, 70.73, 70.08, 69.54 (8 C, OCH₂),

49.06, 48.97, 47.17 (6 C, C-6,6’, CH₂NTs), 21.47 (3 C, CH₃Ts),

142.90–138.14 (10 C, q, Ph), 129.76–127.08 (32 C, Ph);

Anal. calcd. for C₇₅H₉₃N₃O₁₀S₃(1436.7): C 62.70, H 6.52, N

3,9-dioxa-6-aza-undecane)}-(3,6-dithia-octane) (31)

The preparation followed GP4 using 14 (275 mg, 0.20

mmol), 1,8-ditosyloxy-3,6-dithia-octane (15, 108 mg, 0.22

mmol), cesium carbonate (325 mg, 1.0 mmol), DMF

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

297

(10 mL), 20 8C, 3 d. Puriﬁcation was by ﬂash chromatogra-

phy (toluene/ethyl acetate 5:1). Yield 88 mg (29%); glass

temperature 54–58 8C; [

_D+ 19.8 (c 1.0, CHCl₃); ¹H NMR

(400 MHz, CDCl₃): 7.70–7.20 (m, 32 H, Ph), 4.35 (d, 2 H,

520 mg (59%); glass temperature 55–57 8C; [

1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

a

]

+ 39.5 (c

D

d

7.73–7.22 (m, 36

a

]

H, Ph), 4.47 (d, 2 H, H-1,1’), 3.41 (dd, 2 H, H-2,2’), 3.82 (dd, 2

H, H-3,3’), 3.05 (dd, 2 H, H-4,4’), 3.33 (dd, 2 H, H-6a,6a’),

3.22 (dd, 2 H, H-6b,6b’), 3.11 (s, 6 H, OCH₃, OCH₃’), 4.87 (d,

2 H, OCH_ABn, Bn’), 4.73 (d, 2 H, OCH_ABn, Bn’), 4.72 (d, 2 H,

OCH_BBn, Bn’), 4.60 (d, 2 H, OCH_BBn, Bn’), 4.19 (dd, 4 H,

CH₂OTs), 4.00–3.93 (m, 2 H, OCH₂), 3.76–3.44 (m, 12 H, H-

5,5’, OCH₂, CH₂NTs), 2.42, 2.37 (s, 12 H, CH₂Ts); J_1,2= 3.5,

J_2,3= 9.0, J_3,4ꢀ 9.0, J_4,5= 9.0, J_5,6a= 6.5, J_5,6b= 7.5,

d

H-1,1’), 3.34 (dd, 2 H, H-2,2’), 3.75 (dd, 2 H, H-3,3’), 2.92

(dd, 2 H, H-4,4’), 3.58–3.53 (m, 2 H, H-5,5’), 3.83–3.77 (m, 2

H, H-6a,6a’), 2.98 (s, 6 H, OCH₃, OCH₃’), 4.89 (d, 2 H,

OCH_ABn, Bn’), 4.71 (d, 2 H, OCH_ABn, Bn’), 4.69 (d. 2 H,

OCH_BBn, Bn’), 4.56 (d, 2 H, OCH_BBn, Bn’), 3.90–3.84 (m, 2 H,

OCH_A), 3.64–3.59 (m, 2 H, OCH_A), 3.55–3.38 (m, 8 H, OCH₂),

3.37–3.28 (m, 10 H, H-6b,6b’, CH₂NTs), 2.80–2.72 (m, 4 H,

CH₂S), 2.69 (s, 4 H, H₂S), 2.37, 2.36 (s, 9 H, CH₃Ts); J_1,2= 3.5,

²J_6a,6b= 15.0, J_CH,CH= 3.5 and 6.5, ²J_Bn= 11.0 and 12.0 Hz; ¹³

C

NMR (100 MHz, CDCl₃):

d 97.73 (C-1,1’), 79.85 (C-2,2’),

2

J_2,3= 9.0, J_3,4= 9.5, J_4,5= 9.5, J_Bn= 10.5 and 12.0 Hz; ¹³C

81.53 (C-3,3’), 79.74 (C-4,4’), 70.36 (C-5,5’), 50.54 (C-6,6’),

55.23 (OCH₃, OCH₃’), 75.47, 73.30 (4 C, OCH₂Ph), 72.11,

70.95 (4 C, OCH₂), 68.09 (2 C, CH₂OTs), 48.20 (2 C, CH₂NTs),

21.65, 21.48 (4 C, CH₃Ts), 143.93–132.85 (12 C, q, Ph),

129.93–127.49 (36 C, Ph); Anal. calcd. for C₇₈H₉₂N₂O₂₁S₄

(1521.9): C 61.56, H 6.09, N 1.84, S 8.43. Found: C 61.37, H

6.10, N 1.87, S 8.29. FAB-MS: m/z (%) = 1543 (100) [M+Na⁺].

NMR (100 MHz, CDCl₃):

d 97.56 (C-1,1’), 79.75 (C-2,2’),

81.70 (C-3,3’), 80.21 (C-4,4’), 69.22 (C-5,5’), 55.03 (OCH₃,

OCH₃’), 75.46, 73.31 (4 C, OCH₂Ph), 72.12, 70.55, 69.80 (6 C,

OCH₂), 48.67, 48.66, 48.01 (6 C, C-6,6, CH₂NTs), 30.26,

28.89 (4 C, CH₂S), 21.42 (3 C, CH₃Ts), 143.17–137.45 (10 C,

q, Ph), 129.75–127.01 (32 C, Ph);

C₇₇H₉₇N₃O₁₈S₅

(1513.0);FAB-MS: m/z (%) = 1534 (100) [M+Na⁺], 1480

(70) [M⁺-OCH₃].

4.32. Bis{methyl-2,3-di-O-benzyl-6-deoxy-6-[N-tosyl-N-(2-

hydroxyethyl)amino-4-yloxy-a-D-glucopyranoside]}-m-

4.30. Bis-1,5-{methyl-2,3-di-O-benzyl-6-deoxy-6-[N-tosyl-

xylene (34)

N-(2-hydroxyethyl)amino-4-yloxy-a-D-glucopyranoside]}-

(3-oxapentane) (32)

The synthesis followed GP4 using 11 (2.77 g, 39 mmol),

2-(2-chlorethoxy)-tetrahydropyran (7.8 g, 7.8 mL, 47.9

mmol), cesium carbonate (3.9 g, 12 mmol), DMF (30 mL),

80 8C, 2 d. The suspension was ﬁltered over silica gel,

evaporated dissolved in dichloromethane/methanol 1:1

(40 mL) and treated with conc HCl (0.5 mL) for 30 min.

Following neutralisation with NaHCO₃, ﬁltration and

evaporation the raw material was puriﬁed by chromatog-

raphy (dichloromethane/acetone 1:1). Yield 2.1 g (71%);

The synthesis followed GP4 using 5 (1.01 g, 0.9 mmol),

2-(2-chloroethoxy)-tetrahydropyran (4.43 g, 4.5 mL, 26.9

mmol), cesium carbonate (1.47 g, 4.5 mmol), DMF (10 mL),

100 8C, 24 h. The suspension was ﬁltered over silica gel,

evaporated dissolved in dichlormethane/methanol 1:1

(20 mL) and treated with conc HCl (0.5 mL) for 3 h.

Following neutralisationwith NaHCO₃ﬁltration and evap-

oration the raw material was puriﬁed by chromatography

(dichlormethane/acetone 10:1). Yield 710 mg (66%); glass

glass temperature 53–55 8C; [

a] + 44.5 (c 1.0, in CHCl₃);

D

¹H NMR (400 MHz, CDCl₃):

d

7.59–7.15 (m, 32 H, Ph), 4.51

temperature 56–58 8C; [

a

]

_D+ 44.5 (c 1.0, CHCl₃); ¹H NMR

(d, 2 H, H-1,1’), 3.46 (dd, 2 H, H-2,2’), 3.96 (dd, 2 H, H-3,3’),

3.17 (dd, 2 H, H-4,4’), 4.00 (ddd, 2 H, H-5,5’), 3.73 (dd, 2 H,

H-6a,6a’), 2.99 (dd, 2 H, H-6b,6b’), 3.23 (s, 6 H, OCH₃,

OCH₃’), 4.95 (d, 2 H, OCH_ABn, Bn’), 4.76 (d, 2 H, OCH_ABn,

Bn’), 4.91 (d, 2 H, OCH_BBn, Bn’), 4.56 (d, 2 H, OCH_BBn, Bn’),

4.74 (d, 2 H, OCH_CBn, Bn’), 4.62 (d, 2 H, OCH_CBn, Bn’), 3.74

(ddd, 2 H, CH_AOH), 3.65 (ddd, 2 H, CH_AOH), 3.53 (ddd, 2 H,

CH_ANTs), 2.94 (ddd, 2 H, CH_ANTs), 2.52 (b, 2 H, OH,OH),

2.35 (s, 6 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5, J_4,5= 9.5,

(400 MHz, CDCl₃): 7.68–7.24 (m, 28 H, Ph), 4.47 (d, 2 H,

d

H-1,1’), 3.40 (dd, 2 H, H-2,2’), 3.85 (dd, 2 H, H-3,3’), 3.02

(dd, 2 H, H-4,4’), 3.89 (ddd, 2 H, H-5,5’), 3.81 (dd, 2 H, H-

6a,6a’), 3.16 (dd, 2 H, H-6b,6b’), 3.19 (s, 6 H, OCH₃, OCH₃’),

4.89 (d, 2 H, OCH_ABn, Bn’), 4.73 (d, 2 H, OCH_ABn, Bn’), 4.71

(d, 2 H, OCH_ABn, Bn’), 4.58 (d, 2 H, OCH_BBn, Bn’), 3.95–3.65

(m, 4 H, OCH₂), 3.73–3.64 (m, 4 H, CH₂OH), 3.58–3.53 (m, 2

H, CH_ANTs). 3.53–3.45 (m, 4 H, OCH₂), 3.05–2.98 (m, 2 H,

CH_ANTs), 3.27 (b, 2 H, OH,OH’), 2.37 (s. 6 H, CH₃Ts);

2

J_5,6a= 2.5, J_5,6b= 9.5, J_6a,6b= 15.0, J_CH,CH= 3.0 and 6.0,

2

J

_1,2= 3.5, J_2,3= 9.0, J_3,4= 9.0, J_4,5= 9.5, J_5,6a= 2.5, J_5,6b= 9.0,

²J_CH,CH= 11.5 and 14.5, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR

²J_6a,6b= 15.0, ²J_Bn= 10.5 Hz; ¹³C NMR (100 MHz, CDCl₃):

d

(100 MHz, CDCl₃): d 97.81 (C-1,1’), 79.88 (C-2,2’), 81.61 (C-

97.76 (C-1,1’), 79.76 (C-2,2’), 81.54 (C-3,3’), 80.68 (C-4.4’),

69.98 (C-5,5’), 50.78 (C-6,6’), 55.27 (OCH₃, OCH₃’), 75.55,

73.36 (4 C, OCH₂Ph), 72.06. 71.02 (4 C, OCH₂), 61.63 (2 C,

CH₂OH), 52.21 (2 C, CH₂NTs), 21.47 (2 C, CH₃Ts), 143.41–

136.17 (8 C, q, Ph), 129.62–127.58 (28 C, Ph).

3,3’), 79.88 (C-4,4’), 70.28 (C-5,5’), 51.11 (C-6,6’), 55.34

(OCH₃, OCH₃’). 75.69, 74.52, 73.36 (6 C, OCH₂Ph), 61.74

(2 C, CH₂OH), 52.77 (2 C, CH₂NTs), 21.47 (2 C, CH₃Ts),

143.45–135.71 (10 C, q, Ph), 129.64–125.31 (32 C, Ph);

Anal. calcd. for C₆gH₈₀N₂O₁₆S₃(1245.5): C 65.58, H 6.47, N

2.25, S 5.15. Found: C 65.16, H 6.52, N 2.13, S 5.20.

4.31. Bis-1,5-{methyl-2,3-di-O-benzyl-6-deoxy-6-[N-tosyl-

N-(2-tosyloxyethyl)amino-4-yloxy-

a-

D-glucopyranoside]}-

4.33. Bis{methyl-2,3-di-O-benzyl-6-deoxy-6-[N-tosyl-N-(2-

(3-oxapentane) (33)

tosyloxyethyl)]amino-4-yloxy-a-D-glucopyranoside]}-m-

xylene (35)

The synthesis followed GP4 using 32 (700 mg, 0.58

mmol), p-toluene sulfonic acid chloride (242 mg, 1.27

mmol), pyridine (10 mL), -20 8C, 48 h. Puriﬁcation was by

ﬂash chromatography (toluene/ethyl acetate 30:1). Yield

The synthesis followed GP4 using 34 (1.93 g, 1.55

mmol), p-toluene sulfonic acid chloride, pyridine (40 mL), -

20 8C, 5 d. Puriﬁcation was by ﬂash chromatography

298

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

(toluene/ethyl acetate 5:1). Yield 2.06 g (85%); glass

temperature 49–51 8C; [

+ 27.4 (c 1.0, CHCl₃); ¹H

NMR (400 MHz, CDCl₃):

(100 MHz, CDCl₃): d 97.67 (C-1,1’), 79.91 (C-2,2’), 81.70 (C-

a

]

3,3’), 79.71 (C-4,4’), 69.82 (C-5,5’), 55.18 (OCH₃, OCH₃’),

75.48, 73.28 (4 C, OCH₂Ph), 71.99, 70.95 (4 C, OCH₂), 61.41

(2 C, CH₂OH), 52.40, 51.01, 49.41, 49.01 (8 C, C-6,6’,

CH₂NTs), 21.52, 21.49 (4 C, CH₃Ts), 143.58–137.75 (12 C,

q, Ph), 129.83–127.31 (36 C, Ph).

D

d

7.72–7.15 (m, 40 H, Ph), 4.51 (d,

2 H, H-1,1’), 3.47 (dd, 2 H, H-2,2’), 3.93 (dd, 2 H, H-3,3’),

3.21 (dd, 2 H, H-4,4’), 3.72 (ddd, 2 H, H-5,5’), 3.50 (dd, 2 H,

H-6a,6a’), 3.12 (dd, 2 H, H-6b,6b’), 3.14 (s, 6 H, OCH₃,

OCH₃’), 4.94 (d, 2 H, OCH_ABn, Bn’), 4.74 (d, 2 H, OCH_ABn,

Bn’), 4.91 (d, 2 H, OCH_BBn, Bn’), 4.63 (d, 2 H, OCH_BBn, Bn’),

4.74 (d, 2 H, OCH_CBn, Bn’), 4.63 (d, 2 H, OCH_CBn, Bn’), 4.18

(dd, 4 H, CH₂OTs), 3.51–3.44 (m, 2 H, CH_ANTs), 3.31 (ddd, 2

H, CH_ANTs), 2.42, 2.35 (s, 12 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5,

4.36. Bis-1,5-{methyl-2,3-di-O-benzyl-6-deoxy-6-[N-tosyl-

N-(5-tosyloxy-3-tosyl-3-azapentyl)]amino-4-yloxy-a-D-

glucopyranoside}-(3-oxapentane) (38)

2

J_3,4= 9.5, J_4,5= 9.5, J_5,6a= 1.5, J_5,6b= 8.0, J_6a,6b= 15.0,

The synthesis followed GP4 using 37 (950 mg, 0.59

mmol), p-toluene sulfonic acid chloride (260 mg, 1.35

mmol), pyridine (10 mL), À20 8C, 5 d. Puriﬁcation was by

ﬂash chromatography (dichloromethane/acetone 30:1).

2

J_CH,CH= 6.0 and 7.5, J_CH,CH= 14.5, J_Bn= 10.5. 11.0 and

12.0 Hz; ¹³C NMR (100 MHz, CDCl₃):

d 97.72 (C-1,1’), 79.96

(C-2,2’), 81.70 (C-3,3’), 79.02 (C-4,4’), 70.51 (C-5,5’), 50.69

(C-6,6’), 55.29 (OCH₃, OCH₃’), 75.63, 74.50, 73.27 (6 C,

OCH₂Ph), 68.11 (2 C, CH₂OTs), 48.40 (2 C, CH₂NTs), 21.65,

21.47 (4 C, CH₃Ts), 144.95–132.83 (14 C, q, Ph), 130.23–

127.01 (32 C, Ph); Anal. calcd. for C₈₂H₉₂N₂O₂₀S₄(1553.9):

C 63.38, H 5.97, N 1.80, S 8.25. Found: C 62.47, H 5.91, N

1.79, S 8.35.

Yield 782 mg (70%); glass temperature 67–69 8C; [

a] +

D

35.3 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.74–7.24

(m, 44 H, Ph), 4.59 (d, 2 H, H-1,1’), 3.43 (dd, 2 H, H-2,2’),

3.86 (dd, 2 H, H-3,3’), 3.11 (dd, 2 H, H-4,4’), 3.68 (m, 2 H, H-

5,5’), 3.14 (s, 6 H, OCH₃, OCH₃’), 4.88 (d, 2 H, OCH_ABn, Bn’),

4.76 (d, 2 H, OCH_ABn, Bn’), 4.70 (d. 2 H, OCH_BBn, Bn’), 4.62

(d, 2 H, OCH_BBn, Bn’), 4.11 (dd, 4 H, CH₂OTs), 4.05–3.97 (m,

2 H, OCH_A), 3.81–3.75 (m, 2 H, OCH_A), 3.63–3.10 (m, 20 H,

H-6a,6a, H-6b,b,₂, CH₂NTs), 2.42, 2.40. 2.38 (s, 18 H,

CH₂Ts); J_1,2= 3.5, J_2,3= 9.0, J_3,4= 9.5, J_4,5= 9.5, J_{CH, CH}= 5.5

4.34. 1-tert-Butyldimethylsilyloxy-6-tosyloxy-3-tosyl-3-

azapentane (36)

2

1-Tosyloxy-3-tosyl-3-azapentane (8.92 g 21.6 mmol)

was dissolved in pyridine (100 mL) and cooled to -20 8C.

In portions tert-butyldimethylsilylchloride (3.58 g, 23.7

mmol) was added and stirring continued for 24 h at

-20 8C. Then co-distillation with toluene and evaporation

to dryness was followed by chromatographic puriﬁcation

(dichloromethane). Yield 7.8 g (69%); colourless syrup;

and 6.0, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR (100 MHz,

CDCl₃):

d 97.65 (C-1,1’), 79.86 (C-2,2’), 81.59 (C-3,3’), 79.62

(C-4,4’), 70.40 (C-5,5’), 55.25 (OCH₃, OCH₃’), 75.48, 73.12

(4 C, OCH₃Ph), 72.12, 70.96 (4 C, OCH₃), 68.42 (2 C,

CH₃OTs), 50.74, 49.58, 49.41, 48.76 (8 C, C-6,6’, CH₂NTs),

21.66, 21.54, 21.50 (6 C, CH₃Ts), 143.86–132.50 (16 C, q,

Ph), 129.98–127.33 (44 C, Ph); C₉₆H₁₁₄N₄O₂₅S₆(1916.4);

FAB-MS: m/z (%) = 1939 (100) [M+Na⁺].

¹H NMR (400 MHz, CDCl₃):

d 7.75, 7.64, 7.34, 7.27 (m, 8

H, Ph), 4.17 (t, 2 H, CH₂OTs), 3.68 (t. 2 H, CH₂OSi), 3.47,

3.22 (t, 4 H, CH₂NTs), 2.45, 2.42 (s, 6 H, CH₃Ts), 0.84

(s, 9 H, CH₃-t-Bu), 0.20 (s. 6 H, CH,Si), J_CH,CH= 6.0 and

6.5 Hz; Anal. calcd. for C₂₄H₃₇NO₆S₂Si (527.8): C 54.62, H

7.07, N 2.65, S 12.15. Found: C 54.51, H 7.15, N 2.62, S

12.15.

4.37. Bis{methyl-2,3-di-O-benzyl-6-deoxy-6-[N-tosyl-N-(5-

hydroxy-3-tosyl-3-azapentyl)]amino-4-yloxy-a-D-

glucopyranoside}-m-xylene (39)

The synthesis followed GP4 using 11 (1.5 g, 1.3 mmol),

36 (1.76 g, 3.3 mmol), cesium carbonate (2.1 g, 6.5 mmol),

DMF (15 mL), 80 8C, 24 h. The raw material was puriﬁed

by chromatography (toluene/ethyl acetate 7:1) then

dissolved in THF (50 mL) and stirred with tetrabutylam-

moniumﬂuoride (2.2 g, 7.1 mmol) for 24 h at RT. After

evaporation the raw material was puriﬁed by chroma-

tography (toluene/ethyl acetate 1:1). Yield 1.34 g (63%);

4.35. Bis-1,5-{methyl-2,3-di-O-benzyl-6-deoxy-6-[N-tosyl-

N-(5-hydroxy-3-tosyl-3-azapentyl)]amino-4-yloxy-a-D-

glucopyranoside}-(3-oxapentane) (37)

The synthesis followed GP4 using 5 (1.51 g, 1.35 mmol),

36 (2.85 g, 5.4 mmol), cesium carbonate (1.76 g, 5.4 mmol),

DMF (25 mL), 80 8C, 24 h. The raw material was puriﬁed by

chromatography (toluene/ethyl acetate 6:1) then dis-

solved in THF (50 mL) and stirred with tetrabutylammo-

nium ﬂuoride (2.46 g, 7.8 mmol) for 3 h at RT. After

evaporation the raw material was puriﬁed by chromatog-

raphy (dichloromethane/acetone 7:1). Yield 1.35 g (62%);

glass temperature 63–65 8C; [

NMR (400 MHz, CDCl₃): 7.66–7.16 (m, 40 H, Ph), 4.51 (d,

a]

_D+ 23.1 (c 1.0, CHCl₃); ¹H

d

2 H, H-1,1’), 3.46 (dd, 2 H, H-2,2’), 3.94 (dd, 2 H, H-3,3’),

3.27 (dd, 2 H, H-4,4’), 3.71 (ddd, 2 H, H-5,5’), 3.10 (s, 6 H,

OCH₃, OCH₃’), 4.94 (d, 2 H, OCH_ABn, Bn’), 4.76 (d, 2 H,

OCH_ABn, Bn’), 4.92 (d, 2 H, OCH_BBn, Bn’), 4.68 (d, 2 H,

OCH_BBn, Bn’), 4.72 (d, 2 H, OCH_CBn, Bn’), 4.61 (d, 2 H,

OCH_CBn, Bn’), 3.65 (dd, 4 H, CH₂OH), 3.50–3.12 (m, 16 H,

H-6a,6a’, H-6b,b’, OCH₂, CH₂NTs), 2.40, 2.35 (s, 12 H,

CH₃Ts); J_1,2= 3.5, J_2,3= 9.5. J_3,4= 9.5, J_4,5= 9.5, J_5,6= 2.5 and

glass temperature 51–53 8C; [

a] + 28.9 (c 1.0, in CHCl₃);

D

¹H NMR (400 MHz, CDCl₃):

d

7.73–7.23 (m, 36 H, Ph), 4.45

(d, 2 H, H-1,1’), 3.40 (dd, 2 H, H-2,2’), 3.83 (dd, 2 H, H-3,3’),

3.11 (dd, 2 H, H-4,4’), 3.62 (m, 2 H, H-5,5’), 3.05 (s, 6 H,

OCH₃, OCH₃’), 4.88 (d, 2 H, OCH_ABn, Bn’), 4.73 (d, 2 H,

OCH_ABn, Bn’), 4.70 (d, 2 H, OCH_BBn, Bn’), 4.57 (d, 2 H, OCH_B

Bn, Bn’), 4.05–3.15 (m, 28 H, H-6a,6a’, H-6b,b’, OCH₂,

CH₂NTs), 2.40, 2.37 (s, 12 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5,

2

9.5, J_CH,CH= 5.0 and 5.5, J_Bn=0.5, 11.0 und 12.0 Hz; ¹³C

NMR (100 MHz, CDC1₃):

d 97.72 (C-1,1’), 80.01 (C-2,2’),

81.88 (C-3,3)’, 78.96 (C-4,4’), 70.12 (C-5,5’), 55.27 (OCH₃,

OCH₃’), 75.64, 74.58, 73.26 (6 C, OCH₂Ph), 61.28 (2 C,

CH₂OH), 52.37, 50.63, 49.45, 49.44 (8 C, C-6,6’, CH₂NTs),

2

J_3,4= 9.5, J_4,5= 9.5, J_Bn= 11.0 and 12.0 Hz; ¹³C NMR

A. Rathjens, J. Thiem / C. R. Chimie 14 (2011) 286–300

299

21.52, 21.48 (4 C, CH₃Ts), 143.61–135.73 (14 C, q, Ph),

4.40. Cyclo-(N,N’)-bis-1,2-{bis[methyl-2,3-di-O-benzyl-6-

129.83–127.29 (40 C, Ph); Anal. calcd. for C₈₆H₁₀₂N₄O₂₀S₄

(1640.0): C 62.98, H 6.27, N 3.42, S 7.82. Found: C 62.86, H

6.41, N 3.39, S 7.84.

deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside)-m-

xylene}-ethane (42)

The synthesis followed GP4 using 11 (1.0 g, 0.87 mmol),

35 (1.34 g, 0.87 mmol), cesium carbonate (1.41 g, 4.4

mmol), DMF (20 mL), 80 8C, 3 d. Puriﬁcation was by ﬂash

chromatography (toluene/ethyl acetate 4:1). Yield 892 mg

4.38. Bis{methyl-2,3-di-O-benzyl-6-deoxy-6-[N-tosyl-N-(5-

tosyloxy-3-tosyl-3-azapentyl)]amino-4-yloxy-a-D-

glucopyranoside}-m-xylene (40)

(43%); glass temperature 78–85 8C; [

a

]

+ 23.3 (c 1.0,

D

The synthesis followed GP4 using 39 (1.2 g, 0.73

mmol), p- toluene sulfonic acid chloride (350 mg, 1.83

mmol), pyridine (40 mL), -20 8C, 6 d. Puriﬁcation was by

ﬂash chromatography (dichloromethane/acetone 35:1).

CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.56–7.09 (m, 64 H,

Ph), 4.44 (d, 4 H, H-1), 3.38 (dd, 4 H, H-2), 3.84 (dd, 4 H, H-

3), 3.03 (dd, 4 H, H-4), 3.66–3.59 (m, 12 H, H-5, H-6a, H-6b),

2.95 (s, 12 H, OCH₃), 4.92 (d, 4 H, OCH_ABn), 4.73 (d, 4 H,

OCH_ABn), 4.82 (d, 4 H, OCH_BBn), 4.56 (d, 4 H, OCH_BBn), 4.66

(d, 4 H, OCH_CBn), 4.58 (d, 4 H, OCH_CBn), 3.41–3.35 (m, 4 H,

CH_ANTs), 3.18–3.12 (m, 4 H, CH_ANTs), 2.33 (s, 12 H, CH,Ts);

Yield 905 mg (64%); glass temperature 57–61 8C; [

a] +

D

21.3 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.73–7.19

(m, 48 H, Ph), 4.63 (d, 2 H, H-1,1’), 3.49 (dd, 2 H, H-2,2’),

3.97 (dd, 2 H, H-3,3’), 3.29 (dd, 2 H, H-4,4’), 3.75 (m, 2 H, H-

5,5’), 3.16 (s, 6 H, OCH₃, OCH₃’), 4.94 (d, 2 H, OCH_ABn, Bn’),

4.76 (d, 2 H, OCH_ABn, Bn’), 4.94 (d, 2 H, OCH_BBn, Bn’), 4.70

(d, 2 H, OCH_BBn, Bn’), 4.74 (d, 2 H, OCH_CBn, Bn’), 4.67 (d, 2

H, OCH_CBn, Bn’), 4.11 (dd, 4 H, CH₂OTs), 3.50–3.15 (m, 16

H, H-6a,6a’, H-6b,6b’, OCH₂, CH₂NTs), 2.42, 2.41, 2.36 (s, 18

H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5, J_4,5= 9.5, J_CH,CH= 5.5

and 6.0, ²J_Bn= 10.5, 11.0 and 11.5 Hz; ¹³C NMR (100 MHz,

J

_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.0, J_4,5= 9.5, ²J_Bn= 10.5, 11.0 and

11.5 Hz; ¹³C NMR (100 MHz, CDCl₃):

97.52 (4 C, C-1),

d

79.99 (4 C, C-2), 81.88 (4 C, C-3), 79.62 (4 C, C-4). 69.77 (4 C,

C-5), 50.05 (4 C, C-6), 54.95 (4 C, OCH₃), 75.56, 74.81, 73.25

(12 C, OCH₂Ph), 47.76 (4 C, CH₂NTs). 21.51 (4 C, CH₃Ts),

143.02–136.89 (20 C, q, Ph), 129.48–127.55 (64 C, Ph)¸ Anal.

calcd. for C₁₃₂H₁₄₈N₄O₂₈S₄(2366.9): C 66.98, H 6.30, N

2.37, S 5.42. Found: C 66.00, H 6.29, N 2.31, S 5.60. FAB-MS:

m/z (%) = 2502 (100) [M+Cs⁺], 2451 (30) [M+Rb⁺], 2389

(50) [M+Na⁺], 2211 (40) [M⁺-CH₃C₆H₄SO₂].

CDCl₃):

d 97.65 (C-1,1’), 80.00 (C-2,2’), 81.82 (C-3,3’),

79.01 (C-4,4’), 70.51 (C-5,5’), 55.31 (OCH₃, OCH₃’), 75.63,

74.51, 73.11 (6 C, OCH₂Ph), 68.46 (2 C, CH₂OTs), 50.96,

49.63, 48.79, 46.02 (8 C, C-6,6’, CH₂NTs), 21.66, 21.54,

21.49 (6 C, CH,Ts), 145.10–135.59 (18 C, q, Ph), 129.99–

4.41. Cyclo-(N,N’)-bis-1,5-{bis-l,5-[methyl-2,3-di-O-benzyl-

6-deoxy-6-tosylamino-4-yloxy-a-D-glucopyranoside]-(3-

127.07 (48 C, Ph); Anal. calcd. for

C

₁₀₀H₁₁₄N₄O₂₄S₆

oxapentane)}-(3-tosyl-3-azapentane) (43)

(1948.4): C 61.65, H 5.90, N 2.88, S 9.87. Found: C

60.87, H 5.89, N 3.00, S 9.89.

The synthesis followed GP4 using 5 (200 mg, 0.17

mmol), 38 (308 mg, 0.16 mmol), cesium carbonate

(325 mg, 1.0 mmol), DMF (10 mL), 80 8C, 3 d. Puriﬁcation

was by ﬂash chromatography (toluene/ethyl acetate 3:1).

4.39. Cyclo-(N,N’)-bis-1,2-{bis-1,5-[methyl-2,3-di-O-benzyl-

6-deoxy-6-(tosyl)amino-4-yloxy-a-D-glucopyranoside]-(3-

oxapentane)}-ethane (41)

Yield 196 mg (45%); glass temperature 75–78 8C; [

a] +

D

32.2 (c 1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.69–7.24

The synthesis followed GP4 using 5 (200 mg, 0.18

mmol), 33 (270 mg, 0.17 mmol), cesium carbonate

(357 mg, 1.1 mmol), DMF (10 mL), 70 8C, 3 d. Puriﬁcation

was by ﬂash chromatography (toluene/ethyl acetate 3:1).

(m, 64 H, Ph), 4.57 (d, 4 H, H-1), 3.38 (dd, 4 H, H-2), 3.79

(dd, 4 H, H-3), 3.00 (dd, 4 H, H-4), 3.85–3.10 (m, 44 H, H-5,

H-6a, H-6b, OCH₂, CH₂NTs), 3.06 (s, 12 H, OCH₃), 4.89 (d, 4

H, OCH_ABn), 4.62 (d, 4 H, OCH_ABn), 4.71 (d, 4 H, OCH_ABn),

4.55 (d, 4 H, OCH_BBn), 2.34, 2.28 (s, 18 H, CH₃Ts); J_1,2= 3.5,

Yield 211 mg (52%); glass temperature 83 8C; [

a]_D+ 34.2 (c

1.0, CHCl₃); ¹H NMR (400 MHz, CDCl₃):

d

7.67–7.16 (m, 56

J

_2,3= 9.5, J_3,4= 9.0, J_4,5= 9.0, ²J_Bn=11.0 and 12.0 Hz; ¹³C NMR

(100 MHz, CDCl₃): 97.45 (4 C, C-1), 81.78, 80.37, 80.02

H, Ph), 4.45 (d, 4 H, H-1), 3.40 (dd, 4 H, H-2), 3.77 (dd, 4 H,

H-3), 2.95 (dd, 4 H, H-4), 3.57 (dddꢀdd, 4 H, H-5), 3.75

(ddꢀd, 4 H, H-6a), 3.17 (dd, 4 H, H-6b), 2.97 (s, 12 H, OCH₃),

4.89 (d, 4 H, OCH_ABn), 4.71 (d, 4 H, OCHaBn), 4.69 (d, 4 H,

OCH_BBn), 4.59 (d, 4 H, OCH_BBn), 3.90–3.84 (m, 4 H, OCH_A),

3.70–3.63 (m, 4 H, OCH_A), 3.50–3.29 (m, 16 H, OCH₂,

CH₂NTs), 2.34 (s, 12 H, CH₃Ts); J_1,2= 3.5, J_2,3= 9.5, J_3,4= 9.5,

d

(12 C, C-2, C-3, C-4), 69.81 (4 C, C-5), 55.13 (4 C, OCH,),

75.41, 73.05 (8 C, OCH₂Ph), 72.14, 70.70 (8 C, OCH₂), 50.92,

49.13, 48.68 (12 C, C-6,6’, CH₂NTs), 21.43 (6 C, CH,Ts),

143.19–136.64 (20 C, q, Ph), 129.81–127.35 (64 C, Ph).

Acknowledgement

2

J_4,5= 9.5, J_5,6= 0, J_5,6b= 9.5, J_6a,6b= 15.0, J_Bn=11.0 and

12.0 Hz; ¹³C NMR (100 MHz, CDC1₃):

97.49 (4 C, C-1),

d

Support of this work by the Deutsche Forschungsge-

meinschaft and the Fonds der Chemischen Industrie is

gratefully acknowledged.

79.93 (4 C, C-2), 81.77 (4 C, C-3), 80.49 (4 C, C-4), 69.86

(4 C, C-5), 49.80 (4 C, C-6), 55.00 (4 C, OCH₃), 75.51, 73.22

(8 C, OCH₂Ph), 72.09, 70.45 (8 C, OCH₂), 47.49 (4 C,

CH₂NTs), 21.50 (4 C, CH₃Ts), 143.01–137.13 (16 C, q,

Ph), 129.46–127.13 (56 C, Ph); Anal. calcd. for

References

[1] W.D. Curtis, D.A. Laidler, G.H. Jones, J.F. Stoddart, J. Chem. Soc. Chem.

Commun. (1975) 835.

[2] J.F. Stoddart, D.A. Laidler, J. Chem. Soc. Chem. Commun. (1976) 979.

[3] J.F. Stoddart, Chem. Soc. Rev. 8 (1979) 85.

C

₁₂₄H₁₄₈N₄O₃₀S₄(2302.8): C 64.68, H 6.48, N 2.43, S

5.57. Found: C 64.55, H 6.42, N 2.43, S 5.54. FAB-MS: m/z

(%) = 2323 (100) [M+Na⁺], MALD1-MS: m/z = 2322.5

[M+Na⁺].

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Synthesis of carbohydrate-based azamacrocycles by Richman-Atkins cyclisation

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