Convenient Multigram Scale Glycosylations of Scented Alcohols Employing Phase-Transfer Reactions

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Convenient Multigram Scale Glycosylations of Scented

Alcohols Employing Phase‐Transfer Reactions

a

Lars Kröger & Joachim Thiem

a

Institute of Organic Chemistry, University of Hamburg, Martin‐Luther‐King‐Platz 6, 20146,

Hamburg, Germany

Version of record first published: 20 Aug 2006.

To cite this article: Lars Kröger & Joachim Thiem (2003): Convenient Multigram Scale Glycosylations of Scented Alcohols

Employing Phase‐Transfer Reactions , Journal of Carbohydrate Chemistry, 22:1, 9-23

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JOURNAL OF CARBOHYDRATE CHEMISTRY

Vol. 22, No. 1, pp. 9–23, 2003

Convenient Multigram Scale Glycosylations of Scented

Alcohols Employing Phase-Transfer Reactions

y

*

Lars Kr o¨ ger and Joachim Thiem

Institute of Organic Chemistry, University of Hamburg, Hamburg, Germany

ABSTRACT

Various conditions for glycosylation (Koenigs–Knorr, Helferich, trichloroacetimi-

date, Fischer–Raske, phase-transfer methods) of 3-ethoxy-4-hydroxybenzaldehyde

(

ethyl vanillin), 3-hydroxy-2-methyl-4-pyranone (maltol) and 2,5-dimethyl-4-

1

hydroxy-3(2H)-furanone (furaneol ) were evaluated, taking into account yields and

ease of preparation (e.g., utilized donor, catalyst, conditions). The best results were

achieved employing phase transfer catalysis in a two-phase solvent mixture. To

increase water solubility for better applicability, the hitherto unknown maltosides of

the corresponding alcohols were synthesized, again proving the value of phase-

transfer conditions for glycosylation of phenols.

Key Words: Phase-transfer glycosylation; Scented alcohols; Flavorant-release

additives.

INTRODUCTION

As non-volatile flavorant-release additives, glycosides of scented alcohols, which

release the corresponding volatile alcohol under pyrolytic conditions, (e.g., Scheme 1)

[

1]

are of interest.

Such alcohols include 3-ethoxy-4-hydroxybenzaldehyde (ethyl

y

Dedicated to Professor Dr. Peter Welzel on the occasion of his 65th birthday.

*

Correspondence: Dr. Joachim Thiem, Institute of Organic Chemistry, University of Hamburg,

Martin-Luther-King-Platz 6, 20146, Hamburg, Germany; E-mail: thiem@chemie.uni-hamburg.de.

9

DOI: 10.1081/CAR-120019010

0732-8303 (Print); 1532-2327 (Online)

www.dekker.com

Copyright D 2003 by Marcel Dekker, Inc.

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10

Kr o¨ ger and Thiem

Scheme 1. Pyrolysis of ethyl vanillyl b-D-glucopyranoside (8).

vanillin, 1), 3-hydroxy-2-methyl-4-pyranone (maltol, 2) and 2,5-dimethyl-4-hydroxy-

1

3

(2H)-furanone (furaneol , 3). Reported syntheses of b-D-glucopyranosides of these

[2]

alcohols are usually tricky and of unsatisfactory yield requiring an improvement. In

addition, syntheses of the respective b-D-maltosides will give products with a higher

water solubility and thus a superior application feasibility.

RESULTS

Glycosylation of Ethyl Vanillin

The synthetic ethyl vanillin has a strong vanilla-like odor and finds broad

applications in perfumes, pastries and confectioneries having a pleasant aroma. 3-

Methoxy-4-hydroxybenzaldehyde (vanillin), the major component of the rather

expensive natural vanilla, has a slightly higher odor threshold and is more sensitive

to light.

Whereas the glucosylation of ethyl vanillin is reported to proceed in 56% yield by

[1]

the use of potassium carbonate in THF at 110°C (no pressure mentioned), the

application of this method proved not to be successful in our hands in refluxing THF

under normal pressure utilizing five equivalents of acceptor. Therefore we decided to

[3]

evaluate various glycosylation conditions, taking into account yields and ease of

preparation (Scheme 2, Table 1).

[4]

Helferich conditions (entry 1) employing the donor 1,2,3,4,6-penta-O-acetyl-b-

[5]

D-glucopyranose (4) and the promoter tin(IV)-chloride

as catalyst in dichlor-

Scheme 2. Synthesis of ethyl vanillyl b-D-glucopyranoside (8).

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Glycosylations of Scented Alcohols

Table 1. Conditions for the glycosylation of ethyl vanillin.

11

Entry

Donor

Conditions

Yield

1

2

3

4

5

6

7

8

9

4

5

6

SnCl

4

, DCM, 0 °C, 4 h

2

–

BF ꢀEt O, DCM, 40 °C, 48 h

25%

17%

11%

15%

27%

37%

59%

39%

46%

3

Hg(CN)

2

, Tol/MeNO

2

, rt, 24 h

˚

, MS 4 A, DCM, rt, 27 h

Ag CO

2

3

AgOTf, TMU, DCM, ꢁ 30 °C, 3 h

KOH/EtOH, CHCl , 61 °C, 16 h

3

KOH/MeOH, DCM, rt, 8 h

Bu

TMSOTf, DCM, ꢁ 20 °C, 2.5 h

BF O, DCM, ꢁ 18 °C, 2 h

ꢀEt

4

NBr, 1M NaOH, DCM, rt, 45 min

1

0

3

2

omethane led only to the corresponding a-chloride, which was stable under these

[6]

reaction conditions. Exchanging the catalyst to boron trifluoride (entry 2)

enforcing reaction conditions resulted in the desired glycosylation product 7 in a

and

[

7]

[8]

poor yield of 25%. Neither tributylstannylation

phenolic hydroxy group of acceptor 1 to enhance nucleophilicity were able to im-

nor trimethylsilylation

of the

prove yields.

[

9]

Even less satisfying was the use of the expensive and toxic Koenigs–Knorr

[10]

promoters mercury cyanide (entry 3, hydrogen cyanide is released)

of toluene and nitromethane, silver carbonate (entry 4, in the presence of molecular

in a mixture

[

11]

˚

sieves 4 A)

tetramethylurea (TMU) is necessary)

and silver triflate (entry 5, addition of an acid scavenger such as

in dichloromethane utilizing the readily avail-

[12]

able donor 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bromide (5). In all cases, the yield

was well below 20% and an upscaling would be problematic due to environ-

mental issues.

[13]

In contrast, reasonable results were achieved by the Fischer–Raske

utilizing ethanolic potassium hydroxide and the donor 5 in refluxing chloroform

entry 6). As there is no need for exclusion of oxygen or water, the reaction was

method

(

carried out easily, even on a larger scale, yielding 27% of the product 7. A further

improvement (entry 7) was possible by employing a methanolic solution of potassium

hydroxide. In this case we were able to isolate 7 in a yield of 37%, under yet milder

reaction conditions.

[14]

Comparable reaction conditions were employed by the phase-transfer method.

The reaction takes place in an aqueous-organic two-phase-system in the presence of a

cheap and non-toxic phase-transfer catalyst, which forms a lipophilic ion-pair together

with the deprotonated phenolate, which migrates into the organic phase. In an aprotic

nonpolar solvent such as dichloromethane, the ion-pair is not solvated, and the naked

phenolate shows enhanced nucleophilicity. Typical phase-transfer catalysts are

quaternary ammonium salts or crown ethers, being soluble in both the organic and

aqueous phase. Aqueous work-up and crystallization led to product 7 in an excellent

yield of 59% on a 30 g scale (entry 8). Side reactions were b-elimination and hydro-

lysis of the donor.

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12

Kr o¨ ger and Thiem

The trichloroacetimidate method, a widespread and versatile approach for gly-

[

15]

cosylations,

O-(2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl)trichloroacetimidate (6)

was used in an attempt to improve yields. Thus, the highly reactive

16]

[

was con-

densed with 1, catalyzed by the Lewis acids trimethylsilyl trifluoromethanesulfonate

or boron trifluoride (entries 9 and 10, respectively) under anhydrous conditions in

yields of 39 and 46%, respectively.

The advantages of the phase-transfer method are obvious: it does not only

give improved yields, but further the donor 5 is obtained from glucose in just one

step, no toxic or expensive catalysts are required, the reaction is very fast, the con-

ditions are quite mild, and the reaction is carried out easily without exclusion of air

or moisture.

Deprotection was achieved with catalytic amounts of sodium methoxide in me-

thanol giving 8 in 93% yield.

1

Glycosylation of Maltol and Furaneol

The g-pyrone 3-hydroxy-2-methyl-4-pyranone (maltol, 2) is a characteristic aroma

compound of caramel and an intermediate of the Maillard reaction, having a sweet

scent like cotton candy. Since maltol is sensitive to chelating or oxidizing reagents

(e.g., boron trifluoride, silver and mercury salts), attempts to utilize Helferich, trich-

loroacetimidate or Koenigs–Knorr conditions failed. Therefore we focused on the

previously successful Fischer–Raske and phase-transfer methods (Scheme 3, Table 2).

This is possible, as maltol has an aromatic character, and the corresponding alcoholate

is resonance stabilized.

Glucosylation of 2 with 5 in the presence of ethanolic potassium hydroxide in

refluxing chloroform proceeded in only 5% yield (entry 1). Again, methanolic potas-

Scheme 3. Synthesis of maltoyl (10) and furaneoyl b-D-glucopyranosides (12).

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Glycosylations of Scented Alcohols

Table 2. Conditions for the glycosylation of maltol and furaneol .

13

1

Entry

Acceptor

Conditions

Yield

1

2

3

4

5

2

3

KOH/EtOH, CHCl

KOH/MeOH, DCM, rt, 15 h

3

, 61 °C, 20 h

5%

14%

20%

31%

19%

Bu NBr, 1M NaOH, DCM, rt, 3.5 h

4

Bu

4

NBr, 1M NaOH, DCM, 35 °C, 3 h

4

NBr, 1M NaOH, DCM, 35 °C, 45 min

sium hydroxide in dichloromethane at room temperature led to better yields under even

[

17]

milder reaction conditions giving 14% of 9 (entry 2). Looker and Fisher

this synthesis first, but obtained only 12% of the product in acetone as solvent, the

reported

isolated product being contaminated with methyl b-D-glucopyranoside.

Reaction of 2 and 5 under phase-transfer conditions (entry 3) gave product 9 in

2

0% yield. Noteworthy is the dramatic improvement caused by elevating the

temperature by 10°C to a good yield of 31% (entry 4) after purification by crys-

tallization even on a large scale. The reasons for the lower yield compared to the

synthesis of 7 is the superior water solubility of 2, resulting in a lower concentration of

the maltoyl anion in the organic phase. Zempl e´ n deprotection yielded 10 in 70%, due to

some decomposition.

2,5-Dimethyl-4-hydroxy-3(2H)-furanone (furaneol , 3) is an important aroma

compound in many fruits and heated up meat, having a sweet caramel-like scent. The

1

1 6

odor threshold of furaneol is only 0.04 ppb, and thus about 10 lower than maltol.

[

18]

Mayerl et al.

were the first to synthesize the glucoside 11 employing bromide 5 and

an ethanolic potassium hydroxide solution in toluene at 80°C; they obtained the product

in a yield of only 7%. Zempl e´ n deacetylation was reported to proceed under extensive

decomposition, giving after purification by HPLC 12 in 16% yield and a purity of 92%.

Thus the total yield over just two steps was only 1%. Due to keto-enol tautomerism, 12

was a mixture of two diastereomers.

[

19]

Later Roscher et al.

utilized silver carbonate in equimolar amounts under

Koenigs–Knorr conditions followed by an in situ deprotection with ammonia in

methanol. Purification by MLCCC (multilayer coil countercurrent chromatography)

followed by HPLC gave 12 in a yield of 2.7%. Both methods are only practicable for

very small scale synthesis in the lower milligram range.

For a more convenient and higher-yielding method, phase-transfer conditions

proved once again to be the best choice for the glycosylation of aromatic alcohols

(

pleasing yield of 19% after purification by simple flash chromatography. Limitations

Scheme 3, Table 2, entry 5). We were able to isolate 11 in gram quantities in a

1

are the excellent water solubility of furaneol and its instability.

In our hands the reported deacetylations employing sodium methoxide or

ammonia in methanol were not successful, with extensive decomposition observed.

Consequently we developed a better method and were able to deprotect 11 to give a

high yield of 12 (50%), utilizing sodium carbonate in methanol, releasing only low

concentrations of methoxide.

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Kr o¨ ger and Thiem

Scheme 4. Synthesis of malto glycosides 15, 17 and 19.

Maltosylation of the Alcohols 1, 2, and 3

Since the Fischer–Raske and the phase-transfer methology proved to be the most

successful glycosylation conditions for the aforementioned glucosides, these methods

were applied for the first reported synthesis of the corresponding maltosides employing

the donor 2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl)-a-D-gluco-

pyranosyl bromide (13).

Utilizing ethanolic and methanolic potassium hydroxide in the case of acceptor 1

gave 10% and 22% yield of the maltoside 14, respectively (Scheme 4, Table 3, entries

1

4

and 2). Again the phase-transfer catalyzed glycosylation gave the highest yield of

8% within only 60 minutes (entry 3). Deprotection and crystallization furnished the

new product 15 in 85% yield.

Maltosylation of maltol and furaneol was realized under phase-transfer conditions

1

(entries 4 and 5) providing 16 and 18 in good yields of 33% and 22%, respectively.

Subsequent Zempl e´ n deacetylation of the protected maltosides gave the novel malto

glycosides 17 and 19 in 64% and 86% yield, respectively. Surprisingly, deprotection of

16 with sodium methoxide was accomplished in contrast to the glucoside 11 in rather

good yields.

Table 3. Conditions for the glycosylation employing a maltose donor.

Entry

Acceptor

Conditions

Yield

1

2

3

4

5

1

2

3

KOH/EtOH, CHCl

3

, 61 °C, 22 h

10%

22%

48%

33%

22%

KOH/MeOH, DCM, rt, 13 h

Bu NBr, 1M NaOH, DCM, rt, 1 h

4

Bu

4

NBr, 1M NaOH, DCM, 35 °C, 3 h

NBr, 1M NaOH, DCM, 35 °C, 45 min

4

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Glycosylations of Scented Alcohols

15

EXPERIMENTAL

General methods. TLC was performed on precoated aluminum plates (silica gel

0 F₂₅₄, Merck 5554) employing UV-adsorption and charring with 20% sulfuric acid/

6

ethanol for visualization. For column chromatography by the flash procedure, silica gel

1

13

6

0 M, 230–400 mesh, 40–63 mm (Macherey–Nagel), was used. H NMR and

C

NMR spectra were recorded on Bruker AMX-400 MHz (100.62 MHz for C) and

1

3

1

Bruker DRX-500 (125.83 MHz for C). If necessary, assignments were confirmed by

1

H H- and H C-Cosy experiments. Residual non-deuterated solvent was used as an

3

1

1 13

internal standard for determination of chemical shifts. Melting points were determined

with a B u¨ chi apparatus and are not corrected. Optical rotations were measured using a

Perkin Elmer 241 instrument at 578 nm and 20°C. MALDI-TOF-MS was performed on

a Bruker Biflex III with DHB as a matrix in positive reflector mode. Elemental analysis

were performed by the Zentrale Elementanalytik of the Faculty of Chemistry at the

University of Hamburg.

(

Entry 2 (cf. Table 1): To a solution of 1 (665 mg, 4.0 mmol) and 4

4-Formyl-2-ethoxyphenyl) 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (7).

[20]

(390 mg,

˚

1.0 mmol) in anhydrous dichloromethane (10 mL) with activated molecular sieves 4 A

(

added slowly under argon. The mixture was stirred for 48 h under reflux, and then

450 mg) at ꢁ 40°C in a brown glass flask, BF ꢀ Et O (0.25 mL, 2.0 mmol) was

3

2

washed with saturated NaHCO and water. The organic phase was dried, concentrated

3

and purified on silica gel employing petrol ether (50–70)/ethyl acetate (1:1) as eluents

to yield glycoside 7 (123 mg, 0.25 mmol, 25%) under recovery of 4 (167 mg, 0.43

mmol, 43%).

Entry 3: To a solution of 1 (332 mg, 2.0 mmol) and mercury(II)-cyanide (505

[

21]

mg, 2.0 mol) in toluene/nitromethane (20 mL, 1:1 v/v), 5

anhydrous toluene (10 mL) was added over a period of 2 h under argon. After 22 h the

(820 mg, 2.0 mmol) in

mixture was filtered. The organic phase was washed with saturated NaHCO and brine,

3

dried and concentrated. The residue was purified by column chromatography using

petrol ether (50–70)/ethyl acetate (1:1) to give 7 (172 mg, 0.35 mmol, 17%).

Entry 4: To a solution of 1 (166 mg, 1.0 mmol), silver carbonate (550 mg,

˚

.0 mmol) and activated molecular sieves 4 A (220 mg) in anhydrous dichloromethane

2

(

3 mL) in a brown glass flask, a solution of 5 (820 mg, 2.0 mmol) in anhydrous

dichloromethane (2 mL) was added dropwise under argon. The reaction was left for

7 h at room temperature. After filtration through Celite, the organic phase was

2

neutralized with saturated NaHCO , washed with water, dried and concentrated.

3

Column chromatography (petrol ether (50–70)/ethyl acetate 1:1) of the residue gave 7

(

55 mg, 0.11 mmol, 11%).

Entry 5: The reaction was performed in a brown glass flask under argon. To a

solution of 1 (420 mg, 2.5 mmol), tetramethylurea (0.30 mL, 2.5 mmol) and silver

trifluoromethanesulfonate (520 mg, 2.0 mmol) in anhydrous dichloromethane (5 mL) at

ꢁ

30°C, a solution of 5 (820 mg, 2.0 mmol) in anhydrous dichloromethane (10 mL)

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16

Kr o¨ ger and Thiem

was added dropwise over a period of 15 min. The reaction was stirred for 30 min at

30°C and additional 3 h at room temperature. Subsequently the mixture was filtered

ꢁ

through Celite/Carbon, neutralized and washed. The organic phase was dried,

concentrated and purified by flash chromatography on silica gel employing toluene/

ethyl acetate (2:1) as eluents to yield 7 (151 mg, 0.30 mmol, 15%).

Entry 6: A solution of potassium hydroxide (4.7 g, 84 mmol) in ethanol (90 mL)

was added to 1 (16.3 g, 98 mmol) and 5 (36.4 g, 89 mmol) in chloroform (450 mL) and

refluxed for 16 h. The mixture was poured on iced water (800 mL), and the aqueous

phase was extracted with chloroform three times. The combined organic phases were

dried and concentrated. The crude product was crystallized from ethanol giving pure 7

(11.8 g, 23.8 mmol, 27%).

Entry 7: To a solution of 5 (905 mg, 2.2 mmol) in anhydrous dichloromethane

9 mL), 1 (332 mg, 2.0 mmol) in a 0.45 molar solution of potassium hydroxide in

(

anhydrous methanol (4.4 mL) was added dropwise. The reaction was left for 8 h and

subsequently poured on iced water (20 mL). The aqueous phase was extracted with

dichloromethane twice and the combined organic phases were dried, concentrated and

purified by flash chromatography with the solvent system petrol ether (50–70)/ethyl

acetate (1:1) to furnish 7 (366 mg, 0.74 mmol, 37%).

Entry 8: Compounds 1 (33.3 g, 200 mmol), 5 (41.1 g, 100 mmol) and

tetrabutylammonium bromide (32.3 g, 100 mmol) were dissolved in dichloromethane

(350 mL). A 1 molar sodium hydroxide solution (350 mL) was added, and the mixture

was stirred vigorously for 45 min at room temperature. Ethyl acetate (3000 mL) was

added, and the organic phase was washed subsequently three times with 1 molar

sodium hydroxide, three times with water, once with brine, dried and finally

concentrated. The residue was purified twice by crystallization from ethanol to yield

7

(29.3 g, 59 mmol, 59%).

Entry 9: To a solution of 1 (47 mg, 0.28 mmol) and 6 (200 mg, 0.41 mmol) in

˚

anhydrous dichloromethane (7 mL) over molecular sieves 4 A (80 mg) at ꢁ 20°C, a

0

.02 molar solution of trimethylsilyl trifluoromethanesulfonate in anhydrous dichloro-

methane (1 mL) was added under argon. After 2.5 h the mixture was diluted with

dichloromethane, neutralized with saturated NaHCO₃and washed with water. The

organic phase was dried, concentrated and purified by column chromatography on silica

gel with petrol ether (50–70)/ethyl acetate (1:1) as eluents to yield 7 (54 mg, 0.11

mmol, 39%).

Entry 10: To a solution of 1 (14 mg, 84 mmol) and 6 (56 mg, 110 mmol) in

˚

anhydrous dichloromethane (2 mL) over molecular sieves 4 A (80 mg) at ꢁ18°C,

BF ꢀEt O (10.6 mL, 84 mmol) was added under argon. After 2 h the mixture was diluted

3

2

with dichloromethane, neutralized with saturated NaHCO and washed with water. The

3

organic phase was dried, concentrated and purified by column chromatography on silica

gel with petrol ether (50–70)/ethyl acetate (1:1) as eluents to furnish 7 (14 mg, 28

2

0

1

mmol, 46%) as white crystals: [a]_Dꢁ 50.9° (c 1, chloroform); mp 115–117°C; H

4

NMR (400 MHz, CDCl ) d 9.84 (s, 1 H, CHO), 7.34–7.39 (m, 2 H, J

1.5 Hz,

ar-3,ar-5

3

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Glycosylations of Scented Alcohols

17

J_a_r_-₅_,_a_r_-₆7.6 Hz, aryl H-3, aryl H-5), 7.16 (d, 1 H, aryl H-6), 5.31 (dd, 1 H, J₁_,₂7.6 Hz,

J₂_,₃9.7 Hz, H-2), 5.27 (dd, 1 H, J₃_,₄9.2 Hz, H-3), 5.14 (dd, 1 H, J₄_,₅10.2 Hz, H-4),

5

2

.10 (d, 1 H, H-1), 4.23 (dd, 1 H, J₅_,₆_a5.1 Hz, J₆_a_,₆_b12.2 Hz, H-6a), 4.15 (dd, 1 H, J₅_,₆_b

.5 Hz, H-6b), 4.07 (q, 2 H, J_O_E_t7.1 Hz, O–CH –CH ), 3.83 (ddd, 1 H, H-5), 2.03,

2

3

.02, 2.01, 2.00 (4 ꢂ s, 4 ꢂ 3 H, 4 ꢂ COCH ), 1.40 (t, 3 H, O–CH –CH ) ppm;

3

2

3

1

3

C NMR (100.6 MHz, CDCl ) d 191.27 (CHO), 170.85, 170.58, 169.74, 169.45 (4 C,

3

4

ꢂ COCH ), 151.64, 150.55 (2 ꢂ C, aryl C-1, aryl C-2), 133.11 (aryl C-4), 125.56

3

(

aryl C-5), 118.43 (aryl C-6), 112.52 (aryl C-3), 99.84 (C-1), 72.84 (C-3), 72.59 (C-5),

7

1.40 (C-2), 68.69 (C-4), 65.09 (C-6), 62.27 (O–CH –CH ), 21.02, 20.99, 20.97, 20.94

2 3

[1]

(

4 C, 4 ꢂ COCH ), 15.04 (O–CH –CH ) ppm.

3

2

3

(

4-Formyl-2-ethoxyphenyl) -D-glucopyranoside (8). A solution of 7 (39.6 g,

9.8 mmol) in anhydrous methanol (400 mL) was treated with methanolic sodium

7

methoxide (40 mL, 1%) for 15 min. The mixture was neutralized with Amberlite IR-

+

20 (H ) and concentrated. Crystallization from ethanol gave 8 (24.3 g, 74.0 mmol,

1

9

2

0

[1]

3%) as a white powder: [a]₅ꢁ 14.5° (c 1, water); mp 202°C [lit 199–200°C];

78

+

1

MALDI-TOF-MS m/z 351.1 [M + Na] , 367.1 [M + K] ; H NMR (400 MHz, d -

4

MeOH) d 9.74 (s, 1 H, CHO), 7.43 (dd, 1 H, J 1.5 Hz, J_a_r_-₅_,_a_r_-₆8.1 Hz, aryl H-

), 7.40 (d, 1 H, aryl H-3), 7.23 (d, 1 H, aryl H-6), 5.00 (d, 1 H, J₁_,₂7.1 Hz, H-1),

ar-3,ar-5

5

4

.05–4.13 (m, 2H, J_O_E_t7.1 Hz, O–CH –CH ), 3.79 (dd, 1 H, J 2.0 Hz, J₆_a_,₆_b12.2

5,6a

2

3

Hz, H-6a), 3.61 (dd, 1 H, J₅_,₆_b5.6 Hz, H-6b), 3.30–3.49 (m, 4 H, H-2, H-3, H-4, H-5),

1

3

1

2

.36 (t, 3H, O–CH –CH ) ppm; C NMR (100.6 MHz, d -MeOH) d 193.38 (CHO),

2

3

4

54.14, 150.92 (2 ꢂ C, aryl C-1, aryl C-2), 133.27 (aryl C-4), 127.18 (aryl C-5),

17.31 (aryl C-6), 113.82 (aryl C-3), 102.15 (C-1), 78.79 (C-5), 78.36 (C-3), 75.13 (C-

), 71.61 (C-4), 66.48 (C-6), 62.84 (O–CH –CH ), 15.37 (O–CH –CH ) ppm.

2

3

2

3

(2-Methyl-4-oxopyran-3-yl) 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside (9).

Entry 1 (cf. Table 2): A 1 molar solution of potassium hydroxide in ethanol (0.95

mL) was added to 2 (139 mg, 1.1 mmol) and 5 (411 mg, 1.0 mmol) in chloroform

5 mL) and refluxed for 20 h. The mixture was poured on iced water (10 mL), and the

(

aqueous phase was extracted with chloroform three times. The combined organic phases

were dried and concentrated. The crude product was purified on silica gel employing

petrol ether (50–70)/ethyl acetate (1:2) as eluents to give 9 (24 mg, 53 mmol, 5%).

Entry 2: To a solution of 5 (905 mg, 2.2 mmol) in anhydrous dichloromethane

9 mL), 2 (252 mg, 2.0 mmol) in a 0.45 molar solution of potassium hydroxide in

(

anhydrous methanol (4.4 mL) was added dropwise. The reaction was left for 15 h and

subsequently poured on iced water (20 mL). The aqueous phase was extracted with

dichloromethane three times and the combined organic phases were dried, concentrated

and purified by flash chromatography with the solvent system petrol ether (50–70)/

ethyl acetate (1:2) to furnish 9 (124 mg, 0.27 mmol, 14%).

Entry 3: Compounds 2 (4.03 g, 32 mmol), 5 (6.58 g, 16 mmol) and

tetrabutylammonium bromide (5.16 g, 16 mmol) were dissolved in dichloromethane

(

56 mL). A 1 molar sodium hydroxide solution (56 mL) was added, and the mixture

was stirred vigorously for 3.5 h at room temperature. Ethyl acetate (600 mL) was added

and the organic phase was washed subsequently twice with 1 molar sodium hydroxide,

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016

©

18

Kr o¨ ger and Thiem

twice with water, dried and finally concentrated. The residue was purified by column

chromatography employing petrol ether (50–70)/ethyl acetate (1:2) to yield 9 (1.44 g,

3

.2 mmol, 20%).

Entry 4: Compounds 2 (48.4 g, 384 mmol), 5 (52.6 g, 128 mmol) and

tetrabutylammonium bromide (41.3 g, 128 mmol) were dissolved in dichloromethane

(450 mL) and warmed up to 35°C. A 1 molar sodium hydroxide solution (450 mL) was

added, and the mixture was stirred vigorously for 3 h at 35°C. Ethyl acetate (3000 mL)

was added, and the organic phase was washed subsequently three times with 1 molar

sodium hydroxide, twice with water, once with brine, dried and finally concentrated.

Dissolving the residue in hot ethanol and precipitation by addition of petrol ether (50–

2

0

7

0) gave pure 9 (17.9 g, 39.2 mmol, 31%) as white crystals: [a] ꢁ 9.9° (c 0.1,

5

78

[

1]

1

chloroform); mp 147°C [lit 143–145°C]; H NMR (400 MHz, CDCl ) d 7.60 (d, 1

3

H, J_m_a_l_t_y_l₅_,₆5.6 Hz, maltyl H-6), 6.30 (d, 1 H, maltyl H-5), 5.31 (d, 1 H, J₁_,₂7.6 Hz,

H-1), 5.26 (dd, 1 H, J₂_,₃9.7 Hz, J₃_,₄9.2 Hz, H-3), 5.16 (dd, 1 H, H-2), 5.09 (dd, 1 H,

^J⁴,5 10.2 Hz, H-4), 4.17 (dd, 1 H, J₅_,₆_a4.6 Hz, J₆_a_,₆_b12.2 Hz, H-6a), 4.10 (dd, 1 H, J₅_,₆_b

2

.5 Hz, H-6b), 3.63 (ddd, 1 H, H-5), 2.28 (s, 3 H, maltyl CH ), 2.11, 2.01, 2.00, 1.99

3

1

3

(

4 ꢂ s, 4 ꢂ 3H, 4 ꢂ COCH ) ppm; C NMR (125.8 MHz, CDCl ) d 174.03 (maltyl

3

C-4), 170.80, 170.43, 170.38, 169.88 (4 C, 4 ꢂ COCH ), 161.67 (maltyl C-2), 154.13

3

(

maltyl C-6), 141.62 (maltyl C-3), 117.68 (maltyl C-5), 99.75 (C-1), 72.90 (C-3), 72.17

C-5), 71.73 (C-2), 68.85 (C-4), 61.94 (C-6), 21.19, 21.07, 20.98, 20.95 (4 C,

4

ꢂ COCH ), 15.58 (maltyl CH ) ppm.

3

(

.72 mmol) in anhydrous methanol (30 mL) was treated with methanolic sodium

2-Methyl-4-oxopyran-3-yl) b-D-glucopyranoside (10). A solution of 9 (1.70 g,

3

methoxide (13 mL, 1%) for 1 h. The mixture was neutralized with Amberlite IR-120

+

H ) and concentrated. Column chromatography on silica gel (ethyl acetate/methanol

(

2

0

2

:1) gave 10 (746 mg, 2.59 mmol, 70%) as yellowish crystals: [a] ꢁ 7.0° (c 0.1,

5

78

[

1]

+

water); mp 109°C [lit 115–117°C]; MALDI-TOF-MS m/z 289.2 [M + H] , 311.2

+

1

[M + Na] ; H NMR (400 MHz, D O) d 7.87 (d, 1 H, J

5.6 Hz, maltyl H-6),

.36 (d, 1 H, maltyl H-5), 4.72 (m , 1 H, J 7.6 Hz, H-1), 3.66 (dd, 1 H, J₅_,₆_a2.0 Hz,

2

maltyl 5,6

6

J₆_a_,₆_b12.7 Hz, H-6a), 3.55 (dd, 1 H, J₅_,₆_b5.1 Hz, H-6b), 3.34–3.38 (m, 2 H, H-2, H-3),

c 1,2

3

.27–3.30 (m, 1 H, J₄_,₅9.7 Hz, H-4), 3.20 (ddd, 1 H, H-5), 2.28 (s, 3 H, CH ) ppm;

3

1

3

C NMR (100.6 MHz, D O) d 178.22 (maltyl C-4), 165.98 (maltyl C-6), 158.09

2

(

7

maltyl C-2), 143.13 (maltyl C-3), 117.30 (maltyl C-5), 104.55 (C-1), 77.70 (C-5),

7.09 (C-3), 74.91 (C-2), 70.93 (C-4), 61.81 (C-6), 16.55 (CH ) ppm.

3

(2,5R/5S-Dimethyl-4-oxofuran-3-yl) 2,3,4,6-tetra-O-acetyl-b-D-glucopyranoside

11). Compounds 3 (7.93 g, 61.9 mmol), 5 (5.09 g, 12.4 mmol) and tetrabutylammo-

(

nium bromide (3.99 g, 12.4 mmol) were dissolved in dichloromethane (75 mL) and

warmed up to 35°C. A 1 molar sodium hydroxide solution (75 mL) was added, and the

mixture was stirred vigorously for 45 min at 35°C. Ethyl acetate (400 mL) was added,

and the organic phase was washed subsequently three times with 1 molar sodium

hydroxide, twice with water, once with brine, dried and finally concentrated. Flash

chromatography on silica gel employing petrol ether (50–70)/ethyl acetate (1:1) as

eluents gave the 1:1 diastereomeric mixture 11 (1.09 g, 2.4 mmol, 19%) as an

2

78

0

1

amorphous white solid: [a]₅ꢁ 15.3° (c 1, chloroform); H NMR (400 MHz, CDCl )

3

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016

©

Glycosylations of Scented Alcohols

19

d 5.17–5.24 (m, 1 H, H-3), 5.04–5.12 (m, 3 H, H-1, H-2, H-4), 4.41, 4.40 (2 ꢂ q, 1

H, furaneyl H-5), 4.19 (dd, 1 H, J 5.6 Hz, J 12.2 Hz, H-6a), 4.11 (dd, 1 H, J

5,6b

5

,6a

6a,6b

2

4

.5 Hz, H-6b), 3.64–3.71 (m, 1 H, H-5), 2.16, 2.03, 1.99, 1.98 (4 ꢂ s, 4 ꢂ 3H,

ꢂ COCH ), 2.09, 2.08 (2 ꢂ s, 3 H, furaneyl 2-CH ), 1.41, 1.40 (2 ꢂ d, 3 H,

3

1

3

furaneyl 5-CH ) ppm; C NMR (100.6 MHz, CDCl ) d 196.75, 196.71 (2 C, furaneyl

3

C-4), 181.38, 181.10 (2 C, furaneyl C-2), 170.89, 170.48, 170.23, 169.87 (4 C,

4

8

ꢂ COCH ), 133.42, 133.32 (2 C, furaneyl C-3), 100.24, 99.92 (2 C, C-1), 81.28,

3

1.24 (furaneyl C-5), 73.00, 72.97 (2 C, C-3), 72.37, 72.32 (2 C, C-5), 71.50, 71.44 (2

C, C-4), 68.72 (C-2), 62.17, 62.06 (2 C, C-6), 21.18, 21.15, 21.07, 21.00 (4 C,

4

ppm.

ꢂ COCH ), 16.83, 16.63 (2 C, furaneyl 5-CH ), 14.20, 14.19 (2 C, furaneyl 5-CH )

3

[

18]

(

1 (8.2 g, 17.9 mmol) in anhydrous methanol (150 mL), sodium carbonate (8.2 g, 77.4

2,5R/5S-Dimethyl-4-oxofuran-3-yl) b-D-glucopyranoside (12). To a solution of

1

mmol) was added. The reaction mixture was left at room temperature for 4 h, filtered

and concentrated. Purification on silica gel (ethyl acetate/methanol 5:1) gave 12 (2.60

2

0

78

[18]

g, 9.03 mmol, 50%) as an amorphous solid: [a] ꢁ 34.8° (c 0.1, water) [lit

5

2

0

+

1

[

(

a]₅ꢁ 50°]; MALDI-TOF-MS m/z 313.1 [M + Na] , 329.1 [M + K] ; H NMR

89

400 MHz, D O) d 4.82–4.73 (m, 2 H, H-1, furaneyl H-5), 3.87 (dd, 1 H, J

12.2

2 6a,6b

Hz, H-6a), 3.74 (dd, 1 H, J₅_,₆_b5.1 Hz, H-6b), 3.52 (dd, 1 H, J₂_,₃8.6 Hz, J₃_,₄8.6 Hz, H-

), 3.49–3.39 (m, 3 H, H-2, H-4, H-5), 2.35 (s, 3 H, furaneyl 2-CH ), 2.35 (d, 3 H,

3

1

3

furaneyl 5-CH ) ppm; C NMR (100.6 MHz, D O) d 203.30 (furaneyl C-4), 188.68

3

2

(

furaneyl C-2), 136.08 (furaneyl C-3), 106.00 (C-1), 84.71 (furaneyl C-5), 78.88 (C-5),

7

1

8.23 (C-3), 75.75 (C-4), 71.95 (C-2), 63.11 (C-6), 18.16, 18.06 (furaneyl 5-CH ),

3

[18]

6.56 (furaneyl 2-CH ) ppm.

3

(

4-Formyl-2-ethoxyphenyl) 2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-

glucopyranosyl)-b-D-glucopyranoside (14). Entry 1 (cf. Table 3): A 1 molar

solution of potassium hydroxide in ethanol (4.75 mL) was added to 1 (920 mg, 5.5

[

22]

mmol) and 13

(3.5 g, 5.0 mmol) in chloroform (25 mL) and refluxed for 16 h. The

mixture was poured on iced water (40 mL), and the aqueous phase was extracted with

chloroform three times. The combined organic phases were dried and concentrated. The

crude product was purified on silica gel employing petrol ether (50–70)/ethyl acetate

(

1:1) as eluents to give 14 (402 mg, 0.51 mmol, 10%).

Entry 2: To a solution of 13 (1.54 g, 2.2 mmol) in anhydrous dichloromethane

9 mL), 1 (332 mg, 2.0 mmol) in a 0.45 molar solution of potassium hydroxide in

(

anhydrous methanol (4.4 mL) was added dropwise. The reaction was left for 13 h and

subsequently poured on iced water (20 mL). The aqueous phase was extracted with

dichloromethane twice, and the combined organic phases were dried, concentrated and

purified by flash chromatography with the solvent system petrol ether (50–70)/ethyl

acetate (1:1) to furnish 14 (341 mg, 0.43 mmol, 22%).

Entry 3: Compunds 1 (665 mg, 4.0 mmol), 13 (1.40 g, 2.0 mmol) and

tetrabutylammonium bromide (645 mg, 2.0 mmol) were dissolved in dichloromethane

(7 mL). A 1 molar sodium hydroxide solution (7 mL) was added, and the mixture was

stirred vigorously for 1 h at room temperature. Ethyl acetate (100 mL) was added, and

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016

©

20

Kr o¨ ger and Thiem

the organic phase was washed subsequently three times with 1 molar sodium hy-

droxide, three times with water, once with brine, dried and finally concentrated. The

residue was purified by column chromatography employing petrol ether (50–70)/ethyl

2

0

acetate (1:1) to yield 14 (749 mg, 0.95 mmol, 48%) as white crystals: [a]₅+ 2.1° (c

78

1

0

7

.1, chloroform); mp 141°C; H NMR (500 MHz, CDCl ) d 9.86 (s, 1 H, CHO), 7.36–

3

4

.41 (m, 2 H, J

1.5 Hz, J_a_r_-₅_,_a_r_-₆8.7 Hz, aryl H-3, aryl H-5), 7.15 (d, 1 H, aryl

ar-3,ar-5

H-6), 5.42 (d, 1 H, J₁_’_,₂_’4.1 Hz, H-1’), 5.35 (dd, 1 H, J₂_’_,₃_’10.7 Hz, J₃_’_,₄_’9.7 Hz, H-3’),

.30 (dd, 1 H, J₂_,₃7.6 Hz, J₃_,₄8.6 Hz, H-3), 5.12–5.19 (m, 2 H, H-1, H-2), 5.03 (dd, 1

5

H, J₄_’_,₅_’10.2 Hz, H-4’), 4.84 (dd, 1 H, H-2’), 4.49 (dd, 1 H, J₅_,₆_a3.1 Hz, J₆_a_,₆_b9.2 Hz,

H-6a), 4.20–4.26 (m, 2 H, J₅_,₆_b5.1 Hz, J₅_’_,₆_’_a4.1 Hz, H-6b, H-6’a), 4.02–4.13 (m, 4 H,

J₅_’_,₆_’_b2.5 Hz, J_O_E_t7.1 Hz, H-4, H-6’b, O–CH –CH ), 3.96 (ddd, 1 H, H-5’), 3.85 (ddd,

2

3

1

7

1

7

H, J₄_,₅= 9.7, H-5), 2.08, 2.05, 2.03, 2.02, 2.01, 2.00, 1.98 (7 ꢂ s, 7 ꢂ 3 H,

1

3

ꢂ COCH ), 1.41 (t, 3 H, O–CH –CH ) ppm; C NMR (100.6 MHz, CDCl ) d

3 2 3 3

90.91 (CHO), 170.52, 170.45, 170.30, 170.16, 169.96, 169.50, 169.41 (7 C,

ꢂ COCH ), 151.20, 150.15 (2 ꢂ C, aryl C-1, aryl C-2), 132.67 (aryl C-4), 125.34

3

(aryl C-5), 117.81 (aryl C-6), 112.03 (aryl C-3), 98.77 (C-1), 95.75 (C-1’), 75.00 (C-3),

7

4

2

2.70 (C-4), 71.54 (C-5), 71.86 (C-2), 70.10 (C-2’), 69.34 (C-3’), 68.66 (C-5’), 68.11 (C-

’), 64.70 (O–CH –CH ), 62.71 (C-6), 61.60 (C-6’), 20.90, 20.76, 20.71, 20.67, 20.64,

2

3

0.61, 20.58 (7 C, 7 ꢂ COCH ), 14.70 (O–CH –CH ) ppm.

3

2

3

Anal. Calcd for C H O (784.72): C, 53.57; H, 5.65. Found: C, 53.47; H, 5.75.

35 44 20

(

15). A solution of 14 (982 mg, 1.25 mmol) in anhydrous methanol (15 mL) was

4-Formyl-2-ethoxyphenyl) 4-O-(a-D-glucopyranosyl)-b-D-glucopyranoside

(

treated with methanolic sodium methoxide (1.5 mL, 1%) for 10 min. The mixture was

+

neutralized with Amberlite IR-120 (H ) and concentrated. Crystallization from ethanol

2

0

gave pure 15 (520 mg, 1.06 mmol, 85%) as white solid: [a] + 1.2° (c 0.1, water); mp

5

78

+

1

99°C; MALDI-TOF-MS m/z 513.2 [M + Na] , 529.2 [M + K] ; H NMR (400

4

MHz, D O) d 9.67 (s, 1 H, CHO), 7.49 (dd, 1 H, J

1.5 Hz, J_a_r_-₅_,_a_r_-₆8.1 Hz, aryl

ar-3,ar-5

2

H-5), 7.43 (d, 1 H, aryl H-3), 7.21 (d, 1 H, aryl H-6), 5.38 (d, 1 H, J₁_’_,₂_’4.1 Hz, H-1’),

5

3

.19 (d, 1 H, J₁_,₂7.6 Hz, H-1), 4.08–4.17 (m, 2H, J_O_E_t7.1 Hz O–CH –CH ), 3.62–

.89 (m, 10 H, H-2, H-3, H-4, H-5, H-6a, H-6b, H-3’, H-5’, H-6’a, H-6’b), 3.53 (dd, 1

9.7 Hz, J₄_’_,₅_’9.7 Hz, H-4’), 1.36 (t, 3H, O–

2 3

H, J₂_’_,₃_’9.7 Hz, H-2’), 3.37 (dd, 1 H, J

CH –CH ) ppm; C NMR (100.6 MHz, d -MeOH) d 195.11 (CHO), 151.62, 148.36

3’,4’

1

3

2

3

4

(

1

7

2 ꢂ C, aryl C-1, aryl C-2), 131.31 (aryl C-4), 126.94 (aryl C-5), 115.34 (aryl C-6),

12.99 (aryl C-3), 100.07 (C-1’), 99.78 (C-1), 76.74 (C-5), 76.21 (C-3), 75.24 (C-4),

3.23 (C-2), 73.11 (C-5’), 72.86 (C-3’), 72.06 (C-2’), 69.69 (C-4’), 65.68 (O–CH₂–

CH ), 60.85, 60.80 (2 ꢂ C, C-6, C-6’), 15.37 (O–CH –CH ) ppm.

3

2

3

Anal. Calcd for C H O (490.46): C, 51.43; H, 6.17. Found: C, 50.97; H, 6.22.

21 30 13

(

2-Methyl-4-oxopyran-3-yl) 2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-

glucopyranosyl)-b-D-glucopyranoside (16). Compounds 2 (3.78 g, 30 mmol), 13

6.99 g, 10 mmol) and tetrabutylammonium bromide (3.22 g, 10 mmol) were dissolved

(

in dichloromethane (35 mL) and warmed up to 35°C. A 1 molar sodium hydroxide

solution (35 mL) was added, and the mixture was stirred vigorously for 3 h at 35°C.

Ethyl acetate (400 mL) was added, and the organic phase was washed subsequently

twice with 1 molar sodium hydroxide, twice with water, once with brine, dried and

finally concentrated. Flash chromatography on silica gel employing petrol ether(50–

7

0)/ethyl acetate (1:3) as eluents gave 16 (2.44 g, 3.27 mmol, 33%) as a white solid:

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016

©

Glycosylations of Scented Alcohols

21

2

78

0

1

[

a]₅+ 3.9° (c 0.1, chloroform); mp 85°C; H NMR (400 MHz, CDCl ) d 7.60 (d, 1

3

H, J_m_a_l_t_y_l₅_,₆5.6 Hz, maltyl H-6), 6.31 (d, 1 H, maltyl H-5), 5.39 (d, 1 H, J₁_’_,₂_’4.1 Hz,

H-1’), 5.27–5.34 (m, 3 H, J₃_,₄9.2 Hz, J₂_’_,₃_’10.7 Hz, H-1, H-3, H-3’), 4.96–5.05 (m, 2

H, J₄_’_,₅_’10.2 Hz, H-2, H-4’), 4.82 (dd, 1 H, H-2’), 4.52 (dd, 1 H, J₅_,₆_a2.5 Hz, J₆_a_,₆_b12.2

Hz, H-6a), 4.22 (dd, 1 H, J₅_’_,₆_’_a3.6 Hz, J₆_’_a_,₆_’_b12.2 Hz, H-6’a), 4.14 (dd, 1 H, J₅_,₆_b4.1

Hz, H-6b), 4.02 (dd, 1 H, J₅_’_,₆_’_b2.5 Hz, H-6’b), 4.00 (dd, 1 H, J₄_,₅9.7 Hz, H-4), 3.90

(

2

ddd, 1 H, H-5’), 3.59 (ddd, 1 H, H-5), 2.24 (s, 1 H, maltyl CH ), 2.08, 2.07, 2.06,

3

1

3

.03, 2.00, 1.98, 1.97 (7 ꢂ s, 7 ꢂ 3 H, 7 ꢂ COCH ) ppm; C NMR (100.6 MHz,

3

CDCl ) d 172.57 (maltyl C-4), 169.60, 169.52, 169.34, 169.14, 168.88, 168.85, 168.40

3

(

1

7

7 C, 7 ꢂ COCH ), 160.32 (maltyl C-2), 152.71 (maltyl C-6), 140.24 (maltyl C-3),

3

16.35 (maltyl C-5), 98.09 (C-1), 94.45 (C-1’), 73.83 (C-3), 71.38 (C-4), 71.33 (C-5),

1.12 (C-2), 68.98 (C-2’), 68.31 (C-3’), 67.43 (C-5’), 67.05 (C-4’), 60.98 (C-6), 60.45

(

C-6’), 20.03, 19.86, 19.79, 19.70, 19.66, 19.58, 19.57 (7 C, 7 ꢂ COCH ), 14.12

3

maltyl CH ) ppm.

3

Anal. Calcd for C H O (744.66): C, 51.61; H, 5.41. Found: C, 51.42; H, 5.48.

32 40 20

(

17). A solution of 16 (870 mg, 1.17 mmol) in anhydrous methanol (15 mL) was

2-Methyl-4-oxopyran-3-yl) 4-O-(a-D-glucopyranosyl)-b-D-glucopyranoside

(

treated with methanolic sodium methoxide (7 mL, 1%) for 45 min. The mixture was

+

neutralized with Amberlite IR-120 (H ) and concentrated. Column chromatography

(

[

methanol/ethyl acetate 2:1) gave 17 (339 mg, 0.75 mmol, 64%) as yellowish solid:

2

0

+

a]₅+ 13.5° (c 0.1, water); mp 119°C; MALDI-TOF-MS m/z 473.1 [M + Na] ;

78

1

H NMR (400 MHz, D O) d 8.04 (d, 1 H, J

5.6 Hz, maltyl H-6), 6.54 (d,

2

maltyl 5,6

1

3

H, maltyl H-5), 5.41 (d, 1 H, J₁_’_,₂_’3.6 Hz, H-1’), 4.92 (d, 1 H, J₁_,₂8.1 Hz, H-1),

.65–3.86 (m, 8 H, H-3, H-4, H-6a, H-6b, H-3’, H-5’, H-6’a, H-6’b), 3.54–3.60 (m, 2

H, H-2, H-2’), 3.47 (ddd, 1 H, J 9.2 Hz, J₅_,₆_a2.6 Hz, H-5), 3.40 (dd, 1 H, H-4’),

4

,5

1

3

2

.46 (s, 3H, CH ) ppm; C NMR (100.6 MHz, D O) d 177.22 (maltyl C-4), 164.98

3

2

(

7

6

maltyl C-6), 157.05 (maltyl C-2), 142.02 (maltyl C-3), 116.26 (maltyl C-5), 103.20

C-1), 99.90 (C-1’), 76.55, 76.46 (2 ꢂ C, C-3, C-4), 75.30 (C-5), 73.73 (C-2), 73.19,

3.04 (2 ꢂ C, C-3’, C-5’), 72.02 (C-2’), 69.68 (C-4’), 60.85, 60.74 (2 ꢂ C, C-6, C-

’), 15.49 (CH ) ppm.

3

Anal. Calcd for C H O (450.40): C, 48.00; H, 5.82. Found: C, 47.84; H, 5.91.

8 26 13

1

(

2,5R/5S-Dimethyl-4-oxofuran-3-yl) 2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-

acetyl-a-D-glucopyranosyl)-b-D-glucopyranoside (18). Compounds 3 (6.83 g, 53.3

mmol), 13 (7.46 g, 10.7 mmol) and tetrabutylammonium bromide (3.44 g, 10.7 mmol)

were dissolved in dichloromethane (65 mL) and warmed up to 35°C. A 1 molar sodium

hydroxide solution (65 mL) at 35°C was added, and the mixture was stirred vigorously

for 45 min at 35°C. Ethyl acetate (350 mL) was added, and the organic phase was

washed subsequently twice with 1 molar sodium hydroxide, twice with water, once

with brine, dried and finally concentrated. Flash chromatography on silica gel em-

ploying dichloromethane/acetone (8:1) as eluents gave the diastereomeric mixture 18

2

5

0

(

1.78 g, 2.38 mmol, 22%) as white crystals: [a] ₇₈+ 1.0° (c 0.1, chloroform); mp 68°C;

1

H NMR (400 MHz, CDCl ) d 5.40, 5.39 (2 ꢂ d, 1 H, J

4.1 Hz, H-1’), 5.32 (dd, 1

3

1’,2’

H, J

10.7 Hz, J

9.7 Hz, H-3’), 5.27, 5.26 (2 ꢂ dd, 1 H, J 9.1 Hz, J₃_,₄9.2 Hz,

1,2

2

’,3’

3’,4’

2,3

H-3), 5.05, 5.04 (2 ꢂ d, 1 H, J 7.6 Hz, H-1), 5.03 (dd, 1 H, J

10.2 Hz, H-4’),

4’,5’

4

.95, 4.94 (2 ꢂ dd, 1 H, H-2), 4.82 (dd, 1 H, H-2’), 4.53, 4.52 (2 ꢂ dd, 1 H, J

2.5

7.6 Hz, furaneyl H-5), 4.23

fur-5,Me

5

,6a

Hz, J

12.2 Hz, H-6a), 4.42, 4.41 (2 ꢂ q, 1 H, J

6

a,6b

MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016

©

22

Kr o¨ ger and Thiem

(

dd, 1 H, J₅_’_,₆_’_a3.6 Hz, J₆_’_a_,₆_’_b12.2 Hz, H-6’a), 4.16, 4.15 (2 ꢂ dd, 1 H, H-6b), 4.02

dd, 1 H, J₅_’_,₆_’_b2.5 Hz, H-6’b), 4.00, 3.99 (2 ꢂ dd, 1 H, J 9.7 Hz, H-4), 3.91 (ddd, 1

4,5

H, H-5’), 3.66, 3.64 (2 ꢂ ddd, 1 H, H-5), 2.11, 2.06, 2.04, 1.99, 1.96, 1.95, 1.94

(

7 ꢂ s, 7 ꢂ 3 H, 7 ꢂ COCH ), 2.03, 2.02 (2 ꢂ s, 3 H, furaneyl 2-CH ), 1.39, 1.37

3 3

3

1

3

2 ꢂ d, 3 H, furaneyl 5-CH ) ppm; C NMR (100.6 MHz, CDCl ) d 196.77 (furaneyl

C-4), 181.56, 181.24 (1 C, furaneyl C-2), 171.00, 170.96, 170.65, 170.55, 170.40,

1

9

7

70.33, 169.84 (7 C, 7 ꢂ COCH ), 133.46 (furaneyl C-3), 100.08, 99.89 (1 C, C-1),

3

5.95, 95.92 (1 C, C-1’), 81.29 (furaneyl C-5), 75.34 (C-3), 72.87 (C-5), 72.82 (C-4),

2.20 (C-2), 70.41 (C-2’), 69.72 (C-3’), 68.90 (C-5’), 68.42 (C-4’), 62.59 (C-6), 61.88

(

1

C-6’), 21.29, 21.19, 21.17, 21.11, 21.01, 21.00, 20.99 (7 C, 7 ꢂ COCH ), 16.85,

3

6.65 (1 C, furaneyl 5-CH ), 14.17 (furaneyl 2-CH ) ppm.

3 3

Anal. Calcd for C H O (746.67): C, 51.48; H, 5.67. Found: C, 51.50; H, 5.88.

32 42 20

(2,5R/5S-Dimethyl-4-oxofuran-3-yl) 4-O-(a-D-glucopyranosyl)-b-D-glucopyra-

noside (19). A solution of 18 (410 mg, 0.55 mmol) in anhydrous methanol (2 mL)

was treated with methanolic sodium methoxide (1.5 mL, 1%) for 4 h. The mixture was

+

neutralized with Amberlite IR-120 (H ) and concentrated. Column chromatography

(

methanol/ethyl acetate 2:1) gave 19 (214 mg, 0.74 mmol, 86%) as colorless crystals:

2

0

1

[^a^]5 + 3.2° (c 0.1, water); mp 98°C; H NMR (400 MHz, D O) d 5.24 (d, 1 H, J

78

2

1’,2’

3

.6 Hz, H-1’), 4.56–4.62 (m, 2 H, H-1, J_f_u_r_a_n_e_y_l₅_,_M_e7.1 Hz, furaneyl H-5), 3.48–3.73

(m, 8 H, H-3, H-4, H-6a, H-6b, H-3’, H-5’, H-6’a, H-6’b), 3.35–3.43 (m, 2 H, J₅_,₆_a2.5

Hz, J₂_’_,₃_’9.7 Hz, H-5, H-2’), 3.32 (dd, 1 H, J₁_,₂8.1 Hz, J₂_,₃9.7 Hz, H-2), 3.24 (dd, 1 H,

1

3

H-4’), 2.18 (s, 3H, furaneyl 2-CH ), 1.28 (d, 3 H, furaneyl 5-CH ) ppm; C NMR

3

(

100.6 MHz, D O) d 200.84 (furaneyl C-4), 186.35, 186.31 (1 C, furaneyl C-2), 133.68,

2

1

33.66 (1 C, furaneyl C-3), 103.51, 103.48 (1 C, C-1), 99.96 (C-1’), 82.35 (furaneyl

C-5), 76.71, 76.29 (2 C, C-3, C-4), 75.19 (C-5), 73.26, 73.22, 73.06 (3 C, C-2, C-3’,

C-5’), 72.04 (C-2’),69.71 (C-4’), 60.89, 60.80 (2 C, C-6, C-6’), 15.87, 15.78 (1 C,

furaneyl 5-CH ), 14.25, 14.24 (1 C, furaneyl 2-CH ) ppm.

3

ACKNOWLEDGMENTS

Support of this work by H. F. & Ph. F. Reemtsma GmbH, Hamburg, and the Fonds

der Chemischen Industrie, Frankfurt, Germany, are gratefully acknowledged.

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Received May 6, 2002

Accepted September 17, 2002

Article Doi

Convenient Multigram Scale Glycosylations of Scented Alcohols Employing Phase-Transfer Reactions

DOI: 10.1081/CAR-120019010

Source and publish data:

Authors:

Article abstract of DOI:10.1081/CAR-120019010

Full text of DOI:10.1081/CAR-120019010

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