Syntheses of 2,6-anhydroaldonic acids from the corresponding anhydrodeoxynitroalditols (glycopyranosylnitromethanes) and their conversion into methyl esters, amides, and alditols

Carbohydrate Research 311 (1998) 103±119

Syntheses of 2,6-anhydroaldonic acids from the

corresponding anhydrodeoxynitroalditols

(glycopyranosylnitromethanes) and their

conversion into methyl esters, amides, and

alditols

Manfred Dromowicz, Peter Koll *

Department of Chemistry, University of Oldenburg, Carl-von-Ossietzky-Str. 9-11, PO Box 2503,

D-26111 Oldenburg, Germany

Received 27 March 1998; accepted with revisions 10 July 1998

Abstract

2,6-Anhydroaldonic acids were obtained by oxidation of the corresponding anhydrodeoxyni-

troalditols (glycopyranosylnitromethanes) with hydrogen peroxide in alkaline solution. Puri®ca-

tion was achieved via the methyl anhydroaldonates. The syntheses of ®ve 2,6-anhydrohexonic and

eight 2,6-anhydroheptonic acids were accomplished in yields of 44±81%. All corresponding

unprotected and acetylated methyl 2,6-anhydroaldonates were characterised. Ammonolysis of the

former aorded the corresponding amides in quantitative yields; reduction with sodium boro-

Keywords: 2,6-Anhydroaldonic acids; Methyl 2,6-anhydroaldonates; 2,6-Anhydroaldonamides; Anhy-

droalditols; Anhydrodeoxynitroalditols

1. Introduction

trimethylsilyl cyanide, the toxicological problems

associated with mercury can be avoided and gly-

copyranose peracetates can be employed directly

with a Lewis acid as catalyst [4]. Nevertheless,

because of the formation of mixed anomers and

undesired by-products, these methods cannot be

considered as universally applicable for the

synthesis of 2,6-anhydroaldonic acids and their

derivatives.

A highly ecient alternative method has been

developed in this laboratory [5]. It involves the

following steps: cyclodehydration [6] of the nitro-

alditols obtained by the addition of nitromethane

The classical route to 2,6-anhydroaldonic acids

was introduced by Helferich and co-workers [1]

and involves conversion of O-protected glycopyr-

anosyl bromides with mercury(II) cyanide into the

corresponding nitriles (glycopyranosyl cyanides) [2]

which are converted into the methyl esters and

sodium salts of the acids [1]. The isolation of the

corresponding free acids was reported 4 years

later by Fuchs and Lehmann [3]. With the use of

* Corresponding author.

PII S0008-6215(98)00195-5

104

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

to aldoses (Fischer±Sowden reaction [7]) and

subsequent acetylation of the resultant anhydro-

deoxynitroalditols (glycopyranosylnitromethanes).

Treatment of these acetates with phosphorus

trichloride in pyridine yields the fully acetylated

glycopyranosyl cyanides very eciently [5], and

these can be hydrolysed to 2,6-anhydroaldonic

acids [1,3].

In the present paper we report on a more-direct

route to these acids which also starts from glyco-

pyranosylnitromethanes and uses hydrogen per-

oxide as an oxidising agent.

lower aldoses formed by loss of C-1 [unpublished

results]. Only these cases resemble the Bõlik reac-

tion [8] just mentioned. At pH values below 8, no

reaction occurred.

In the case of the anhydronitroalditols, entirely

dierent results were obtained. Furanoid anhydro-

deoxynitroalditols (glycofuranosylnitromethanes)

generally underwent severe decomposition on

treatment with hydrogen peroxide in alkaline

media, and consequently these routes were not fol-

lowed any further.

In contrast, pyranoid anhydrodeoxynitroalditols

(glycopyranosylnitromethanes) [6], being more

stable, when treated with hydrogen peroxide _ꢁin

aqueous potassium carbonate (pH ꢀ14) at 20 C

underwent conversion into the corresponding 2,6-

anhydroaldonic acids [12,13]. Although most of the

starting material had already been consumed after

16 h, prolongation of the reaction times from 48

up to 72 h aorded almost quantitative yields.

Removal of the potassium cations with exchange

resin and treatment of the crude residues obtained

by evaporation of the solvents with boiling dry

methanol led to the corresponding methyl esters

under the in¯uence of the residual nitric acid. Two

general routes (A and B) for the puri®cation of the

acids are outlined in Scheme 1. Route A (steps a±

b±c±d±e) involved acetylation of the crude methyl

esters with acetic anhydride in pyridine and

separation of the acetates by chromatography on

silica gel. Deacetylation [14] and saponi®cation,

followed by acidi®cation, gave the free aldonic

acids. Route B (steps a±b±e) is more direct, but

requires more sophisticated chromatographic

equipment for the puri®cation of the unprotected

methyl esters.

Four pyranoid anhydrodeoxynitrohexitols (ꢀ-

glycopyranosylnitromethanes, derived from the

pentoses l-arabinose, d-lyxose, d-ribose, and d-

xylose) and eight 2,6-anhydrodeoxynitroheptitols

(ꢀ-glycopyranosylnitromethanes, derived from the

eight d-hexoses), each bearing an equatorial

nitromethyl group [6], were oxidised and the crude

2,6-anhydroaldonic acids were puri®ed by the

foregoing procedures. In addition, 2,6-anhydro-d-

altro-hexonic acid (13a, Table 1, derived from 2,6-

anhydro-1-deoxy-1-nitro-d-altro-hexitol [13,15]),

the ꢁ anomer of 2,6-anhydro-d-allo-hexonic acid

(3b), and its esters were synthesised because of the

ready availability of compounds having this con-

®guration. In contrast to the other compounds

studied, all of which have the ꢀ-con®guration at

2. Results and discussion

In 1974, Bõlik [8] reported that addition of

hydrogen peroxide to aqueous (and thus alkaline)

solutions of sodium salts of 1-deoxy-1-nitroalditols

in the presence of catalytic amounts of molybdate,

tungstate, or vanadate anions led exclusively to the

aldoses formed similarly in a Nef reaction [9]. The

latter, by contrast, requires strong acidic reaction

conditions. It was stated explicitly that the catalyst

is essential for this alternative approach to higher

aldoses, which circumvents the intricacies of the

Nef reaction. Later on [10] it was found that a

reaction, formally constituting

methane addition, competes at high pH.

a

retro-nitro-

In 1980, Olah et al. [11] reported more generally

on the transformation of primary and secondary

nitroalkanes into aldehydes and ketones, respec-

tively, in yields between 76 and 96% by treatment

with hydrogen peroxide (30%) in methanol±water

in the presence of potassium carbonate. We applied

these reaction conditions, which do not demand

contamination of the reaction mixture by a cata-

lyst, to the readily available deoxynitroalditols and

their 2,6-anhydrides, with the objective of prepar-

ing aldoses and anhydroaldoses, in spite of the

aforementioned statements of the previous authors

[8,10].

By oxidation of acyclic nitroalditols with hydro-

gen peroxide in aqueous potassium carbonate (pH

ꢀ14) for the reaction times given in the literature

procedure [11], the aldoses derived by loss of C-1

were produced and completely degraded within

several days [unpublished results]. However, when

the reaction was carried out near pH 9 (sodium

hydrogencarbonate), aldoses were produced by

oxidative loss of the nitro group as in the Nef

reaction, together with high proportions of the

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

105

Scheme 1. (a) H₂O₂(30%, aq), K₂CO₃, 20 ^ꢁC, 48±72 h; (b) dry MeOH, HNO₃, re¯ux, 16 h; (c) Ac₂O, pyridine, 20 ^ꢁC, 6±16 h; (d)

NaOMe, dry MeOH, 20 ^ꢁC, 1 h; (e) NaOH (0.5 N, aq), 60 ^ꢁC, 2 h, then Amberlite IR-120 (H⁺); (f) NH₃, MeOH, 5 ^ꢁC, 6 h; (g)

NaBH₄(0.3 M, aq), Amberlite IR-120 (H⁺), 0±5 ^ꢁC, 12 h.

5

C-2 and adopt the C₂conformation, 13a and its

derivatives have the ꢁ-con®guration at C-2 and

adopt the ²C₅conformation. All of the compounds

described therefore have the carboxyl groups in

the thermodynamically favourable equatorial

positions.

anhydroalditols 1,5-anhydro-l-gluco-hexitol (4e)

[22], 2,6-anhydro-l-glycero-l-galacto-heptitol (7e,

described previously [18,23] as 2,6-anhydro-d-

glycero-l-manno-heptitol), the meso compound

2,6-anhydro-meso-d-glycero-d-gulo-heptitol (8e)

[24,25,26], and 2,6-anhydro-d-glycero-d-galacto-

heptitol (11e, the enantiomer of 7e) [27,28]

were obtained in yields greater than 90%.

By treating the methyl 2,6-anhydroaldonates

with cold saturated ammoniacal methanol the cor-

responding 2,6-anhydroaldonamides were obtained

in quantitative yields. This reaction can also be

applied to the per-O-acetylated methyl esters, but

reaction of ammonia with the acetate groups yiel-

ded acetamide, which was dicult to separate from

the desired products by fractional crystallisation.

Therefore, although the 2,6-anhydroaldonic acid

amides could be isolated by chromatographic

methods, it is more convenient to deacetylate the

protected methyl esters before ammonolysis.

On reduction of methyl 2,6-anhydroaldonates 4b

[16], 7b [3,17,18], 8b [3,19], and 11b [19,20] by a

modi®ed Wolfrom and Thompson procedure [21]

with aqueous sodium borohydride in the presence

of cationic exchange resin, the corresponding

Table 1 gives a survey of all compounds pre-

pared. Their structures were con®rmed by NMR

data, which are summarised in Tables 2±4.

The chemical-ionisation mass spectroscopy

(CIMS) fragmentation patterns (Table 5) of the

hydroxy acids (a series) and hydroxy esters (b series)

were characterised by loss of the C-2 substituents

([M+H]⁺ROH and [M+H]⁺ROH CO with

R=H or Me) followed sequentially by the loss of

two water molecules, and are thus analogous to

those of the free aldoses [29,30]. Because of the

formal loss of formaldehyde at the primary

hydroxy group, the anhydroheptonic acids showed

also the fragments found for their hexonic analo-

gues. The O-acetylated methyl esters (c series), in

106

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

Table 1

2,6-Anhydroaldonic acids, their OH-free and fully O-acetylated methyl esters, their amides and four anhydroalditols

Compound

Con®guration

Derived from

R¹

R²R³R⁴R⁵R⁶R⁷

R⁸

Route Yield%

1a

1b [17]

1c

1d

2a

2b

2c

2d

3a

3b

3c

3d

4a

4b [16]

4c

4d

4e

5a

5b

5c

5d

6a

6b

6c

l-manno

l-arabinose

d-lyxose

d-ribose

CO₂H

CO₂Me

CONH₂

CO₂H OH

CO₂Me OH

CO₂Me OAc

CONH₂OH

CO₂H

CO₂Me

CONH₂

CO₂H

CO₂Me

CONH₂

CH₂OH

CO₂H

CO₂Me

CONH₂

CO₂H OH

CO₂Me OH

CO₂Me OAc

CONH₂OH

CO₂H

CO₂Me

CONH₂

CH₂OH

CO₂H

CO₂Me

CONH₂

CH₂OH

CO₂H

H

OH OH

OAc OAc

OH OH

H

OH

OAc

OH

H

OH

OAc

OH

OAc

OH

H

OH

OAc

OH

H

OH

OAc

OH

H

A

c

B

c

B

c

A

c

57^a

71^a

87^a

98^b

64^a

70^a

91^a

93^b

59^a

87^a

71^a

98^b

50^a

70^a

91^a

95^b

90^b

59^a

78^a

73^a

87^b

44^a

71^a

91^a

93^b

54^a

74^a

90^a

92^b

86^b

62^a

75^a

87^a

86^b

89^b

75^a

78^a

99^a

96^b

81^a

79^a

82^a

99^b

75^a

87^a

86^a

91^b

87^b

65^a

85^a

77^a

l-manno

H

d-galacto

H

OH

OAc

OH

H

OH

OAc

OH

OAc

OH

OAc

OH

OH CH₂OH

OAc CH₂OAc

OH CH₂OH

OAc CH₂OAc

OH CH₂OH

d-galacto

H

d-allo

H

OH

OAc

OH

d-allo

d-ribose

d-allo

d-ribose

d-allo

d-gulo

d-xylose

d-allose

OH OH

OAc OAc

OH OH

d-gulo

l-gluco

d

d-glycero-d-allo

d-glycero-d-gluco

d-glycero-l-manno

l-glycero-l-galacto

d-glycero-d-gulo

OH

OAc

OH

H

B

c

A

c

A

c

d-allose

d-altrose

d-galactose

d-glucose

d-gulose

d-idose

6d

7a [3,17]

7b [3,17,18]

7c

7d [18]

7e [18,23]

8a [3,19,26]

8b [3,19]

H

OH OH

OAc OAc

OH OH

OAc OAc

OH OH

H

CH₂OH

CH₂OAc

CH₂OH

d

H

OH CH₂OH

OAc CH₂OAc

OH CH₂OH

H

OH CH₂OH

OAc CH₂OAc

OH CH₂OH

H

A

c

8c [1,19,26,31] d-glycero-d-gulo

8d

d-glycero-d-gulo

d-glycero-l-talo

d-glycero-l-ido

8e [24±26]

9a

9b

9c

9d

10a

10b

10c

10d

H

d

OH

OAc

OH

H

OH OH

OAc OAc

OH OH

OAc OAc

OH OH

H

CH₂OH

CH₂OAc

CH₂OH

CH₂OAc

CH₂OH

A

c

B

c

B

c

CO₂Me

CONH₂

CO₂H OH

CO₂Me OH

CO₂Me OAc

CONH₂OH

CO₂H OH

CO₂Me OH

CO₂Me OAc

CONH₂OH

CH₂OH OH

CO₂H OH

CO₂Me OH

CO₂Me OAc

d-glycero-l-ido

d-idose

H

d-glycero-l-ido

d-idose

H

d-glycero-l-ido

d-idose

H

11a

d-glycero-d-galacto

d-glycero-l-altro

d-mannose

d-talose

H

OH

OAc

OH

OAc

H

OH

OAc

11b [19,20]

11c [19,32]

11d

11e [27,28]

12a

12b

d

CH₂OH

CH₂OAc

B

d-talose

12c [32]

(continued)

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

107

Table 1Ðcontd

12d

13a

13b

13c

13d

d-glycero-l-altro

d-altro

d-talose

d-ribose

CONH₂OH

H

OH

H

Ð

OH

Ð

H

Ð

CH₂OH

c

e

c

92^b

CO₂H OH OH OH

CO₂Me OH OH OH

CO₂Me OAc OAc OAc

CONH₂OH OH OH

Ð

60^a

48^a

d-altro

31^a

100^b

Ð

a

Based on the corresponding anhydrodeoxynitroalditol.

Based on the corresponding methyl anhydroaldonate.

Ammonolysis of the corresponding methyl anhydroaldonate.

Reduction of the corresponding methyl anhydroaldonate.

Direct crystallisation.

b

c

d

e

parallel manner, lost the C-2 substituents and then

two molecules of acetic acid and ketene. They,

therefore, show analogous fragmentation paths to

those of the acetylated aldopyranoses [29]. In

addition, fragmentation of the protonated dimers

[2M+H]⁺could be observed. Fragmentation was

not detected in the cases of the amides (d series),

only the [M+H]⁺and [2M+H]⁺species being

observed. The fragmentation of the anhydroalditols

was exclusively characterised by the loss of water.

In order to obtain a complete set of data, the IR

spectra from the crystalline unprotected com-

pounds and all fully O-acetylated methyl esters

were determined. Because of the similarity of the

compounds it seemed necessary for us to list the

signi®cant peaks, even in the ®ngerprint region.

The samples were dissolved 24 h before measure-

ments to allow equilibrations. The concentrations

of all samples were 1% (w/v). Hydroxylic com-

pounds were measured in H₂O, acetylated esters in

CDCl₃. Elemental analyses were carried out by use

1

of an Erba-Science analyser, model 1104. The H

(500.13 MHz) and ¹³C (125.75 MHz) NMR spectra

were recorded with a Bruker AMX R500 spectro-

meter. The assignment of signals of the carbon

1

atoms was done by H±¹³C correlated 2D-spectro-

scopy using the software ``INVCH''. The correla-

tion of the hydrogen atoms was done in cases of

1

doubt by H±¹H correlated spectra with the pro-

gram ``COSYHH''. All ¹H NMR spectra measured

in D₂O were referred to internal Me₂CO (¹H ꢃ

2.09, ¹³C ꢃ 30.5). All samples measured in CDCl₃

refer to internal CHCl₃[ꢃ 7.24 or 77.0 (middle sig-

nal of the CDCl₃-triplet), respectively]. IR spectra

were recorded on a Philips PU 9706 spectrometer.

Crystalline samples were incorporated in KBr pel-

lets. Syrupy compounds were dissolved in CCl₄and

held between NaCl monocrystalline plates. The

measurements of the chemical-ionisation mass

spectra (CIMS) were carried out on a Finnigan

MAT 95 including the data system DEC 5000.

Crystalline samples were applied directly onto the

target, syrups were dissolved in H₂O or MeOH

before application. The reactant gas was isobutane.

For chromatographic separations by HPLC and

MPLC the following equipment was used: pump:

Knauer HPLC Pump 64; detector: Knauer Dier-

ential Refractometer; integrator: Shimadzu C-R3A

Chromatopac; fraction collector: Isco Cygnet

Fraction Collector with a Knauer Peak Detector of

the type 77; HPLC: precolumn: Nucleosil 100 C18

(30 mmÂ16 mm) (Knauer), separation column:

Lichrosorb RP-18 (250Â25 mm) (Merck); MPLC:

separation column: column ``Labochrom'' con-

taining Pyrex-borosilicate glass (750Â10 mm) with

adjustable adapters of Labomatic, length of the gel

3. Experimental

General methods.ÐAll solvents used for reac-

tions were distilled before use. The progress of

reactions was observed by TLC (Merck, silica gel

F₂₅₄), with detection by charring with H₂SO₄

(10%). Column chromatography was performed

on silica gel 60 (Merck, 63±200 ꢂm). For TLC and

column chromatography the following solvent sys-

tems (s.s.) were used (v/v): s.s. 1, 7:7:6:2:2 EtOAc±

EtOH±AcOH (50%)±MeOH±n-BuOAc; s.s. 2, 10:1

tert-BuOMe±petroleum ether (PE) (40/60); s.s. 3,

5:3:1 EtOAc±MeOH±toluene; s.s. 4, 1:1 EtOAc±PE

(60±80); s.s. 5, 2:1 EtOAc±PE (60±80); s.s. 6, 3:1

EtOAc±PE (60±80); s.s. 7, 19:1 CH₂Cl₂±Me₂CO.

Amberlite IR-120 (H⁺-form) cation-exchange

resin and Amberlite IRA-400 (HCO₃-form)

anion-exchange resin were employed for deionisa-

tions. Melting points were determined on the heat-

ing table of a Leitz Laborlux 12 microscope and

are uncorrected. Optical rotations were measured

at 20 ^ꢁC with a Perkin±Elmer 241 MC polarimeter.

108

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

Table 2

¹³C NMR data^afor 2,6-anhydroaldonic acids and derivatives, chemical shifts

Compound

C-1

C-2

C-3

C-4

C-5

C-6

C-7

OMe

1a^b

173.2

171.7

167.8

174.5

173.0

171.2

167.0

174.3

174.1

172.7

168.3

175.1

173.2

171.6

167.7

174.1

69.1

174.4

173.0

168.0

175.4

173.9

172.4

167.2

175.2

173.2

171.8

167.4

174.6

61.8^d

173.1

171.9

167.2

174.4

61.4

174.1

172.7

168.0

175.6

173.9

172.5

167.6

175.4

172.9

171.5

166.5

174.2

61.7^d

172.8

171.5

166.7

174.4

172.9

171.4

167.3

174.3

78.7

76.0

79.3

78.4

78.2

76.1

78.6

74.3

74.5

73.3

74.3

78.7

78.8

76.3

79.1

69.7

74.0

74.3

73.4

74.0

74.1

75.8

73.5

74.5

78.6

78.8

76.8

78.7

80.3

77.0

76.4

77.1

79.7

74.7

75.1

73.4

74.7

75.1

75.4

74.2

75.7

77.3

77.5

75.8

77.8

78.7

78.0

78.2

76.4

78.6

78.1

78.3

76.1

78.7

68.7^d

68.7

67.3^d

68.8^d

70.2

70.1

68.6

69.7

69.2

67.5

69.1

71.5

69.2

71.7

77.8

69.2

69.3

67.4

69.3

71.0

69.0

70.4

68.6

66.6

69.1

67.6

77.9

78.2

69.4

78.2

70.1

66.1

66.2

66.1

66.5

69.3^d

68.4^d

66.3^d

68.7

70.2

70.3

68.5

69.7

69.5

70.3

70.4

66.4

69.7

70.7

66.9

70.1

73.0

72.9

70.0

73.3

73.9

73.7

71.0

74.0

70.0

70.1

67.5

70.3

77.1

77.0

71.8

77.3

70.0^d

70.9

67.8

70.9

70.1

70.0

66.0

70.0

73.9

73.8

71.4

73.9

74.3

71.5

71.6

73.4

71.9

77.6

70.3

66.4

70.2

68.5^d

69.4^d

65.6^d

68.7

73.7

73.6

71.5

73.9

74.3

69.1

67.9

69.0

68.0

67.8

67.5

68.2

68.5^d

68.3

67.2^d

69.0^d

66.3

66.2

65.8

66.4

66.6

66.5

66.0

66.5

68.9

69.1^d

68.3

69.2

80.6^d

66.6

66.0

66.5

64.1

64.8

64.2

69.0

67.1

69.1

69.5

69.4

69.5

68.0

69.4

70.1

69.4

67.7

69.4

67.9

64.9

68.1

66.9

66.8

65.6

67.0

67.6

68.7

68.6

65.0

69.2

68.8

66.1

68.9

69.7

69.8

66.2

70.1

68.6

68.8

66.7

69.0

64.7

64.8

63.6

64.5

68.8

69.0^d

66.1

69.0

61.2

75.2

75.4

72.3

75.0

75.7

74.3

72.1

75.8

79.1

79.3

74.6

78.9

78.7

79.7

80.0

76.1

79.6

79.7

75.2

75.4

72.3

75.1

76.2

76.3

72.8

76.3

79.8

80.0

76.3

79.9

80.3

79.2

79.3

74.9

79.3

70.4

70.5

68.3

70.6

Ð

53.2

52.5

Ð

1b [17]^b

1c^c

1d^b

2a^b

Ð

2b^b

53.0

52.5

Ð

2c^c

2d^b

3a^b

Ð

3b^b

53.2

52.7

Ð

3c^c

3d^b

4a^b

Ð

4b^b

53.2

52.8

Ð

53.2

52.7

Ð

4c^c

4d^b

4e^b

Ð

5a^b

61.3

62.3

61.2

61.7

62.7

61.8

61.4

61.5

61.7^d

61.0

62.0

61.0

61.4

61.3

61.8

61.5

61.8

62.2

62.1

61.3

62.6

61.4

61.8^d

61.7

61.6

61.9

Ð

5b^b

5c^c

5d^b

6a^b

Ð

6b^b

53.0

52.2

Ð

6c^c

6d^b

7a [17]^b

7b [17,18]^b

7c^c

Ð

53.2

52.8

Ð

53.3

52.9

Ð

7d [18]^b

7e [18] [18]^b

8a [19]^b

8b [19]^b

8c [19]^c

8d^b

8e^b

9a^b

9b^b

53.1

52.6

Ð

9c^c

9d^b

10a^b

10b^b

10c^c

10d^b

11a^b

11b [19]^b

11c [19]^c

11d^b

11e^b

12a^b

12b^b

12c^c

12d^b

13a^b

13b^b

13c^c

13d^b

Ð

53.0

52.5

Ð

53.1

52.5

Ð

53.1

52.5

Ð

53.1

52.5

Ð

a

Chemical shifts ꢃ in ppm.

Recorded in D₂O.

Recorded in CDCl₃.

Assignments may be interchanged.

b

c

d

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

109

Table 3

¹H NMR data^afor 2,6-anhydroaldonic acids and derivatives, chemical shifts

Compound

H-2

H-3

H-4

H-5

H-6a

H-6b or H-7a

H-7b

OMe

1a^b

3.702±3.746

3.790

3.998

3.591

4.102

4.202

4.218

3.947

4.014

4.053

4.222

3.862

3.766

3.827

3.976

3.648

4.051

4.094

4.306

3.938

4.400

4.444

4.432

4.230

3.770

3.813

3.971

3.628±3.684

3.386±3.446

3.377±3.434

3.990

3.360±3.423

4.079

4.114

4.274

3.958

4.425

4.468

4.453

4.235

4.232

4.283

4.265

4.050

4.192

4.233

4.286

3.994

4.118

4.182

4.237

3.913

3.702±3.746

3.732

5.376

3.654

4.188

4.174

5.720

4.110

3.676

3.662

5.123

3.608

3.410

3.407

5.127

3.378

3.616

3.612

5.144

3.579

4.051

4.043

5.128

4.004

3.680

3.675

5.346

3.628±3.684

3.845

3.887

5.181

3.725

3.861

3.852

5.238

3.813

3.923

3.905±3.930

5.079

3.926

4.187

4.179

5.667

4.126

4.139

4.125

5.548

4.078

4.123

4.121

5.558

4.050

3.583

3.882 3.846

3.882 3.842

5.287 4.106

3.875 3.577

3.683 3.074

3.707 3.103

5.238 3.298

3.718 3.118

3.722 3.459

3.717 3.447

5.014 3.674

3.714 3.433

3.514 3.203

3.512 3.205

4.964 3.374

3.515 3.189

3.506 3.544±3.594

3.501 3.532±3.582

4.957 3.996

3.515 3.565

3.678 3.606

3.602 3.670

4.969 3.922

3.674 3.584±3.644

3.853 3.595

3.851 3.593

5.427 3.919

3.848 3.581±3.617

3.576

3.574

3.695

3.860

3.853

3.906

4.281

3.942

3.667

3.659

3.948

3.656

3.891

4.218

3.895

3.755^d

3.748^d

4.186

3.586

3.606^d

3.774^d

4.110±4.163

3.584±3.644^d

3.660

3.648

4.145

3.628±3.684

3.598

3.585

4.232

3.612

3.635

3.623

4.067

3.636

3.738

4.200

3.746

3.619

4.230

3.622

3.759

3.748

4.201^d

3.764

3.560

3.563

3.712

3.567

Ð

1b [17]^b

1c^c

3.582

5.119

3.560

3.511

3.520

5.070

3.505

4.018

4.015

5.587

4.034

3.350

3.346

5.205

3.336

4.060

4.051

5.668

4.051

3.930

3.921

5.287

3.932

3.554

3.547

5.079

3.550

3.681

3.742

Ð

1d^b

2a^b

Ð

2b^b

3.670

3.723

Ð

3.676

3.718

Ð

3.681

3.722

Ð

3.685

3.730

Ð

2c^c

2d^b

3a^b

3b^b

3c^c

3d^b

4a^b

4b^b

4c^c

4d^b

Ð

5a^b

3.544±3.594^d

3.532±3.582^d

4.186

3.752

3.778^d

3.602^d

4.110±4.163

3.797^d

3.596

3.589

4.145

3.581±3.617

3.767

3.760

4.133

3.762

3.586

3.579

4.142

3.591

3.631

3.627

4.243

3.647

3.797

3.795

4.139

3.817

3.634

3.627

4.170^d

3.649

Ð

5b^b

5c^c

5d^b

6a^b

Ð

6b^b

3.674

3.623

Ð

6c^c

6d^b

7a [17]^b

7b [17]^b

7c^c

Ð

3.692

3.735

Ð

7d^b

8a^b

3.386±3.446 3.302 3.350

3.377±3.434 3.291 3.346

Ð

8b^b

3.692

3.727

Ð

8c [19,31]^c

8d^b

5.238

5.078 3.696

3.360±3.423 3.315 3.343

9a^b

3.927

3.919

5.343

3.915

3.931

3.729 3.794

3.725 3.778

4.945 4.109

3.727 3.809

3.581 3.806

Ð

9b^b

3.688

3.723

Ð

9c^c

9d^b

10a^b

10b^b

10c^c

10d^b

11a^b

11b^b

11c [19,32]^c

11d^b

12a^b

12b^b

12c [32]^c

12d^b

13a^b

13b^b

13c^c

13d^b

Ð

3.905±3.930 3.582 3.802

3.687

3.727

Ð

5.079

3.872

3.595

3.591

5.053

3.584

3.723

3.712

5.095

3.708

3.740

3.738

5.124

3.720

4.803 4.083

3.580 3.814

3.469 3.279

3.464 3.272

5.201 3.648

3.466 3.310

3.789 3.534

3.788 3.518

5.247 3.901

3.786 3.554

3.819 3.954

3.820 3.956

5.103 4.235

3.817 3.984

Ð

3.681

3.678

Ð

3.691

3.687

Ð

3.684

3.717

Ð

a

Chemical shifts ꢃ in ppm.

Recorded in D₂O.

Recorded in CDCl₃.

b

c

d

Assignments may be interchanged.

110

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

Table 4

¹H NMR data^afor 2,6-anhydroaldonic acids and derivatives, coupling constants

Compound

³J_2,3

³J_3,4

³J_4,5

³J_5,6a

³J_5,6b/³J_6,7a

²J_6a,6b/³J_6,7b

²J_7a,7b

1a

b

9.1

8.1

9.5

ꢀ1.0

1.4

1.3

9.2

9.4

9.7

9.5

8.9

9.1

10.1

10.2

10.1

1.4

1.5

1.4

9.6

9.9

b

8.6

8.9

9.5

3.2

3.4

3.3

3.1

2.5

2.8

2.6

9.0

8.7

9.1

2.8

2.6

2.7

3.7

3.8

9.5

9.6

10.2

8.5

b

3.8

3.4

3.3

ꢀ3.3

9.6

9.7

10.2

9.7

2.9

2.8

2.9

8.9

8.8

8.7

8.6

2.9

2.8

2.7

2.6

3.1

3.2

3.3

3.4

3.3

b

2.6

2.7

4.0

b

10.5

5.5

10.7

9.9

10.2

10.1

10.5

10.6

9.5

10.7

9.8

10.0

10.3

9.9

9.7

8.6

10.4

10.0

1.2

1.3

2.0

b

5.5

10.2

5.6

4.9

5.2

5.1

4.9

5.4

5.2

5.5

b

12.6

12.7

12.8

13.6

b

11.2

11.3

11.1

11.0

11.1

10.8

11.3

11.6

11.2

b

Ð

b

14.5

b

14.7

b

11.7

12.3

12.4

b

12.4

12.5

12.4

12.0

11.8

9.3

11.9

11.7

11.8

11.5

11.8

12.3

12.4

12.3

11.9

11.4

12.0

Ð

1b [17]

1c

1d

2a

2b

2c

2d

3a

3b

3c

3d

4a

4b

4c

4d

5a

5b

5c

5d

6a

6b

6c

6d

7a [17]

7b [17]

7c

b

4.4

5.4

b

2.5

ꢀ1.4

2.0

ꢀ6.0

ꢀ4.6

6.1

9.0

8.8

6.6

8.8

5.6

5.7

5.0

5.1

7.7

7.6

5.7

7.8

7.9

6.8

8.1

6.4

5.9

6.6

8.0

7.8

6.4

8.2

1.2

1.6

1.3

ꢀ5.5

ꢀ3.4

1.9

3.2

b

6.5

3.8

2.1

2.0

2.2

1.9

4.4

4.5

5.0

4.3

3.8

4.0

6.0

3.5

1.9

2.1

2.4

2.1

4.0

4.2

6.4

3.7

12.8

13.3

12.7

b

0.9

7d

8a

8b

<0.5

9.7

9.6

10.1

9.6

1.2

1.0

1.3

1.4

1.2

9.7

9.8

10.0

9.7

b

9.8

b

9.4

b

3.2

3.1

3.2

3.1

b

9.2

b

8c [19,31]

8d

9a

9b

9c

10.2

10.3

10.2

1.3

<1.0

1.2

1.3

1.2

1.5

1.3

1.8

1.6

1.8

1.3

3.8

3.9

3.8

3.2

2.9

ꢀ3.1

2.9

9.7

9.6

10.0

9.6

3.5

b

3.7

ꢀ3.3

3.3

3.4

3.2

3.0

9d

10a

10b

10c

10d

11a

11b

11c [19,32]

11d

12a

12b

12c [32]

12d

13a

13b

13c

13d

b

<1.0

3.2

3.4

3.5

3.6

3.4

3.2

b

3.9

ꢀ3.4

3.3

3.2

3.6

3.2

1.3

0.9

1.3

ꢀ1.3

2.0

2.3

Ð

2.2

1.9

a

Coupling constants in Hz.

Signals of higher order.

b

bed: 600 mm, ®lling: packed with cationic exchange

resin of the type Dowex¹50 W X 4 (H⁺-form),

200±400 mesh, and subsequently loaded with

Nd³⁺-solution (NdCl₃ÂH₂O, 15% solution) until

a constant bed volume was reached.

General procedure (g.p.) 1: synthesis of methyl

2,6-anhydroaldonates from anhydrodeoxynitro-

alditols.ÐThe anhydrodeoxynitroalditol (10 mmol)

in H₂O (10 mL) was cooled on an ice bath and

treated with H₂O₂(30%, aq, 10 mL). K₂CO₃(2.4 g)

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

111

Table 5

Observed CIMS ions for 2,6-anhydroaldonic acids and derivatives

Compounds

[2M+H]⁺

[M+H]⁺

ROH

CO

H₂O

97

127/97^c

not found

127

Other

Ð

1a±4a, 13a

5a±12a

1b±4b, 13b

5b±12b

357

417

385

445

179

209/179^c

193

161^a

191^a/161^c

161^b

133

115

163/133^c

133

163

145/115^c

115

145

381^d

175^e

391^f, 205^e

223

191^b

Compounds

[2M+H]⁺

[M+H]⁺

HCO₂Me

HOAc

CH₂CO

Ð

1c±4c, 13c

5c±12c

1d±4d, 13d

5d±12d

637

781

355

415

319

391

178

208

259/577^g

331/721^g

199/517^g

271/661^g

139/457^g

211/601^g

97/415^g

169/559^g

Ð

no further fragmentation observed

m/z for all values.

a

R=H.

R=Me.

b

c

Fragmentation after loss of HCHO.

[2M+H ₂H₂O]⁺.

[M+H H₂O]⁺, no further fragmentation from this fragment observed.

[2M+H 3H₂O]⁺.

Fragment of the dimer.

d

e

f

g

was added and the solution allowed to stand for

48 h at 20 ^ꢁC. If the solution contained no peroxide

after this time, further H₂O₂(30%, aq, 5 mL) was

added and the reaction time was extended for

another 24 h. The excess of H₂O₂was decomposed

by addition of a small amount of MnO₂(ꢀ1 mg) at

The acetylated ester was crystallised in most cases

from the solvent mentioned. Often prior puri®cation

by column chromatography was necessary.

General procedure (g.p.) 3: Synthesis of methyl

2,6-anhydroaldonates by deacetylation.ÐThe fully

O-acetylated methyl 2,6-anhydroaldonate (1 g) was

ꢁ

0 C. After ®ltration, cation-exchange resin was

kept for 1 h at 20 C in dry MeOH (30 mL) con-

added slowly until no further generation of CO₂

cou_ꢁld be observed. The H₂O was distilled o at

30 C and the crude anhydroaldonic acid dried

under high vacuum overnight. The residue was

dissolved in dry MeOH (100 mL) and heated for

16 h under re¯ux. During the last hour activated

charcoal (ꢀ0.1 g) was added. After cooling, the

solution was ®ltered and the HNO₃removed by

addition of anion-exchange resin. The ion exchanger

was ®ltered o, and cation-exchange resin used to

achieve neutrality. The methyl 2,6-anhydro-

aldonate was dried in vacuo.

taining NaOMe (1 M, 1 mL). The progress of the

deacetylation was observed by TLC (s.s. 3). The

solution was neutralised by addition of cation-

exchange resin. The resin was ®ltered o and

washed with MeOH. The combined eluates were

concentrated to a syrup in vacuo.

General procedure (g.p.) 4: Synthesis of 2,6-

anhydroaldonic acids from methyl 2,6-anhydro-

aldonates.ÐThe

methyl

(10 mmol) in NaOH (0.5 M, aq, 22 mL) was heated

2,6-anhydroaldonate

ꢁ

for 2 h at 60 C. After cooling the Na⁺-ions were

removed by addition of cation-exchange resin. The

resin was ®ltered o and washed with water. The

solvent was removed by distillation at 35 ^ꢁC.

General procedure (g.p.) 5: Synthesis of 2,6-

anhydroaldonic acid amides from methyl 2,6-anhy-

droaldonates.ÐThe methyl 2,6-anhydroaldonate

(100 mg) in M_ꢁeOH (5 mL), satd with NH₃was kept

for 6 h at ꢀ5 C. The solvent was removed by dis-

tillation and the amide was crystallised in most

cases directly from H₂O or MeOH.

General procedure (g.p.) 2: Acetylation of

methyl 2,6-anhydroaldonates.ÐThe methyl 2,6-

anhydroaldonate (500 mg) in Ac₂O (1.5 mL) and

ꢁ

abs. pyridine (2.2 mL) was stirred for 1 h at 0 C,

then allowed to warm to 20 ^ꢁC. The progress of the

reaction was monitored by TLC (s.s. 3). After

complete conversion (6±16 h) the mixture was

poured into ice±water (15 mL). After 2 h the solu-

tion was extracted with CH₂Cl₂, and the extract

washed successively with HCl (5 M, aq), NaHCO₃

(satd, aq) and H₂O, dried (NaSO₄), and con-

centrated to a syrup. Residual traces of AcOH

were removed by azeotropic distillation with toluene.

General procedure (g.p.) 6: Synthesis of

anhydroalditols from methyl 2,6-anhydroaldo-

nates.ÐAn ice-cooled solution of the methyl 2,6-

anhydroaldonate (2 mmol) in H₂O (20 mL) was

112

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

treated with cation-exchange resin (ꢀ5 mL

volume). Freshly prepared NaBH₄(0.3 M, aq,

25_ꢁmL) was added slowly under vigorous stirring at

0 C. Subsequently solid NaBH₄(ꢀ200 mg) was

added and stirring continued for 1 h. The pH value

was adjusted to 8±9 by addition of cation-exchange

resin or solid sodium borohydride. The solution

(O±H), 1720 (CO), 1115, 1100, 1035 (C±O±C, C±

O, C±C); CIMS: m/z (%) 357 (2), 179 (100), 161

(21), 133 (27), 115 (11), 97 (5). Anal. found: C,

40.36; H, 5.68.

2,6-Anhydro-d-gulo-hexonic acid (4a). Ester 4b

[16] (384 mg, 2 mmol) was saponi®ed as described

ꢁ

in g.p. 4 to give 4a (317 mg, 89%): mp 172 C

ꢁ

was kept for 12 h at ꢀ5 C and the Na⁺-ions were

(from H₂O); [ꢁ]_d9.2^ꢁ; R_f(s.s. 1) 0.34; IR (KBr): ꢄ

3360 (O±H), 1720 (CO), 1095, 1055, 995 (C±O±C,

C±O, C±C); CIMS: m/z (%) 357 (2), 179 (100), 161

(12), 133 (18), 115 (26), 97 (12). Anal. found: C,

40.44; H, 5.65.

removed by addition of cation-exchange resin. The

resin was ®ltered o and washed with H₂O. The

combined eluates were concentrated to dryness in

vacuo. The solid was dissolved in MeOH and con-

centrated again to remove boric acid as trimethyl

borate. This process was repeated until no tri-

methyl borate could be detected.

2,6-Anhydroheptonic acids.ÐAnal. Calcd for

C₇H₁₂O₇(208.17): C, 40.39; H, 5.81.

2,6-Anhydro-d-glycero-d-allo-heptonic acid (5a).Ð

Ester 5b (444 mg, 2 mmol) was saponi®ed as

described in g.p. 4 to aord 5a (358 mg, 86%): mp

110 ^ꢁC (from H₂O); [ꢁ]_d+13.4^ꢁ; R_f(s.s. 1) 0.32; IR

(KBr): ꢄ 3530, 3400 (O±H), 1725 (CO), 1210,

1195, 1085, 1045 (C±O±C, C±O, C±C); CIMS: m/z

(%) 417 (6), 381 (40), 209 (42), 191 (100), 163 (6),

145 (7), 127 (5), 179 (4), 161 (7), 133 (22), 115 (6),

97 (6). Anal. found: C, 40.30; H, 5.80.

2,6-Anhydrohexonic acids.ÐAnal. Calcd for

C₆H₁₀O₆(178.14): C, 40.45; H, 5.66.

2,6-Anhydro-l-manno-hexonic acid (1a). Ester

1b [17] (500 mg, 2.6 mmol) was saponi®ed as

described in g.p. 4 to give 1a (460 mg, 99%): [ꢁ]_d

+51.6^ꢁ; R_f(s.s. 1) 0.29; CIMS: m/z (%) 357 (1),

179 (100), 161 (32), 133 (28), 115 (12), 97 (2). Anal.

found: C, 40.30; H, 5.66.

2,6-Anhydro-d-galacto-hexonic acid (2a). Ester

2b (400 mg, 2.08 mmol) was saponi®ed as described

in g.p. 4 to aord 2a (326 mg, 88%): mp 152 C

(from H₂O); [ꢁ]_d41.6^ꢁ; R_f(s.s. 1) 0.30; IR

(KBr): ꢄ 3430 (O±H), 1720 (CO), 1215, 1110,

1075 (C±O±C, C±O, C±C); CIMS: m/z (%) 357 (1),

179 (100), 161 (38), 133 (72), 115 (14), 97 (7). Anal.

found: C, 40.43; H, 5.68.

2,6-Anhydro-d-glycero-d-gluco-heptonic acid (6a).

Ester 6b (444 mg, 2 mmol) was saponi®ed as

described in g.p. 4 to aord 6a (342 mg, 82%): mp

155 ^ꢁC (from H₂O); [ꢁ]_d+58.2^ꢁ; R_f(s.s. 1) 0.24; IR

(KBr): ꢄ 3490, 3360 (O±H), 1720 (CO), 1220,

1080, 1065 (C±O±C, C±O, C±C); CIMS: m/z (%)

417 (1), 381 (1), 209 (32), 191 (100), 163 (32), 145

(27), 127 (7), 179 (76), 161 (3), 133 (5), 115 (7), 97

(3). Anal. found: C, 40.31; H, 5.83.

ꢁ

2,6-Anhydro-d-altro-hexonic acid (13a).Ð(a) 2,6-

Anhydro-1-deoxy-1-nitro-d-altro-hexitol

[13,15]

2,6-Anhydro-d-glycero-l-manno-heptonic

(7a). Ester 7b [3,17,18] (1.11 g, 5.00 mmol) was

acid

(500 mg, 2.59 mmol) was converted as described in

g.p. 1. The work-up was terminated before the

esteri®cation was started. 13a crystallised directly

after concentration of the mother liquor, contain-

ing HNO₃. Recrystallisation _ꢁfrom H₂O aorded

13a (275 mg, 60%): mp 228 C (from H₂O); [ꢁ]_d

30.3^ꢁ; R_f(s.s. 1) 0.19; IR (KBr): ꢄ 3470 (O±H),

1690 (CO), 1240, 1115, 980 (C±O±C, C±O, C±C);

CIMS: m/z (%) 357 (1), 179 (100), 161 (13), 133

(18), 115 (4), 97 (1). Anal. found: C, 40.38; H, 5.67.

2,6-Anhydro-d-altro-hexonic acid (13a). (b) Ester

13b (150 mg, 0.78 mmol) was saponi®ed as descri-

bed in g.p. 4 to give 13a (123 mg, 89%). The

experimental data matched the values mentioned in

procedure (a).

saponi®ed as des_ꢁcribed in g.p. 4 to give 7a (932 mg,

ꢁ

90%): mp 159 C (from H₂O), lit. 177 C [3,17];

[ꢁ]_d+53.8^ꢁ, lit. [ꢁ]₅₇₈²²+62.5^ꢁ(c 1.0, H₂O) [3], lit.

[ꢁ]_d²⁰+57.8^ꢁ(c 0.86, H₂O) [17]; R_f(s.s. 1) 0.19; IR

(KBr): ꢄ 3500, 3380, 3180 (O±H), 1700 (CO),

1405 (O±H), 1100, 1075 (C±O±C, C±O, C±C);

CIMS: m/z (%) 417 (1), 381 (9), 209 (14), 191 (100),

163 (9), 145 (7), 127 (3), 179 (3), 161 (2), 133 (2), 115

(3), 97 (1). Anal. found: C, 40.26; H, 5.80.

2,6-Anhydro-d-glycero-d-gulo-heptonic acid (8a).

Ester 8b [3,19] (889 mg, 4 mmol) was saponi®ed as

described in g.p. 4 to give syrupy 8a (830 mg,

100%): mp lit. 169 ^ꢁC [3,19]; [ꢁ]_d+18.9^ꢁ, lit.

[ꢁ]₅₇₈+25.0^ꢁ(c 1.0, H₂O) [3]; R_f(s.s. 1) 0.27;

22

2,6-Anhydro-d-allo-hexonic acid (3a). Ester 3b

(400 mg, 2.08 mmol) was saponi®ed as des_ꢁcribed in

g.p. 4 to aord 3a (324 mg, 88%): mp 84 C (from

H₂O); [ꢁ]_d22.5^ꢁ; R_f(s.s. 1) 0.34; IR (KBr): ꢄ 3400

CIMS: m/z (%) 417 (2), 381 (1), 209 (36), 191

(100), 163 (18), 145 (13), 127 (11), 179 (82), 161

(38), 133 (14), 115 (36), 97 (4). Anal. found: C,

40.26; H, 5.79.

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

113

2,6-Anhydro-d-glycero-l-talo-heptonic acid (9a).

Ester 9b (400 mg, 1.8 mmol) was saponi®ed as

described in g.p. 4 to aord 9a (369 mg, 98%): [ꢁ]_d

0.4^ꢁ; R_f(s.s. 1) 0.29; CIMS: m/z (%) 417 (1), 381

(58), 209 (6), 191 (100), 163 (5), 145 (4), 127 (8),

179 (2), 161 (2), 133 (2), 115 (2), 97 (16). Anal.

found: C, 40.38; H, 5.82.

2,6-Anhydro-d-glycero-l-ido-heptonic acid (10a).

Ester 10b (300 mg, 1.35 mmol) was saponi®ed as

described in g.p. 4 to give 10a (277 mg, 99%): [ꢁ]_d

+24.4^ꢁ; R_f(s.s. 1) 0.27; CIMS: m/z (%) 417 (1),

381 (89), 209 (6), 191 (100), 163 (19), 145 (22), 127

(11), 179 (52), 161 (5), 133 (6), 115 (10), 97 (3).

Anal. found: C, 40.25; H, 5.83.

2,6-Anhydro-d-glycero-d-galacto-heptonic acid

(11a). Ester 11b [19,20] (889 mg, 4 mmol) was

saponi®ed as described in g.p. 4 to aord 11a

(737 mg, 89%): mp 184 ^ꢁC (from H₂O); [ꢁ]_d+1.7^ꢁ;

R_f(s.s. 1) 0.17; IR (KBr): ꢄ 3380 (O±H), 1720

(CO), 1235, 1160, 1110 (C±O±C, C±O, C±C);

CIMS: m/z (%) 417 (3), 381 (8), 209 (59), 191

(100), 163 (26), 145 (13), 127 (4), 179 (36), 161 (2),

133 (5), 115 (5), 97 (2). Anal. found: C, 40.28; H,

5.80.

(100), 175 (8), 161 (1), 133 (2), 115 (4). Anal.

found: C, 43.76; H, 6.30.

Methyl 2,6-anhydro-d-altro-hexonate (13b). (a)

One drop of conc. H₂SO₄was added to a solution

of 13a (178 mg, 1 mmol) in dry MeOH (5 mL) and

heated for 12 h under re¯ux. After cooling to 20 ^ꢁC

the solution was neutralised with Amberlite IRA-

400 (HCO₃). The resin was ®ltered o, washed

successively with H₂O and the combined solutions

were concentrated to aord 13b (158 mg, 82%): mp

ꢁ

105 C (from MeOH); [ꢁ]_d31.5^ꢁ; R_f(s.s. 3) 0.67;

IR (KBr): ꢄ 3400 (O±H), 1725 (CO), 1225, 1100

(C±O±C, C±O, C±C); CIMS: m/z (%) 385 (93), 193

(100), 175 (2), 161 (4), 133 (8), 115 (2). Anal.

found: C, 43.75; H, 6.31.

Methyl 2,6-anhydro-d-altro-hexonate (13b). (b)

A mixture of 2,6-anhydro-1-deoxy-1-nitro-d-altro-

hexitol [13,15] and 2,6-anhydro-1-deoxy-1-nitro-d-

allo-hexitol [13,15] (1 g, 5.18 mmol) was converted

as described in g.p. 1. The syrup (915 mg), con-

taining crude methyl 2,6-anhydro-d-altro-hexonate

(13b) and methyl 2,6-anhydro-d-allo-hexonate (3b),

was separated by MPLC with H₂O as eluent at a

¯ow of 0.5 mL/min. The second fraction contained

13b (379 mg, 38%). The experimental data mat-

ched the values mentioned in procedure (a).

2,6-Anhydro-d-glycero-l-altro-heptonic

(12a). Ester 12b (667 mg, 3 mmol) was saponi®ed

acid

as described in g.p. 4 to give 12a (548 mg, 88%):

ꢁ

Methyl 2,6-anhydro-d-allo-hexonate (3b). (a) 2,6-

mp 169 C (from H₂O); [ꢁ]_d+33.1^ꢁ; R_f(s.s. 1)

Anhydro-1-deoxy-1-nitro-d-allo-hexitol

[13,15]

0.15; IR (KBr): ꢄ 3400 (O±H), 1750 (CO), 1300

(O±H), 1250, 1225, 1140, 1120, 1100, 1035 (C±O±C,

C±O, C±C); CIMS: m/z (%) 417 (2), 381 (9), 209

(32), 191 (100), 163 (13), 145 (6), 127 (2), 179 (22),

161 (2), 133 (3), 115 (5), 97 (2). Anal. found: C,

40.36; H, 5.83.

(579 mg, 3 mmol) was converted as described in

g.p. 1. The crude ester was puri®ed by MPLC with

H₂O as eluent at a ¯ow of 0.5 mL/min to give 3b

(407 mg, 71%): mp 82 ^ꢁC (from H₂O); [ꢁ]_d29.9^ꢁ;

R_f(s.s. 3) 0.67; IR (KBr): ꢄ 3390 (O±H), 1725

(CO), 1095, 1035 (C±O±C, C±O, C±C); CIMS:

m/z (%) 385 (87), 193 (100), 175 (11), 161 (9), 133

(5), 115 (2). Anal. found: C, 43.62; H, 6.28.

Methyl 2,6-anhydro-d-allo-hexonate (3b). (b) A

mixture of 2,6-anhydro-1-deoxy-1-nitro-d-allo-

hexitol [13,15] and 2,6-anhydro-1-deoxy-1-nitro-d-

altro-hexitol [13,15] (1 g, 5.18 mmol) was converted

as described for 13b. The ®rst MPLC-fraction

contained 3b (335 mg, 34%). The experimental

data matched the values mentioned in procedure

(a).

Methyl 2,6-anhydrohexonates.ÐAnal. Calcd for

C₇H₁₂O₆(192.17): C, 43.75; H, 6.29.

Methyl 2,6-anhydro-l-manno-hexonate (1b).

Ester 1c (2 g, 6.28 mmol) was deacetylated as

described in g.p. 3 to give 1b (1.05 g, 87%): mp

ꢁ

100 C (from EtOH±MeOH), lit. 92 C [17]; [ꢁ]_d

+42.2^ꢁ, lit. [ꢁ]_d+21.1^ꢁ(c 0.54, MeOH) [17]; R_f

20

(s.s. 3) 0.57; IR (KBr): ꢄ 3420 (O±H), 1730 (CO),

1235, 1105 (C±O±C, C±O, C±C); CIMS: m/z (%)

385 (9), 193 (100), 175 (2), 161 (2), 133 (5), 115 (3).

Anal. found: C, 43.70; H, 6.31.

Methyl 2,6-anhydro-d-gulo-hexonate (4b). Ester

4c (3 g, 9.43 mmol) was deacetylated as described in

Methyl 2,6-anhydro-d-galacto-hexonate (2b). 2,6-

Anhydro-1-deoxy-1-nitro-d-galacto-hexitol [6,15,33]

(1.5 g, 7.77 mmol) was converted as described in

ꢁ

g.p. 3 to aord 4b (1.65 g, 91%): mp 101 C (from

MeOH); [ꢁ]_d25.8^ꢁ; R_f(s.s. 3) 0.64; IR (KBr): ꢄ

3380 (O±H), 1730 (CO), 1220, 1090, 1055 (C±O±C,

C±O, C±C); CIMS: m/z (%) 385 (99), 193 (100),

175 (8), 161 (1), 133 (3), 115 (5). Anal. found: C,

43.68; H, 6.29.

ꢁ

g.p. 1 to give 2b (1.14 g, 76%): mp 171 C (from

MeOH); [ꢁ]_d30.4^ꢁ; R_f(s.s. 3) 0.51; IR (KBr): ꢄ

3380 (O±H), 1740 (CO), 1260 (O±H), 1105, 1075

(C±O±C, C±O, C±C); CIMS: m/z (%) 385 (7), 193

114

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

Methyl 2,6-anhydroheptonates.ÐAnal. Calcd for

C₈H₁₄O₇(222.20): C, 43.24; H, 6.35.

puri®ed in several runs by HPLC at a ¯ow of 4 mL/

min with H₂O as eluent to give 10b (1.83 g, 82%):

[ꢁ]_d+34.3^ꢁ; R_f(s.s. 3) 0.60; CIMS: m/z (%) 445

(12), 391 (14), 223 (100), 205 (11), 191 (26), 163 (4),

145 (3), 127 (1). Anal. found: C, 43.33; H, 6.36.

Methyl 2,6-anhydro-d-glycero-d-galacto-heptonate

(11b). 2,6-Anhydro-1-deoxy-1-nitro-d-glycero-d-

galacto-heptitol [6,15,19,27,33] (4.46 g, 20 mmol)

was converted as described in g.p. 1 to aord 11b

(3.82 g, 86%): mp 158 C (from MeOH), lit. 99 C

[19]; [ꢁ]_d+5.1^ꢁ; R_f(s.s. 3) 0.36; IR (KBr): ꢄ 3470,

3380 (O±H), 1710 (CO), 1095, 1065 (C±O±C, C±

O, C±C); CIMS: m/z (%) 445 (81), 391 (22), 223

(100), 205 (13), 191 (7), 163 (3), 145 (3), 127 (2).

Anal. found: C, 43.28; H, 6.37.

Methyl 2,6-anhydro-d-glycero-l-altro-heptonate

(12b). 2,6-Anhydro-1-deoxy-1-nitro-d-glycero-l-

altro-heptitol [34] (446 mg, 2 mmol) was converted

as described in g.p. 1. The crude ester (420 mg) was

puri®ed by MPLC with H₂O as eluent at a ¯ow_ꢁof

0.5 mL/min to give 12b (340 mg, 77%): mp 162 C

(from H₂O±MeOH); [ꢁ]_d+35.5^ꢁ; R_f(s.s. 3) 0.34;

IR (KBr): ꢄ 3400 (O±H), 1750 (C O), 1250, 1145,

1120, 1095, 1035 (C±O±C, C±O, C±C); CIMS: m/z

(%) 445 (95), 391 (12), 223 (100), 205 (53), 191

(14), 163 (2), 145 (3), 127 (1). Anal. found: C,

43.34; H, 6.36.

Methyl 2,6-anhydro-d-glycero-d-allo-heptonate

(5b). 2,6-Anhydro-1-deoxy-1-nitro-d-glycero-d-allo-

heptitol [15,19] (446 mg, 2 mmol) was converted as

described in g.p. 1. The crude ester (400 mg) was

puri®ed by HPLC at a ¯ow of 2 mL/min with H₂O

as eluent to give 5b (322 mg, 73%): mp 85 ^ꢁC (from

MeOH); [ꢁ]_d+13.5^ꢁ; R_f(s.s. 3) 0.51; IR (KBr): ꢄ

3480, 3420 (O±H), 1675 (CO), 1245, 1125, 1115,

1080, 945 (C±O±C, C±O, C±C); CIMS: m/z (%)

445 (19), 391 (14), 223 (100), 205 (3), 191 (85), 163

(3), 145 (5), 127 (3). Anal. found: C, 43.11; H, 6.37.

Methyl 2,6-anhydro-d-glycero-d-gluco-heptonate

(6b). Ester 6c (1 g, 2.56 mmol) was deacetylated as

described in g.p. 3 to aord 6b (520 mg, 91%): mp

141 ^ꢁC (from H₂O); [ꢁ]_d+63.8^ꢁ; R_f(s.s. 3) 0.49; IR

(KBr): ꢄ 3450, 3330 (O±H), 1725 (CO), 1220,

1145, 1070 (C±O±C, C±O, C±C); CIMS: m/z (%)

445 (92), 391 (27), 223 (100), 205 (10), 191 (5), 163

(3), 145 (4), 127 (3). Anal. found: C, 43.27; H, 6.37.

Methyl 2,6-anhydro-d-glycero-l-manno-heptonate

(7b). Ester 7c (3 g, 7.69 mmol) was deacetylated as

described in g.p. 3 to give 7b (1.53 g, 90%): mp

ꢁ

109 C (from MeOH), lit. 141 C [3,17], lit. 121±

22

ꢁ

123 C [18]; [ꢁ]_d+48.4^ꢁ, lit. [ꢁ]₅₇₈+56.5^ꢁ(c 1.0,

H₂O) [3], lit. [ꢁ]_d+57.5^ꢁ(c 1.11, H₂O) [17], lit.

20

[ꢁ]_d

32^ꢁ(c 0.12, H₂O) [18]; R_f(s.s. 3) 0.44; IR

Methyl

3,4,5-tri-O-acetyl-2,6-anhydrohexon-

20

(KBr): ꢄ 3360 (O±H), 1730 (CO), 1245, 1085 (C±

O±C, C±O, C±C); CIMS: m/z (%) 445 (82), 391 (7),

223 (100), 205 (78), 191 (12), 163 (3), 145 (2), 127

(2). Anal. found: C, 43.22; H, 6.33.

ates.ÐAnal. Calcd for C₁₃H₁₈O₉(318.28): C,

49.06; H, 5.70.

Methyl 3,4,5-tri-O-acetyl-2,6-anhydro-l-manno-

hexonate (1c). 2,6-Anhydro-1-deoxy-1-nitro-l-

manno-hexitol [6,15,17,33] (1.93 g, 10 mmol) was

converted as described in g.p. 1. The unprotected

ester 1b [17] (1.78 g) was acetylated as described in

g.p. 2. Column chromatography on silica gel with

Methyl 2,6-anhydro-d-glycero-d-gulo-heptonate

(8b). Ester 8c [1,19,26,31] (3 g, 7.69 mmol) was

deacetylated as described in g.p. 3 to give 8b

ꢁ

(1.49 g, 87%): mp 121 C (from H₂O±EtOH), lit.

22

119 C [3], lit. 116 C [19]; [ꢁ]_d+14.7^ꢁ, lit. [ꢁ]₅₇₈

s.s. 4 aorded 1c (2.26 g, 71%): mp 76 C (from

ꢁ

+16.5^ꢁ(c 1.0, H₂O) [3]; R_f(s.s. 3) 0.60; IR (KBr): ꢄ

3400 (O±H), 1730 (C O), 1100, 1075 (C±O±C,

C±O, C±C); CIMS: m/z (%) 445 (88), 391 (13), 223

(100), 205 (8), 191 (14), 163 (3), 145 (4), 127 (4).

Anal. found: C, 43.18; H, 6.34.

Methyl 2,6-anhydro-d-glycero-l-talo-heptonate

(9b). Ester 9c (1 g, 2.56 mmol) was deacetylated as

described in g.p. 3 to aord 9b (563 mg, 99%): [ꢁ]_d

5.3^ꢁ; R_f(s.s. 3) 0.57; CIMS: m/z (%) 445 (97), 391

(7), 223 (100), 205 (60), 191 (57), 163 (5), 145 (4),

127 (3). Anal. found: C, 43.15; H, 6.36.

Et₂O); [ꢁ]_d+18.2^ꢁ; R_f(s.s. 4) 0.48; ¹H NMR

(CDCl₃): ꢃ 1.995, 2.039, 2.100 (3s, 9 H, 3ÂAc), cf.

Table 3; ¹³C NMR (CDCl₃): ꢃ 20.6, 20.6, 20.8,

169.6, 169.7, 170.2 (3ÂAc), cf. Table 2; IR (KBr): ꢄ

1750 (CO), 1230, 1055 (C±O±C, C±O, C±C);

CIMS: m/z (%) 637 (2), 577 (1), 517 (1), 457 (1),

415 (1), 319 (57), 259 (100), 199 (18), 139 (8), 97

(1). Anal. found: C, 48.87; H, 5.68.

Methyl 3,4,5-tri-O-acetyl-2,6-anhydro-d-galacto-

hexonate (2c). Ester 2b (192 mg, 1 mmol) was

acetylated as described in g.p. 2 to give 2c (280 mg,

88%): mp 139 ^ꢁC (from EtOAc±Et₂O); [ꢁ]_d84.3^ꢁ;

Methyl

2,6-anhydro-d-glycero-l-ido-heptonate

1

(10b). 2,6-Anhydro-1-deoxy-1-nitro-d-glycero-l-ido-

heptitol [34] (2.23 g, 10 mmol) was converted as

described in g.p. 1. The crude ester (1.9 g) was

R_f(s.s. 4) 0.31; H NMR (CDCl₃): ꢃ 1.983, 2.010,

2.075 (3s, 9 H, 3ÂAc), cf. Table 3; ¹³C NMR

(CDCl₃): ꢃ 20.4, 20.5, 20.6, 169.6, 169.6, 169.9

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

115

(3ÂAc), cf. Table 2; IR (KBr): ꢄ 1755 (CO),

1250, 1210, 1060 (C±O±C, C±O, C±C); CIMS: m/z

(%) 637 (5), 577 (1), 517 (1), 457 (1), 415 (1), 319

(100), 259 (79), 199 (12), 139 (5), 97 (1). Anal.

found: C, 48.96; H, 5.70.

Et₂O); [ꢁ]_d+6.3^ꢁ; R_f(s.s. 5) 0.67; ¹H NMR

(CDCl₃): ꢃ 1.978, 2.049, 2.139, 2.150 (4s, 12 H,

4ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): ꢃ 20.4,

20.5, 20.7, 20.8, 168.9, 169.0, 169.7, 170.7 (4ÂAc),

cf. Table 2; IR (KBr): ꢄ 1750 (CO), 1230, 1050

(C±O±C, C±O, C±C); CIMS: m/z (%) 781 (19), 721

(67), 661 (84), 601 (22), 559 (18), 391 (100), 331 (31),

271 (18), 211 (8), 169 (2). Anal. found: C, 49.06; H,

5.66.

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydro-d-gly-

cero-d-gluco-heptonate (6c). 2,6-Anhydro-1-deoxy-

1-nitro-d-glycero-d-gluco-heptitol [34] (1.34 g,

6 mmol) was converted as described in g.p. 1. The

unprotected crude ester 6b (1.22 g) was ®rst acety-

lated as described in g.p. 2 and then puri®ed by

column chromatography on silica gel with s.s. 4.

The eluate crystallised in needles after concentra-

tion of the column fraction giving 6c (1.65 g, 71%):

Methyl

3,4,5-tri-O-acetyl-2,6-anhydro-d-altro-

hexonate (13c). Ester 13b (192 mg, 1 mmol) was

acetylated as described in g.p. 2 and then puri®ed

by column chromatography on silica gel with s.s. 5

giving 13c (265 mg, 83%): [ꢁ]_d+17.5^ꢁ; R_f(s.s. 5)

0.44; ¹H NMR (CDCl₃): ꢃ 1.959, 2.037, 2.072 (3s, 9

H, 3ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): ꢃ 20.4,

20.4, 20.9, 169.5, 169.7, 170.3 (3ÂAc), cf. Table 2;

IR (CCl₄): ꢄ 1730 (CO), 1250, 1215 (C±O±C, C±

O, C±C); CIMS: m/z (%) 637 (63), 577 (8), 517 (2),

457 (1), 415 (35), 319 (100), 259 (82), 199 (11), 139

(9), 97 (50). Anal. found: C, 49.10; H, 5.69.

Methyl

3,4,5-tri-O-acetyl-2,6-anhydro-d-allo-

ꢁ

1

hexonate (3c). Ester 3b (192 mg, 1 mmol) was

acetylated as described in g.p. 2. Column chroma-

tography on silica gel with s.s. 4 aorded 3c

mp 119 C; [ꢁ]_d10.3^ꢁ; R_f(s.s. 4) 0.27; H NMR

(CDCl₃): ꢃ 1.868, 1.962, 1.995, 2.042 (4s, 12 H,

4ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): ꢃ 20.2,

20.3, 20.4, 20.5, 168.6, 168.8, 169.0, 170.4 (4ÂAc),

cf. Table 2; IR (KBr): ꢄ 1740 (CO), 1250, 1225,

1150, 1050 (C±O±C, C±O, C±C); CIMS: m/z (%)

781 (20), 721 (23), 661 (4), 601 (2), 559 (3), 391

(100), 331 (41), 271 (5), 211 (9), 169 (2). Anal.

found: C, 49.05; H, 5.67.

(278 mg, 87%): [ꢁ]_d14.9^ꢁ; R_f(s.s. 4) 0.48; H

1

NMR (CDCl₃): ꢃ 1.979, 1.981, 2.124 (3s, 9 H,

3ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): ꢃ 20.4,

20.5, 20.6, 169.1, 169.3, 169.7 (3ÂAc), cf. Table 2;

IR (CCl₄): ꢄ 1750 (CO), 1220, 1050 (C±O±C,

C±O, C±C); CIMS: m/z (%) 637 (7), 577 (1), 517

(1), 457 (1), 415 (1), 319 (100), 259 (12), 199 (2),

139 (4), 97 (1). Anal. found: C, 49.05; H, 5.72.

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydro-d-gly-

cero-l-manno-heptonate (7c).Ð2,6-Anhydro-7-de-

oxy-7-nitro-l-glycero-l-galacto-heptitol [15,17,35,36]

(4.46 g, 20 mmol) was converted as described in

g.p. 1. The unprotected ester 7b [3,17,18] (4.12 g)

was acetylated as described in g.p. 2. 7c (4.13 g)

crystallised directly from Et₂O. Column chroma-

tography on silica gel with s.s. 7 and crystallisation

from Et₂O aorded another 1.62 g of 7c (5.75 g,

Methyl

3,4,5-tri-O-acetyl-2,6-anhydro-d-gulo-

hexonate (4c). 1,5-Anhydro-6-deoxy-6-nitro-l-gluco-

hexitol [15,22] (1.93 g, 10 mmol) was converted as

described in g.p. 1. The unprotected ester 4b [16]

(1.85 g) was acetylated as described in g.p. 2. Col-

umn chromatography on silica gel with s.s. 5 gave

ꢁ

4c (2.24 g, 70%): mp 113 C (from EtOAc±Et₂O);

1

[ꢁ]_d40.1^ꢁ; R_f(s.s. 5) 0.72; H NMR (CDCl₃): ꢃ

74%): mp 150 C; [ꢁ]_d+17.4^ꢁ; R_f(s.s. 7) 0.50; H

NMR (CDCl₃): ꢃ 1.971, 2.017, 2.023, 2.144 (4s, 12

H, 4ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): ꢃ 20.6,

20.6, 20.6, 20.6, 169.6, 170.0, 170.2, 170.4 (4ÂAc),

cf. Table 2; IR (KBr): ꢄ 1740 (CO), 1265, 1230

(C±O±C, C±O, C±C); CIMS: m/z (%) 781 (5), 721

(7), 661 (2), 601 (1), 559 (4), 391 (100), 331 (87),

271 (18), 211 (14), 169 (8). Anal. found: C, 49.11;

H, 5.66.

ꢁ

1

2.008, 2.012, 2.013 (3s, 9 H, 3 ÂAc), cf. Table 3;

¹³C NMR (CDCl₃): ꢃ 20.5, 20.6, 20.6, 169.5, 169.6,

169.9 (3ÂAc), cf. Table 2; IR (KBr): ꢄ 1750

(CO), 1230, 1055 (C±O±C, C±O, C±C); CIMS:

m/z (%) 637 (21), 577 (16), 517 (4), 457 (2), 415 (3),

319 (81), 259 (100), 199 (20), 139 (13), 97 (2). Anal.

found: C, 48.92; H, 5.70.

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydrohept-

onates.ÐAnal. Calcd for C₁₆H₂₂O₁₁(390.34): C,

49.23; H, 5.68.

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydro-d-gly-

cero-d-gulo-heptonate

(8c).Ð2,6-Anhydro-1-de-

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydro-d-glycero-

d-allo-heptonate (5c). Ester 5b (667 mg, 3 mmol)

was acetylated as described in g.p. 2 and puri®ed

by column chromatography on silica gel with s.s.

5 to give 5c (911 mg, 78%): mp 75 ^ꢁC (from MeOH±

oxy-1-nitro-d-glycero-d-gulo-heptitol [15,19,36,37]

(4.46 g, 20 mmol) was converted as described in

g.p. 1. The unprotected ester 8b [3,19] (4.23 g) was

acetylated as described in g.p. 2. Column chroma-

tography on silica gel with s.s. 7 aorded 8c (5.84 g,

116

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

ꢁ

75%): mp 152 C_ꢁ(from EtOAc±Et₂O), lit. 107±

(CDCl₃): ꢃ 1.920, 1.979, 2.020, 2.047 (4s, 12 H,

4ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): ꢃ 20.4,

20.4, 20.5, 20.6, 169.4, 169.6, 169.8, 170.5 (4ÂAc),

cf. Table 2; IR (KBr): ꢄ 1745 (CO), 1230, 1060

(C±O±C, C±O, C±C); CIMS: m/z (%) 781 (16), 721

(4), 661 (1), 601 (1), 559 (2), 391 (100), 331 (68),

271 (9), 211 (9), 169 (7). Anal. found: C, 49.04; H,

5.68.

ꢁ

109 C [1], lit. 142 C [19], lit. 145±146 C [26], lit.

149 C [31]; [ꢁ]_d+3.7^ꢁ, lit. [ꢁ]_d+20.18^ꢁ(c ꢀ4,

ꢁ

20

CHCl₃) [1], lit. [ꢁ]_d+5^ꢁ(c 5, CHCl₃) [26], lit.

20

23

[ꢁ]₅₈₉

23^ꢁ(c 0.2, CHCl₃) [31]; R_f(s.s. 7) 0.52; ¹H

NMR (CDCl₃): ꢃ 1.993, 2.001, 2.006, 2.065 (4s, 12

H, 4ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): ꢃ 20.5,

20.6, 20.6, 20.7, 169.3, 169.3, 170.2, 170.6 (4ÂAc),

cf. Table 2; IR (KBr): ꢄ 1740 (CO), 1250, 1220

(C±O±C, C±O, C±C); CIMS: m/z (%) 781 (11), 721

(7), 661 (2), 601 (1), 559 (2), 391 (100), 331 (72),

271 (9), 211 (10), 169 (7). Anal. found: C, 49.08; H,

5.67.

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydro-d-gly-

cero-l-altro-heptonate (12c).ÐEster 12b (222 mg,

1 mmol) was acetylated as described in g.p. 2 and

puri®ed by column chromatography on silica gel

ꢁ

with s.s. 7 to aord 12c (333 mg, 85%): mp 119 C

(from EtOAc); [ꢁ]_d+35.5^ꢁ, lit. [ꢁ]_d

24.0^ꢁ(c not

25

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydro-d-gly-

cero-l-talo-heptonate (9c).Ð2,6-Anhydro-7-deoxy-

7-nitro-l-glycero-l-gluco-heptitol

1

indicated, CHCl₃) [32]; R_f(s.s. 7) 0.47; H NMR

(CDCl₃): ꢃ 1.910, 1.973, 2.005, 2.045 (4s, _ꢁ12 H,

4ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): 20.3,

20.4, 20.4, 20.5, 169.3, 169.5, 170.0, 170.3 (4ÂAc),

cf. Table 2; IR (KBr): ꢄ 1730 (CO), 1220, 1060

(C±O±C, C±O, C±C); CIMS: m/z (%) 781 (3), 721

(1), 661 (1), 601 (1), 559 (1), 391 (100), 331 (29),

271 (4), 211 (6), 169 (4). Anal. found: C, 49.23; H,

5.68.

[34]

(2.23 g,

10 mmol) was converted as described in g.p. 1. The

unprotected ester 9b (2.05 g) was acetylated as

described in g.p. 2. Column chromatography on

silica gel with s.s. 4 aorded 9c (3.05 g, 78%): [ꢁ]_d

+8.8^ꢁ; R_f(s.s. 4) 0.42; H NMR (CDCl₃): ꢃ 1.949,

1

2.001, 2.118, 2.121 (4s, 12 H, 4ÂAc), cf. Table 3;

¹³C NMR (CDCl₃): ꢃ 20.4, 20.7, 20.7, 20.7, 168.8,

169.1, 169.4, 170.4 (4ÂAc), cf. Table 2; IR (CCl₄):

ꢄ 1745 (CO), 1260, 1225, 1055 (C±O±C, C±O, C±

C); CIMS: m/z (%) 781 (19), 721 (6), 661 (7), 601

(3), 559 (2), 391 (100), 331 (69), 271 (16), 211 (13),

169 (3). Anal. found: C, 49.08; H, 5.66.

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydro-d-gly-

cero-l-ido-heptonate (10c).ÐEster 10b (300 mg,

1.35 mmol) was acetylated as described in g.p. 2

and puri®ed by column chromatography on silica

gel with s.s. 6 to aord 10c (412 mg, 79%): mp

119 ^ꢁC (from Et₂O); [ꢁ]_d13.1^ꢁ; R_f(s.s. 6) 0.69; ¹H

NMR (CDCl₃): ꢃ 2.024, 2.031, 2.067, 2.127 (4s, 12

H, 4ÂAc), cf. Table 3; ¹³C NMR (CDCl₃): ꢃ 20.5,

20.6, 20.7, 20.7, 167.9, 169.1, 169.4, 170.5 (4ÂAc),

cf. Table 2; IR (KBr): ꢄ 1740 (CO), 1240, 1210,

1050 (C±O±C, C±O, C±C); CIMS: m/z (%) 781 (8),

721 (6), 661 (2), 601 (1), 559 (1), 391 (100), 331

(95), 271 (22), 211 (15), 169 (17). Anal. found: C,

49.11; H, 5.68.

Methyl 3,4,5,7-tetra-O-acetyl-2,6-anhydro-d-gly-

cero-d-galacto-heptonate (11c).ÐEster 11b [19,20]

(300 mg, 1.35 mmol) was acetylated as described in

g.p. 2. 11c (290 mg) crystallised directly from 1:1

EtOAc±Et₂O. The remaining syrup was puri®ed by

column chromatography on silica gel with s.s. 2

and crystallised from 1:1 EtOAc±Et₂O to give

another 166 mg of 11c (456 mg, 87%): mp 102 C,

lit. 93 C [19]; [ꢁ]_d42.2^ꢁ, lit. [ꢁ]_d

indicated, CHCl₃) [32]; R_f(s.s. 2) 0.54; H NMR

2,6-Anhydrohexonamides.ÐAnal. Calcd for

C₆H₁₁NO₅(177.16): C, 40.68; H, 6.26; N, 7.91.

2,6-Anhydro-l-manno-hexonamide (1d). Ester 1b

[17] (100 mg, 0.52 mmol) was converted as descri-

bed in g.p. 5 giving 1d (90 mg, 98%): [ꢁ]_d70.7^ꢁ;

R_f(s.s. 3) 0.24; CIMS: m/z (%) 355 (6), 178 (100).

Anal. found: C, 40.52; H, 6.24; N, 7.93.

2,6-Anhydro-d-galacto-hexonamide (2d). Ester 2b

(200 mg, 1.04 mmol) was converted as described in

g.p. 5 to aord 2d (172 mg, 93%): mp 177 ^ꢁC (from

aq MeOH); [ꢁ]_d4.4^ꢁ; R_f(s.s. 3) 0.32; IR (KBr): ꢄ

3400, 3360, 3300, 3200 (O±H, N±H), 1670 (C O),

1105, 1080 (C±O±C, C±O, C±C); CIMS: m/z (%)

355 (94), 178 (100). Anal. found: C, 40.60; H, 6.25;

N, 7.89.

2,6-Anhydro-d-altro-hexonamide (13d). Ester 13b

(100 mg, 0.52 mmol) was converted as described in

g.p. 5 giving 13d (92 mg, 100%): [ꢁ]_d65.2^ꢁ; R_f

(s.s. 3) 0.41; CIMS: m/z (%) 355 (69), 178 (100).

Anal. found: C, 40.80; H, 6.26; N, 7.94.

2,6-Anhydro-d-allo-hexonamide (3d). Ester 3b

(100 mg, 0.52 mmol) was converted as described in

g.p. 5 aording 3d (90 mg, 98%): [ꢁ]_d13.8^ꢁ; R_f

(s.s. 3) 0.36; CIMS: m/z (%) 355 (70), 178 (100).

Anal. found: C, 40.60; H, 6.24; N, 7.93.

2,6-Anhydro-d-gulo-hexonamide (4d). Ester 4b

[16] (200 mg, 1.04 mmol) was converted as described

ꢁ

44.0^ꢁ(c not

in g.p. 5 to aord 4d (175 mg, 95%): mp 172 C

ꢁ

25

(from H₂O±MeOH); [ꢁ]_d11.9^ꢁ; R_f(s.s. 3) 0.36;

1

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

117

IR (KBr): ꢄ 3390 (O±H, N±H), 1620 (CO), 1110,

1080 (C±O±C, C±O, C±C); CIMS: m/z (%) 355

(32), 178 (100). Anal. found: C, 40.58; H, 6.27; N,

7.90.

as described in g.p. 5 to aord 11d (169 mg, 91%):

ꢁ

mp 218 C (from H₂O); [ꢁ]_d+39.4^ꢁ; R_f(s.s. 3)

0.18; IR (KBr): ꢄ 3390, 3320, 3230 (O±H, N±H),

1670 (CO), 1105, 1065 (C±O±C, C±O, C±C);

CIMS: m/z (%) 415 (18), 208 (100). Anal. found:

C, 40.54; H, 6.34; N, 6.73.

2,6-Anhydro-d-glycero-l-altro-heptonamide (12d).

Ester 12b (200 mg, 0.9 mmol) was converted as

described in g.p. 5 to aord 12d (172 mg, 92%): mp

210 ^ꢁC (from H₂O); [ꢁ]_d+74.7^ꢁ; R_f(s.s. 3) 0.14; IR

(KBr): ꢄ 3430, 3330, 3250 (O±H, N±H), 1675

(CO), 1105, 1070 (C±O±C, C±O, C±C); CIMS:

m/z (%) 415 (14), 208 (100). Anal. found: C, 40.52;

H, 6.30; N, 6.75.

2,6-Anhydroheptonamides.ÐAnal. Calcd for

C₇H₁₃NO₆(207.18): C, 40.58; H, 6.32; N, 6.76.

2,6-Anhydro-d-glycero-d-allo-heptonamide (5d).

Ester 5b (100 mg, 0.45 mmol) was converted as

described in g.p. 5 to aord 5d (81 mg, 87%): mp

182 ^ꢁC (from H₂O); [ꢁ]_d+21.0^ꢁ; R_f(s.s. 3) 0.30; IR

(KBr): ꢄ 3380, 3200 (O±H, N±H), 1675 (CO),

1065, 1035 (C±O±C, C±O, C±C); CIMS: m/z (%)

415 (12), 208 (100). Anal. found: C, 40.44; H, 6.33;

N, 6.73.

2,6-Anhydro-d-glycero-d-gluco-heptonamide (6d).

Ester 6b (200 mg, 0.9 mmol) was converted as

described in g.p. 5 to give 6d (173 mg, 93%): mp

Anhydrohexitol.ÐAnal. Calcd for C₆H₁₂O₅

(164.16): C, 43.90; H, 7.37.

1,5-Anhydro-l-gluco-hexitol (4e). Ester 4b [16]

(500 mg, 2.6 mmol) was converted as described in

g.p. 6 to aord 4e (385 mg, 90%): mp 140 ^ꢁC (from

ꢁ

183 C (from H₂O); [ꢁ]_d+154.6^ꢁ; R_f(s.s. 3) 0.27;

IR (KBr): ꢄ 3300 (O±H, N±H), 1660 (CO), 1125,

1110, 1070 (C±O±C, C±O, C±C); CIMS: m/z (%)

415 (6), 208 (100). Anal. found: C, 40.47; H, 6.32;

N, 6.76.

2,6-Anhydro-d-glycero-l-manno-heptonamide (7d).

Ester 7b [3,17,18] (200 mg, 0.9 mmol) was con-

verted as described in g.p. 5 to aord 7d (172 mg,

92 %): mp 194 ^ꢁC (from H₂O), lit. 196±197 ^ꢁC [18];

[ꢁ]_d+59.1^ꢁ, lit. [ꢁ]_d²⁰+67.8^ꢁ(c 1.15, H₂O) [18]; R_f

(s.s. 3) 0.21; IR (KBr): ꢄ 3390, 3310 (O±H, N±H),

1655 (CO), 1105, 1075, 1055 (C±O±C, C±O, C±C);

CIMS: m/z (%) 415 (15), 208 (100). Anal. found:

C, 40.49; H, 6.32; N, 6.75.

2,6-Anhydro-d-glycero-d-gulo-heptonamide (8d).

Ester 8b [3,19] (200 mg, 0.9 mmol) was converted

as described in g.p. 5 to aord 8d (160 mg, 86%):

mp 205 ^ꢁC (from H₂O±MeOH); [ꢁ]_d+29.0^ꢁ; R_f(s.s.

3) 0.27; IR (KBr): ꢄ 3400, 3260, 3140 (O±H, N±H),

1655 (CO), 1080, 1055 (C±O±C, C±O, C±C);

CIMS: m/z (%) 415 (10), 208 (100). Anal. found:

C, 40.51; H, 6.30; N, 6.77.

MeOH), lit. 141±142 ^ꢁC [22]; [ꢁ]_d40.6^ꢁ, lit. [ꢁ]_d

25

40.4^ꢁ(c 2.6, H₂O) [22]; R_f(s.s. 3) 0.36; H NMR

1

(D₂O): ꢃ 3.134 (dd, 1 H, J_1a,1b11.2 Hz, J_1a,2

10.8 Hz, H-1a), 3.182±3.234 (dd, 1 H, J_4,5ABX, H-

4), 3.182±3.234 (ddd, 1 H, J_5,6a5.6 Hz, J_5,6b1.9 Hz,

H-5), 3.292 (dd, 1 H, J_3,48.9 Hz, H-3), 3.448 (ddd,

1 H, J_2,39.1 Hz, H-2), 3.541 (dd, 1 H, J_6a,6b

12.1 Hz, H-6a), 3.738 (dd, 1 H, H-6b), 3.840 (dd, 1

H, J_1b,25.4 Hz, H-1b); IR (KBr): ꢄ 3410, 3340, 3240

(O±H), 1105, 1075, 1010 (C±O±C, C±O, C±C);

CIMS: m/z (%) 329 (88), 311 (1), 293 (2), 165

(100), 147 (4), 129 (46). Anal. found: C, 43.73; H,

7.37.

Anhydroheptitols.ÐAnal. Calcd for C₇H₁₄O₆

(194.19): C, 43.30; H, 7.27.

2,6-Anhydro-l-glycero-l-galacto-heptitol

(7e).

Ester 7b [3,17,18] (500 mg, 2.25 mmol) was con-

verted as descri_ꢁbed in g.p. 6 to aord 7e (377 mg,

86%): mp 140 C (from EtOH±MeOH), lit. 121±

122 ^ꢁC (hemihydrate) [18,23]; [ꢁ]_d+33.1^ꢁ, lit. [ꢁ]_d

20

2,6-Anhydro-d-glycero-l-talo-heptonamide (9d).

Ester 9b (100 mg, 0.45 mmol) was converted as

described in g.p. 5 giving 9d (88 mg, 96%): [ꢁ]_d

+1.5^ꢁ; R_f(s.s. 3) 0.24; CIMS: m/z (%) 415 (12),

208 (100). Anal. found: C, 40.58; H, 6.33; N, 6.76.

2,6-Anhydro-d-glycero-l-ido-heptonamide (10d).

Ester 10b (200 mg, 0.9 mmol) was converted as

described in g.p. 5 aording 10d (185 mg, 99%):

[ꢁ]_d+72.7^ꢁ; R_f(s.s. 3) 0.43; CIMS: m/z (%) 415

(20), 208 (100). Anal. found: C, 40.66; H, 6.35; N,

6.79.

+29.0^ꢁ(c 1.92, H₂O) [18], lit. [ꢁ]_d²⁰+32.6^ꢁ(c 1.32,

H₂O) [23]; R_f(s.s. 3) 0.20; ¹H NMR (D₂O): ꢃ 3.228

(ddd, 1 H, J_2,39.8 Hz, H-2), 3.421 (dd, 1 H, J_3,4

9.5 Hz, H-3), 3.501 (dd, 1 H, J_4,53.2 Hz, H-4),

3.516 (ddd, 1 H, J_6,7a8.2 Hz, J_6,7b3.9 Hz, H-6),

3.563 (dd, 1 H, J_1a,1b12.1 Hz, J_1a,26.6 Hz, H-1a),

3.571 (dd, 1 H, H-7b), 3.631 (dd, 1 H, J_7a,7b

11.6 Hz, H-7a), 3.786 (dd, 1 H, J_1b,22.2 Hz, H-

1b), 3.813 (dd, 1 H, J_5,61.3 Hz, H-5); IR (KBr): ꢄ

3400 (O±H), 1105, 1085, 1050, 1010 (C±O±C, C±O,

C±C); CIMS: m/z (%) 389 (19), 195 (100), 177 (3),

159 (22), 141 (2), 123 (12). Anal. found: C, 43.21;

H, 7.24.

2,6-Anhydro-d-glycero-d-galacto-heptonamide (11d).

Ester 11b [19,20] (200 mg, 0.9 mmol) was converted

118

M. Dromowicz, P. Koll/Carbohydrate Research 311 (1998) 103±119

È

2,6-Anhydro-meso-d-glycero-d-gulo-heptitol (8e).

Ester 8b [3,19] (500 mg, 2.25 mmol) was converted

K. Utimoto, and T. Horiie, Tetrahedron Lett., 23

(1982) 237±238.

[5] P. Koll and A. Fortsch, Carbohydr. Res., 171

(1987) 301±315.

[6] A. Fortsch, H. Kogelberg, and P. Koll, Carbohydr.

Res., 164 (1987) 391±402.

[7] P. Koll, C. Stenns, W. Seelhorst, and

H. Brandenburg, Liebigs Ann. Chem., (1991) 201±

206 and literature cited therein; P. Koll,

H. Brandenburg, W. Seelhorst, C. Stenns, and

H. Kogelberg, Liebigs Ann. Chem., (1991) 207±211

and literature cited therein.

[8] V. Bõlik, Collect. Czech. Chem. Commun., 39 (1974)

1621±1624.

[9] J.U. Nef, Justus Liebigs Ann. Chem., 280 (1894)

263±291.

[10] V. Bõlik, L. Petrus, and J. Zemek, Chem. Zvesti, 30

(1976) 693±697.

[11] G.A. Olah, M. Arvanaghi, Y.D. Vankar, and

G.K.S. Prakash, Synthesis, (1980) 662±663.

[12] P. Koll and M. Dromowicz, Abstr. Eur. Carbohydr.

Symp., 6th, Edinburgh, 1991, B56.

as described in g.p. 6 to give 8e (388 mg_ꢁ, 89%): mp

ꢁ

199 C (from aq EtOH), lit. _ꢁ199±201 C [24], lit.

ꢁ

203±205 C [25], lit. 204±205 C [26]; [ꢁ]_d00.1^ꢁ,

lit. [ꢁ]_d²⁰+3.1^ꢁ(c 5.87, H₂O) [24], lit. [ꢁ]_d²⁰0^ꢁ(c 2,

H₂O) [25], lit. [ꢁ]_d²⁰00.1^ꢁ(c and solvent not indi-

cated) [26]; R_f(s.s. 3) 0.30; ¹H NMR (D₂O): ꢃ 3.219

(dd, 2 H, J_3,4=J_4,58.9 Hz, H-3, H-5), 3.281 (ddd, 2

H, J_2,3=J_5,69.8 Hz, H-2, H-6), 3.355 (dd, 1 H, H-4),

3.564 (dd, 2 H, J_1a,1b=J_7a,7b12.2 Hz, J_1a,2=J_6,7a

5.9 Hz, H-1a, H-7a), 3.767 (dd, 2 H, J_1b,2=J_6,7b

2.2 Hz, H-1b, H-7b); IR (KBr): ꢄ 3450, 3260 (O±H),

1100, 1080, 1030, 1010 (C±O±C, C±O, C±C); CIMS:

m/z (%) 389 (57), 195 (100), 177 (5), 159 (34), 141

(7), 123 (18). Anal. found: C, 43.23; H, 7.26.

2,6-Anhydro-d-glycero-d-galacto-heptitol (11e).

Ester 11b [19,20] (500 mg, 2.25 mmol) was con-

verted as described in g.p. 6 to give 11e (381 mg,

ꢁ

87%): mp 141 C (_ꢁfrom aq EtOH), lit. 142±144 C

[27], lit. 129±130 C [28]; [ꢁ]_d33.5^ꢁ, lit. [ꢁ]_d

33.6^ꢁ(c 1.5, H₂O) [27], lit. [ꢁ]_d

25

[13] M. Dromowicz, PhD thesis, University of Old-

enburg, Germany, 1995.

33.4^ꢁ(c 1.5,

25

H₂O) [28]; R_f(s.s. 3) 0.20; ¹H NMR (D₂O): ꢃ 3.228

(ddd, 1 H, J_6,7a6.6 Hz, J_6,7b2.2 Hz, H-6), 3.421

(dd, 1 H, J_5,69.8 Hz, H-5), 3.501 (dd, 1 H, J_4,5

9.5 Hz, H-4), 3.516 (ddd, 1 H, J_2,31.3 Hz, H-2),

3.563 (dd, 1 H, J_7a,7b12.1 Hz, H-7a), 3.571 (dd, 1 H,

J_1b,23.9 Hz, H-1b), 3.631 (dd, 1 H, J_1a,1b11.6 Hz,

J_1a,28.2 Hz, H-1a), 3.786 (dd, 1 H, H-7b), 3.813 (dd,

1 H, J_3,43.2 Hz, H-3); IR (KBr): ꢄ 3400 (O±H),

1105, 1085, 1050, 1010 (C±O±C, C±O, C±C); CIMS:

m/z (%) 389 (33), 195 (100), 177 (5), 159 (29), 141

(4), 123 (23). Anal. found: C, 43.15; H, 7.25.

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Germany, 1991.

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Carbohydr. Res., 97 (1981) C1±C4.

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bohydr. Chem., 2 (1963), 65±68.

Acknowledgements

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Article Doi

Syntheses of 2,6-anhydroaldonic acids from the corresponding anhydrodeoxynitroalditols (glycopyranosylnitromethanes) and their conversion into methyl esters, amides, and alditols

DOI: 10.1016/S0008-6215(98)00195-5

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