Benzyl Ester of O-(Cyclooctyl-2-acetamido-2,3-dideoxy-ꢀ-D-glucopyranosid-3-yl)-D-lactoyl-L-alanyl-D-
isoglutamine (8a). A suspension of 5a (0.51 g, 1.12 mmol) in anhydrous dioxane (30 mL) was stirred, treated in portions with
NaH (0.18 g, 4.50 mmol, 60% suspension), heated to 95°C, held at that temperature for 1 h, cooled to 65°C, treated with
(S)-2-bromopropanoic acid (200 ꢅL, 2.23 mmol), held at 65°C for another 3 h, and cooled. The excess of NaH was decomposed
by EtOH. The mixture was concentrated, poured into cold H O (50 mL), acidified by HCl (2 M) to pH 3–4, and extracted (6a)
2
with CHCl (3 ꢇ 30 mL). The extract was dried over anhydrous Na SO and evaporated.
3
2
4
The resulting partially protected muramic acid 6a (0.63 g, 1.42 mmol) was used without further purification, dissolved
in anhydrous THF (10 mL), stirred, and treated with HOSu (200 mg, 1.70 mmol) and DCC (350 mg, 1.70 mmol).
The precipitate of dicyclohexylurea was filtered off after 3 h and rinsed with solvent (5 mL). The filtrate was treated with
the trifluoroacetate of L-alanyl-D-isoglutamine benzyl ester [prepared by treating the corresponding Boc-derivative with
trifluoroacetic acid (690 mg, 1.70 mmol) followed by evaporation to dryness] and Et N to pH 8. When the reaction was
3
finished (TLC monitoring using system 3), the reaction mixture was evaporated. The residue was dissolved in CHCl (70 mL)
3
and washed with HCl (1 M, 20 mL), saturated NaHCO solution (20 mL), and H O (20 mL). The organic layer was dried over
3
2
anhydrous Na SO and evaporated. The residue was purified by CC (gradient elution by CHCl –2-PrOH, 50:1ꢆ10:1) to
2
4
3
afford 7a (0.68 g, 75%) [benzyl ester of O-(cyclooctyl-2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-ꢀ-D-glucopyranosid-
3-yl)-D-lactyl-L-alanyl-D-isolgutamine].
Analogous syntheses were used for the benzyl ester of O-(cyclodecyl-2-acetamido-2,3-dideoxy-4,6-O-isopropylidene-
ꢀ-D-glucopyranosid-3-yl)-D-lactyl-L-alanyl-D-isolgutamine (7b, 0.28 g, 46%) and the benzyl ester of O-(cyclopentadecyl-2-
acetamido-2,3-dideoxy-4,6-O-isopropylidene-ꢀ-D-glucopyranosid-3-yl)-D-lactyl-L-alanyl-D-isolgutamine (7c, 0.67 g, 61%).
Protected glycopeptide 7a (0.68 g, 0.83 mmol) was dissolved inAcOH (70%, 10 mL) with heating on a boiling-water
bath, held at that temperature for 15 min, and evaporated to dryness. The residue was co-evaporated with toluene.
CC (gradient elution by CHCl –2-PrOH, 60:1ꢆ5:1) isolated 8a (0.34 g, 52%), mp 138–142°C, [ꢁ]
–4° (c 1.0, EtOH).
3
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Table 2 lists the PMR spectrum.
Analogous preparations were used for the benzyl ester of O-(cyclodecyl-2-acetamido-2,3-dideoxy-ꢀ-D-glucopyranosid-
3-yl)-D-lactyl-L-alanyl-D-isolgutamine (8b), yield 0.13 g (49%), amorphous substance, [ꢁ] –9° (c 0.67, EtOH) and the
546
benzyl ester of O-(cyclopentadecyl-2-acetamido-2,3-dideoxy-ꢀ-D-glucopyranosid-3-yl)-D-lactyl-L-alanyl-D-isolgutamine (8c),
yield 0.15 g (54%), amorphous substance, [ꢁ] –2° (c 1.0, EtOH). Table 2 lists the PMR spectra.
546
O-(Cyclooctyl-2-acetamido-2,3-dideoxy-ꢀ-D-glucopyranosid-3-yl)-D-lactyl-L-alanyl-D-isolgutamine (9a).
Benzyl ester 8a (160 mg, 0.21 mmol) was dissolved in a THF–H O mixture (10 mL, 9:1) and hydrogenated over Pd/C (50 mg,
2
10%) at room temperature for 2 h. When the reaction was finished (TLC monitoring using systems 4 and 5), the catalyst was
filtered off and rinsed with the solvent mixture (5 mL). The filtrate was evaporated. The residue was triturated in Et O to
2
afford 9a (140 mg, 99%), amorphous substance, [ꢁ] –3° (c 0.67, EtOH). Table 2 lists the PMR spectrum.
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Analogous preparations were used for O-(cyclodecyl-2-acetamido-2,3-dideoxy-ꢀ-D-glucopyranosid-3-yl)-D-lactyl-
L-alanyl-D-isolgutamine (9b), yield 93 mg (81%), amorphous substance, [ꢁ] –6° (c 0.67, EtOH) and O-(cyclopentadecyl-
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2-acetamido-2,3-dideoxy-ꢀ-D-glucopyranosid-3-yl)-D-lactyl-L-alanyl-D-isolgutamine (9c), yield 100 mg (77%), amorphous
substance, [ꢁ] –6° (c 0.67, EtOH). Table 2 lists the PMR spectrum.
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