Optically-detectable enzyme substrates and their method of use
a technology of enzyme substrates and substrates, which is applied in the field of enzyme substrates, can solve problems such as threatening the ability to treat bacterial infections
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example 1
7-phenoxyacetamidocephalosporanic acid (1)
[0293] Phenoxyacetic acid (0.50 g, 3.3 mmol) was dissolved in 5 mL of methylene chloride and the solution was cooled in an ice / water bath. (COCl)2 was added to the solution followed by 3 drops of DMF. The reaction mixture was stirred for 20 min in the bath before the solvent was removed in vacua. The residue was dissolved in toluene, which was removed in vacuo. The residue was then dissolved in 5 mL of dioxane and added dropwise to a stirred and ice / water bath-cooled mixture of 7-aminocephalosporanic acid (0.60 g, 2.2 mmol), 1 M Et3NH2CO3 buffer (13.5 mL, 13.5 mmol) and dioxane (5 mL). After the reaction mixture was stirred overnight at rt, the solvent was removed in vacuo. The residue was dissolved in water, which was removed in vacuo. The residue was dissolved in chloroform and loaded onto a silica gel column. The resulting solution was eluted using chloroform:methanol:acetic acid (6:2:0.1). The product-containing fractions were concentra...
example 2
Preparation of b: Compounds 2-3
a) Allyl 7β-(phenoxy)acetamido)-3-(acetoxymethyl)-3-cephem-4-carboxylate (2)
[0294]
[0295] 7-Phenoxyacetamidocephalosporanic acid 1 (0.676 g, 1.66 mmol) was dissolved in 20 mL of CH3CN. i-Pr2NEt (0.38 mL, 2.2 mmol) and allyl bromide (0.16 mL, 1.8 mmol) were added to the reaction mixture, which was then stirred for 72 h at rt. The solvent was removed in vacuo, dissolved in 30 mL of 5% HCl, and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with water (30 mL), brine (30 mL), and dried over sodium sulfate. After filtering, the solvent was removed in vacuo. The residue was dissolved in chloroform and loaded onto a silica gel column, which was eluted using chloroform:ethyl acetate (5:1). The eluate containing the desired product was then evaporated to yield 2 (0.334 g, 45%).
b) Allyl 7β-((2-thien-2-yl)acetamido)-3-(acetoxymethyl)-3-cephem-4-carboxylate (3)
[0296]
[0297] Compound 3 was prepared from cephalothin sodium salt (Sigma) a...
example 3
Preparation of c: Compounds 4-5
a) Allyl 7β-(phenoxy)acetamido)-3-(iodomethyl)-3-cephem-4-carboxylate (4)
[0298]
[0299] Compound 2 (0.288 g, 0.646 mmol) was dissolved in 5 mL of dry methylene chloride and the solution was cooled in an ice / water bath. Me3Sil (0.20 mL, 1.4 mmol) was added to the cooled solution. The reaction mixture was stirred for 20 min in the cooled bath, then stirred for 40 min at rt and diluted with ethyl acetate (80 mL). The solution was washed with 10% sodium thiosulfate (2×30 mL), sat. sodium bicarbonate (2×30 mL), brine (30 mL), and dried over sodium sulfate. After filtering, the solvent was removed in vacuo to yield 4 (0.248 g, 75%).
b) Allyl 7β-((2-thien-2-yl)acetamido)-3-(iodomethyl)-3-cephem-4-carboxylate (5)
[0300]
[0301] Compound 5 was prepared from 3 according to the literature procedure of Jungheim et al., J. Org. Chem., 57: 2334-2340 (1992).
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