Cephalosporanes

DO A n fl II NO, lls salt with 7- phcnylacetylamino)-cephalosporanic acid Is an antiinfeefive agent 906... 

Cephalosporanic acid, 3 -deacetoxy-, 7, 289 Cephalosporin, 3 -deacetoxy-absorption, 7, 293 synthesis, 7, 293 Cephalosporin, 3,4-dihydro-synthesis, 7, 292 Cephalosporin, 7a-hydroxy-synthesis, 7, 290 Cephalosporin C, 7, 288 as pharmaceutical, 1, 152 total synthesis, 7, 294 Woodward s total synthesis, 7, 294 Cephalosporin C, deacetoxy-synthesis, 7, 292 Cephalosporins, 7, 267, 285-298 7-acylamino substituent configuration, 7, 290 analogues synthesis, 7, 288 as antibiotics, 2, 519 3, 1038 application, 7, 296... 

Chemical Name 7-[2-Methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetamido]-cephalosporanic acid... 

To this solution was added at one time the above-obtained ethyl acetate solution at -15°C, and the resulting mixture was stirred for 1 hour at -10°C to -15°C. The reaction mixture was cooied to -30°C, and water (80 ml) was added thereto. The aqueous layer was separated, adjusted to pH 4.5 with sodium bicarbonate and subjected to column chromatography on Diaion HP-20 resin (Mitsubishi Chemical Industries Ltd.) using 25% aqueous solution of isopropyl alcohol as an eluent. The eluate was lyophilized to give 7-[2-methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetamido] cephalosporanic acid (syn isomer) (1.8 g), MP 227°C (decomp.). 

Amino-cephalosporanic acid Cyanoacetyl chloride Sodium hydroxide... 

After having been dried over sodium suifate and evaporated under vacuum, this extract gives as a solid residue 14.7 g of crude 7-cyanoacetylamino-cephalosporanic acid which is purified by chromatography on 30 times its own weight of silica gel. The fractions eluted with chloroform plus acetone (7 3) furnish a product which crystallizes from acetone plus ether in the form of needles melting at 168° to 170°C with decomposition. 

D-Phenylglycine 7-Amino-cephalosporanic acid Isobutyl chloroformate... 

The reaction product mixture is a homogenous solution having a pH of about 6. It is evaporated under vacuum to a semisolid residue. To the residue are added 35 ml of water and a few drops of triethylamine to raise the pH to 8. The aqueous solution obtained thereby is extracted successively with 50 ml and 35 ml portions of ethyl acetate, the pH being adjusted to 2 at each extraction with hydrochloric acid. The extracts are combined, filtered, dried over sodium sulfate, stripped of solvent, and evaporated under vacuum. The product is 7-(N-carbobenzoxy-D-o -aminophenylacetamido)cephalosporanic acid in the form of a yellow-white amorphous solid weighing 1.10 g. 

Of this material 1.0 g is dissolved in 150 ml of warm 95% ethyl alcohol. To the solution is added 1.0 g of 5% palladium on carbon catalyst, and the mixture is hydrogenated at room temperature and atmospheric pressure by bubbling hydrogen into it for 3 hours with stirring. The hydrogenation product is filtered. The solid phase, comprising the catalyst and the desired product, is suspended in ethyl acetate and water and adjusted to pH 2 with hydrochloric acid. The suspension is filtered to remove the catalyst. The aqueous phase is separated from the filtrate, and is evaporated under vacuum to recover the desired product, 7-(D-a-aminophenylacetamido)cephalosporanic acid. 

Thienylacetamido)cephalosporanic acid sodium salt may be produced from 2-ihienyl-acetyl chloride, obtainable by treatment of 2-ihienylacetlc acid [Ernst, fler/c/ife, 19 (1886)... 

Common Name Sodium 7-(pyrid-4-ylthioacetamido)cephalosporanate... 

The mixture was filtered, the ethyl acetate layer separated and washed with three 100 ml portions of water, dried over Na2S04, filtered and treated with 30 ml of sodium 2-ethyl-hexanoate in n-butanol (34 ml = 0.1 mol). The oil which settled out was scratched to induce crystallization. After stirring for 20 minutes the product, sodium 7-(a-bromoacet-amido)cephalosporanate, was scraped from the sides of the flask and collected. The filter cake was washed with several portions of acetone, air dried, and dried in vacuo over P Os. The yield was 22.5 g and decomposed at 193°C. 

Stirring was continued an additional 90 minutes and then 50 ml of ethyl acetate was added. Forty percent H3PO4 was added dropwise with vigorous stirring until pH 2.5 to 3 was obtained. The product crystallized immediately and was filtered off, washed several times with water and then three times with 25 ml portions of ethyl acetate, following which it was air dried. The yield was 2.9 g of crystals that decomposed at 167° to 168°C. The IR and NMR spectra were consistent with the desired product, 7-(o -(2-pyrimidinylthio)acet-amido] -cephalosporanic acid monohydrate. 

However the acid is prepared, the sodium salt may be prepared as described in U.S. Patent 3,503,967 Five liters of methylene chloride were added to a clean dry vessel equipped with stirrer. 7-[a(4-pyridylthio)acetamido] cephalosporanic acid (1,000 g) was added to the vessel, followed by 350 ml of triethylamine. The resultant solution was treated with decolorizing charcoal for 15 minutes and filtered. A solution of sodium-3-ethyl-hexanoate (27.3%) in butanol-methylene chloride was added to the filtrate with stirring. Seven thousand five hundred milliliters of acetone was added. Crystallization occurred while stirring was continued several hours under dry conditions. The crystals were collected by filtration, washed with large volumes of acetone, and then dried in vacuo at 50°C to yield about 950 g of the title compound. 

C2i H2fiN205S 35246-64-/) see ti.v-Cefprozil diphenylmethyl 7-methoxy-7-[2-(2-thienyl)acetamido]-cephalosporanate... 

C9H,C10 53491-30-8) see Phenoxybenzamine 7-(phenylacetamido)cephalosporanic acid sodium salt (C gH]7N2Na09S 26382-85-4) see to-Cefprozil phenylacetic acid... 

The oral activity and clinical acceptance of cephalexin (14) has led to the appearance of a spate of similar molecules. Cefadroxyl (16) is an example. The design of this drug would seem to have derived from the success of amoxycillin. The synthesis of cefadroxyl was accomplished by N-acylation of 7-aminodesacetyl-cephalosporanic acid (7 ADCA) after blocking the carboxy group with (CH30)2CH3SiCl (to 15). The... 

One of the few successful analogues in the p-1act am series with an aliphatic side chain is ceph-ac trile (23). It was made by reacting 7-amino-cephalosporanic acid with cyanoacetyl chloride in the... 

The reaction of cephalosporanic acid (1598) and cyclopenteno(6)pyri-dine in a 3 1 mixture of water and acetone in the presence of potassium iodide and ascorbic acid at 66-68°C for 4 hr gave the pyridiniumceph-3-ene-4-carboxylate derivative (1599) in 14% yield (84GEP3316796). 

Cefoxitin and cefotetan, which are cephamicins and differ from other cephalosporins principally in the presence of a methoxy group at position 7 of the cephalosporanic system, which significantly increases their resistibility with respect to beta-lactamases, belong to the second-generation cephalosporins. 

Cephalexin 7- (D-a-Aminophenylacetamido) cephalosporanic acid Aromatic alkylation, amination, imine formation, amidation (sidechain), fermentation, deamidation (penicillin nucleus), acid-catalyzed ring expansion... 

---