Gist-Brocades N.v.

Hermanus Jacobus Kooreman

Jan Verweij

Hong Sheng Tan

Jan L Van Os

Cornelis Vos

Jacobus Den Admirant

Hendrik Marten Jongsma

A new antibiotic (now called dihydromocimycin) being a yellow, salt-forming weak acid and its non-toxic, pharmaceutically acceptable salts produced by a novel microorganism called Streptomyces ramocissimus, a sample of which is deposited in the collection of 'Centraal Bureau voor Schimmel-cultures' at Baarn, The Netherlands, under No. CBS 190.69, or mutants thereof, which antibiotic has antibacterial properties and has been found to be effective against Treponema dysentry, one of the most common swine diseases. Dihydromocimycin may also be converted into mocimycin which is an antibiotic which also possesses growth-promoting properties when added to animal feeds by a dehydrogenation reaction using selenium dioxide as the dehydrogenating agent. The dehydrogenation reaction may be carried out in the presence of a suitable organic solvent.

Dihydromocimycin antibiotics

Novel 6-substituted amino-penicillanic acid anhydrides useful in the process for the preparation of 7-substituted amino-desacetoxycephalosporanic derivatives comprising converting a 6-substituted amino-penicillanic acid sulfoxide into an anhydride of a 6-substituted amino-penicillanic acid sulfoxide, heating the said acid anhydride intermediate at a temperature up to at most 160.degree. C in a dry inert organic solvent with an anhydrous acid which is capable of causing ring expansion of the penam ring to a .DELTA..sup.3 -cephem ring, in the presence of a silicon-containing compound capable of (a) removing water formed during the ring enlargement of the penam structure fast enough to prevent water hydrolysis of the acid anhydride moiety present and (b) forming neutral or basic products on hydrolysis, the aforesaid acid being strong enough not to be, or not to a substantial extent to be, silylated under the reaction conditions employed, and hydrolyzing the resulting compound in situ to form the .DELTA..sup.3 -7-substituted amino-desacetoxycephalosporanic acid as such or as a salt, such as alkali metal, alkaline earth metal or amine salt.

Preparation of 7-substituted amino-desacetoxycephalosporanic acid

Process for the preparation of 7-substituted amino-desacetoxycephalosporanic derivatives comprising converting a 6-substituted amino-penicillanic acid sulfoxide into an anhydride of a 6-substituted amino-penicillanic acid sulfoxide, heating the said acid anhydride intermediate at a temperature up to at most 160.degree. C in a dry inert organic solvent with an anhydrous acid which is capable of causing ring expansion of the penam ring to a .DELTA..sup.3 -cephem ring, in the presence of a silicon-containing compound capable of (a) removing water formed during the ring enlargement of the penam structure fast enough to prevent water hydrolysis of the acid anhydride moiety present and (b) forming neutral or basic products on hydrolysis, the aforesaid acid being strong enough not to be, or not to a substantial extent to be, silylated under the reaction conditions employed, and hydrolyzing the resulting compound in situ to form the .DELTA..sup.3 -7-substituted amino-desacetoxycephalosporanic acid as such or as a salt, such as alkali metal, alkaline earth metal or amine salt and to the novel sulfoxide acid anhydrides formed therein.

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Delft, Netherlands

Hermanus Jacobus Kooreman