Gist-brocades N.v.

Gist-brocades B.v.

Dsm N.v.

Van Veen, Gerardus J.

Verweij, Jan

Kalter, Jan

Henniger, Peter W.

Hirs, Henri G.j.

Grootveld, Herman H.

Jan Verweij

Johannes Wilhelmus Lambers

Hendrik A Witkamp

Hong Sheng Tan

Hein Simon Koger

Herman H Grootveld

Jan J DeKoning

Jan Metske Van Der Laan

Andreas Hoekema

Erik De Vroom

Roelof Ary Bovenberg

Bertus Pieter Koekman

Pieter Gijsbert Weber

Everardus J Leenderts

Jan J De Koning

Hermanus Jacobus Kooreman

Henri G Hirs

Robertus Mattheus De Pater

Peter W Henniger

Jan Kalter

Gerardus J Van Veen

Henri Gj Hirs

Hendrik Adrianus Witkamp

Jan Jacobus De Koning

Novel phytosphingosine-based analogs of ceramide I, methods for the preparation of these novel compounds, cosmetic and pharmaceutical compositions containing such compounds, and methods for the use thereof are described.

Phytosphingosine-based ceramide I analogs

Linoleoylamide based ceramide derivative and its use in cosmetic

Process for the efficient production of 7-ADCA via 3-(carboxyethylthio)

Retinoylamide based derivatives of sphingoid bases

Process for the efficient production of 7-ADCA via

Ceramide 3 derivatives based on monounsaturated fatty acids

A cephalosporin compound substituted in the 7-position with a (cyclo)alkylideneammonio group of formula (II) ##STR1## wherein X' is an anion from an acid HX, R.sub.1 and R.sub.2 are individually a C.sub.1 -C.sub.16 alkyl group, or R.sub.1 and R.sub.2 together with the carbon atom to which they are attached form a cycloalkylidene ring with up to 8 carbon atoms and a process for the preparation which compounds are useful intermediates.

Cephem derivatives

A process is provided for the preparation of 3-methylene and 3-halomethylene cepham derivatives via 3-phosphoniomethyl-3-cephem derivatives, which in turn can be prepared from 3-halomethyl-3-cephem derivatives. The preparation can be carried out with or without isolating the intermediate phosphonium cephem compounds. The 3-methylene and 3-halomethylene cepham derivatives and in particular the 1-oxo and 1,1-dioxo cepham compounds are also prepared by reducing a 3-halomethyl-3-cepham derivative with activated metal, preferably zinc or magnesium.

Process for the preparation of 3-exomethylene cepham derivatives

A process is provided for the preparation of 3-methylene and 3-halomethylene cepham derivatives via 3-phosphoniomethyl-3-cephem derivatives, which in turn can be prepared from 3-halomethyl-3-cephem derivatives. The preparation can be carried out with or without isolating the intermediate phosphonium cephem compounds. The 3-methylene and 3-halomethylene cephem derivatives and in particular the 1-oxo and 1,1-dioxo cephem compounds are also prepared by reducing a 3-halomethyl-3-cephem derivative with activated metal, preferably zinc or magnesium.

Cepham derivatives

Process for the preparation of 7.beta.-amino-3-substituted methyl-3-cephem-4-carboxylic acid derivatives, new intermediates comprising 7.beta.-(cyclo)alkylideneammonio-3-halomethyl-3-cephem-4-carbox ylic acid derivatives and 7.beta.-amino/ammonio-3-bromomethyl-3-cephem-4-carboxylic acid derivatives and the processes for the preparation of these intermediates.

Process for the preparation of cephem compounds

A process for the preparation of 7.beta.-acylamino-3-substituted-3-cephem-4-carboxylic acid compounds comprising reacting at -70.degree. C. to 0.degree. C. in an inert organic solvent phosphorus pentachloride with a cephalosporin compound in the presence of an olefinic compound having at least one carbon-carbon double bond having not more than three hydrogen atoms attached thereto capable of removing chlorine at least in part by addition to a carbon-carbon double bond.

Cephalosporin deoxygenation process

Novel azetidine derivatives of the formula ##STR1## wherein R.sub.1 is an acylamido group, R.sub.2 is selected from the group consisting of ##STR2## wherein R.sub.4, R.sub.5 and R.sub.6 are individually selected from the group consisting of hydrogen, lower alkyl and lower alkenyl, n is 2 or 3 and -- in the case when formula IIB is a phenyl -- this group may carry 1 to 4 substituents selected from the group consisting of halogen, lower alkyl, lower alkenyl and phenyl, and R.sub.3 is lower alkyl optionally substituted with 1 or 2 phenyls which phenyl groups may be substituted with nitro and a process for their preparation and process for the preparation of cephalosporanic acid derivatives using the azetidines of formula I as intermediates.

Process for preparing cephalosporin derivatives

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

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Leiden, Netherlands

Jan Verweij