Ciba-geigy Corporation

Hansuli Wehrli

Riccardo Scartazzini

Georg Anner

Beat Muller

Karoly Kocsis

Karl Schaffner

Adrian Marxer

Charles Meystre

Oskar Jeger

Compounds of the formula ##STR1## in which the index n represents an integer of from 1 to 4,

Cephem compounds having a terminal aminocarboxylic acid grouping and

When 3-(2-hydroxyiminoacetylamino)-2-oxo-azetidine compounds are treated with reactive derivatives of carbonic acid half-esters in aqueous media in the presence of bases a fragmentation takes place which, in addition to 3-amino-2-oxo-azetidines, also yields nitriles which, compared with the 2-hydroxyiminoacetyl group, have one less carbon atom. The resulting products are intermediates for the preparation of nocardicin-like antibiotics. The deacylation procedure of this specification offers advantages over the multi-stage deacylation procedure known hitherto, inasmuch as higher yields of 3-amino-2-oxoazetidine compounds are obtained and the acyl group can be obtained in the form of a nitrile which is shorter by one carbon atom.

Fragmentation procedure for preparing 3-amino-azetidinones

An advantageous method for the manufacture of steroidal lactones of the spironolactone and canrenone type involves the following reaction sequence: bromination of a 3.beta. ,17-dihydroxy-17.alpha. -pregn-5-en-21-carboxaldehyde in basic or neutral medium, oxidation of the 5,6-dibromo compound with hexavalent chromium compounds under basic or neutral conditions, dehydrobromination with inorganic basic agents, such as lithium halides in the presence of lithium carbonate, or with organic bases, such as pyridine, oxidation of the steroid-4,6-diene compound so obtained having in the 17-position the same substituents as the starting material mentioned, with compounds of hexavalent chromium in acid solution, optionally after pretreatment with an acid or, in particular, with a thiocarboxylic acid (to introduce the 7.alpha.-acylthio group, e.g. if spironolactone is to be manufactured). The new process gives better yields than those hitherto described.

Process for the manufacture of steroid carboxylic acid lactones

Compounds of the general formula ##STR1## wherein R.sub.1 represents a hydrogen atom or a lower alkyl group, which contain a double bond in 5-position and a methyl group in 10-position, or three double bonds in the position 1,3 and 5)10), and which can contain an additional double bond in the 9(11)-position, are manufactured by a novel process, in which a 17-oxosteroid of the general formula ##STR2## wherein R.sub.1 ' represents a hydrogen atom, a lower alkyl group or an acyl group, and which contains double bonds and optionally a methyl group in the positions indicated above, is reacted with an organometallic compound of the formula

Process for the manufacture of spiro compounds of the steroid series

The invention is for a selective reduction of the 20- oxo group in .DELTA..sup.16 -steroid-14.beta.,18-diol-20-ones of the pregnane series to form the two epimeric 20-alcohols having the 20 S and 20 R configuration. The process is especially intended for the manufacture of alkaloids of the batrachotoxin type, particularly for batrachotoxinine A, which is a pregnane derivative having a 20 S alcohol grouping, and epimers and derivatives, such as epi-batrachotixinine A or 7,8-dihydrobatrachotoxinine A. The process is characterized by reducing the said .DELTA..sup.16 -steroid-14.beta.,18-diol-20-ones in form of their 14,18-ketals, for instance the 14,18 acetonides and using appropriate complex light metal hydrides and operating at appropriate temperatures. The separation of the two isomers is easy and can be effected by the usual physical operations, such as crystallization or chromatography. In the 14.beta.,18,20-triols obtained the 18-hydroxy group can be dehydrogenated to the corresponding 18-aldehydes, which are intermediates necessary in the synthesis of the said pharmacological interesting substances, such as batrachotoxin, by treatment with a sulphoxide in the presence of a carboxylic acid anhydride.

Growing community of inventors

Reinach, Switzerland

Hansuli Wehrli