Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-10-23
1999-01-05
Shah, Mukund J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
540221, C07D50104, C07D49904
Patent
active
058564748
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP95/01538 filed Apr. 24, 1995.
This invention relates to new intermediates in the preparation of cephalosporins. Particularly it relates to a compound of formula ##STR2## wherein either .alpha.) R.sup.a denotes hydrogen or a silyl group; R.sup.b denotes a group of formula --OR.sup.c, wherein R.sup.c denotes hydrogen or alkyl; and R.sup.c and R.sup.d together denote a bond; or and R.sup.c together denote an imino group of formula .dbd.N--Y, wherein Y denotes alkyl, aryl or heterocyclyl; or hydrogen, if R.sup.d denotes hydrogen; or, R.sup.a denotes hydrogen or a silyl group, if R.sup.d denotes a silyl group; and R.sup.b and R.sup.c together denote the oxo group;
In one particular aspect the invention relates to a compound of formula ##STR3## wherein X.sup.- denotes the anion of an inorganic or organic acid and R.sub.1 denotes hydrogen or an alkyl group.
In another particular aspect the invention relates to a compound of formula ##STR4## wherein R denotes hydrogen or a silyl group.
In another particular aspect the invention relates to a compound of formula ##STR5## wherein Y and R are as defined above in free form or salt form.
Alkyl, aryl or heterocyclyl in the meaning of Y include unsubstituted alkyl, aryl or heterocyclyl; or, by amino, dialkylamino, hydroxy, alkoxy, alkyl, aryl, nitro, halogen, carbalkoxy or carbamido substituted alkyl, aryl or heterocyclyl, Y, denotes preferably tert.-butyl, phenyl, naphthyl or pyrimidinyl.
If not otherwise stated herein alkyl includes an alkyl group having 1 to 22, for example 1 to 12, such as 1 to 8 carbon atoms, preferably lower alkyl, such as (C.sub.1-4)alkyl. An alkyl group may be unsubstituted or substituted by groups which are inert under relevant reaction conditions. A silyl group is preferably a silyl protecting group and includes a conventional silyl protecting group, such as a triallylsilyl group, for example the trimethylsilyl group. An aryl group includes aryl having 6 to 18 carbon atoms, preferably phenyl, napthyl. An aryl group may be unsubstituted or substituted by groups which are inert under relevant reaction conditions. Hetreocyclyl include heterocyclic groups mentioned below in the meaning of R.sub.5 and R.sub.6. A heterocyclic group may be unsubstituted or substituted by groups which are inert under relevant reaction conditions.
A compound of formula Ia wherein R.sup.a and R.sup.d denote hydrogen is a tautomeric aldehyde form of a compound of formula I in free base form wherein R.sub.1 denotes hydrogen; A compound of formula II may be used as an intermediate in the production of a compound of formula I.
A compound of formula IA, particularly a compound of formula I, Ia or II, is an useful intermediate in the production of highly active antibiotics. It may be used to prepare a wide variety of cephalosporins which are substituted at the nitrogen atom in position 7 and in position 3 of the cephalosprin structure with a wide variety of groups which are useful groups in respect to the activity of the corresponding cephalosporin. A compound of formula I is as such, or, in equilibrium with its tautomeric aldehyde form of formula Ia wherein R denotes a silyl group, suitable as starting material, for example for Wittig reactions, for decarbonylation reactions, for the production of most varied aldehyde derivatives. At the same time one is free to form desired derivatives in position 7, for example by acylation.
Examples of highly active antibiotics which may be obtained from the compounds of the invention in conventional manner are ceftibuten as an example for a decarbonylation product; cefixim, cefdinir, E-1077 or, the compounds of EP 620 225, for example the compounds A to P of EP 620 225, as examples for Wittig products; or compounds having the structure of formula A, disclosed in EP 392 796, as a thioacetal (the thioacetal structure of formula A may be prepared for example according to J. Antibiotics 44(4), 415-21(1991): ##STR6## Processes for the production of a 3-formyl-cephalosporin or of a compound of formula I, which
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Ascher Gerd
Ludescher Johannes
Sturm Hubert
Wieser Josef
Biochemie Gesellschaft m.b.H.
Dohmann George R.
Shah Mukund J.
Sripada Pavanaram K.
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