Oxazolidinones

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Oxazolidinones are members of a group of saturated heterocyclic compounds that have both a nitrogen and an oxygen atom in a five-membered ring and contain a carbonyl group. This creates either a cyclic ester (a lactone ), a cyclic amide (a lactam ), a ketone, or a carbamate ( urethane ). The parent compounds of the group are 1,3- oxazolidine and 1,2-oxazolidine (isoxazolidine), from which three oxazolidinones are derived.

From left to right: 1,2-oxazolidin-3-one, 1,2-oxazolidin-4-one, 1,2-oxazolidin-5-one; 1,3-oxazolidin-2-one , 1,3-oxazolidin-4-one, 1,3-oxazolidin-5-one

1,3-Oxazolidin-2-ones have long been used as auxiliaries in preparative chemistry . Some oxazolidinones belong to a group of antibiotics . The first commercially available active ingredient was cycloserine ( 4-amino-1,2-oxazolidin-3-one ) as a drug against tuberculosis in 1956. Other oxazolidinones include linezolid and eperezolid .

Auxiliaries

In preparative chemistry, 1,3-oxazolidin-2-ones serve as auxiliaries. The substance to be converted is substituted with an Evans auxiliary before the actual reaction . The voluminous auxiliary directs the reaction in such a way that a reaction product is preferentially formed stereoselectively :

Electrophilic substitution using an Evans auxiliary

After the reaction, the Evans auxiliary (here with lithium hydroxide and hydrogen peroxide ) must be split off again.

Antibiotics

Cycloserine [(4 R ) -4-amino-1,2-oxazolidin-3-one] has been used as a drug against tuberculosis .

The medically active oxazolidinones belong to the antibacterially active drugs and are protein biosynthesis inhibitors (just like the tetracyclines , aminoglycosides , lincosamides and macrolides ). Oxazolidinones inhibit the beginning of the synthesis of a peptide strand at the point where the ribosome , messenger or messenger RNA and start tRNA- AS complex assemble. They mostly have a bacteriostatic effect on Gram-positive bacteria; Cycloserine also inhibits Gram-negative bacteria and Mycobacterium tuberculosis .

Bone marrow suppression has been described as a side effect and the blood count should be checked. In Germany, cycloserine itself is not used as a drug for drug production because of its strong neurotoxic side effects, but in the form of the condensation product with terephthalaldehyde, terizidone , which is also neurotoxic and is therefore only used as a second choice antituberculotic. In Germany, tedizolid and linezolid are used as reserve antibiotics.

Individual evidence

  1. ^ FA Carey, RJ Sundberg, Organic Chemistry, Wiley-VCH Verlag 2004 ISBN 3-527-29217-9 .
  2. a b A. W. Frahm, HHJ Hager, F. v. Bruchhausen, M. Albinus, H. Hager: Hager's Handbook of Pharmaceutical Practice: Volume 4: Substances AK. , Birkhäuser, 1999, ISBN 978-3-540-52688-9 .
  3. ^ Mutschler, drug effects, 9th edition, Wissenschaftliche Verlagsgesellschaft Stuttgart 2008, ISBN 978-3-8047-1952-1 .