Process for the preparation of 2-penem compounds.

摘要

in which R₁ is hydrogen, lower alkyl, acylamino,
wherein R₄ is hydrogen, lower alkyl, aryl or heteroaryl, R₅ is hydrogen or an hydroxy protecting group, and R₈ is halogen, , -SR₉ (wherein R₉ is lower alkyl, hydrogen or an -S protecting group), or the group
in which one of R₁₀ and R₁₁ is an -N protecting group and the other is chosen from hydrogen, lower alkyl, aryl, aralkyl and acyl, or R₁₀ and R₁₁ are independently chosen from hydrogen, lower alkyl, aralkyl, aryl and acyl with the proviso that when one is hydrogen the other is acyl,
R₂ is lower alkyl, aryl, aralkyl, aminoalkyl, N-protected amino alkyl, hydroxyalkyl, O-protected hydroxyalkyl, thioalkyl, thioaryl, thioheteroaryl, an optionally esterfied a-amino acid residue, an optionally esterfied a-(N protected) amino acid residue or an optionally esterfied alkylcarboxy group;R₃ is nitrile, tetrazolyl, or -COOR₆ wherein R₆ is hydrogen, the radical C(Hal)₃ -Alk in which Hal is halogen and Alk represents an alkylene radical, lower alkyl, aryl, an allylic group, a metabolisable ester group, or a carboxy protecting group;X and Z are independently sulfur, oxygen, the radical =NR₇ in which R₇ is hydrogen, acyl, lower alkyl; aryl, or an N-protecting group, or -(CH₂)_n- in which n is 1 or 2; subject to the following provisos:
(i) Z and X cannot simultaneously be(̵CH₂)̵_n in which n is 1 or 2;(ii) when X is S, Z is O or =NR₇;(iii) when X is O, Z is O, S or =NR₇;(iv) when X is -CH₂-, Z is =NR₇; except that when R₇ is H or lower alkyl and R₂ is lower alkyl then R₁ cannot be acylamino;(v) when X is (̵CH₂)̵₂, Z is =N_R7;and the pharmaceutically acceptable salts. Compounds of formula 1 are antibacterial agents which can be incorporated into pharmaceutical compositions or used as intermediates in the preparation of such agents.