Studies related to penicillins. Part 24. A novel thiazolidine ring enlargement of penam dioxides

Abstract

In the presence of hydrochloric acid, (3S,5R,6R)-3-diazoacetyl-2,2-dimethyl-6-phenoxyacetamidopenam 1,1-dioxide (4c) was converted into the corresponding 3-chloroacetyl derivative (4b), which reacted with 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) to give (7R,8R)-2-isopropylidene-8-phenoxyacetamido-5-oxa-6-thia-1-azabicyclo[5.2.0]nonane-3,9-dione 6-oxide (9a). The last-cited compound was also produced when (3S,5R,6R)-3-hydroxyacetyl-2,2-dimethyl-6-phenoxyacetamidopenam 1,1-dioxide (4d) was subjected to the action of DBN followed by thionyl chloride. Whereas a 1 : 1.6 mixture of the oxathiazabicyclononane oxide (9a) and its 8S-diastereoisomer (9b) resulted when the diazoacetylpenam dioxide (4c) was treated with DBN followed by hydrochloric acid, (7R,8S)-2-isopropylidene-8-phenylacetamido-5-oxa-6-thia-1-azabicyclo[5.2.0] nonane-3,9-dione 6-oxide (9c) was the sole product from the corresponding reaction involving (3S,5R,6R)-3-diazoacetyl-2,2-dimethyl-6-phenylacetamidopenam 1,1-dioxide (4e). Corresponding enlargements of the thiazolidine ring of (3S,5R)-3-diazoacetyl-2,2-dimethylpenam 1,1-dioxide (6d) and its 6S-chloro derivative (6e) were induced by DBN followed by hydrochloric acid to give (7R)-2-isopropylidene-5-oxa-6-thia-1-azabicyclo[5.2.0]nonane-3,9-dione 6-oxide (9d) and its 8S-chloro derivative (9e). In all cases, the oxathiazabicyclononane oxides were produced as single diastereoisomers although their configuration at position 6 was not established.