76131-72-1Relevant articles and documents
Total Synthesis of Analogues of the β-Lactam Antibiotics. Part 3. 2-Ethoxycarbonyl Derivatives of Carbapen-1-em-3-exo-carboxylates and Carbapenam-3-exo-carboxylates
Sharma, Rajiv,Stoodley, Richard J.,Whiting, Andrew
, p. 2361 - 2370 (2007/10/02)
t-Butyl 2-ethoxycarbonylcarbapen-1-em-3-exo-carboxylate (7a) has been synthesised by a strategy involving final closure of the 1,2-bond using an intramolecular Wittig condensation.Hydroxyalkylation of the azetidinone nitrogen of 4-vinylazetidin-2-one with t-butyl α,α-dihydroxyacetate followed by treatment of the product (12a) with thionyl chloride-2,6-dimethylpyridine gave t-butyl α-chloro-α-(2-oxo-4-vinylazetidin-1-yl)acetate (12b) which underwent chlorine displacement with ethyl (triphenylphosphoranylidene)acetate (10b).The resultant phosphorane (9a) was converted into the carbapen-1-em (7a) by sequential treatment with trifluoroacetic acid, ozone, dimethyl sulphide, and potassium hydrogen carbonate.A similar reaction sequence was used to prepare p-nitrobenzyl 2-ethoxycarbonylcarbapen-1-em-3-exo-carboxylate (7b).An attempt to deprotect the t-butyl ester moiety of compound (7a) with trifluoroacetic acid resulted in β-lactam cleavage to give α-acetic acid (21a).Hydrogenolysis of the carbapen-1-em (7b) in the presence of sodium hydrogen carbonate gave initially the sodium salt (7c) and then sodium 2-ethoxycarbonylcarbapenam-3-exo-carboxylate as a 1:2 mixture of 2-endo- (24a) and 2-exo-isomers (25a).Whereas hydrogen added predominantly to the endo-face of the alkene moiety of the carbapen-1-em (7a) to give mainly compound (25c), diazomethane attacked largely from the exo-face to give mainly the cycloadduct (32).Under thermal conditions, the last-cited compound was transformed into t-butyl 2-ethoxycarbonyl-1-methylcarbapen-1-em-3-exo-carboxylate (33).Under conditions in which the carbapen-1-em (7a) underwent complete deuterium exchange at position 3, the relative (33) underwent ca. 25percent deuterium exchange at position 3.
