Nuclear analogs of β-lactam antibiotics. XV. Synthesis of 6-substituted 2-methylpenem-3-carboxylic acids

Abstract

The synthesis of 6-substituted 2-methylpenem-3-carboxylic acids is described. The dianion 6 was prepared insitu from 2-methylpenem-3-carboxylic acid (5) by the addition of two equivalents of n-butyllithium in THF at −78 °C. This dianion reacted with deuterated acetic acid, acetone, acetaldehyde, benzaldehyde, and methyl thiomethylsulfonate to give 6-deuterio-, 6-(2′-hydroxy-2′-propyl)-, 6-(1′-hydroxyethyl)-, 6-(1′-hydroxybenzyl)-, 6-methylthio-2-methylpenem-3-carboxylic acids and their sodium or potassium salts, 7–11, respectively. The stereochemistry of the products is also discussed.