A novel class of conformationally constrained, masked cysteines: Synthesis of 2-alkyl- and 2-arylsulfanyl-1-aminocyclopropanecarboxylic acids

A convenient synthesis of 4-sulfanylmethylene-5(4H)-oxazolones 3 was realized starting from 4-(chloromethylene)oxazolone 1 and mercaptans 2. Oxazolones 3 were used as starting materials for the preparation of unknown 2-sulfanyl-1-aminocyclopropanecarboxylic acid derivatives 5 and 7. Oxazolones 3 were cyclopropanated at the exocyclic double bond with diazomethane, giving a mixture of the two (Z)- and (E)-spirocyclopropane oxazolones 4 with good diastereoselectivity. These were then treated with ethanol and DMAP to produce the corresponding carboxylates 5. The trityl derivative 5d was converted into a mixture of diastereoisomeric disulfides 6 using iodine in ethanol solution. Disulfides 6 are convenient synthons for the preparation of 3-sulfanyl-substituted 2,3-methanoamino acids 7.