Lactam-like Chaperone Inhibitors

Huntgren etal, US Patent 6,495,539 (December 17, 2002) Assignee Washington University 

L-Ethyl cysteinate and Na2C03 were dissolved in a minimum amount of water and acetic anhydride (1.05 eq) and formic acid (1.2 eq) added. The pH of the solution was kept basic by the addition of solid Na2C03 and the mixture stirred 60 minutes. The solids were removed and the mixture extracted 3 times with chloroform. The organic phase was neutralized with 6M HCl, concentrated, the residue suspended in benzene containing a catalytic amount of paratoluenesulfonic acid and refluxed over night with a Dean-Stark trap. Thereafter the organic phase was evaporated, dissolved in chloroform, washed with NaHC03, and the product isolated. 

2-Dimethyl-5-[(2-hydroxyl-2-phenyl)]methylene-l,3-dioxane-4,6-dione 

A solution of benzoyl chloride (60 mmol) dissolved in 50 ml CCI3H was added dropwise over 1 hour to a cold solution of 2,2-dimethyl-l,3-dioxane-4,6-dione (Meldrum s acid) (50 mmol) dissolved in 150 ml CCI3H containing 4-dimethylamino-pyridine (100 mmol). The cold mixture reacted one hour while stirring and then stood at ambient temperature for one hour. The mixture was washed three times with 30 ml 10% HCl, the organic 

6R)-6-Benzoyl-7-oxo-4-thia-3,3-dimethyl-azabicyclo-[3.2.0]heptane-2-carboxylic acid, etbyl ester 

---