No abstract

The preparation and characterisation of the hexapeptides derived from vancomycin and vancomycin CDP-1 by Edman degradation are described.Vancomycin (1) is an antibiotic isolated from Nocardia orientalis (formerly called Streptomyces orientalis), which acts by inhibiting cell-wall biosynthesis in bacteria. It is clinically important in the treatment of methicillin-resistant Staphylococcus aureus infections and Clostridium dijficile-induced pseudomembranous colitis.1 Since bacteria do not appear to

~~Dianions generated from S-t-butyl acetothioacetate (1 ) were alkylated with a variety of electrophiles at the y-carbon centre. Treatment of the alkylated products with 2-hydroxy esters in the presence of silver( I) salts gave transesterif ied acetoacetate derivatives in good yields. These acetoacetates were cyclised efficiently to acyltetronic acid derivatives using tetrabutyl ammonium fluoride in TH F solution at room temperature. B y an appropriate choice of substituents the total syntheses of the fungal metabolite natural products carlosic, carolic, and carlic acids have been achieved.* Structure (46) was also confirmed by X-ray crystallography; we thank Dr. D. J. Williams, Imperial College, for this result.

The preparations of the hexapeptides (3) and (6) derived from the antibiotic vancomycin (1)' are described. The conformation of the N-terminal regions of (3) and (6) are discussed and compared t o previous observations made on vancomycin. The hexapeptides lack any significant binding capability relative to vancomycin, and the reasons for this are discussed.

A n approach to a macrocyclic lactam designed t o bind to a carboxylate anion is described. The diaryl ether 8 was synthesised b y Ullmann coupling of the protected 3hydroxyphenylglycine derivative 7 and (E) -4-bromocinnamic acid methyl ester. Elaboration of an optically pure (R) -tyrosine synthon was achieved by transfer of electrophilic azide t o the N-acyl oxazolidinone 12. The synthesis of a model system is also described.Paper 1/00705J