AMINO-ACID CONSTITUENTS OF RISTOCETIN-A

The glycopeptide antibiotic ristocetin A, elaborated by Nocardia lurida, is one of a class which interferes with biosynthesis of bacterial cell wall by complexing with peptide precursors terminating in D-Ala-D-Ala. The site of activity within the antibiotic lies in the peptide fragment. The heptapeptide from ristocetin A has been shown to contain ristomycinic acid (12) and actinoidinic acid (17), which are dimeric coupling products between hydroxylated phenylglycines, and dechlorovancomycinic acid (23a), which is a trimeric coupling product between;P-hydroxyphenylglycine and two β-hydroxytyrosines. The structure of ristomycinic acid has been established from spectra of the bis(amino acid) and derivatives and by oxidation of the O-methylated derivative to give substituted oxybis(benzoates) 4 and 5 which were independently synthesized by Ullmann condensations. The structure of actinoidinic acid was established similarly using an independent synthesis of substituted bibenzoate 8. Comparison was also made with a sample of actinoidinic acid obtained from vancomycin. Dechlorovancomycinic acid was destroyed both during acidic and basic hydrolysis of ristocetin; the structure assignment of 23a is based upon indirect evidence. Oxidation of O-methylated aglycoristocetin yielded tribenzoate 7; base hydrolysis in the presence of NaBH4 yielded 9 and glycine. Compound 9 arises by reduction of aldehydes resulting from retro-aldol reactions of the β-hydroxytyrosine residues. © 1979, American Chemical Society. All rights reserved.