Stoffwechselprodukte von Mikroorganismen, 189. Strukturaufklärung und Partialsynthese des Nucleosidantibiotikums Nikkomycin B

Abstract

Das Kulturfiltrat von Streptomyces tendae, aus dern die Nucleosidantibiotika Nikkomycin Z2) (la) und Nikkomycin X3) ( l b ) isoliert werden konnten, lieferte noch Nikkomycin B (7), das anstelle des 3-Hydroxypyridin-Systems von 1 einen p-Hydroxyphenyl-Rest im Aminosaurebaustein 6 enthalt. Dieser ist peptidartig mit einer 5-Aminohexuronsaure verkniipft, an die 4-Formyl-4-imidazolin-2-011 N-glykosidisch gebunden ist. Die Ableitung der Konstitution des neuen Aminosaurebausteins gelang durch Massenspektrometrie und Synthese eines Diastereomerengemisches der 2-An1ino-4-hydroxy-4-@-hydroxyphenyl)-3-methylbuttersaure (6). In der biologischen Aktivitat ist Nikkomycin B von den genannten Vertretern dieser Gruppe nicht zu unterscheiden. Metabolites of Microorganisms, 1891) -Structure Elucidation and Partial Synthesis of the Nucleoside Antibiotic Nikkomycin BIn the culture filtrate of Streptomyces tendae, from which the nucleoside antibiotics nikkomycin Z2) (la) and nikkomycin X3) (lb) were isolated, a third component, nikkomycin B (7), was found. This new antibiotic contains ap-hydroxyphenyl residue instead of a 3-hydroxypyridyl residue in the amino acid moiety (6). The amino acid is linked to a 5-amino hexuronic acid to which 4-formyl-4-imidazolin-2-0ne is bound as an N-glycoside. The structure of the new amino acid constituent could be derived by mass spectrometry and was confirmed by synthesis of a mixture of diastereomers of 2-amino-4-hydroxy-4-(p-hydroxyphenyl)-3-methylbutyric acid.Die Nikkomycine sind Nucleosidantibiotika mit fungiziden Eigenschaften, die in ihrer Struktur an die Gruppe der Polyoxine erinnern4). Ihre biologische Wirkung beruht auf einer Hemmung der Chitinbiosynthese. Der Erzeugerstamm Sfrepfornyces fendae produziert hauptsachlich die bereits beschriebenen Komponenten Nikkomycin Z2) (la) und Nikkomycin X3) (lb).

The Dihydroxyacetone Unit—A Versatile C3Building Block in Organic Synthesis

“…[54] Double allylic alcohols are found as subunits of many natural products, for example, in metabolites with ionophoric activity isolated from marine sponges and microorganisms. [55] Starting from the dioxanone hydrazone (S)-37, a variety of a-substituted protected ketodiols 74 could be synthesized by the procedure described (90-94 % ee; Scheme 22). A racemization-free Wittig methylenation of these ketones gave the exocyclic olefins 75.…”

Production of Nikkomycins Bx and Bz by Mutasynthesis with Genetically Engineered Streptomyces tendae TUE901.

“…The signals of the AA'BB' coupling system appeared at d 6.72 and S 7.06. The HMBCspectrum revealed that the chemical shifts of the carbon atoms 5-C and 8-C are chemical shift values typical for /?ara-substituted moieties of similar structures 9) Numbering of atoms see Figure 3.…”

Use of Tn4560 to generate nikkomycin non-producing mutants of Streptomyces tendae

“…2 were obtained when Amberlite fractions containing peaks on HPLC were pooled and again analysed by HPLC. It is known that wild-type produces several chemically related nikkomycins that have biological activity, with nikkomycin Z and X being the most abundant in culture broths [4,[13][14][15]. The nikkomycin Z and X peaks in wild-type (Fig.…”