Synthesis and biological activity of chiral tetrahydrofuranyl amino acids as building moieties of pamamycin analogues.
A new synthetic route to chiral tetrahydrofuranyl amino acids is described starting with D-glucose. The 17-step and a 20-step procedures, respectively, furnished compounds of the general formulas 1 and 2 mimicking the dimethylamino carboxylic acid part of pamamycin (3). In comparison with the absolute stereochemistry of 3 the acyclic compounds 1a-c and 2a-c are enantiomers. Despite of the presence of a dimethylamino function they showed neither antibacterial activity nor protonophoric effects on an artificial bilayer membrane suggesting that the macrodiolide ring of 3 forms an indispensable prerequisite for the known interaction of this antibiotic with biological systems.
Krüger-Velthusen
E
E
Hans-Knöll-Institute for Natural Products Research, Jena, Germany.
Jütten
P
P
Grigoriev
P A
PA
Gräfe
U
U
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008567:Membranes, Artificial; D008826:Microbial Sensitivity Tests; D009930:Organic Chemicals; D011522:Protons; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D005663:Furans; D018942:Macrolides; D008567:Membranes, Artificial; D009930:Organic Chemicals; D011522:Protons; C024500:pamamycin