Myxochelins B, C, D, E and F: A New Structural Principle for Powerful Siderophores Imitating Nature

Abstract

The synthesis of the natural siderophore myxochelin B (1S) and its enantiomer 1R is described. 1S and 1R served as precursors for the synthesis of new hexadentate siderophores, the myxochelins C (7S) and CR (7R), D (14S) and DR (14R), E (19S) and (RS)‐F (26R, S), with 2,3‐dihydroxybenzoate (DHB) ligands and the simple backbones of asymmetric 1,2,n‐triamino‐n‐alkanes. For the myxochelins C, D, E and F n is 6 (from lysine), 5 (from ornithin), 4 (from asparagine amide) and 7 [from (±)‐2‐aminopimelic acid], respectively. The additional amino functions in the starting compounds were provided by dehydration of the corresponding primary amides, and subsequent reduction of the nitriles by cobalt boride in methanol. All new siderophores supply bacteria with ferric ions with an efficiency which depends on their chain length and stereochemistry. They show significant activity against the cytomegalo virus.

Myxochelin- and Pseudochelin-Derived Lipoxygenase Inhibitors from a Genetically Engineered Myxococcus xanthus Strain

“…Myxochelin B ( 2 ) : [α] 20 D −8.63 (c 0.87, MeOH); UV/vis (MeOH) λ max (log ε): 249 (sh) (3.97), 314 (3.56) nm; NMR data as previously reported …”

“…[α] 20 D −8.63 (c 0.87, MeOH); UV/vis (MeOH) λ max (log ε): 249 (sh) (3.97), 314 (3.56) nm; NMR data as previously reported. 18 Pseudochelin A (3): [α] 20 D −24.12 (c 0.28, MeOH); UV/vis (MeOH) λ max (log ε): 253 (3.96), 319 (3.42) nm; NMR data as previously reported. 12 Myxochelin B 1 (2a): [α] 20 D −9.26 (c 0.45, MeOH); UV/vis (MeOH) λ max (log ε): 248 (sh) (3.84), 316 (3.23) nm; 1 H and 13 C NMR data, see Tables 3 and 4…”

Myxobacteria as a Source of New Bioactive Compounds: A Perspective Study

“…It is believed that a similar pathway of inhibiting 5-LO is associated with the strong anticancer activity of myxochelin [ 153 , 155 ]. Of the different Myxochelins, which are either isolated from Angiococcus disciformis (strain And30) or synthesized [ 155 , 156 ], Myxochelin C is capable of inhibiting HCMV (IC 50 value of 0.7 g/mL) [ 150 , 157 ]. It opens avenues for testing other known siderophores, such as nannochelins, hylachelins and myxochelin analogues, in the future for their possible role in inhibiting HCMV [ 158 ].…”

Bioengineering of Anti‐Inflammatory Natural Products

“…[79] Moreover, 5-LOX is crucially involved in various inflammatory processes, making this enzyme an important drug target. [79] Due to their comparatively low structural complexity, the myxochelins can be efficiently prepared by total synthesis, [80][81][82] which already enabled an extensive testing of analogues with regard to their 5-LOX inhibitory properties. [83] Noteworthy, several derivatives were also produced by biosynthetic engineering, as this approach omitted the repeated use of identical linear transformations.…”