Bicyclomycin

X-ray crystallographic images of the bicyclomycin-rho complex have been used to define the rho antibiotic-binding site and understand the molecular basis for its mode of action.

[4] Bicyclomycin is a crystalline, colorless, water-soluble, and weakly basic substance (mp 187-189 °C) that is soluble in methanol, and sparingly in ethanol, is practically insoluble in most organic solvents, and is unstable in alkaline solution.

Bicyclomycin, initially produced on large scale from the fermentation harvest of an improved strain of S. sapporonensis,[5] has also been synthesised; many derivatives have also been prepared.

Dehydration to the key olefin proceeded in good overall yield followed by bridgehead carbanion oxidation with molecular oxygen gave the single hydroxylation product 4.

Protection of the C-1'-hydroxyl as the corresponding trifluoroacetate followed by cleavage of the acetonide and p-methoxybenzyl groups with ceric ammonium nitrate followed by methanolysis on silica gel gave racemic bicyclomycin 6.

The (1 S , 6 R , 1’ S , 2’ S )-stereochemistry and pharmacophore (in orange and black) required for good activity
Synthetic route to Bicyclomycin
Synthetic route to Bicyclomycin