Antibiotika aus Gleitenden Bakterien, L – Chemische Modifikation von Sorangicin A und Struktur‐Wirkungs‐Beziehung II: Derivate aus Reduktions‐, Oxidations‐ und Umlagerungsreaktionen

Antibiotics from Gliding Bacteria, L. – Chemical Modification of Sorangicin A and Structure‐Activity Relationship II: Derivatives Obtained by Reduction, Oxidation and Rearrangement Reactions The synthesis of 38 derivatives of sorangicin A ( 1 ) with modifications of the three hydroxyl groups and the conjugated triene is described. By oxidation and reduction reactions 21‐desoxy‐21‐oxo sorangicin ( 8 ), 21‐ epi ‐sorangicin ( 9 ) and 21‐desoxysorangicins 14 , 15 were obtained. With protection of the 21,22‐diol the 24,25‐didehydro‐25‐desoxysorangicin ( 18 ), 25‐desoxy‐25‐oxosorangicins 21 , 22 and 25‐ epi ‐sorangicins 23 , 24 were prepared. Further, the 25‐oxo derivatives 21 , 22 were transformed into the oximes 25 – 28 and the 25‐desoxy‐25,25‐difluoro sorangicin ( 31 ). Catalytic reduction of sorangicin A ( 1 ) gave the 37,43‐dihydro derivative 35 , thermolysis the cyclohexadienes 36, 37 and fluoride‐induced isomerisation the 36,38,40‐trienol ethers 38 , 39 . – Activities against Staphylococcus aureus, Escherichia coli , and in vitro inhibition of RNA polymerase of selected derivatives were examined. With most compounds a reduced biological activity was observed, some derivatives retained their activity ( 23 – 28 , 31 ) and three were improved for certain strains ( 18 , 21 , 22 ) although they showed reduced enzyme inhibition activity.