1375951-01-1Relevant academic research and scientific papers
Synthesis and evaluation of novel analogues of ripostatins
Tang, Wufeng,Liu, Shuang,Degen, David,Ebright, Richard H.,Prusov, Evgeny V.
, p. 12310 - 12319 (2015/03/31)
Ripostatins are polyene macrolactones isolated from the myxobacterium Sorangium cellulosum. They exhibit antibiotic activity by inhibiting bacterial RNA polymerase (RNAP) through a binding site and mechanism that are different from those of current antibacterial drugs. Thus, the ripostatins serve as starting points for the development of new anti-infective agents with a novel mode of action. In this work, several derivatives of ripostatins were produced. 15-Desoxyripostatin A was synthesized by using a one-pot carboalumination/cross-coupling. 5,6-Dihydroripostatin A was constructed by utilizing an intramolecular Suzuki cross-coupling macrolactonization approach. 14,14-Difluororipostatin A and both epimeric 14,14-difluororipostatins B were synthesized by using a Reformatsky type aldol addition of a haloketone, Stille cross-coupling, and ring-closing metathesis. The RNAP-inhibitory and antibacterial activities are presented. Structure-activity relationships indicate that the monocyclic keto-ol form of ripostatin A is the active form of ripostatin A, that the ripostatin C5-C6 unsaturation is important for activity, and that C14 geminal difluorination of ripostatin B results in no loss of activity.
Total synthesis of RNA-polymerase inhibitor ripostatin B and 15-deoxyripostatin A
Tang, Wufeng,Prusov, Evgeny V.
, p. 3401 - 3404 (2012/06/29)
Keep me skipped: A highly convergent total synthesis of ripostatin B, an inhibitor of the bacterial RNA polymerase, is described. The key steps to construct and avoid isomerization of the skipped triene are a double Stille cross-coupling reaction and a ring-closing metathesis. Furthermore, 15-deoxyripostatin A, a stable and conformationally locked analogue of ripostatin A (see scheme, 15-OH group red), was prepared and tested in vivo. Copyright
