ABSTRACT
Small-molecule agonists and antagonists of bacterial quorum sensing can enhance our understanding of this form of cell-cell communication. A recent effort has discovered effective modulators of the autoinducer-1 circuit for bacterial quorum sensing by the synthesis and evaluation of a small library of aryl-substituted acyl-homoserine lactone analogues. This series highlights the sensitivity to structure of the contrasting responses of agonism and antagonism of the natural signal and identifies an analogue that provokes the same response as the natural signal but at 10-fold lower concentration, a "superagonist".
Subject(s)
4-Butyrolactone/analogs & derivatives , Anti-Bacterial Agents , Gram-Negative Bacteria , 4-Butyrolactone/agonists , 4-Butyrolactone/antagonists & inhibitors , Aliivibrio fischeri/drug effects , Aliivibrio fischeri/genetics , Aliivibrio fischeri/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Gene Expression Regulation, Bacterial/drug effects , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/genetics , Gram-Negative Bacteria/metabolism , LigandsABSTRACT
[Structure: see text] Use of a palladium-mediated alkoxycarbonylation/lactonization process provides a variable route to analogs of the plakortones. Four different analogs, including natural plakortone B, have been synthesized via this route.
Subject(s)
Lactones/chemical synthesis , Animals , Catalysis , Lactones/metabolism , Molecular Structure , Palladium , Porifera/metabolismABSTRACT
Arene ligand exchange in the (eta(6)-arene)Cr(CO)(2)L series can be accelerated if the ligand L is an electronically unsymmetrical bidentate ligand. The system evaluated here employs derivatives of tris(pyrrolyl)phosphine as L. A series of 2-L'-substituted pyrroles was prepared, where the substituents include: L' = -SMe, -CH(2)SMe, -SPh, -CH(2)SPh, -SCF(3), -S-tBu, -CO(2)Me, -CONMe(2), -2-pyridinyl, and -PPh(2). Reaction with ClP(pyrrolyl)(2) gave a new series of phosphines, (2-L'-pyrrolyl)(pyrrolyl)(2)P. Each of these phosphines was converted to (arene)Cr(CO)(2)[P(2-L'-pyrrolyl)(pyrrolyl)(2)P) complexes. The substituents L'are proposed to provide temporary coordination to the Cr and to lower the barrier to arene exchange. The series was evaluated where the arene in the complex (departing) is benzene, fluorobenzene, toluene, o-xylene, m-xylene, or p-xylene and the incoming arene is C(6)D(6), chlorobenzene-d(5), anisole-d(8), fluorobenzene-d(5), toluene-d(8), o-xylene-d(10), m-xylene-d(10), p-xylene-d(10), or mesitylene-d(12). Most of the new complexes showed a significant increase in the rate of arene exchange due to the side chain unit L'. The strongest effects were seen with the examples where X = -CO(2)Me, -CONMe(2), and -(2-pyridinyl), allowing exchange with a half lifetime as low as 8 h/22 degrees C.
ABSTRACT
In the bicyclo[7.3.1]tridec-4-ene-2,6-diyne framework characteristic of calicheamicin, DFT calculations predict that the chair conformer should be much more reactive toward cycloaromatization compared to the boat form. A functionalized derivative of this framework with an added two-atom bridge to enforce the boat conformation was synthesized and shown to be stable at 23 degrees C. Cleavage of the bridge releases the conformational lock and cycloaromatization proceeds with t1/2 42.5 min/23 degrees C, presumably through the chair conformation. This confirms the prediction based on computation and points to a new principle for triggering the enediyne toxins.
Subject(s)
Alkynes/chemistry , Bridged-Ring Compounds/chemistry , Cyclohexanes/chemistry , Molecular Conformation , ThermodynamicsABSTRACT
[reaction: see text] The amino sugar side chain (2) from C-1027Chr was synthesized in 12 steps from mannose. The key reactions are an internal displacement by nitrogen to introduce the cis amino group at C-4 and the methylation of an enolate at C-5.
