Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• Figure 1B) was determined as the optimal natural AHL for SdiA (EC50 = 3 nM, as determined using a cell-based reporter for SdiA), and its homocysteine thiolactone analog (Figure 1B) was found to be three-fold more potent (EC50 = 1 nM). We sought to build on these prior studies in the current work and

• resistant head groups coupled to native-like alkyl tails, or aryl tails from known active PHLs or POHLs [53][54]. Notably, this sub-library contained a range of thiolactone analogs, including the L-OOHL thiolactone analog, for comparison to the work of Janssens et al. [20]. We also included a set of AHLs

• tested (E22, E15, and E16) tested and one thiolactone POHL analog (RN22) activated SdiA by more than 75% at 1 μM. This finding is in stark contrast to our previous studies of POHLs in other LuxR-type receptors, as we have largely only found them to be antagonists. For instance, para-iodo E22, the most

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• module would be responsible for double-bond shift and ring opening of the thiirane 173 with concomitant nucleophilic attack of the thiolate on the thioester, leading to thiolactone 165 formation along with the cleavage from the multienzyme. As all key genes are also present in the clusters of the other

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• thiolactone is generated in AIP biosynthesis (Figure 9). Autoinducing peptides are secreted molecules that form part of a quorum-sensing system in Staphylococcus [121]. Heterologous expression in E. coli showed that only AgrD (precursor peptide) and AgrB (peptidase) are required for AIP biosynthesis, although

• thioester acyl–enzyme intermediate that is then attacked by Cys28 of AgrD to generate a 16-membered thiolactone [120] (Figure 9). Radical SAM-catalysed oxidative cross-linking The majority of characterised cyclic RiPPs are generated by standard ionic reactions. In contrast, radical mechanisms permit

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• interaction. In addition, adducts 76 and 77 were easily transformed into the corresponding carboxylic acids 79 and 80 by treatment with periodic acid (Scheme 14) and thiolactone 81 by simple ring opening of the latter under mild acidic conditions. Phosphine-catalyzed γ-addition to allenoates and alkynoates

Novel tetracyclic structures from the synthesis of thiolactone-isatin hybrids

• Renate Hazel Hans,
• Hong Su and
• Kelly Chibale

Beilstein J. Org. Chem. 2010, 6, No. 78, doi:10.3762/bjoc.6.78

• 7701, South Africa 10.3762/bjoc.6.78 Abstract A simple and straightforward synthetic approach to potential anti-infective thiolactone-isatin hybrids led to the discovery of novel tetracyclic compounds which bear a macrocylic motif containing an unusual bridged amide bond. Keywords: bridged amides

• ; hybrids; isatin; tetracycles; thiolactomycin; thiolactone; Introduction Hybrid structures have been found in nature and their synthesis has become a useful drug discovery strategy for new anti-infective agents [1]. Improved pharmacokinetics, therapeutic and toxicity profiles have been reported for

• libraries and concomitantly shortens the time needed to identify potential leads [5]. The focus of this study is on the synthesis of hybrids with monomers derived from natural products thiolactomycin (1) and isatin (2) (Figure 2). The former is a thiolactone antibiotic known for its remarkable selectivity