Asymptotically cylindrical Calabi-Yau 3-folds from weak Fano 3-folds

We prove the existence of asymptotically cylindrical (ACyl) Calabi-Yau 3-folds starting with (almost) any deformation family of smooth weak Fano 3-folds. This allow us to exhibit hundreds of thousands of new ACyl Calabi-Yau 3-folds; previously only a few hundred ACyl Calabi-Yau 3-folds were known. We pay particular attention to a subclass of weak Fano 3-folds that we call semi-Fano 3-folds. Semi-Fano 3-folds satisfy stronger cohomology vanishing theorems and enjoy certain topological properties not satisfied by general weak Fano 3-folds, but are far more numerous than genuine Fano 3-folds. Also, unlike Fanos they often contain P^1s with normal bundle O(-1) + O(-1), giving rise to compact rigid holomorphic curves in the associated ACyl Calabi-Yau 3-folds. We introduce some general methods to compute the basic topological invariants of ACyl Calabi-Yau 3-folds constructed from semi-Fano 3-folds, and study a small number of representative examples in detail. Similar methods allow the computation of the topology in many other examples. All the features of the ACyl Calabi-Yau 3-folds studied here find application in arXiv:1207.4470 where we construct many new compact G_2-manifolds using Kovalev's twisted connected sum construction. ACyl Calabi-Yau 3-folds constructed from semi-Fano 3-folds are particularly well-adapted for this purpose.Comment: 107 pages, 1 figure. v3: minor corrections, changed formattin

Room-Temperature Alternative to the Arbuzov Reaction: The Reductive Deoxygenation of Acyl Phosphonates

The reductive deoxygenation of acyl phosphonates using a Wolff−Kishner-like sequence is described. This transformation allows direct access to alkyl phosphonates from acyl phosphonates at room temperature. The method can be combined with acyl phosphonate synthesis into a one pot, four-step procedure for the conversion of carboxylic acids into alkyl phosphonates. The methodology works well for a variety of aliphatic acids and shows a functional group tolerance similar to that of other hydrazone-forming reactions

Synthesis of indoles via alkylidenation of acyl hydrazides

Indoles have been synthesised via alkylidenation of acyl phenylhydrazides using phosphoranes and the Petasis reagent, followed by in situ thermal rearrangement of the product enehydrazines. The Petasis reagent provides an essentially neutral equivalent of the [acid-catalysed] Fischer indole synthesis, but with acyl phenylhydrazides as starting substrates. Alkylidene triphenylphosphoranes convert aroyl phenylhydrazides to indoles, but acyl phenylhydrazides derived from aliphatic carboxylic acids undergo a Brunner reaction to form indolin-2-ones

Regioselective Reactions of Highly Substituted Arynes

The fully regioselective reactivity of four new highly substituted silyl aryl triflate aryne precursors in aryne acyl-alkylation, acyl-alkylation/condensation, and heteroannulation reactions is reported. The application of these more complex arynes provides access to diverse natural product scaffolds and obviates late-stage functionalization of aromatic rings

Binding to medium and long chain fatty acyls is a common property of HEAT and ARM repeat modules.

Covalent post-translational modification (PTM) of proteins with acyl groups of various carbon chain-lengths regulates diverse biological processes ranging from chromatin dynamics to subcellular localization. While the YEATS domain has been found to be a prominent reader of acetylation and other short acyl modifications, whether additional acyl-lysine reader domains exist, particularly for longer carbon chains, is unclear. Here, we employed a quantitative proteomic approach using various modified peptide baits to identify reader proteins of various acyl modifications. We discovered that proteins harboring HEAT and ARM repeats bind to lysine myristoylated peptides. Recombinant HEAT and ARM repeats bind to myristoylated peptides independent of the peptide sequence or the position of the myristoyl group. Indeed, HEAT and ARM repeats bind directly to medium- and long-chain free fatty acids (MCFA and LCFA). Lipidomic experiments suggest that MCFAs and LCFAs interact with HEAT and ARM repeat proteins in mammalian cells. Finally, treatment of cells with exogenous MCFAs and inhibitors of MCFA-CoA synthases increase the transactivation activity of the ARM repeat protein β-catenin. Taken together, our results suggest an unappreciated role for fatty acids in the regulation of proteins harboring HEAT or ARM repeats

Studies on the acylation of 4-(2-aminoethylthio)-7-nitrobenzofurazan: the role of bases in promoting the formation of fluorescent S-acyl derivatives through S–N Smiles rearrangement

The acylation of 4-(2-aminoethylthio)-7-nitrobenzofurazan has been investigated. Depending on the use of the base, a competitive Smiles rearrangement occurs during the acylation step leading to the formation of N-acyl and/or fluorescent S-acyl derivatives. The acylating agent also affects the ratio of N/S acylated isomers

Bi-acylation of cellulose: determining the relative reactivities of the acetyl and fatty-acyl moieties

The global reaction between acetic anhydride and a fatty acid yields, at equilibrium, an asymmetric acetic-aliphatic anhydride in a medium containing finally: acetic-fatty anhydride, acetic anhydride, fatty acid, acetic acid and fatty anhydride. No solvent or catalyst was used to evaluate the impact of the actual reactivity of the anhydrides. The competition between the formation of acetyl and fatty acyl ester functions was evaluated by determining the ratio of acetyl/fatty acyl groups grafted on solid cellulose. The influence of temperature, reaction time, and length of fatty chain on the total degree of substitution and on the ratio of acetyl/fatty acyl ester functions was investigated. For the first time, a correlation has been established between esterification and the length of the aliphatic chain of the fatty acid. Reactivity of the medium decreased with the number of carbons in the fatty acid, raised to the power 2.37

NMR Studies of Escherichia Coli Acyl Carrier Protein: Dynamic and Structural Differences of the Apo- and Holo-forms

Two indicators of conformational variability of Escherichia coli acyl carrier protein (ACP) have been investigated, namely backbone dynamics and chemical shift variations of ACP. Hydrophobic interactions between the 4′-PP prosthetic group and the hydrophobic pocket enclosed by the amphipathic helices resulted in chemical shift perturbations in the residues near the prosthetic group binding sites and contact sites in the hydrophobic pockets upon conversion from apo- to holo-forms. At pH 7.9, destabilization of ACP due to negative charge repulsions and the deprotonated state of His 75 resulted in observed chemical shift changes in the C-terminal region. Model-free analysis showed that the α1α2 loop region near the prosthetic group binding site in ACP shows the greatest flexibility (lowest S2 values) and this result may suggest these flexibilities are required for structural rearrangements when the acyl chain binds to the prosthetic group of ACP. Flexibility of ACP shown in this study is essential for its ability to interact with functionally different enzyme partners specifically and weakly in the rapid delivery of acyl chain from one partner to another

Biocatalytic Synthesis of Stereospecific Triketide Lactones using Polyketide Synthases

Polyketide synthases are modular enzymes that create and modify large acyl chains. The domains and modules of polyketide synthases allow us to create molecules that resemble naturally occurring products by applying a biocatalytic in vitro in vivo approach to a diketide acyl chain. We showed that a triketide lactone of desired stereochemistry could be made using a domain and module from the polyketide synthase found in Saccharopolyspora erythraea, 6-Deoxyerythronolide B Synthase. Future projects will explore this approach using different domains and modules.Biochemistr