N-Alkylation of organonitrogen compounds catalyzed by methylene-linked bis-NHC half-sandwich ruthenium complexes.

An efficient ruthenium-catalyzed N-alkylation of amines, amides and sulfonamides has been developed employing novel pentamethylcyclopentadienylruthenium(II) complexes bearing the methylene linked bis(NHC) ligand bis(3-methylimidazol-2-ylidene)methane. The acetonitrile complex 2 has proven particularly effective with a broad range of substrates with low catalyst loading (0.1-2.5 mol%) and high functional group tolerance under mild conditions. A total of 52 N-alkylated organonitrogen compounds including biologically relevant scaffolds were synthesized from (hetero)aromatic and aliphatic amines, amides and sulfonamides using alcohols or diols as alkylating agents in up to 99% isolated yield, even on gram-scale reactions. In the case of sulfonamides, it is the first example of N-alkylation employing a transition-metal complex bearing NHC ligands.

Deconjugative α-Alkylation of Cyclohexenecarboxaldehydes: An Access to Diverse Terpenoids.

A general and efficient method for the deconjugative α-alkylation of α,ß-unsaturated aldehydes promoted by a synergistic effect between tBuOK and NaH, which considerably increases the reaction rate under mild conditions, is reported. The ß,γ-unsaturated aldehyde, resulting from the α-alkylation, is transformed in high yield into the corresponding allyl acetate via a lead(IV) acetate-mediated oxidative fragmentation. This strategy could be used for the construction of the carbon skeleton of a wide variety of alkyl or arylterpenoids.

Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGFα Release and Adult Mouse Neurogenesis.

A small library of phorbol 12,13-diesters bearing low lipophilicity ester chains was prepared as potential neurogenic agents in the adult brain. They were also used in a targeted UHPLC-HRMS screening of the latex of Euphorbia resinifera. Two new 12-deoxy-16-hydroxyphorbol 13,16-diesters were isolated, and their structures were deduced using two-dimensional NMR spectroscopy and NOE experiments. The ability of natural and synthetic compounds to stimulate transforming growth factor alpha (TFGα) release, to increase neural progenitor cell proliferation, and to stimulate neurogenesis was evaluated. All compounds that facilitated TGFα release promoted neural progenitor cell proliferation. The presence of two acyloxy moieties on the tigliane skeleton led to higher levels of activity, which decreased when a free hydroxyl group was at C-12. Remarkably, the compound bearing isobutyryloxy groups was the most potent on the TGFα assay and at inducing neural progenitor cell proliferation in vitro, also leading to enhanced neurogenesis in vivo when administered intranasally to mice.

Bond reactivity indices approach analysis of the [2+2] cycloaddition of jatrophane skeleton diterpenoids from Euphorbia gaditana Coss to tetracyclic gaditanone.

The reaction mechanism of the intramolecular [2 + 2] cycloaddition from a jatrophane precursor to the gaditanane skeleton, an unprecedented 5/6/4/6-fused tetracyclic ring framework recently isolated from Euphorbia spp., was studied using the bond reactivity indices approach. Furthermore, six diterpenoids, including three undescribed jatrophanes isolated from E. gaditana Coss, were described. The structures of these compounds were deduced by a combination of 2D NMR spectroscopy and ECD data analysis.

Synthesis of Degraded Limonoid Analogs as New Antibacterial Scaffolds against Staphylococcus aureus.

Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) have become serious infections in humans and ruminants. S. aureus strains are showing rapid changes to develop resistance in traditional antibiotic-containing systems. In the continuous fierce fight against the emergent multi-drug resistant bacterial strains, straightforward and scalable synthetic procedures to produce new active molecules are in demand. Analysis of molecular properties points to degraded limonoids as promising candidates. In this article, we report a simple synthetic approach to obtain degraded limonoid analogs as scaffolds for new antibacterial molecules. The minimum inhibitory concentrations against S. aureus were evaluated for the stereoisomer mixtures by the broth microdilution method. Analysis of results showed that the acetylated derivatives were the most active of them all.

Mild Epoxidation of Allylic Alcohols Catalyzed by Titanium(III) Complexes: Selectivity and Mechanism.

A novel methodology for the epoxidation of a broad range of primary, secondary, and tertiary allylic alcohols is described using tert-butyl hydroperoxide as oxidant and Ti(III) species generated by reduction of Ti(IV) complexes, with manganese (0) in 1,4-dioxane under mild reaction conditions. The reaction proceeded with wide substrate scope and high chemo- and diastereoselectivity. A mechanistic pathway for the reaction is also discussed.

Lathyrane Diterpenes from the Latex of Euphorbia laurifolia.

Two new macrocyclic diterpenes, 2-epi-latazienone (4) and 15ß-acetoxy-7ß-nicotinoyloxy-3ß,8α-di-(2-methylpropanoyloxy)-4αH,9αH,l1αH-lathyra- 5E,12E-dien-14-one (5), and three known lathyrane-type diterpenes (1-3) were isolated from Euphorbia laurifolia latex. Their structures were determined on the basis of a detailed analysis of their 1D and 2D NMR spectroscopic and mass spectral data.

Efficient O-Acylation of Alcohols and Phenol Using Cp2TiCl as a Reaction Promoter.

A method has been developed for the conversion of primary, secondary, and tertiary alcohols, and phenol, into the corresponding esters at room temperature. The method uses a titanium(III) species generated from a substoichiometric amount of titanocene dichloride together with manganese(0) as a reductant, as well as methylene diiodide. It involves a transesterification from an ethyl ester, or a reaction with an acyl chloride. A radical mechanism is proposed for these transformations.

Biological activity of natural sesquiterpenoids containing a gem-dimethylcyclopropane unit.

The biological activities of aristolane, aromadendrane, ent-1,10-secoaromadendrane, 2,3-secoaromadendrane, ent-5,10-cycloaromadendrane, bicyclogermacrene, lepidozane, and maaliane terpenoids which contain the gem-dimethylcyclopropyl unit are described. Particular attention is given to their anti-viral, anti-microbial and cytotoxic activities. In the main text there are 119 references covering the literature from 1963-2014. The ESI contains tables listing 332 of these terpenoids, their occurrence and biological activity together with the related references.

nor-Mevaldic acid surrogates as selective antifungal agent leads against Botrytis cinerea. Enantioselective preparation of 4-hydroxy-6-(1-phenylethoxy)tetrahydro-2H-pyran-2-one.

Solvent-free desymmetrisation of meso-dialdehyde 1 with chiral 1-phenylethan-1-ol, led to preparation of 4-silyloxy-6-alkyloxytetrahydro-2H-pyran-2-one (+)-3a with a 96:4 dr Deprotected lactone (+)-19a and the related racemic lactones 16a-18a present a lactone moiety resembling the natural substrate of HMG-CoA reductase and their antifungal properties have been evaluated against the phytopathogenic fungi Botrytis cinerea and Colletotrichum gloeosporioides. These compounds were selectively active against B. cinerea, while inactive against C. gloeosporioides.

Biologically active diterpenes containing a gem-dimethylcyclopropane subunit: an intriguing source of PKC modulators.

Covering: 1973 to 2013. The biological activities of tigliane, lathyrane, ingenane, casbane, jatropholane and premyrsinane diterpenoids which contain the gem-dimethylcyclopropyl unit are described. Particular attention is given to their anti-viral, anti-microbial and cytotoxic activities. In the main text there are 132 references. The electronic supplementary information contains tables listing 424 of these diterpenoids, their occurrence and biological activity together with the references.