In Search of Wasserman's Catenane.

We repeat the earliest claimed [2]catenane synthesis, reported by Wasserman over 60 years ago, in order to ascertain whether or not a nontemplate, statistical synthesis by acyloin macrocyclization does indeed form mechanically interlocked rings. The lack of direct experimental evidence for Wasserman's catenane has led to it being described as a "prophetic compound", a technical term used in patents for claimed molecules that have not yet been synthesized. Contemporary synthetic methods were used to reconstruct Wasserman's deuterium-labeled macrocycle and other building blocks on the 10-100 g reaction scale necessary to generate, in principle, ∼1 mg of catenane.

Sequence-Selective Decapeptide Synthesis by the Parallel Operation of Two Artificial Molecular Machines.

We report on the preparation of a decapeptide through the parallel operation of two rotaxane-based molecular machines. The synthesis proceeds in four stages: (1) simultaneous operation of two molecular peptide synthesizers in the same reaction vessel; (2) selective residue activation of short-oligomer intermediates; (3) ligation; (4) product release. Key features of the machine design include the following: (a) selective transformation of a thioproline building block to a cysteine (once it has been incorporated into a hexapeptide intermediate by one molecular machine); (b) a macrocycle-peptide hydrazine linkage (as part of the second machine) to differentiate the intermediates and enable their directional ligation; and (c) incorporation of a Glu residue in the assembly module of one machine to enable release of the final product while simultaneously removing part of the assembly machinery from the product.

A Brief Review of Caprylidene (Axona) and Coconut Oil as Alternative Fuels in the Fight Against Alzheimer's Disease.

Type 3 diabetes mellitus has been coined to describe an alternative pathologic pathway of Alzheimer's disease (AD). The insulin resistance and impaired insulin signaling seen on positron-emission tomography scans in the brain of those affected by AD support this disease hypothesis. Two products-the medical food caprylidene (Axona) and coconut oil-seek to target the underlying pathology of type 3 diabetes mellitus by providing an alternative fuel source in the brain.

A Brief Review of Three Common Supplements Used in Alzheimer's Disease.

Individuals with Alzheimer's disease (AD) and their caregivers are using supplements in an effort to halt the progression of the disease. Individuals at risk for or fearing Alzheimer's may use these supplements to try to prevent the disease. Senior care pharmacists are accessible and uniquely qualified to answer questions, make recommendations, and attempt to make drug therapy safe and effective for these individuals.

Total Synthesis of Peniphenones A-D via Biomimetic Reactions of a Common o-Quinone Methide Intermediate.

The total synthesis of peniphenones A-D has been achieved via Michael reactions between appropriate nucleophiles and a common o-quinone methide intermediate. This strategy, which was based on a biosynthetic hypothesis, minimized the use of protecting groups and thus facilitated concise syntheses of the natural products. The most complex target, the benzannulated spiroketal peniphenone A, was synthesized enantioselectively in nine linear steps from commercially available starting materials.

Selective aliphatic carbon-hydrogen bond activation of protected alcohol substrates by cytochrome P450 enzymes.

Protected cyclohexanol and cyclohex-2-enol substrates, containing benzyl ether and benzoate ester moieties, were designed to fit into the active site of the Tyr96Ala mutant of cytochrome P450cam. The protected cyclohexanol substrates were efficiently and selectively hydroxylated by the mutant enzyme at the trans C-H bond of C-4 on the cyclohexyl ring. The selectivity of oxidation of the benzoate ester protected cyclohexanol could be altered by making alternative amino acid substitutions in the P450cam active site.

Biomimetic total synthesis of ent-penilactone A and penilactone B.

The total synthesis of ent-penilactone A and penilactone B has been achieved via biomimetic Michael reactions between tetronic acids and o-quinone methides. A five-component cascade reaction between a tetronic acid, formaldehyde, and a resorcinol derivative that generates four carbon-carbon bonds, one carbon-oxygen bond, and two stereocenters in a one-pot synthesis of penilactone A is also reported.

Structural reassignment of cytosporolides A-C via biomimetic synthetic studies and reinterpretation of NMR data.

A structure revision for the recently isolated fungal meroterpenoids, cytosporolides A-C, is suggested based on biosynthetic speculation and reinterpretation of existing spectroscopic data. The structure revision is supported by a biomimetic synthetic study, featuring a [4 + 2] cycloaddition reaction between a presumed o-quinone methide intermediate and β-caryophyllene.