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Addition of lithiodimethylphenylsilane to chiral naphthylxazolines in a diastereofacial fashion, followed by methyl iodide trapping produces two vital intermediates in the synthetic sequence for (-)-aphanorphine and (-)-eptazocine. Existing procedures enable the conversion of these intermediates into (-)-aphanorphine and (-)-eptazocine. X-ray crystallography helps determine the absolute configuration of these intermediates.

The low-temperature Evans-Tishchenko coupling of a range of functionalized heteroaryl aldehydes with [beta]-hdyroxy ketones in the presence of a Sm(III) catalyst is achieved with high diastereoselectivity. A retro-aldol aldol-Tishchenko reaction has competed with the desired Evans-Tishchenko reaction and the identification of the byproducts has allowed the corresponding aldol-Tishchenko reaction to be optimized for heteroaryl aldehydes.

The preparation of the TBDPS protected glycolate derivative of thiol auxiliary with excellent anti:syn selectivity and high facial selectivity in glycolate aldol reactions with a range of aldehydes is described. The thiol auxiliary is readily displaced under mild conditions to yield alcohol and ester derivatives of the glycolate aldol adducts.

A novel approach for detecting Cu(I) based upon a catalytic effect that relies on the sensitization of a europium complex by a pendant dansyl antenna is reported. Formation of the luminescent device is brought about by the Huisgen 1,3-dipolar cycloaddition reaction catalyzed by the G[S.sup.-]-Cu(I) complex.

The diastereoselective addition of lithiosilanes to chiral naphthalenes in ether or THF yields 1,1-substituted tetralins or dihydronaphthalenes. The reaction mechanism includes azaenolate trapping and protodesilylation. The reaction is efficient and yields products with high enantiomeric excess.

Describes the first total synthesis of both (-)-ebelactone A and (-)-ebelactone B. Description of synthetic challenges provided by complex group of beta-lactones enzyme inhibitors; Use of reagent- and substrate-derived stereocontrol; Minimal use of protecting groups.

Stimulated Raman scattering (SRS) microscopy represents a powerful method for imaging label-free drug distribution with high resolution. SRS was applied to image label-free ponatinib with high sensitivity and specificity in live human chronic myeloid leukemia (CML) cell lines. This was achieved at biologically relevant, nanomolar concentrations, allowing determination of ponatinib uptake and sequestration into lysosomes during the development of acquired drug resistance and an improved understanding of target engagement.

Two approaches to the synthesis of biotinylated derivatives of the stress-activated protein kinase (SAPK) pathway activator anisomycin have been investigated. Attachment of the biotin moiety to the central core was achieved either through the use of a classical displacement reaction on alpha-halo carbonyl derivatives of biotin or through a copper(I)-catalyzed 1,3-dipolar Huisgen cycloaddition ("click") coupling of biotinylated azides to propargyl-marked analogues of anisomycin. In each case, the resultant N-linked molecular probes were found to be active in SAPK pathway immunoblot assays, while their O-linked counterparts were inactive. However, in sharp contrast to the classical coupling approach which results in low coupling yields, the aqueous "click" coupling process was found to deliver high yields of biotinylated probes, making it the conjugation method of choice. A survey of the available methods for the addition of a propargyl marker onto a range of chemical functionalities strongly suggests that this copper(I)-catalyzed 1,3-dipolar Huisgen cycloaddition approach to biotinylation may be generally applied.

A new approach to the synthesis of medium-ring lactones is reported based on sequential Evans-Tishchenko and ring-closing metathesis (RCM) reactions. High diastereoselectivity (>95:5) is demonstrated in the Evans-Tishchenko reaction of unsaturated aldehydes with unsaturated beta-hydroxy ketones, and conditions for the RCM cyclization of the resultant dienes have been optimized to give high yields of medium ring lactones. The synthetic utility of this sequence is demonstrated through generation of the fully functionalized core of octalactin A. [reaction: see text].

Synthesis of a new thiol auxiliary (1) is readily achieved (in five or six steps, >74% overall yield from norephedrine) and is shown to give high diastereoselectivity in boron-mediated anti-aldol reactions with a range of aldehydes. This new thiol auxiliary may be directly displaced by a range of nucleophiles under very mild conditions, to give the corresponding phosphonate esters, alcohols, acids, SNAC thiolesters, and methyl esters.

[reaction: see text] A new approach to the synthesis of the antibiotic anisomycin is reported that relies upon a key aldol disconnection. The glycolate aldol coupling proceeds in 75% yield and with >95% diastereoselectivity, which allows the 13-step synthesis to proceed in 35% overall yield.