Bioorthogonal catalytic cross-coupling reactions of biomolecules with fluorescent dyes can provide synthetic access to novel optical probes and methodology for the detection and chemometric analysis of complex mixtures. Alkene cross-metathesis is compatible with a wide variety of functional groups using organic or aqueous conditions, but unfavorable kinetics with substituted alkenes, undesired side reactions such as homodimerization, secondary metathesis, and the formation of regioisomers remain as significant limitations to this approach. These limitations can be overcome through the identification of highly reactive alkene partners for cross metathesis labeling. Allylic sulfides have been identified as privileged substrates for cross metathesis. We synthesized a series of substituted fluorescent triazaborolopyridinium HPY-dyes to evaluate the effects of allylic sulfide and sulfone moieties in alkene cross-metathesis reactions. The sulfone derivative exhibited rapid cross metathesis reactivity with mono-, di- and trisubstituted alkenes. Regioselectivity was assessed for a series of functionalized isoprenyl compounds and polyisoprenoids including squalene and co-enzyme Q10. Quantitative determination of labeled product mixtures was achieved using high-performance liquid chromatography with photodiode array detection at the maximum absorbance (505 nm) of the HPY fluorophore. The presence of boron in the HPY fluorophore provides isotopic fine structure verification for unambiguous compound identification of labeled products using high resolution, accurate mass measurement FT-ICR mass spectrometry. This cross metathesis approach holds promise for the synthesis of unsaturated lipid probes and for the analysis of complex lipid mixtures.

Efficient cross metathesis of allyl sulfones with isoprenoids for the synthesis of fluorescent lipid probes

253rd National Meeting (2017)

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