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Integrating multiple functionalities into individual nanoscale complexes is of tremendous importance in biomedicine, expanding the capabilities of nanoscale structures to perform multiple parallel tasks. Here, the ability to enhance two different imaging technologies simultaneously—fluorescence optical imaging and magnetic resonance imaging—with antibody targeting and photothermal therapeutic actuation is combined all within the same nanoshell-based complex. The nanocomplexes are constructed by coating a gold nanoshell with a silica epilayer doped with Fe 3 O 4 and the fluorophore ICG, which results in a high T 2 relaxivity (390mm ―1 s ―1 ) and 45× fluorescence enhancement of ICG. Bioconjugate nanocomplexes target HER2+ cells and induce photothermal cell death upon near-IR illumination.

N-Carboxymethyl 3-hydroxypiperidine (6) undergoes substitution at C(6) via reductive cleavage of N,S-acetal 8a with lithium naphthalenide (LN) and trapping of the resulting carbanionic intermediate 9 with different electrophiles to give adducts 10. N,S-Acetal 8a also undergoes C-S homolysis and trapping of the resulting radical provides an alternative entry to 2-substituted-5-­hydroxypiperidines.

Regioselective C-C-bond formation reactions at 2,3-dibromobenzofuran (1) and 2,3,5-tribromobenzofuran (6) were studied. Pd-catalyzed Sonogashira and Negishi cross-coupling occurred with perfect regioselectivity at carbon atom C-2 to provide 2-substituted 3-bromobenzofurans (12, 14) and 3,5-dibromobenzofurans (17, 18) in 50-91% yield. A regioselective displacement of the bromine substituents in 3,5-dibromobenzofurans 18 was achieved by a halogen-metal exchange reaction at carbon atom C-3 and by a Ni-catalyzed Kumada cross-coupling at C-5. The methodology was applied to the synthesis of eupomatenoids 3, 4, 5, 6, and 15 (5). The synthesis of these compounds was achieved in overall yields of up to 60%.

Six different eupomatenoids ( 1a–c , 1f–h ) were prepared from 2,3,5-tribromobenzofuran ( 2 ) in a concise and high-yielding synthetic sequence. The overall yields vary between 29 and 60% over four to six steps. Key to the success of the syntheses is the high regioselectivity achieved in three Pd(0)- and Ni(0)-catalyzed cross-coupling reactions which were conducted consecutively. The order of substitution at the benzofuran nucleus is C-2, C-5 and C-3.