RESUMO
Among the known hydrosilylation or carbosilylation conditions of alkynes, anti-addition of the two units across the triple bond is considered rare compared to the syn counterpart. For anti-silylative vicinal difunctionalizations, transition-metal catalysts, such as ruthenium or palladium complexes, are generally required. Accordingly, silyl alkali metals have not been employed for those anti-addition transformations. Here we demonstrate that silyllithiums can add across the triple bond of a series of propargylic alkoxides regioselectively in an anti-fashion. Upon treatment with a variety of electrophiles, the trisubstituted alkenyl lithium intermediates were transformed into highly functionalized ß-silyl allylic alcohols with high regiocontrol, eventually providing tri- or tetrasubstituted alkenylsilanes stereoselectively. A classic trick for anti-addition with propargylic alkoxides has transformed anti-silylative functionalizations into a robust and reliable strategy.
RESUMO
Opioid peptides are key regulators in cellular and intercellular physiological responses, and could be therapeutically useful for modulating several pathological conditions. Unfortunately, the use of peptide-based agonists to target centrally located opioid receptors is limited by poor physicochemical (PC), distribution, metabolic, and pharmacokinetic (DMPK) properties that restrict penetration across the blood-brain barrier via passive diffusion. To address these problems, the present paper exploits fluorinated peptidomimetics to simultaneously modify PC and DMPK properties, thus facilitating entry into the central nervous system. As an initial example, the present paper exploited the Tyr1-ψ[( Z)CFâCH]-Gly2 peptidomimetic to improve PC druglike characteristics (computational), plasma and microsomal degradation, and systemic and CNS distribution of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu). Thus, the fluoroalkene replacement transformed an instable in vitro tool compound into a stable and centrally distributed in vivo probe. In contrast, the Tyr1-ψ[CF3CH2-NH]-Gly2 peptidomimetic decreased stability by accelerating proteolysis at the Gly3-Phe4 position.
