RESUMO
The highly secure blood-brain barrier (BBB) restricts drug access to the brain, limiting the molecular toolkit for treating central nervous system (CNS) diseases to small, lipophilic drugs. Development of a safe and effective BBB modulator would revolutionise the treatment of CNS diseases and future drug development in the area. Naturally, the field has garnered a great deal of attention, leading to a vast and diverse range of BBB modulators. In this review, we summarise and compare the various classes of BBB modulators developed over the last five decades-their recent advancements, advantages and disadvantages, while providing some insight into their future as BBB modulators.
RESUMO
Two concise syntheses of the natural products cis-sylvaticin and sylvaticin are reported, using oxidative cyclization methodology as the key step. A sequential solvolysis/hydride shift/intramolecular reduction cascade was used to establish the trans stereochemistry of one of the THF rings of sylvaticin.
Assuntos
Produtos Biológicos/química , Produtos Biológicos/síntese química , Furanos/química , Furanos/síntese química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/química , Alcenos/química , Ciclização , Hidroxilação , Oxirredução , EstereoisomerismoAssuntos
Oxazóis/química , Catálise , Ligantes , Metais/química , Oxazóis/síntese química , EstereoisomerismoRESUMO
We report the good to high-yielding three-step synthesis of non-symmetrical bis(oxazoline)-containing ligands possessing an N-thienylaniline unit. The convergent synthesis employed a palladium-catalysed aryl amination of 2-(2'-bromothiophene)nitrile as the key step, with sixteen ligands prepared in total. These ligands were subsequently applied in the chromium-catalysed enantioselective Nozaki-Hiyama-Kishi allylation of benzaldehyde with an optimal enantioselectivity of 73%.
Assuntos
Benzaldeídos/química , Compostos de Anilina/química , Catálise , Cromo/química , Ligantes , Paládio/química , Estereoisomerismo , Especificidade por SubstratoRESUMO
A series of symmetric and non-symmetric bis(oxazoline) ligands were applied in the Nozaki-Hiyama-Kishi methallylation of a range of aromatic and aliphatic aldehydes. A non-symmetrical ligand with tert-butyl/benzyl-substituted oxazolines provided the highest enantioselectivity of 99.5% for the methallylation of benzaldehyde.
