ABSTRACT
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.
ABSTRACT
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.
Subject(s)
Biological Products/chemistry , Biological Products/chemical synthesis , Furans/chemistry , Furans/chemical synthesis , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/chemistry , Alkenes/chemistry , Cyclization , Hydroxylation , Oxidation-Reduction , StereoisomerismSubject(s)
Oxazoles/chemistry , Catalysis , Ligands , Metals/chemistry , Oxazoles/chemical synthesis , StereoisomerismABSTRACT
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%.
Subject(s)
Benzaldehydes/chemistry , Aniline Compounds/chemistry , Catalysis , Chromium/chemistry , Ligands , Palladium/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
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.
