Cyclobutanes are increasingly used in medicinal chemistry in the search for relevant biological properties. Important characteristics of the cyclobutane ring include its unique puckered structure, longer CÀ C bond lengths, increased CÀ C π-character and relative chemical inertness for a highly strained carbocycle. This review will focus on contributions of cyclobutane rings in drug candidates to arrive at favorable properties. Cyclobutanes have been employed for improving multiple factors such as preventing cis/trans-isomerization by replacing alkenes, replacing larger cyclic systems, increasing metabolic stability, directing key pharmacophore groups, inducing conformational restriction, reducing planarity, as aryl isostere and filling hydrophobic pockets.[a] M. R. van der Kolk, M.
Functionalizing polymersomes remains a challenge due to the limitation in reaction conditions applicable to the chemistry on the surface, hindering their application for selective targeting. In order to overcome this limitation, functionalization can be introduced right before the self-assembly. Here, we have synthesized a library (32 examples) of PEG-b-PS and PEG-b-PDLLA with various functional groups derived from the amine-functionalized polymers, leading to functionally active polymersomes. We show that polymersome formation is possible via the general method with all functionalized groups and that these handles are present on the surface and are able to undergo reactions. Additionally, this methodology provides a general synthetic tool to tailor the functional group of the polymersome right before self-assembly, without limitation on the reaction conditions.
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