A P-C bond-forming reaction between silyl phosphonites and Morita-Baylis-Hillman acetates (MBHAs) is explored as a general alternative towards medicinally relevant β-carboxyphosphinic structural motifs. Conversion rates of diversely substituted MBHAs to phosphinic acids 9 or 14 that were recorded by using (31) P NMR spectroscopy revealed unexpected reactivity differences between ester and nitrile derivatives. These kinetic profiles and DFT calculations support a mechanistic scenario in which observed differences can be explained from the "lateness" of transition states. In addition, we provide experimental evidence suggesting that enolates due to initial P-Michael addition are not formed. Based on the proposed mechanistic scenario in conjunction with DFT calculations, an interpretation of the E/Z stereoselectivity differences between ester and nitriles is proposed. Synthetic opportunities stemming from this transformation are presented, which deal with the preparation of several synthetically capricious phosphinic building blocks, whose access through the classical P-Michael synthetic route is not straightforward.

Cell microencapsulation holds great promise as a therapeutic strategy for the controlled and sustained delivery of biologically relevant agents. The authors developed cell-laden microgel scaffolds with excellent long-term viabilities by combining bioorthogonal strain promoted azide-alkyne cycloaddition (SPAAC) and droplet-based microfluidic templating. Star-shaped polyglycerol hexaazide, α,ω-bis azido-linear polyglycerol or polyethylene glycol as well as dendritic polyglycerol-(polycyclooctyne) served as bioinert hydrogel precursors. The authors demonstrate for the first time the generation of entirely polyglycerol-based microcapsules with excellent stability and full retention of viability of the packed cells for longer than 3 weeks. As a result, our microgel particles could be used for long-term immunoisolation of cells enabling their study during encapsulation.

SummaryIn this work we present for the first time the synthesis of novel 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) derivatives that can be used as tools in the emerging field of epigenetics for deciphering chemical biology of TET-mediated processes.

No abstract