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We report the practical, scalable synthesis of a range of N-methyl allylic amines. Primary and secondary allylic alcohols underwent a regioselective Mitsunobu reaction with readily accessible N-Boc ethyl oxamate to deliver the corresponding N-Boc allylic amines, including in enantiopure form via stereospecific substitution. Subsequent N-methylation and Boc deprotection without chromatography yielded the amine products as hydrochloride salts. This method solves the problem of converting commercially available alcohols into often volatile N-methyl allylic amines, many of which have limited commercial availability.

Anthracyclines are effective drugs in the treatment of various cancers, but their use comes with severe side effects. The archetypal anthracycline drug, doxorubicin, displays two molecular modes of action: DNA double-strand break formation (through topoisomerase II alpha poisoning) and chromatin damage (via eviction of histones). These biological activities can be modulated and toxic side effects can be reduced by separating these two modes of action through alteration of the aminoglycoside moiety of doxorubicin. We herein report on the design, synthesis, and evaluation of a coherent set of configurational doxorubicin analogues featuring all possible stereoisomers of the 1,2-amino-alcohol characteristic for the doxorubicin 3-amino-2,3-dideoxyfucoside, each in nonsubstituted and N,N-dimethylated forms. The set of doxorubicin analogues was synthesized using appropriately protected 2,3,6-dideoxy-3-amino glycosyl donors, equipped with an alkynylbenzoate anomeric leaving group, and the doxorubicin aglycon acceptor. The majority of these glycosylations proceeded in a highly stereoselective manner to provide the desired axial alpha-linkage. We show that both stereochemistry of the 3-amine carbon and N-substitution state are critical for anthracycline cytotoxicity and generally improve cellular uptake. N,N-Dimethylepirubicin is identified as the most potent anthracycline that does not induce DNA damage while remaining cytotoxic.

The off-plane dynamics in the frequency window from 1 THz (4 meV) to 3 THz (12 meV) in multiple phospholipid bilayers as studied by means of neutron scattering is presented. A weak inelastic signal is observed, indicating that off-plane dynamics is dominated by the disordered inter-layer water. A collective mode is detected which shows a low-momentum dispersion similar to that of bulk water, while a more complex dynamics is found on increasing the momentum transfer.

We review the main achievements accomplished in the study of the coherent collective dynamics of phospholipid membranes, i.e., the collective vibrational excitations active on the sub-picoseconds to picoseconds time scale and terahertz frequencies, over a length scale comparable to the angstrom length scale. The first descriptions of the terahertz collective spectrum, mainly assigned to a single longitudinal acoustic-like mode similarly to simple liquids, have been progressively replaced by a complex scenario, with longitudinal and transverse acoustic-like and optic-like inelastic excitations. Complex phenomena (avoided crossing mechanisms between modes, a phonon gap introduced by the disorder and a slow- to fast-sound transition) have been highlighted in the dispersion curves of lipid bilayers. Systematic and comprehensive studies along the lines of the investigations reviewed here contribute to understand the role of the collective (coherent) chain dynamics in the passive transport across bilayers, in the formation of water wires inside dynamic defects in lipid bilayers and in other biological functions of biomembranes.