New Helical Folds in α‐Peptides with Alternating Chirality

Abstract

In α-peptides, the 8/10 helix is theoretically predicted to be energetically unstable and has not been experimentally observed so far. Based on our earlier studies on 'helical induction' and 'hybrid helices', we have adopted the 'end-capping' strategy to induce the 8/10 helix in α-peptides by using short α/β-peptides. Thus, α-peptides containing a regular string of α-amino acids with alternating chirality were end capped by α/β-peptides with 11/9-helical motifs at the termini. Extensive NMR spectroscopy studies of these peptides revealed the presence of a hitherto unknown 8/10-helical pattern; the H-bonds in the shorter pseudorings were rather weak. The approach of using short helical motifs to induce new mixed helices in α-peptides could provide avenues for more versatile design strategies.

Constrained Cyclic β,γ‐Diamino Acids from Glutamic Acid: Synthesis of Both Diastereomers and Unexpected Kinetic Resolution

“…Hydrogenation of compound 5c with Pd/(OH) 2 gave 14 as an inseparable mixture of diastereomers (dr = 70: 30) in 85 % yield [only a small amount of the less polar compound, the major diastereomer, whose configuration was assigned as ( R,γS)-14, could be isolated as a pure compound by chromatography]. The structure of compound 13 was unambiguously determined after the next step.…”

“…The structure of compound 13 was unambiguously determined after the next step. Thus, we had access to both diastereomers of compound 15, which can be used as functionalized and constrained -amino acids (see the work of Sharma's group [30,31] ). We then attempted the reduction of lactams 5c and 13 (Scheme 3).…”

“…According to literature reports, such amino acids, either -with a five-membered-ring substituent, [30,31] or γwith a six-membered ring, [10,12,14] have great potential to induce interesting conformations when inserted into peptide sequences. Depending on the nitrogen-protecting group of compound 10, we were able to direct the reaction towards the six-membered ring (PG = Ts, Boc) or the fivemembered ring (PG = Alloc).…”