Synthesis of rigid tryptophan mimetics by the diastereoselective Pictet-Spengler reaction ofβ³-homo-tryptophan derivatives with chiralα-amino aldehydes

Abstract

The Pictet-Spengler (PS) cyclizations of β(3)-hTrp derivatives as arylethylamine substrates were performed with L-α-amino and D-α-amino aldehydes as carbonyl components. During the PS reaction, a new stereogenic center was created, and the mixture of cis/trans 1,3-disubstituted 1,2,3,4-tetrahydro-β-carbolines was obtained. The ratio of cis/trans diastereomers depends on the stereogenic centre of used amino aldehyde and the size of substituents. It was confirmed by 1H and 2D NMR (ROESY) spectra. The conformations of cyclic products were studied by 2D NMR ROESY spectra. Products of the PS condensation after removal of protecting group(s) can be incorporated into a peptide chain as tryptophan mimetics with the possibility of the β-turn induction.

The Pictet-Spengler Reaction Updates Its Habits

“…N-substituted aryl ethylamines 20 [27,31,35,36,39,40], allene-containing-tryptophan 21 [42], trifluoromethylated precursors 22 [55], and spirocyclic lactams embodying Trp 23 [56] were the most interesting amine substrates. Conversely, isatins 24 [44][45][46], enaminone 25 [52], (S)-2,3-Oisopropylidene-L-glyceraldehyde 26 [53], pyridoxal 27 [60], L/D-amino aldehydes 28 [57,63], and 11 C-labeled formaldehyde 29 [58] were the most notable carbonyl components (Figure 1). We wish to highlight few papers concerning the P-S cyclization of THIQs [32][33][34][35][36] and THBCs [38,43,51,55].…”

Design, synthesis, and biological evaluation of 2‐substituted‐2,3,4,9‐tetrahydrospiro‐β‐carboline‐3‐carboxylic acid derivatives as first‐in‐class mast cell stabilizers

“…Furthermore, there are key heterocyclic scaffolds and pharmacophores like 4 H ‐chromen‐4‐one (cromolyn), pyrido[1,2‐ a ]‐pyrimidin‐4‐one (pemirolast), phthalazin‐1‐one (azelastine), pyrano[3,2‐ g ]quinolone (nedocromil), and cyclohepta[3,4‐ b ]thiophen‐4‐one (ketotifen) which are well tolerated for mast cell stabilization activity. Recently the role of tryptophan in the suppression of mast cell activation has been confirmed by Silwal et al Tetrahydro‐β‐carboline is a constrained analog of tryptophan . Furthermore, dichotomine C, ML120B, and PS‐1142 are derivatives of β‐carboline which possess potent anti‐allergic effects.…”