Questioning the γ-gauche effect: stereoassignment of 1,3-disubstituted-tetrahydro-β-carbolines using¹H–¹H coupling constants

Abstract

Are γ-gauche interactions in trans-tetrahydro-β-carbolines responsible for upfield 13C NMR shifts (Δδ) of C1 and C3 relative to their cis-isomers?

Structure Revision of Protoaculeine B, a Post-translationally Modified N-Terminal Residue in the Peptide Toxin Aculeine B

“…In addition, cis -tetrahydro-β-carboline 13 (Scheme , Figure A,B) showed a long-range COSY cross-peak at H-4b/H-1 (δ 3.04/δ 4.76) (for NMR spectra, see the Supporting Information), which is observed in the COSY spectrum of natural pACU-B ( 2 ) at δ 2.95/δ 4.77 (see discussion above) . Note that such long-range coupling through five bonds, for which we previously annotated homoallylic coupling, is rare but is often observed in tetrahydro-β-carbolines . The important medium-intensity NOESY cross-peak was also observed for model compound 13 (Figure B) in a possible pseudochair conformation at H-3/H-1 (δ 4.13/δ 4.76), which appeared at δ 4.01/δ 4.77 in natural pACU-B ( 2 ).…”

“…3 Note that such long-range coupling through five bonds, for which we previously annotated homoallylic coupling, 3 is rare but is often observed in tetrahydro-β-carbolines. 17 The important medium-intensity NOESY cross-peak was also observed for model compound 13 (Figure 5B) in a possible pseudochair conformation at H-3/H-1 (δ 4.13/δ 4.76), which appeared at δ 4.01/δ 4.77 in natural pACU-B (2). Thus, model cis-13 satisfied the COSY and NOESY correlations of natural pACU-B (2).…”