Fig 1.
Designed enantiomeric inhibitors synthesized.
Fig 2.
Synthesis of the Ac–L-pSer–Ψ[(Z)CH = C]-D-Pip–NEA inhibitor (2R,5S)-1.
Fig 3.
Synthesis and determination of the stereochemistry of derivative (2S,3R)-13.
Cyclic compounds 13 were synthesized. 1H NMR coupling constants (J) were used to determine the relative stereochemistry at the carbons to which Ha and Hb are attached.
Fig 4.
Determination of the (Z)-alkene stereochemistry of intermediate (2R,5S)-6.
The 1D nOe 1H NMR. Irradiation of 1Hf shows an nOe at 1Hm and not at 1Hh.
Fig 5.
Determination of the stereochemistry of Still-Wittig intermediates 6.
(A) Compound (2S,5R)-14 was synthesized to rigidify intermediate (2R,5S)-6 for nOe determination. (B) Structure of (2S,5R)-14 with lettering of the protons, structure of the major conformation showing nOe interactions, the 1H NMR and 1D nOe spectra in CDCl3 (400 MHz) are shown. Irradiation of Hi shows an nOe at Hh. Irradiation of Hg shows an nOe at Hi’. (C) The stereochemistry of enantiomer (2R,5S)-14 was determined. Structure with lettering of the protons, structure of the major conformation showing nOe interactions, and a 1D nOe spectrum in CDCl3 (400 MHz) are shown. Irradiation of Hg shows an nOe at Hi’.
Fig 6.
Determination of the stereochemistry of of (2S,5S)-14.
The 2D NOESY spectrum is shown with lettering of the major conformation showing key nOe interactions. Crosspeaks between Hi and Hh, and between He and Hi’ show the stereochemistry given.