Electron impact ionization mass spectra of lithocholyl amides: Evidence for a C(20) to C(23) rearrangement involving the loss of a C₄H₉ fragment

Abstract

Amides of lithocholic acid (3a-hydroxy-5~-cholan-24-oic acid) with daminocaproic acid and Caminobutyric acid were prepared and examined by electron impact ionization mass spectrometry. Both these compounds gave an unusual [ M -57 1 + fragment. Since the product-ion analysis of [ M -57 1 + revealed the presence of fragments corresponding to the intact steroid nucleus in addition to that of the original amino acid (daminocaproic acid or Caminobutyric acid), we concluded that the integrity of the steroid amide had been retained in this fragment. The absence of this fragment from the product-ion spectrum of [M -CH3]+ rules out the sequential loss from the molecular ion of 15 + 42 u as the origin of this signal. Mass spectrometry of the 2d13C-labeUed lithe cholylcaproylamide showed the retention of the label in the [ M -571 + fragment. In contrast, the corresponding compound labelled with deuterium at C(23) showed a significant loss of the label during the formation of this product ion at [ M -581 +. In addition, through a combination of derivatization and tandem mass spectrometry, it was demonstrated that this loss of 57 u represented a rearrangement with the expulsion of a C,H, radical from the side-chain spanning C(20) to C(23) resulting in a truncated steroid-amide fragment. This fragmentation pattern has not been observed in bile acid conjugates with N-a-amino acids.

Direct Synthesis of Esters and Amides from Unprotected Hydroxyaromatic and -aliphatic Carboxylic Acids

“…N -Lithocholylpyrrolidine amide (3k): white needles from ether (93%); mp 167−168 °C; IR (neat) ν = 3406, 2934, 2863, 1626, 1446, 1041 cm -1 ; 1 H NMR δ 3.62 (m, 1H), 3.46 (t, J = 6.87 Hz, 2H), 3.42 (t, J = 6.73 Hz, 2H), 2.36−2.1 (m, 2H), 1.97−0.92 (m, 37H), 0.64 (s, 3H); 13 C NMR δ 172.2, 71.7, 56.4, 56.0, 46.5, 45.6, 42.7, 42.0, 40.4, 40.1, 36.4, 35.8, 35.5, 35.3, 34.5, 31.7, 30.9, 30.5, 28.2, 27.1, 26.4, 26.1, 24.4, 24.2, 23.3, 20.8, 18.5, 12.0. Anal.…”