Chromic acid degradation of natural (-)-stercobilin (1) yields 2(R)-methyl-3(R)-ethylsuccinimide (+2), whereby the absolute configuration of 1 at the chiral centers C-1, C-2, C-7, and C-8 is established. The substituted oxo-tetrahydrodipyrromethane precursor, 5, for the total synthesis of (-)-stercobilins 3 and 4, in which the relative configuration between the asymmetric centers is known, yields 2(S)-methyl-3(S)-ethylsuccinimide (-2) under the same conditions of degradation. Nuclear magnetic resonance studies of 1 and 3 show that in 1 the hydrogen atoms at C-2 and C-2', as well as those at C-7 and C-7', are trans relative to one another. Accordingly, natural (-)-stercobilin possesses the 2'(S), 7'(S) configuration, and has the configuration formula 6(1 (R), (7), in which the relative configurations of triads of chiral centers (C-1, C-2, C-2', and C-7', 0-7, 0-8) were unequivocally established on the basis of the precursors used in the syntheses. The high values of the optical rotation of both 3 and 4 further supported assignment of the same configurations of these compounds at C-2' and C-7'. The thinlayer chromatographic (TLC) behavior, infrared spectra, and electronic spectra of 3 and 4 were indistinguishable from those of 1. However, only isomer 3 had the same DebyeScherrer diagram as that of the natural product. It therefore appeared that 3 and 1 were identical, and that the relative configuration of natural (-)-stercobilin was thus established. However, the observation (C. J. Watson, unpublished data) that 3 did not yield the crystalline complex with iron (III) chloride characteristic of 1 (11, 12), but of no other urobilinoid thus far examined (12), caused us furthermore to compare the results of oxidative degradation of 5 and of natural (-)-stercobilin (1). Determination of the absolute configuration of 3 should be possible by oxidative degradation of the precursor 5 to 2-methyl-3-ethyl-succinimide (2), whose absolute configuration was established previously by Brockmann Jr. and coworkers (8-10).
MATERIALS AND METHODSThe NMR spectra were recorded with a Varian HA-100 nuclear magnetic resonance spectrometer, the ORD spectra with a Cary 60 recording spectropolarimeter, and the CD spectra with a Roussel-Jouan Dichrograph II.Chromic acid oxidation of 5 26 mg of 5 ([a]D20 = -105oC in methanol) dissolved in 3 ml of tetrahydrofuran were added dropwise to a solution of 12 g of CrO3 in 80 ml of 15% H2S04. The mixture was stirred for 3 hr at 800C. After cooling, this solution was diluted with 150 ml of water and extracted eight times with 100-ml portions of ether. The combined ether phase was shaken with 400 ml of a saturated solution of NaHCO3 and dried over Na2SO4. The ether was than removed in a flash evaporator. The degradation mixture (11.5 mg) was separated by means of preparative TLC on a 20 X 20 cm plate (silica gel HF254 + 366, Merck, layer thickness 0.8 mm, petroleum ether (40-600C)-ethyl acetate-isopropyl alcohol 44:5:1). The zone visible in ultraviolet light was removed, and the degradation im...
