The Structure of the Antibiotic Hedamycin. I. Chemical, Physical and Spectral Properties

Abstract

SummaryInterpretation of the chemical and spectral (IR., UV., lH-and I3C-NMR.) properties of the antitumor antibiotic hedamycin (C41H50N2011) suggests that the molecule contains a methyl substituted 1 -hydroxyanthraquinone nucleus, an a, ,&unsaturated ketone, two sugar-like tetrahydropyran rings (4 and 8) and an aliphatic chain 2, presumably with an epoxy group (see the Scheme).

The Antibiotics of the Pluramycin Group (4 H-Anthra [1,2-b] pyran Antibiotics)

“…The error was not detected since the elemental analysis could not reveal it. Ten years later a correct molecular ion could be obtained and persilylation of hedamycin further helped, but the rather heavy derivative obtained was not easy to measure either (82,84). Newer techniques, recently reviewed by HOWE and JARMAN (40), now make mass spectrometry a valuable tool for confirmation of molecular weights in the pluramycin series.…”

“…Quite typical 1 H -1 H coupling patterns are obtained in ring E which allow a reasonable assignment of the configurations (84). In contrast, proton-proton coupling in ring F does not help much, since the sequence of coupling protons is interrupted at C(4"), and since the conformation of ring F in solution is a rather flexible one (see below).…”

“…The three methyl doublets just discussed often overlap, especially when a low field NMR spectrometer is used. It was, however, possible to resolve these signals in the case of hedamycin (17) at 100 MHz when the spectrum was recorded in deuteropyridine (84).…”

“…Neutral or weakly acidic solutions of these compounds are yellow, whereas alkaline solutions are purple. Reduction with hydrogen (79,84), zink or dithionite (18) yields products which are readily reoxidized in the atmosphere. The hydroquinone form could be trapped The formation of colored complexes with many metal ions was reported for hedamycin (17) (84) and other compounds (51): reddish brown with Fe3+, purple with Mg2+, violet with Ba 2+ or Co 2 +, dull red with Cu 2 +, brownish violet to blue with Ni 2 +.…”

The Structure of the Antibiotic Hedamycin. V. Crystal structure and absolute configuration

“…The corresponding 'H, 'H-coupling constants calculated from the Karplus equation [7] would be 1, 5 and 0 Hz. These values, when compared with the experimental data of 3, 7 and 5 Hz [8], indicate that the conformation of hedamycin in solution is hardly the one the molecule displays in the crystal. Thus, despite the astounding crystal conformation found, we believe that our earlier discussion of the conformation of ring F in solution [3], which pointed rather to a flexible twist form, is still valid.…”