Identification and isotopic labelling of the diastereotopic methyl groups of the prenyl-derived 2-hydroxyisopropyl residues of natural products: the rotenoid dalpanol

Abstract

The 2-hydroxyisopropyl (1 -hydroxy-1 -methylethyl) segment derived from a prenyl residue occurs in a number of natural products, including the rotenoid dalpanol, and the aim of this work is the identification and isotopic labelling of the (pro-R) and (pro-S)-methyls of the latter compound. The identification sequence involves linkage between (4′-E)-labelled rot-2′-enonic acid and the labelled (5′S,6′R)-stereoisomer of dalpanol (5′-epidalpanol)via the (2′R,3′R)-epoxide of absolute configuration known from X-ray analysis. Dalpanol of the natural (5′R)-series is labelled in the (6′S)-methyl with deuterium by this sequence and the procedure is applicable to 3H, 13C- and 14C labelling since such 7′-labelled specimens of rotenone, the precursors of 4′-labelled rot-2′-enonic acids, are available from our earlier work.A second labelling method employs the separable rotenone (5′R,6′S)- and (5′R,6′R)-epoxides, which are reduced with lithium aluminium deuteride, followed by reoxidation at C-12a to give both 2H-labelled (5′R,6′S)- and (5′R,6′R)-dalpanols. Oxymercuriation at the 6′,7′-double bond of rotenone is selective, though not specific, for the si-face, leading mainly to the (6′R)-mercuriated product. Purification of the latter, followed by reduction with sodium borotritide, provides an excellent means for the preparation of specifically radiolabelled (5′R,6′S)-dalpanol. Monitoring was by 3H NMR spectroscopy, which is more revealing than the deuterium equivalent.