Ieva L. Reich

Mechanism of the Lithium-Tellurium, Lithium-Iodine and Lithium-Mercury Exchange Reactions: Hypervalent Tellurium and Iodine Ate Complexes

Abstract The lithium-tellurium exchange is among the fastest of the lithium-metalloid exchange reactions; only the lithium-iodine exchange is slightly faster. Tellurium, iodine and mercury ate complexes are formed when diphenyl telluride, iodobenzene or diphenylmercury are treated with phenyllithium in THF. The mechanism of the lithium-tellurium exchange, (as well as the Li/I and Li/Hg) proceeds through such ate complex intermediates. Monomeric phenyllithium is the reactive form of phenyllithium (the dimer does not participate detectably). Tetraphenyltellurium and triphenyliodine also form hypervalent ate complexes under suitable conditions.

Direct evidence that an arene oxide is a metabolic intermediate of 2,2′,5,5′-tetrachlorobiphenyl

Abstract Radiolabeled arene oxide was recovered from incubations containing [3H]-2,2′,5,5′-tetrachlorobiphenyl (3H-TCB), unlabeled 2,2′,5,5′-tetrachlorobiphenyl-3,4-oxide (TCBAO), 3,3,3-trichloropropene-1,2-oxide (TCPO), NADPH, and liver microsomes from phenobarbital-induced rats. No labeled arene oxide was generated in the absence of NADPH, nor during the metabolism of unlabeled TCB in the presence of [3H]-H2O. The recovered oxide (radiolabeled and carrier) was characterized by mobility on silica gel and by conversion to 3- and 4-hydroxy-TCB. Formation of a dihydrodiol metabolite was apparently blocked by inhibition of epoxide hydrase. These data provide the first direct evidence that arene oxides are intermediates of halogenated biphenyl metabolism.

The Role of Ate Complexes in the Lithium-Sulfur, Lithium-Selenium and Lithium-Tellurium Exchange Reactions

Hypervalent ate complexes are presumptive intermediates in the metal-halogen, metal-tellurium, and related exchange reactions. The effect of o,o′-biphenyldiyl vs. diphenyl substitution on formation of tellurium ate complexes was studied by a kinetic technique and by NMR spectroscopy. Only a modest increase in the association constant (Kate) was measured. When Li/M exchanges of o,o′-biphenyldiyl sulfides and selenides were made intramolecular by means of a m-terphenyl framework (12-S, 12-Se, 21), enormous increases (>109) in the rate of Li/S and Li/Se exchange were observed compared to acyclic models. Apparently, these systems are ideally preorganized to favor the T-shaped geometry of the hypervalent intermediates. For the selenium systems, ate complex intermediates (20-Se, 26) were detected spectroscopically in THF- or THF/HMPA-containing solutions. A DNMR study showed that Li/Se exchange was substantially faster than exchange of the lithium reagents with the ate complex. Therefore, these ate complexes are not on the actual Li/Se exchange pathway.

Ergosteroids V: Preparation and biological activity of various D-ring derivatives in the 7-oxo-dehydroepiandrosterone series

Our previous finding that D-ring seco derivatives of dehydroepiandrosterone retained biologic activity (Reich et al., Steroids 1998;63:542-53) motivated us to synthesize and test a number of steroids in which the D-ring is retained but altered in various ways. Several new steroids were synthesized and characterized by (1)H and (13)C NMR spectroscopy. The availability of a number of closely related compounds allowed detailed (13)C chemical shift correlations. Using the induction of two thermogenic enzymes in rats, liver mitochondrial glycerophosphate dehydrogenase (GPDH) and cytosolic malic enzyme, as criteria of biologic activity some 30 compounds were assayed. Hydroxylation of dehydroepiandrosterone (DHEA) at the 16 alpha position was previously shown to diminish activity (Lardy et al., Steroids 1998;63:158-65); the corresponding 7-oxo compound is fully active. Hydroxylation at the 15 beta position of DHEA, 7-oxo-DHEA, or 16 alpha-hydroxy-7-oxo-DHEA greatly diminished the induction of GPDH but induction of malic enzyme was retained. Most 5,15 diene steroids tested had 2 weak, or no, ability to enhance the formation of GPDH but did increase malic enzyme.