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New hybrid fullerene–steroid derivatives were prepared by using the Bingel–Hirsch protocol, by treatment of [60]fullerene with malonates bearing the appropriate steroid moieties obtained, in turn, from the functionalization of epiandrosterone, an important naturally occurring steroid hormone. Monocycloadduct C60‐steroid conjugates were obtained by functionalization of ring A or ring D of the steroid moiety. We have also described the multistep preparation of a [60]fullerene hybrid dumbbell endowed with two fullerene units connected through an epiandrosterone molecule by a cyclopropanation reaction. The new compounds have been spectroscopically characterized and their redox potentials, determined by cyclic voltammetry, reveal three reversible reduction waves for monocycloadducts (8, 9 and 11, 12), whereas dumbbell‐type derivative 10 exhibits the best electron‐accepting abilities of the Bingel‐type fullerene–steroid series. Theoretical calculations at semiempirical (AM1) and single point B3LYP‐D3/6‐31G+(d,p) levels have predicted the most stable conformations for the hybrid compounds and allow explaining the observed regioselectivity in the cyclopropanation reaction with dimalonate 7 during the synthesis of the dumbbell derivative.

The design and synthesis of fullerene-steroid hybrids by using Prato's protocol has afforded new fullerene derivatives endowed with epiandrosterone, an important naturally occurring steroid hormone. Since the formation of the pyrrolidine ring resulting from the 1,3-dipolar cyloaddition reaction takes place with generation of a new stereogenic center on the C2 of the five member ring, the reaction proceeds with formation of a diastereomeric mixture [compounds 6 and 7 in 70:30 ratio, and 8 and 9 in 26:74 ratio (HPLC)] in which the formation of the major diasteroisomers 6 and 9 is consistent with an electrophilic attack of [60]fullerene by the Re face. The chiroptical properties of these conjugates reveal typical Cotton effects in CD spectra that have been used to assign the absolute configuration of the new fulleropyrrolidines. The electrochemical study of the new compounds reveals the presence of four quasi-reversible reduction waves which are cathodically shifted in comparison with the parent C 60 .

Cyclopropanations between C60 and readily available malonates bearing different steroid moieties (4–6) by the Bingel–Hirsch protocol has allowed the synthesis of a new series of hybrid functionalized chimeras (7–9). Whereas cycloadducts 7 and 8 showed the expected chemical structures, the presence of the diene moiety in the ergosterol unit of malonate 6 resulted in the production of the corresponding cycloadduct with an additional oxygen molecule. A thorough spectroscopical study (1H and 13C NMR, COSY, DEPT, HMQC, and HMBC) allowed the structure of monocycloadduct 9 to be unambiguously unraveled as that of an endoperoxide, as a result of the sensitizing effect of the C60 unit, which efficiently promotes the addition of excited singlet oxygen to the diene moiety of the steroid. Cyclic voltammetry of hybrids 7–9, as well as their electronic spectra, support the exclusive formation of the corresponding monoadducts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

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