Functional Chimeras: New Bingel–Hirsch‐Type Steroid–Fullerene Hybrids

Abstract

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)

[60]Fullerene Hybrids Bearing “Steroid Wings”: A Joined Experimental and Theoretical Investigation

“…[28] In this sense, the Bingel-Hirsch methodology has allowed us to obtain a variety of methanofullerenes coupled to different steroid moieties such as cholesterol, -sitosterol, and ergosterol, which are soluble in different organic solvents and potential molecular prototypes to explore the bio-medical applications of C 60 -steroids conjugates. [29] In addition, our group has also developed a synthetic strategy to prepared dumbbell-type fullerene-steroid hybrids, endowed with two [60]fullerene moieties covalently attached through the naturally occurring steroid hormone epiandrosterone. The two C 60 moieties were introduced considering a combination of Bingel-Hirsch cyclopropanation reactions and 1,3-dipolar cycloaddition processes considering steroid dimalonate units adequately functionalized.…”

“…Over the years ours research groups have collaborated in the design and preparation of C 60 ‐steroid conjugates considering several synthetic protocols . In this sense, the Bingel–Hirsch methodology has allowed us to obtain a variety of methanofullerenes coupled to different steroid moieties such as cholesterol, β‐sitosterol, and ergosterol, which are soluble in different organic solvents and potential molecular prototypes to explore the bio‐medical applications of C 60 ‐steroids conjugates . In addition, our group has also developed a synthetic strategy to prepared dumbbell‐type fullerene‐steroid hybrids, endowed with two [60]fullerene moieties covalently attached through the naturally occurring steroid hormone epiandrosterone.…”

Diastereoselective Synthesis of Steroid–[60]Fullerene Hybrids and Theoretical Underpinning

“…Alternatively, steroids are ideal blocks of molecular construction widely used in the design of drugs, due to their biological activity and specific interaction with hormone receptors . It has been demonstrated that the covalent functionalization of C 60 with a steroid unit changes its physicochemical properties, in particular its solubility and biocompatibility …”

Morphological characterization of fullerene–androsterone conjugates

“…The covalent linkage of C 60 to moieties, such as porphyrins [3], anionic polymethine cyanine [4], and other bioactive molecules such as amino acids [5], peptides [6–7], nucleotides, sugars and steroids [8–9], have allowed the solubilization of these hybrid derivatives in aqueous media, thus enhancing certain biological activities. For the potential use of C 60 derivatives as drug delivery systems, the size of the particles is important.…”