Fullerene-amino derivatives

The strain introduced in the addition compounds causes them to readily eliminate and revert back to the parent fullerene. This makes mass spectroscopic identification of derivatives particularly difficult. A further difficulty encountered in the chemistry of fullerenes lies in the multitude of addition products that can, in principle, be obtained. For example, for C60 the number of products discounting isomers that can be produced on addition of a reagent X2 will equal the number of double bonds, i.e. 30. If isomers are included then many hundreds are possible. Development of C60 chemistry is therefore very much more difficult than that of benzene. It is also complicated by the low solubility of C60 in organic solvents, and by the fact that derivatives are themselves mostly more soluble, which facilitates polysubstitution hydroxy and amino derivatives of C60 are water-soluble. The additions are described under the two main categories outlined above. 

Condensing racemic l,2-methano[70]fullerene-71-carboxylic acid obtained by hydrolysis of its tert-butyl ester (( )-260, Scheme 1.25),243 with an amino derivative of zinc tetraphenylporphyrin, Imahori, Yamazaki, Sakata, and coworkers synthesized a C7o-containing dyad.355,446 Comparison with the C60-analogue showed that photoinduced electron transfer from the singlet excited Zn-porphyrin to the fullerene is faster in the C70 derivative. 

Fullerene amino acid derivatives have merited special attention in relation with the biological application [275-280], The photochemical reactions of Ceo with amino acid esters have been utilized to obtain fullerene amino acid derivatives [281,282]. For example, the photochemical addition of iminodiacetic methyl ester to Ceo provides a pyrrolidine ring-fused fullerene carboxylate, C6o(MeOOCCHNHCHCOOMe) [281]. Although the mechanistic detail has yet to be elucidated, a possible sequence... 

Photochemical reactions of and amines have also been used in the preparation of fullerene amino acid derivatives. In the reactions, Cgo was irradiated in the presence of amino acid esters to form fulleropyrrolidines [130,131]. 

Treatment of isoxazoline-fiised [60]fullerene 48 with NaOMe in the presence of MeOH gave the p-hydroxy nitrile derivative 49 in good yield <00SL361>. The synthesis of the enantiomerically pure cyclopropane amino acid 51 covalently attached to a fulleroisoxazoline has been achieved . 

Recently, the possibility to use C60 as anti-inflammatory compound has been reported (Huang et al., 2008). Fullerene-xanthine hybrids have been studied to determine if nitric oxide (NO) and tumor necrosis factor-alpha (TNF-a) production in lipopolysaccharide (LPS)-activated macrophages can be inhibited by hybrid administration, finding positive results. The presence of xanthine moiety seems to be essential for the inhibition of LPS-induced TNF-a production, while the fullerene portion ameliorates the efficiency in LPS-induced NO production blockage, leading to a new promising class of potent anti-inflammatoiy agents. It is necessary to mention also the opposite results obtained by an amino acid fullerene derivative tested on human epidermal keratinocytes at concentration from 0.4 to 400 pg/mL. 

The reverse reaction to the Bingel cyclopropanation - the so-called retro-Bingel reaction - was developed by Diederich, Echegoyen and coworkers [70] and opens up the possibility to remove the Bingel-addend completely. This removal was successfully done with Cjq malonates [70, 71], dialkoxyphosphorylmethano[60]-fullerene [72], methano[60]fullerenyl amino acid derivatives [73] and also with... 

Figure 3 Comparison of absorption and fluorescence (inset) spectra of different classes of C6oderivatives themethano-C6oderivative l -carboxy-l,2-methano[60]fullerene the pyrrolidino-C6o derivative N-ethyl-trans-2, 5 -dimethylpyrrolidino[3, 4 l,2][60] fullerene 33 (Fig. 24) (- - -),[B14al the C60 derivative 2-hydroxy-tetrahydrofu-ran[4, 5 l,2] [60]fullerene (—), and the amino-C60 derivative 3 (Fig. 4) AW -dimethyl-piperazine [2, 3 l,2][60]fullerene (-). (From Ref. 65.)...

Bunker et al. also reported approximately three aminofullerene derivatives (3, 32, 33, Fig. 25) that show intramolecular electron transfer from the amino group to the singlet excited state of the fullerene core [189], Although the intramolecular electron transfer shares some characteristics with the classical twisted intramolecular charge transfer in molecules represented by p-N,N-dimethylaminobenzonitrile the amino-C6o derivatives are in fact better classified as redoxdyads [189],... 

Figure 25 Different amino fullerene derivatives. (From Refs. 65, 189.)...

Gan et al. used amino acids such as piperidino acetic acid or morpholino acetic acid in photochemical reactions with C60 [231,232]. Whereas the reaction of the ester derivatives of the amino acids result in the formation of pyrrolidine-fused C6o derivatives, the reaction of the free amino acids give the 1-substituted l,2-dihydro[60]fullerenes 57a-b (Scheme 22). In a typical experiment a methanol solution of the amino acid 56a-b was added to a toluene solution of C6o and irradiated with a 250 W overhead projector lightbulb. Prolonged irradiation led to multiadducts. To avoid hydroxylation of C60 the pH of the amino acid solution should be no more than 9.0. 

As mentioned previously, photocycloaddition reactions are a useful method for obtaining fullerene derivatives fused directly to heterocycles. Such compounds have attracted much interest because they might have interesting properties, e.g., amino acid fullerene derivatives as biologically active compounds or pyrrolidino-fullerenes as key precursors for a great number of fullerenes donor-acceptor bridged dyads and triads. Fullerenes functionalized with silicon compounds are of great interest in materials science. The synthesis of these compounds will be described in this section. 

The reaction with azomethine ylides is an important dass of [3+2]pyrrolidine derivatives of > (Figure 2.60). Immonium salts, aziridines, oxazolidines or silylated ammonium compounds are sources of the yUde structure. The sequence is often carried out according to Prato in a first step an amino acid (like N-methylglycine) is reacted with an aldehyde or ketone. Subsequent reaction with C > then gives the desired pyrrolidine derivative. A multitude of these is accessible by choosing suitable functionalization of the nitrogen atom or the two carbon atoms in the ring (e.g., by choice of a functionalized aldehyde). 

---