Synthesis and Characterization of Mono- and Bis-methano[60]fullerenyl Amino Acid Derivatives and Their Reductive Ring-Opening Retro-Bingel Reactions

Abstract

The addition of N-(diphenylmethylene)glycinate esters (Ph2C=NCH2CO2R) 3-6 to [60]fullerene under Bingel conditions gives, respectively, the methano[60]fullerenyl iminoesters 7-10. Upon treatment of 7-9 with sodium cyanoborohydride, in the presence of a protic or a Lewis acid, a novel reductive ring-opening reaction occurred to give the corresponding 1,2-dihydro[60]fullerenyl glycine derivatives 11-13. Using tethered bis-N-(diphenylmethylene)glycinate esters 33 and 34derived from m- and p-benzenedimethanol scaffolds, the corresponding bis-methano[60]fullerenyl iminoesters 35-38 were synthesized under double Bingel reaction conditions. The m-benzenedimethanol derivative 33 gave the trans-4 (35) and cis-3 (36) regioisomeric bisadducts in a ratio of 80:20. The analogous para-tethered derivative 34 afforded the trans-3 (37) and trans-4 (38) regioisomers in a 80:20 ratio. The regiochemistry of the major bisadducts 35 and 37 (via the trans-esterified 39) were unequivocally determined using 2D INADEQUATE and C-C TOCSY NMR experiments. The regiochemistry of these bis-additions were unexpected on the basis of literature precedents. These results unequivocally show that the regiochemistry of tethered bis-additions is not solely dependent on the nature of the tether. A mixture of the trans-4 and cis-3 nonsymmetrical bisadducts 45 and 46 was obtained from the double-Bingel cyclopropanation of a bis-N-(diphenylmethylene)glycinate tether based on a 1,3-naphthyldimethanol scaffold. The regiochemistry of these compounds (45 and 46) was identified by correlation with the diethyl esters 40 and 47, prepared by trans-esterification of 35/45 and 36/46, respectively. The INADEQUATE and molecular modeling experiments allowed topological mapping of the fullerene surfaces of the bis-methano[60]fullerenes 38 and 42. Reductive ring-opening reactions on the tethered bis-methano[60]fullerenes 35-37, 45, and 46 gave none of the expected bis-fullerenylglycinates rather the reductive ring-opening-retro-Bingel products, the 1,2-dihydro[60]fullerenylglycinates 48, 49, 52, and 53. These compounds resulted from the reductive ring-opening of one methanoimino ester moiety and a retro-Bingel reaction of the other. Under analogous reductive ring-opening-retro-Bingel conditions, the nontethered bis-methano[60]fullerene 40 afforded the 1,2-dihydro[60]fullerenylglycinate 12. Thus, it was concluded that the tether was not the driving force for the reductive elimination of one of the methano groups.

Fullerene‐Derivatized Amino Acids: Synthesis, Characterization, Antioxidant Properties, and Solid‐Phase Peptide Synthesis

“…In contrast to the 1 H NMR spectrum, the shift differences for the two diastereomers are recognizable in the 13 C spectrum, as most of the carbons near one chiral center or between the two chiral centers give a pair of signals of essentially equal intensity differing in chemical shift by [8][9][10][11][12][13][14][15][16] ppb (digital resolution = 0.76 ppb) (Figure 4). That such pairs of signals are observed is not surprising since 13 C chemical shifts are known to be very sensitive to remote changes in stereochemistry.…”

“…Cationic Baa-(Lys) 9 -OH (13) and Baa-LysA C H T U N G T R E N N U N G (FITC)-(Lys) 8 -OH (14, where FITC = fluorescein isothiocyanate), anionic Baa-(Glu) 4 -(Gly) 3 -Ser-OH (15), and Baa-(Glu) 4 -(Gly) 3 -Ser-Cys-OH (16) peptide sequences have been prepared. The anionic peptide 15 was also compared to the parent amino acid for antioxidant activity.…”

“…To date, several approaches have been taken towards synthesizing fullerene-based amino acids. [8][9][10][11][12][13] All of these compounds are derived from aliphatic amino acids and commonly employ ester or amide linkages. In contrast, an additional requirement of our general synthetic apAbstract: A series of [60]fullerene-substituted phenylalanine (Baa) and lysine derivatives have been prepared by the condensation of 1,2-(4'-oxocyclohexano)fullerene with the appropriately protected (4-amino)phenylalanine and lysine, respectively.…”

Regioselective Synthesis of Novel e‐Edge‐[60]fullerenylmethanodihydropyrroles and 1,2‐Dihydromethano[60]fullerenes.

“…In related tethered bismalonate and tethered bis-N-diphenylmethyleneglycinate ester [60]fullerene adducts, these benzylic protons are usually diastereotopically split into pairs of doublets arising from a lack of a corresponding plane of symmetry. [8,9] The 1 H NMR spectrum of 12 showed three singlets at 4.01 (3H), 4.02 (3H) and 4.13 (3H), corresponding to three sets of non-equivalent methyl ester protons. The 13 C NMR spectra of 6 and 12 showed 29 fulleryl sp 2 resonances, two of which where clearly half-intensity resonances (C-52 and C-60, Figure 1), indicating Cs-symmetry for both bis-adducts.…”

“…[3] We recently reported that the addition of N-(diphenylmethylene)glycinate esters under these conditions, and their corresponding tethered analogs, gave [60]fullerenyldihydropyrroles and the corresponding bis-adducts, respectively. [4][5][6][7][8] The tether used was 1,3-benzene dimethanol and the regiochemical outcome was trans-4 and cis-3 in a 3 : 1 ratio. The corresponding bis-malonate derivative, linked by the identical tether, yielded exclusively the cis-2 bis-methano[60]fullerene.…”