Doctor of Philosophy
Department of Chemistry
Hawkins, William C., Towards functional nanomaterials: the synthesis and characterisation of fullerenyl peptides, Doctor of Philosophy thesis, Department of Chemistry, University of Wollongong, 2007. http://ro.uow.edu.au/theses/1211
Previous work within our group reported that the addition of N- (diphenylmethylene)glycinate esters to fullerene under Bingel conditions gave methanofullerenes. Likewise tethered bis-N-(diphenylmethylene)glycinate esters, provided the corresponding bis-methanofullerenyl iminoesters. Previous efforts to deprotect the N-terminus and C-terminus of these methanofullerenes were unsuccessful, however a novel reductive ring-opening of these compounds was discovered which provided α-fullerenyl glycinate derivatives.
Chapter 2 reports the structural re-assignment of the reaction products from the addition of N-(diphenylmethylene)glycinate esters to fullerene under Bingel reaction conditions. The addition products were unequivocally assigned as diphenylfullerenyldihydropyrroles rather than the previously reported methanofullerenyl derivatives. Mechanistic details were proposed to account for the formation of the fullerenyldihydropyrroles and their reductive ring-opening products.
Reductive removal of the N-benzhydryl group of a ring-opened fullerenyl glycinate derivative provided ethyl α-fullerenylglycinate, the first reported acyclic α- substituted fullerenyl amino ester. Subsequent amide coupling to N-protected amino acid chlorides provided fullerenyldipeptides. Preliminary results indicated that the Fmoc protecting group can be removed from the N-terminus of a fullerenyl dipeptide under basic conditions, and the resulting amine can be coupled to a N-protected amino acid under standard EDCI/HOBt coupling conditions to deliver tripeptides “capped” with fullerenylglycinate. Alternatively the tert-butyl and ethyl fullerenyldihydropyrroles were shown to be readily converted to their corresponding carboxylic acids which then could be coupled to ethyl L-phenylalaninate in good yield. Unfortunately all efforts to ring-open the resultant fullerenyldihydropyrrole peptide were unsuccessful.
In Chapter 3, alternative iminoglycinates were examined in an effort to achieve a methanofullerene adduct from the Bingel reaction. Despite concluding that all iminoglycinates examined were unsuitable precursors for the generation of stable methanofullerenyl derivatives, the reductive ring-opening of an unstable tert-butylidenemethano[ 60]fullerenyl derivative was achieved. Additionally, three new methods to generate fulleropyrrolidines from iminoglycinates were found, namely; intramolecular Mannich reaction, Mn(III) mediated radical addition and reduction of alkylfullerenylpyrroles. Importantly, a method for the generation of a stable, protected methanofullerenyl amino acid was discovered using α-bromophthylglycinate and the Bingel reaction.
Chapter 4 details the structural re-assignment of the reaction products from the addition of tethered bis-N-(diphenylmethylene)glycinate esters to fullerene under Bingel reaction conditions. These reactions provided bisdiphenylfullerenyldihydropyrroles and not the previously reported bismethanofullerenyl derivatives. The regiochemical outcomes however, remain as originally reported. The reductive ring-opening of tethered and non-tethered bis-adducts was achieved albeit in low yield. Intriguingly, only a portion of the expected isomers were observed.
Tether removal of the fullerenyldihydropyrroles to form fullerenyl biscarboxylic acids and subsequent amide coupling to L-phenylalaninate esters delivered the first reported fullerenyl bis-peptides. Mono-transesterification of the trans-4 bisadduct provided a key intermediate for the synthesis of tris-adducts, this was subsequently coupled to ethyl malonyl chloride, then subjected to Bingel cyclopropanation reaction conditions to afford two tris-adducts. However, the regiochemistries were not determined as the overall reaction yields were poor and could not be further enhanced.
Chapter 5, details preliminary mechanistic investigations into the fragmentation of malonyl methanofullerenes in the gas phase using ESI-MS and tandem MS.