Approaches towards aminopyruvates and syn-aromatic aminodiols

• Main Author: Faulkner, Simon
• Published: University College London (University of London) 2007
• Subjects: 547.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.497763

The thesis describes synthetic approaches towards chiral aromatic aminodiols, an important structural motif that can also potentially be prepared via the sequential use of transketolase (TK) and transaminase (TA). Syntheses of aminopyruvates and analogues as novel TK donors are also described. Initially, the aims of this Ph. D. are laid out in Chapter 1 a literature review of the uses of enzymes in chemoenzymatic syntheses is covered. In particular, carbon-carbon bond forming enzymes (TK) from a family of thiamine pyrophosphate enzymes are discussed. The latter part of Chapter 1 explores the use of TAs to convert ketone groups to amino groups stereoselectively. Chapter 2 is concerned with current synthetic strategies towards the synthesis of aminodiols and the Sharpless asymmetric aminohydroxylation (AA). This is a key reaction in establishing chiral aminoalcohol functionalities. The results and discussion are described in Chapter 3 to Chapter 5. Chapter 3 outlines a systematic approach towards nitrogen containing pyruvate donors, via a number of synthetic protocols, for potential use with TK and TK mutants. Finally, a TK mimetic reaction is presented with the successful synthesis of 3-phthalimidopyruvate. Synthetic approaches towards aromatic aminodiols via a short reaction sequence for use as HPLC standards are outlined in Chapter 4. Initially, one-pot methodologies were explored to access both syn and arcf/'-diastereomers and are described. Using 'masked' aromatic syn-aminodiols, the methodology for producing aromatic sy/7-aminodiols via a short reaction sequence is described along with the synthesis of cinnamate precursors for the Sharpless asymmetric aminohydroxylation (AA) reaction. Finally, the results of Sharpless AA reactions via homogeneous and heterogeneous catalytic conditions with cinnamate precursors are presented in Chapter 5. An overall summary and future areas of research in the future are discussed in Chapter 6, whilst a formal description of the experimental methods and procedures employed in this thesis are presented in Chapter 7.