Studies towards the synthesis of the aminopolyol antibiotic zwittermicin A

The problems caused by Phytophthora medecaginis; together with the isolation, biological activity and biosynthesis of zwittermicin A (which shows potential as an inhibitor of this disease) are reviewed. Studies towards the synthesis of the aminopolyol antibiotic zwittermicin A I will be described. (Fig. 6438) Chapter 2 outlines the approaches investigated towards the synthesis of the nitrogen-rich fragment II which include: enzymatic separation of racemic 2,3-diaminopropionic acid using a D-amino acid oxidase; and synthetic routes based on a Hofmann rearrangement of N-protected asparagine. Chapter 3 describes studies towards the synthesis of aminopolyol species IV from threonine-derived ketone V and the serine-derived aldehyde VI. Methodology for the “matched” lithium-mediated aldol reaction between these two components was developed, together with directed reductions of the resultant aldol adducts to give either syn or anti diol relationships. The future application of this methodology to the total synthesis of zwittermicin A is discussed in Chapter 4. Chapter 5 presents a preliminary study of high pressure conditions for enantioselective organocatalytic aldol reactions.