Laboratory emulation of polyketide biosynthesis: an iterative, aldol-based, synthetic entry to polyketide libraries using (R)- and (S)-1-(benzyloxy)-2-methylpentan-3-one, and conformational aspects of extended polypropionates

Abstract

Iterative, one-directional, boron-mediated aldol chain extensions, using the dipropionyl reagent (R)-1-(benzyloxy)-2-methylpentan-3-one 7, have enabled the highly diastereoselective assembly of the stereoregular heptapropionates 5 and 6. The synthetic sequence developed permits structural diversity through variation in the stereochemical nature of the aldolisation and reduction steps, together with the choice of the chiral ketone employed at each iteration. The heptapropionate 5 has been shown to represent an example of a fully flexible molecule, whose backbone nevertheless adopts a single preferred conformation. It forms part of a family of conformationally controlled polyols, exploiting the avoidance of syn-pentane interactions and the preference for preorganisation through intramolecular hydrogen bonding.