Preparation and structure of oligolides from (R)-3-hydroxypentanoic acid and comparison with the hydroxybutanoic-acid derivatives: A small change with large consequences

Article abstract of DOI:10.1002/hlca.19940770727

Cyclic oligomers of (R)-3-hydroxyvaleric acid (3-HV) are prepared from the monomer by three different methods, giving various ratios of the oligomers. The macrocycles containing three to twelve 3-HV units (12- to 48-membered rings) are isolated in pure form by chromatography. The triolide 3 can be separated by distillation and isolated on large scale. Biopol, the copolymer of (R)-3-hydroxybutanoic acid (3-HB) and (R)-3-hydroxyvaleric acid (3-HV), is degraded to mixtures of Me- and Et-substituted triolides ('mixolides') with high crystallization tendency. The X-ray crystal structures of the tetrolide 4, pentolide 5, hexolide 6, heptolide 7, and of two 'mixolides' (with inclusions of solvent) have been determined and are compared with those of the corresponding 3-HB derivatives reported previously. From the structural data, a 3₁ and a 2₁ helix of 3-HV can be modelled, and the latter one compared with helix structures of P(3-HB) and P(3-HV) derived from stretch-fibre X-ray scattering. Crystals of a water-containing NaSCN complex of the triethyl triolide 3 were obtained in good quality for X-ray analysis. The structure contains an interesting array of C=O and H₂O O-atoms around the Na⁺ ions along a channel-type tube (a-axis of the crystal) which may be relevant to the role of P(3-HB) and P(3-HV) as components of cellular ion channels.