Synthesis and Structure of Linear and Cyclic Oligomers of 3-Hydroxybutanoic Acid with Specific Sequences of (R)- and (S)-Configurations

Abstract

To study the stereoselectivity of enzymatic cleavage of poly(3-hydroxybutyrates) (PHB) in a well-defined system (purified depolymerase and monodisperse substrate of specific relative configuration), linear and cyclic oligomers of HB (OHBs) containing (R)- and (S)-3-hydroxybutanoate residues were synthesized. The starting material (R)-HB was prepared from natural sPHB, and (S)-HB by enantioselective reduction of 3-oxobutanoate with yeast or with H2/Noyori-Taber catalyst (Scheme 2). The HB building blocks were then protected (O-benzyl/tert-butyl ester; Scheme 3) and coupled to give dimers 3, 4, tetramers 5 – 9, and octamers 10 – 18; for analytical comparison, a 3mer, 5mer, 6mer, and 7mer (19 – 22) were also prepared. Two of the tetramers were subjected to macrolactonization conditions (Yamaguchi) to give the cyclic tetramers 23 and 25 and octamers 24 and 26. All new compounds were fully characterized (m.p., [α]D, CD, IR, 1H- and 13C-NMR, MS, elemental analysis). Single-crystal X-ray structure analyses were performed with oligolides 24 and 25 (Figs. 2 and 4), and the structures, as well as the crystal packing, were compared with those of analogs containing only (R)-HB units or consisting of 3-amino- instead of 3-hydroxybutanoic-acid moieties.