Synthesis and structure of linear and cyclic oligomers of 3-hydroxybutanoic acid with specific sequences of (R)- and (S)-configurations

To study the stereoselectivity of enzymatic cleavage of poly(3-hydroxybutyr ates) (PHB) in a well-defined system (purified depolymerase and monodispers e substrate of specific relative configuration), linear and cyclic oligomer s of HE (OHBs) containing (R)- and (S)-3-hydroxybutanoate residues were syn thesized. The starting material (R)-HB was prepared from natural sPHB, and (S)-HB by enantioselective reduction of 3-oxobutanoate: with yeast or with H-2/Noyori-Taber catalyst (Scheme 2). The HE building blocks were then prot ected (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 subj ected to macrolactonization conditions (Yamaguchi) to give the cyclic tetra mers 23 and 25 and octamers 24 and 26. All new compounds were fully charact erized (m.p., [alpha](D), CD, IR, H-1- and C-13-NMR, MS, elemental analysis ). Single-crystal X-ray structure analyses were performed with oligolides 2 4 and 25 ( Figs. 2 and 4), and the structures, as well as the crystal packi ng, were compared with those of analogs containing only (R)-HB units or con sisting of 3-amino- instead of 3-hydroxybutanoic-acid moieties.