SYNTHESIS OF MONODISPERSE LINEAR AND CYCL IC OLIGO[(R)-3-HYDROXYBUTANOATES] CONTAINING UP TO 128 MONOMERIC UNITS

Using benzyl ester/(tert-butyl)diphenylsilyl ether protection, (COCl)( 2)/pyridine esterification conditions, and a fragment-coupling strateg y (with H-2/Pd-C debenzylation and HF pyridine desilylation), linear o ligomers of (R)-3-hydroxybutanoic acid (3-HB) containing up to 125 3-H B building blocks (mel. weight > 11000 Da) are assembled (Schemes 1, 2 , 5, and 6). In contrast io the previously employed protecting-group c ombination, and due to the low-temperature esterifying conditions, thi s procedure leads to monodisperse oligomers: all steps occur without l oss of single 3-HB units. The product oligomers with two, one, and no terminal protecting groups (mostly prepared in multi-gram amounts) are characterized by all standard spectroscopic methods, especially by ma ss spectroscopy (Figs. 2 and 3), by their optical activity, and by ele mental analyses, Cyclization of the oligo[(R)-3-hydroxybutanoic acids] with up to 32 3-HB units, using thiopyridine activation and CuBr2 for the ring closure, produces oligolides consisting of Lip to 125 ring a toms (Scheme 7). Mixed oligolides containing 3-HB and (R)-3-hydroxypen tanoic units are prepared from the corresponding linear trimers, using Yamaguchi's method for the ring closure (Scheme 8 and Fig. 4 (X-ray c rystal structures of two folded conformers)). Comparisons of melting p oints (Table 1), of [alpha](20)(365) values (Tables 2 and 3), of H-1-N MR coupling constants (Table 3), and of molecular volume/hydroxyalkano ate unit (Table 4) of linear and cyclic oligomer derivatives and of th e high-molecular-weight polymer show that the monodisperse oligomers a ppear to be surprisingly good models for the polymer. Besides this ins ight, our synthesis is supplying the samples to further test the role of P(3-HB) (ca. 140 units) as a component of complexes forming channel s through cell-wall phospholipid bilayers.