Synthese monodisperser linearer und cyclischer Oligomere der (R)‐3‐Hydroxybuttersäure mit bis zu 128 Einheiten

Abstract

Monodisperse Linear and Cyclic Oligo[(R)-3-hydroxybutanoates~ Conitaining up to 128 Monomeric UnitsUsing benzyl ester/(leri-buty1)diphenylsilyl ether protection, (COCl)'/pyridine esterification conditions, and a fragment-coupling strategy (with H,/Pd-C debenzylation and H F .pyridine desilylation), linear oligomers of (R)-3-hydroxybutanoic acid (3-HB) containing up to 128 3-HB building blocks (mol. weight > 11 000 Da) are assembled (Schemes I , 2,5, and 6 ) . In contrast to the previously employed protecting-group combination, and due to the low-temperature esterifying conditions, this procedure leads to monodisperse oligomers: all steps occur without loss of single 3-HB units. The product oligomers with two, one, and no terminal protecting groups (mostly prepared in multi-gram am.ounts) are characterized by all standard spectroscopic methods, especially by mass spectroscopy (Figs. 2 and 3 ) , by their optical activity, and by elemental analyses. Cyclization of the oligo[(R)-3-hydroxybutanoic acids] with up to 32 3-HB units, using thiopyridine activation and CuBr, for the ring closure, produces oligolides consisting of up to 128 ring atoms (Scheme 7). Mixed oligolides containing 3-HB and (R)-3-hydroxypentanoic units are prepared from the corresponding linear trimers, using Yamuguchi's method for the ring closure (Scheme 8 and Fig. 4 (X-ray crystal structures of two folded conformers)). Comparisons of melting points (Table I ) , of [a]:& values (Tables 2 and 3), of 'H-NMR coupling constants (Table 3 ) , and of molecular volume/hydroxyalkanoate unit (Table 4 ) of linear and cyclic oligomer derivatives and of the high-molecularweight polymer show that the monodisperse oligomers appear to be surprisingly good models for the polymer. Besides this insight, our synthesis is supplying the samples to further test the role of P(3-HB) (ca. 140 units) as a component of complexes forming channels through cell-wall phospholipid bilayers.

Proof for a nonproteinaceous calcium-selective channel in Escherichia coli by total synthesis from ( R )-3-hydroxybutanoic acid and inorganic polyphosphate

“…An exponential fragment-coupling strategy was employed to prepare the 128-mer of 3-hydroxybutyrate (HB 128 ) (32). This synthetic polymer has a molecular mass of 11,000 kDa, which is close to that of E. coli PHB (ca.…”

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

“…Of the stereoisomeric dimers 3a ± d, ent-3b ± d, 4b ± d, and ent-4b ± d, only the fully protected compounds of type d 8 ) could be purified by destillation. The other dimers (type a ± c 8 )) had to be purified by chromatography 16 ).…”

Synthesis of Amino-Acid-, Carbohydrate-, Coumarin-, and Biotin-Labelled Oligo[(R)-3-Hydroxybutanoic Acids] (OHB)

“…All other reagents were used as purchased from Fluka or Senn. Compounds 1 ± 3 were synthesized as described in [15]. For h.v.`10 À4 mbar, a turbomolecular pump Balzers TSH065 was employed.…”

“…Monodisperse OHBs 1 ± 3 were synthesized by a segment-coupling strategy previously developed by us [15] (Scheme 1). The subsequent derivatization at the hydroxy and not at the carboxy terminus of the OHBs was chosen for two reasons: i) previous patch-clamp experiments had indicated the necessicity of a free carboxylate function for successful incorporation and stability of OHBs in planar lipid membranes [8], and ii) OHBs tend to fragment via b-elimination under basic conditions [15] (following a mechanism in which an OHB-species activated at the carboxy terminus turned out to be a key intermediate). Thus, derivatization involving the carboxy functionality would have been limited to reaction conditions used in the segment coupling synthesis (via an acid chloride), whereas coupling at the hydroxy end should allow the use of more diversified and more drastic reaction conditions.…”