152996-90-2Relevant academic research and scientific papers
Synthesis and structure of linear and cyclic oligomers of 3- hydroxybutanoic acid with specific sequences of (R)- and (S)-configurations
Bachmann, Beat M.,Seebach, Dieter
, p. 2430 - 2461 (2007/10/03)
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 (Scheme2). The HB building blocks were then prolected (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.
Conformational Analysis of Oligomers of (R)-3-Hydroxybutanoic Acid in Solutions by 1H NMR Spectroscopy
Li, Jun,Uzawa, Jun,Doi, Yoshiharu
, p. 1683 - 1689 (2007/10/03)
Oligomers of (R)-3-hydroxybutanoic acid (3-HB) with different end groups and chain lengths have been prepared as model compounds of bacterial poly[(R)-3-hydroxybutanoate] [P(3-HB)]. They were studied in terms of their conformational behavior generated by rotation about CH2CH bond of 3-HB units in solutions. The conformational behaviors of 3-HB oligomers were investigated in various solvents by analysis of vicinal coupling in the 500-MHz 1H NMR spectra. For all 3-HB oligomers studied in this work, 3-HB units without hydroxy group were found, in every solvent, to adopt similar conformational distributions to those of P(3-HB) polymer backbone in solutions, in which trans and gauche conformers are preferable, while the other gauche conformer is strongly disfavored. On the other hand, 3-HB units adjacent to hydroxy terminal group in 3-HB oligomers show different conformational behaviors relative to those of other 3-HB units. In non-polar organic solvents, only gauche conformer is predominant, due to the formation of an intramolecular hydrogen bond between hydroxy and carbonyl groups, while in polar organic solvents, the conformer distributions are similar to those of 3-HB units without hydroxy groups. In aqueous solution, for 3-HB units adjacent to hydroxy terminal group, the fractions of gauche conformer are still higher than those of trans conformer due to the formation of an intramolecular hydrogen bond.
Cyclische Oligomere von (R)-3-Hydroxybuttersaeure: Herstellung und strukturelle Aspekte
Plattner, Dietmar A.,Brunner, Andreas,Dobler, Max,Mueller, Hans-Martin,Petter, Walter,et al.
, p. 2004 - 2033 (2007/10/02)
Cyclic Oligomers of (R)-3-Hydroxybutanoic acid: Preparation and Structural Aspects The oligolids containing three to ten (R)-3-hydroxybutanoate (3-HB) units (12 through 40-membered rings 1-8) are prepared from the hydroxy acid itself, its methylester, its lactone ('monolide') or its polymer (poly(3-HB), mol. wt. ca. 106 Dalton) under three sets of conditions: i) treatment of 3-HB (10) with 2,6-dichlorobenzoyl chloride/pyridine and macrolactonization under high dilution in toluene with 4-(dimethylamino)pyridine (Fig.3); ii) heating a solution (benzene, xylene) of the β-lactone 12 or of the methyl ester 13 from 3-HB with the tetraoxadistanna compound 11 as trans-esterification catalyst (Fig.4); iii) heating a mixture of poly(3-HB) and toluene-sulfonic acid in toluene/1,2-dichloroethane for prolonged periods of time at ca. 100 deg (Fig.6).In all three cases, mixtures of oligolides are formed with the triolide 1 being the prevailing component (up to 50percent yield) at higher temperatures and with longer reaction times (thermodynamic control, Fig.3-6).Starting from rac-β-lactone rac-12, a separable 3:1 to 3:2 mixture of the l,u- and l,l-triolide diastereoisomers rac-14 and rac-1,respectively, is obtained.An alternative method for the synthesis of the octolide 6 is also described: starting from the appropriate esters 15 and 17 and the benzyl ether 16 of 3-HB, linear dimer, tetramer, and octamer derivatives 18-23 are prepared, and the octamer 23 with free OH and CO2H group is cyclised (->6) under typical macrolactonization conditions (see Scheme).This 'exponential fragment coupling protocol' can be used to make higher linear oligomers as well.The oligolids 1-8 are isolated in pure form by vacuum distillation, chromatography, and crystallization, an important analytical tool for determining the composition of mixtures being 13C-NMR spectroscopy (each oligolide has a unique and characteristic chemical shift of the carbonyl C-atom with the triolide 1 at lowest, the decolide 8 at highest field).The previously published X-ray crystal structures of triolide 1, pentolide 3, and hexolide 4 (two forms), as well as those of the l,u-triolide rac-14, of tetrolide ent-2, of heptolide 5, and of two modifications of octolide 6 described herein for the first time are compared with each other (Figs.7-10 and 12-15, Tables 2 and 5-7) and with recently modelled structures (tables 3 and 4, Fig.11).The preferred dihedral angles τ1 to τ4 found along the backbone of nine oligolide structures (the hexamer and the larger ones have folded rings!) are mapped and statistically evaluated (Fig.16, Tables 5-7).Due to the occurrence of two conformational minima of the dihedral angle O-CO-CH2-CH (τ3 = +151 or -43 deg), it is possible to locate two types of building blocks for helices in the structures at hand: a right-handed 31 and a left-handed 21 helix; both have a ca. 6 Angstroem pitch, but very different shapes and dispositions of the carbonyl groups (Fig.17)....
