139629-08-6Relevant articles and documents
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)....
