Cyclische Oligomere von (R)-3-Hydroxybuttersaeure: Herstellung und strukturelle Aspekte

Article abstract of DOI:10.1002/hlca.19930760518

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)....