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

Cyclic Oligomers of (R)-3-Hydroxybutanoic Acid: Preparation and Structural Aspects The oligolides 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 methyl ester, 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° (Fig. 6). In all three cases, mixtures of oligolides are formed with the triolide 1 being the prevailing component (up to 50% yield) at higher temperatures and with longer reaction times (thermodynamic control, Figs. 3–6). Starting from rac-β-lactone rac- 12 , a separable 3:1 to 3:2 mixture of the l,u- and the l,l-triolide diasteroisomers 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 cyclized (→ 6 ) under typical macrolactonization conditions (see Scheme). This ‘exponential fragment coupling protocol’ can be used to make higher linear oligomers as well. The oligolides 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 the nine oligolide structures (the hexamer and the larger ones all 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°), 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 Å pitch, but very different shapes and dispositions of the carbonyl groups (Fig. 17). The 2₁ helix thus constructed from the oligolide single-crystal data is essentially superimposable with the helix derived for the crystalline domains of poly(3-HB) from stretched-fiber X-ray diffraction studies. The absence of the unfavorable (E)-type arrangements around the OC? OR bond (‘cis-ester’) from all the structures of (3-HB) oligomers known so far suggests that the model proposed for a poly(3-HB)-containing ion channel (Fig. 2) must be modified.     

Structural Aspects of the Enantioselectivity of Tartrates with α-Amino-alcohol Salts. Part II. Crystal structures of (1R, 2S)-norephedrine hydrochloride and (1R, 2R)- norpseudoephedrine hydrochloride

Enantioselective host-guest complexes between α-amino-alcohol salts and chiral tartrates can not be crystallised up to now. To study structural aspects of their enantioselectivity, crystal structures of the components were determined. Norephedrine was used as a reference guest α-amino-alcohol. (1R, 2S)-Norephedrine hydrochloride (monoclinic, space group P2₁ Z = 4, a = 8.455, b = 10.331, c = 12.570 Å, β = 107.45°) and (1R, 2R)-norpseudoephedrine hydrochloride (monoclinic, space group P2₁ Z = 2, a = 5.493, b = 8.052, c = 11.986 Å, β = 104.62°) both adopt M-synclinal conformations with respect to the ammonium and hydroxy groups. Rather short intramolecular N…?O distances indicate interaction between ammonium and hydroxy groups.     

3,7-Dioxaazelaamides as Ionophores for Lithium Ion Selective Liquid Membrane Electrodes

Lipophilic neutral carriers were synthesized which show Li⁺/Na⁺ selectivities of up to ca. 80 in highly lipophilic liquid membranes. The sensor membranes exhibit improved response times and increased lifetimes as compared to systems described earlier. They allow reliable measurements of Li⁺ in blood serum within the clinical concentration range. A 1:1 Li⁺/ionophore complex of one representative (N,N,N′,N′-tetracyclohexyl-5,5-dimethyl-3,7-dioxaazelaamide) has been prepared, and its structure was elucidated by X-ray analysis.     

Radical cyclization cascade involving ynamides: an original access to nitrogen-containing heterocycles

A radical cascade involving a 5-exo-dig cyclization followed by a 6-endo-trig radical trapping transforms ynamides into heterogeneous polycyclic compounds in good yields. This leads interestingly to the formation of isoindols, isoindolinones, and pyridoisoindolones. [reaction: see text]