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.     

On critical exponents for some quasilinear parabolic equations

We study the Cauchy problem for the quasilinear parabolic equation where p > 1 is a parameter and ψ is a smooth, bounded function on (1, ∞) with ? ? sψ′(s)/ψ(s) ? θ for some θ > 0. If 1 < p < 1 + 2/N, there are no global positive solutions, whereas if p > 1 + 2/N, there are global, positive solutions for small initial data.     

On the error of compound quadrature formulas forr-convex functions

LetC _m be a compound quadrature formula, i.e.C _m is obtained by dividing the interval of integration [a, b] intom subintervals of equal length, and applying the same quadrature formulaQ _n to every subinterval. LetR _m be the corresponding error functional. Iff ^(r) > 0 impliesR _m [f] > 0 (orR _m [f] < 0),=" then=" we=" say=">C _m is positive definite (or negative definite, respectively) of orderr. This is the case for most of the well-known quadrature formulas. The assumption thatf ^(r) > 0 may be weakened to the requirement that all divided differences of orderr off are non-negative. Thenf is calledr-convex. Now letC _m be positive definite or negative definite of orderr, and letf be continuous andr-convex. We prove the following direct and inverse theorems for the errorR _m [f], where , denotes the modulus of continuity of orderr:

Sphere orders

Ann-sphere order is a finite partially ordered set representable by containment ofn-spheres in Euclidean (n+1)-space. We present a sequence {P _i } of ordered sets such that eachP _i is ann-sphere order only forni; one consequence is that we are able to determine the dimension of a Euclidean space-time manifold from the finite suborders of its causality order.Research supported by ONR grant N00014 85-K-0769.