Polymerization of Cyclic Monomers, 10,

Methyl 2‐(bicyclo[3.1.0]hex‐1‐yl)acrylate ( 1 ) was synthesized from methyl 2‐(cyclopentene‐1‐yl)‐2‐hydroxyacetate by cyclopropanation, followed by oxidation to the corresponding bicyclic 2‐oxoacetate and Wittig olefination with methyltriphenylphosphonium bromide. Initiated with 2,2′‐azoisobutyronitrile at 65 °C in chlorobenzene, the radical homopolymerization of 1 occurred with opening of the cyclopropane ring leading to a polymer with a glass transition temperature of 90 °C. The reactivity of 1 in radical copolymerization was higher than that of methyl methacrylate.

     

Stereochemistry of the Inhibition of δ-Chymotrypsin with Optically Active Bicyclic Organophosphates: 31P-NMR studies

The inhibition of δ-chymotrypsin with optically active, axially and equatorially substituted trans-3-(2,4-dini-trophenoxy)-2,4-dioxa-3λ⁵-phospbubicyclo[4.4.0]decan-3-ones ( = hexahydro-4H-1,3,2-benzodioxaphosphorin 3-oxides) was investigated. Their inhibitory power was determined by kinetic measurements, and the stereochemical course of the reaction of stoichiometric amounts of the enzyme and inhibitor was monitored with ³¹P-NMR spectroscopy at pH 7.8. The irreversible inhibitors show significant enantioselectivity (the (S_p)-enantiomer reacting faster) and yield diastereoisomeric, covalently phosphorylated derivatives of δ-chymotrypsin. ³¹P-NMR Spectroscopic studies of the inhibition by the axially substituted inhibitor revealed for the racemic (±) -2a first a resonance at –4.4 ppm and later, while inhibition proceeded, a second one at –4.5 ppm. The reaction with optically active (+) -2a showed only one signal at –4.4 ppm and its enantiomer (–) -2a only one signal at –4.5 ppm. Using the equatorially substituted racemic epimer (±) -2b , we observed the main resonance at –5.3 ppm and two minor ones at –4.4 and –4.5 ppm. The optically active compound (+) -2b showed two peaks at –4.5 and –5.3 ppm, whereas its antipode (–) -2b revealed two signals at –4.4 and –5.3 ppm. Comparing the ³¹P chemical shifts of the corresponding covalent phosphoserine derivatives 4a (-5.7 ppm, axial) and 4b (-4.5 ppm, equatorial) shows the inhibition with the axial compounds 2a to proceed via neat inversion of the configuration at the P-atom, whereas the equatorial epimers 2b with a higher conformational flexibility seem to follow a different stereochemical pathway which results in both inversion and retention.     

Synthesis of Modified Tripeptides and Tetrapeptides as potential bisubstrate inhibitors of the epidermal growth factor receptor protein tyrosine kinase

The synthesis of a series of bisubstrate inhibitors of the epidermal growth factor receptor protein kinase (EGF-R PTK) consisting of small pep tides linked covalently to adenosine via appropriate triphosphate substitutes is described. Boc-Glu(O^tBu)-Tyr-Leu-OBzl ( 5 ) and Ac-Glu(O^tBu)-Tyr-Leu-Arg(Pmc)-NH₂ ( 8 ; Pmc = 2,2,5,7,8-pentamethylchroman-6-sulfonyl) were prepared by standard peptide chemistry, (Scheme 1), then modified at the OH group of tyrosine either with adipic anhydride or with 4-(chlorosulfonyl)benzoic acid, 4-(chlorosulfonyl)-2-hydroxybenzoic acid, or benzene-1,4-disulfonyldichloride (Scheme 2), and finally coupled with the 5′-OH group of 2′,3′-O-isopropylideneadenosine (Scheme 3). In addition, N⁶-[(benzyloxy)carbonyl]-2′,3′-O-isopropylidene-adenosine 5′-(hydrogenhexanedioate) ( 26 ), an ATP substitute, was coupled with the morpholide of 5 (Scheme 4). Removal of the protecting groups gave the bisubstrate analogs 23, 24 , and 28. The compounds synthesized were tested as inhibitors of the EGF-R PTK. The most active bisubstrate-type inhibitor was 24 , composed of the tripeptide sequence H-Glu-Tyr-Leu-OBzl, the 2-hydroxy-4-sulfonylbenzoyl moiety, and adenosine; it showed an IC₅₀ value of 33 μM.     

Bi-Lipschitz parameterization of surfaces

We consider surfaces Z homeomorphic to the plane with complete, possibly singular Riemannian metrics. If we have _ZK⁺<2– for the positive and _ZK^–<C for the negative part of the integral curvature, then Z is L-bi-Lipschitz equivalent to ² with L depending only on >0 and C>0. This result implies a conjecture by J. Fu.Supported by NSF grant DMS-0200566.     

An ab initioCI calculation of the triplet–triplet absorption spectrum of naphthalene

The triplet–triplet absorption spectrum of naphthalene (³B_1g ← ³B_2u; ³A_g ← ³B_2u) was calculated using an ab initio method with a STO -3G basis set and moderately large configuration interaction. Eight bands were found in the region 18,000–45,000 cm^?1 and compared with those of the experimental spectrum. The strongest band observed at about 44,000 cm^?1 was assigned to a ³A_g ← ³B_2u tansition. The excited triplet and singlet ground-state electronic charge distributions are compared.     

Synthese und Circulardichroismus optisch aktiver Carotinoidmodelle

Synthesis and Circular Dichroism of Optically Active Carotenoid Models The synthesis of the following optically active carotenoidic model compounds are described: (—)-(3,S,3′S)-3,3′-diisopropenyl-16,17,18,16′,17,18′-hexanor-β,β-carotene ( 1 ), (3R,3′R)-19,20,19′,20′-Metranor-zeaxanthin ( 2 ) and (6R,6′R)-19,20, 19′,20′-tetranor-ε,ε-carotene ( 3 ). These compounds were synthesized for the following reasons: (1) the presence of methyl groups at C(1), C(1′), C(5), C(5′) of cyclic carotenoids profoundly affects the torsional angle of the C(6), C(7)- and C(6′), C(7′)-bonds. Sign and magnitude of this angle are, according to recent theories [4] [5], responsible for a helical chromophore and for strong conservative [4] Cotton effects. CD. measurements of 1 give experimental support to these state- 1 exhibits weaker and less temperature dependent Cotton effects. Of more significance, the shape of the curve is no longer conservative, as expected. This constitutes experimental evidence for the contention that the β-endgroups and the polyene chain indeed form an inherently dissymmetric chromophore in optically active β, β-carotene derivatives; (2) the slightly S-shaped form of the polyene chain of carotenoids, shown by X-ray analyses [12] [13], is mainly ascribed to the presence of the methyl groups in the chain. Models 2 and 3 therefore are assumed to be linear. CD. studies of these compounds should consequently give information about the influence of deviation from Linearity and planarity of the polyene on the CD. spectra of carotenoids. CD measurements of 2 and 3 show that the lack of methyl groups does not alter the general type of the curve. Only the intensity and to some extent the position of the Cotton effects are influenced. Carotenoids with the ε-endgroup possess inherently symmetric but asymmetrically distorted chromophores. The assumption that non-conservative CD. spectra could become conservative upon cooling [4] is experimentally confirmed by model 3 . The rule stating that pairs of all-(E) and mono-(Z) isomers of carotenoids with only one cyclic endgroup should have CD. spectra with the same sign [5] is disproved by the CD. spectra of four stereoisomeric rubixanthins (s. Fig. 5). The UV./VIS. spectrum of 3, λ_max 447 (ε 216000), 418 (ε 189000) exhibits the highest molecular extinction ever reported for a carotenoid.     

Synthesis of 2-Oxo-2H-[1,2,4]oxadiazolo-[2,3-c]pyrimidine-5-carbamates

Thermal cyclization of the pyrimidine-N-oxide dicarbamate 2 gives a 95:5 mixture of the 2-oxo-2H-[1,2,4]oxadiazolo[2,3-a]- and [2,3-c]pyrimidinecarbamates 3 and 4. An efficient procedure for the conversion of 3 to 4 , and vice versa, is described.     

Chromatographic enrichment and enantiomer separation of axially chiral polybrominated biphenyls in a technical mixture

The separation properties of different chromatographic methods regarding the enantioselective separation of axially chiral (atropisomeric) polybrominated biphenyls (PBB) were studied. For this purpose, the technical hexabromobiphenyl product Firemaster BP-6 was characterised by gas-chromatography coupled to electron capture detection (GC/ECD) and electron-capture negative ion mass spectrometry (GC/ECNI-MS) as well as by liquid chromatographic fractionating on active carbon and celite. Twelve individual PBBs including potential atropisomeric PBBs were isolated from Firemaster BP-6 by reversed-phase high-performance liquid chromatography (HPLC) on three serially coupled octadecylsilane columns. Six of the 12 isolated PBBs (three tri-ortho and di-ortho substituted PBBs, respectively) were separated into atropisomers on a HPLC column containing permethylated beta-cyclodextrin on silica. Moreover, the temperature dependency of the enantiomer separations is discussed. Gas chromatographic enantiomer separation of PBBs is a very demanding task due to high elution temperatures. However, the atropisomers of one tri-ortho substituted PBB congener (PBB 149) could be resolved on a column coated with randomly modified heptakis(6-O-tert.-butyldimethylsilyl-2,3-di-O-methyl)-beta-cyclodextrin in OV 1701.     

Single molecule spectroscopy. Perylene in the Shpol''skii matrix n-nonane

Single perylene molecules in the Shpol'skii matrix n-nonane have been investigated at 1.7 K using a frequency-doubled cw Ti: sapphire laser as an excitation source. Fluorescence excitation spectra within the inhomogeneously broadened 0-0 absorption band around 443.8 nm were taken. The combination of high fluorescence quatumm yield and low intersystem crossing rate with a relatively short-lived triplet state allowed the direct observation of fluorescence photon bunches. The time distribution of the resulting emission gaps for the specific single molecule studied in detail leads to a triplet lifetime of τ_p = 1.1 ± 0.5 ms.     

Umamidierungsreaktionen an cyclischen Amino-amid-Systemen. 3. Mitteilung über Umamidierungsreaktionen

Transamidation Reactions with Cyclic Amino-amides Lactames which are substituted at the nitrogen atom by a 3-aminopropyl residue are transformed under base catalysis to cyclic amino-amides enlarged by 4 ring atoms. The formed ring must be at minimum 12-membered. Scheme 2 illustrates this result: the 8-membered 7 is transamidated in 96% yield to the 12-membered ring 8 (in the presence of potassium 3-aminopropylamid in 1, 3-propanediamine), the 9-membered 10 to the 13-membered ring 11 (97%) and the 11-membered 14 to the 15-membered ring 15 . Furthermore, the 13-membered ring 27 (Scheme 5) is transformed to the 17-membered 28 . In the case of the 15-membered lactame 15 it is demonstrated that 14 is not formed back under the conditions of the transamidation. Large ring lactames which are substituted at the nitrogen atom by a 3-(alkylamino) propyl group lead under base catalysis to an equilibrium mixture, e.g. the 17-membered 26 is in equilibrium with the 21-membered 29 . This result is similar to the behavior of the corresponding open-chain amino-amides [2]. Because of transannular interactions, the 11-membered ring 2 is not stable: transamidation of the 7-membered 1 (Scheme 1) doesn't give the expected 2 , but its water elimination product 3 in small yield. The N-tosyl derivative of 2 , namely 20 , is synthesized by an independent route (Scheme 3). Detosylation of 20 yields the 7-membered 1 instead of 2 . Concerning the mechanism of this interesting reaction see Scheme 4.