Push-pull-Cyclobutadiene

Two push-pull-cyclobutadienes 10b and 10c are prepared by reaction of two eq. of the corresponding acetylenes having electrondonating and electronaccepting groups ( 4 ) with one eq. of HBF₄ to cyclic cyanine salts, followed by elimination of HBF₄ with KOC(CH₃)₃. These cyclobutadienes, stable in cristalline form at room temperature respectively for a short time ( 10b R?CH₃) or for several days ( 10c R?OCH₃), are extremely reactive in solution towards various nucleophiles and electrophiles. Cleavage of the nascent cyclobutenes leads to butadienes. The cyclobutadienes 10 dimerise thermally to cyclooctatetraenes 18 .     

Versuche zur Synthese von polymergebundenen `Push-Pull'-Acetylenen

In view of possible applications of `push-pull' acetylenes 1 and `push-pull' olefins 2 as potential non-linear optics materials, synthetic attempts towards polymers of type 4 and 6 (Scheme 2) have been undertaken. Two so far unknown `push-pull' acetylenes 1a , b with R=styrene, have been prepared under carefully controlled conditions which quite surprisingly fail to give polymers 4a , b by anionic or radical-induced polymerization. On the other hand, `push-pull' acetylenes may be reacted with commercially available poly(4-vinylphenol) to give polymers 6c , d with a 40 – 70% conversion of phenol units.     

Synthesis and conformational analysis by 1H NMR and restrained molecular dynamics simulations of the cyclic decapeptide [Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly]

Summary The design of enzyme mimics with therapeutic and industrial applications has interested both experimental and computational chemists for several decades. Recent advances in the computational methodology of restrained molecular dynamics, used in conjunction with data obtained from two-dimensional ¹H NMR spectroscopy, make it a promising method to study peptide and protein structure and function. Several issues, however, need to be addressed in order to assess the validity of this method for its explanatory and predictive value. Among the issues addressed in this study are: the accuracy and generizability of the GROMOS peptide molecular mechanics force field; the effect of inclusion of solvent on the simulations; and the effect of different types of restraining algorithms on the computational results. The decapeptide Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly, which corresponds to the sequence of ACTH_1–10, has been synthesized, cyclized, and studied by two-dimensional ¹H NMR spectroscopy. Restrained molecular dynamics (RMD) and time-averaged restrained molecular dynamics (TARMD) simulations were carried out on four different distance-geometry starting structures in order to determine and contrast the behavior of cyclic ACTH_1–10 in vacuum and in solution. For the RMD simulations, the structures did not fit the NOE data well, even at high values of the restraining potential. The TARMD simulation method, however, was able to give structures that fit the NOE data at high values of the restraining potential. In both cases, inclusion of explicit solvent molecules in the simulation had little effect on the quality of the fit, although it was found to dampen the motion of the cyclic peptide. For both simulation techniques, the number and size of the NOE violations increased as the restraining potential approached zero. This is due, presumably, to inadequacies in the force field. Additional TARMD vacuum-phase simulations, run with a larger memory length or with a larger sampling size (16 additional distance-geometry structures), yielded no significantly different results. The computed data were then analyzed to help explain the sparse NOE data and poor chymotryptic activity of the cyclic peptide. Cyclic ACTH_1–10, which contains the functional moieties of the catalytic triad of chymotrypsin, was evaluated as a potential mimic of chymotrypsin by measurement of the rate of hydrolysis of esters of L-and d-phenylalanine. The poor rate of hydrolysis is attributed to the flexibility of the decapeptide, the motion of the side chains, which result in the absence of long-range NOEs, the small size of the macrocycle relative to that of the substrate, and the inappropriate orientation of the Gly, His, and Ser residues. The results demonstrate the utility of this method in computer-aided molecular design of cyclic peptides and suggest structural modifications for future work based on a larger and more rigid peptide framework.     

Säurekatalysierte Umlagerung von 9-Hydroxyfuranoeremophilanen zu Eremophilanlactonen

Acid-Catalyzed Rearrangement of 9-Hydroxyfuranoeremophilanes to Eremophilanlactones 9-Hydroxyfuranoeremophilanes 1–3 are the main components of freshly harvested rhizomes of P. hybridus (furanopetasin chemovar, Table, Fig. 1). They easily and quantitatively rearrange in the presence of traces of acid to give an epimeric mixture of 8-H-eremophilanlactones 4–6 (eremophilenolides, Table, Figs. 4 and 5). Besides subsequent oxidation (see 4 → 7 ), this is the most important reaction occuring during drying and storage of rhizomes of P. hybridus (Figs. 1 and 3). A reasonable mechanism of the rearrangement is presented, and spectroscopic structure elucidation of 8-H-eremophilanlactones is discussed.     

Chloracylierung und Bromacylierung von Carbonylverbindungen: Eine in Vergessenheit geratene Carbonylreaktion. I. Präparative Anwendungsbreite

Chloroacylation and bromoacylation of carbonyl compounds: A forgotten carbonyl reaction. I. Scope of the reaction Aliphatic, α,β-unsaturated and aromatic aldehydes as well as aliphatic ketones react with acyl halides to (α-haloalkyl)esters. These bifunctional derivates contain two leaving groups of different reactivity. The scope of this scarcely of this scarcely known carbonyl reaction is discussed.     

«Push-Pull»-Acetylene als Hilfsmittel zur Synthese von Amiden

Amide Synthesis by Means of ‘Push-Pull’-Acetylenes ‘Push-Pull’-acetylenes react easily with carbon acids, Addition of amines to the crude reaction mixture gives amides in an excellent yield by a simple one-pot procedure. Because of the high selectivity of the acetylenes 1 towards carboxylic functions and of the high selectivity of the enol esters 4 towards amine functions, ‘push-pull’-acetylenes could be excellent reagents for peptide synthesis.     

Die Umlagerung substituierter Aminoacrylderivate. Präparative anwendungsbreite

The addition of carboxylic acids to dimethylamino-propinal ( 1a ) and 4-dimethyl-amino-but-3-in-2-on ( 1b ) gives, after rearrangement of the very instable primary adducts ( 2 ), Z-3-acetoxy-N,N-dimethylacrylamides and -crotonamides 3 to 8 in excellent yields and in a stereospecific manner. Similarly, the adducts of HCl and HBr to the alkynes 1a and 1b may be rearranged at low temperature by traces of acid to cis/trans equilibria of 3-halo-acrylamides and -crotonamides 9 and 10 . - On the other hand, treatment of 3-alkoxy-3-dimethylaminoacrolein with traces of acid yields alkylesters of E-3-dimethylaminoacrylic acid ( 12 , X = OR). - The preparative aspects of the rearrangement are discussed, and a brief outline of the spectroscopic properties of the compounds 3 to 8 is given.     

Synthetic Attempts towards Polymers with Pentafulvene Structural Units

Synthetic attempts towards fully conjugated polymers 9 with pentafulvene-diyl structural units are described. Cationic polymerization of pentafulvenes 1a (R = X = Me) and 1b (R = X = MeS) nearly quantitatively gives polymers 8a and 8b with typical M_n and M_w values of 38800 and 53750, respectively, for 8a , and 12000 and 35900, respectively, for 8b . Key step of the conversion 8a → 9a (Scheme 6) is a quantitative bromination 8a → 32a , the structure of 32a being confirmed by analytical data as well as by spectroscopic comparison with model compound 23 . Best results in view of two-fold the HBr elimination 32a → 9a are obtained with Et₃N, but so far elimination has not been complete. Synthetic sequences are optimized with model compound 21 (Scheme 4). Here again, bromination 21 → 23 is quantitative, while two-fold HBr elimination 23 → 22 with Et₃N proceeds in 51% yield. Dibromide 23 easily undergoes HBr elimination followed by a Br shift to give bromide 29 . Contrary to cationic polymerization, anionic polymerization of simple pentafulvenes 1 to 2 (which would be attractive in view of the conjugated polymers 3 ) is not successful: For pentafulvene 1b (R = X = MeS), the main reaction is Diels-Alder-type dimerization 1b → 15b (Scheme 2), even under anionic conditions.     

Bilden sich aus Pentafulven und Cyclopentadien [6+4]-Cycloaddukte??

Does [6+4] Cycloaddition between Pentafulvene and Cyclopentadiene Take Place? Reaction of a 1:1 mixture of cyclopentadiene (CPD) and pentafulvene ( 1a ) at 20° gives a complex mixture. The low-molecular-weight part mainly consists of pure and mixed dimers (ca. 73 %) besides corresponding trimers (ca. 20%) and some corresponding oligomers according to GC/MS investigations (Fig. 1). The 3 predominant ‘mixed dimers’ between CPD and 1a have been separated, and structures 4 – 6 (Scheme 3) are assigned according to 400- and 600-MHz ¹H-NMR investigations. These results show that HOMO(CPD)-LUMO(fulvene) interactions are important in pentafulvene cycloadditions. Dimer 6 results from [6+4] cycloaddition followed by [1,5]-H shifts.     

Bis (2,4,6,8-cyclononatetraen-1-yl)methane

Bis (2,4,6,8-cyclononatetraen-1-yl)methanes Bis (2,4,6,8-cyclononatetraen-1-yl)methanes ( 2a–c ) have been prepared by reaction of all-cis-cyclononatetraenide with 1,1-dichlorodimethyl ether as well as with carbenium ion precursors 9b and 9c . The title compounds 2 are attractive precursors of highly delocalised nonafulvenes of type 3 ; however, elimination experiments 2→3 failed so far.