The aqueous trimethylamine mediated Baylis-Hillman reaction

Aqueous trimethylamine mediated Baylis-Hillman coupling of alkyl acrylates with aldehydes is described

Methanolic trimethylamine mediated Baylis-Hillman reaction

Application of methanolic trimethylamine, the tertiary amine containing minimum number of carbon atoms with lowest possible molecular weight, for mediating the Baylis-Hillman coupling of various aldehydes with activated olefins viz. methyl acrylate, acrylonitrile and acrolein is described

Synthese und Konformations Analyse von Jasplakinolidanaloga sowie ein Vorschlag zur Synthese der Stereotetrade von Cruentaren A

Die Dissertation enthält zwei Kapitel. Kapitel I enthält die effiziente Synthese frei entworfener Amino- und Hydroxycarbonsäuren welche, nach anschliessender Überführung in die entsprechenden Peptide, eine konformelle Fixierung des Molekülteils über nicht bindende Wechselwirkungen, wie die syn-pentan sowie die 1,3 allylische Wechselwirkung, ermöglichen. Die Gestaltung dieser Carbonsäuren berücksichtigt die Gegebenheiten des Depsipeptids Jasplakinolid, in dessen Polypropionatteil die selben Bedingungen herrschen. Die Synthese der Säuren wurde über wenige Reaktionsschritte mit guten Ausbeuten realisiert. Die anschließende Verknüpfung dieser Säuren in mit einer Vielzahl an Tripeptiden ergab die originellen Analoga von Jasplakinolid. Diese Analoga erhielten aufgrund der Carbonsäuren die erwarteten, limitierten Konformationen und liegen überwiegend als trans-Rotamere vor. Die Eingliederung einer dieser Hydroxysäuren in den Tripeptidteil von Chondramid C führte zu Normethylchondramid C welches eine vergleichbare biologische Aktivität wie Jasplakinolid aufwies (IC 50 = 0,25 μM). Kapitel II gibt einen Überblick über die Bemühungen zur Synthese der Stereotetrade von Cruentaren A. Die Schlüsselschritte in der vorgelegten Synthese sind die assymetrische Evans Aldolreaktion sowie die Dihydroxylierung nach Sharpless. Da die Dihydroxylierung keine gute Diastereoselektivität ergab, ist es von interesse einen anderen Syntheseweg einzuschlagen um die diastereomerenreine Stereotetrade zu erhalten. Es sollte noch erwähnt werden dass diese Synthese an Effizienz gewinnt wenn beide Isomere nach der Dihydroxylierung getrennt werden können.The dissertation contains two chapters. Chapter one includes the efficient synthesis of rationally designed amino- and hydroxy acids which upon incorporation into peptides creates conformational constraint due to non bonded interactions such as syn-pentane and 1,3-allylic strain. The design of the novel amino and hydroxy acids was guided by the poly propionate part of the depsipeptide jasplakinolide. The syntheses of amino- and hydroxy acids were executed in few steps with good yields. Incorporation of these acids into various tripeptides gave the novel analogues of jasplakinolide. These analogues got very good restricted conformations and were mostly populated as trans rotamers. Incorporating one of these hydroxy acid into the tripeptide portion of chondramide C led to nor methyl chondramide C which had very good biological activity comparable to jasplakinolide (IC50 = 0.25 µM). Chapter two describes the efforts towards the synthesis of stereotetrad of cruentaren A. The key steps in this synthesis were asymmetric Evans syn aldol reaction and a Sharpless dihydroxylation reaction. As the dihydroxylation did not provide good diastereoselectivity, it is necessary to follow some other pathway to create the diastereomerically pure stereotetrad. But, it should be noted that the synthesis will become efficient if both isomers could be separated from each other after Sharpless dihydroxylation step

Synthesis of Chondramide A Analogues with Modified β‐Tyrosine and Their Biological Evaluation

Starting from cinnamates 9 , obtained by Wittig reaction or Heck coupling, the diols 17 were prepared by asymmetric dihydroxylation. This was followed by a regioselective substitution of the 3‐OH group with hydrazoic acid under Mitsunobu conditions. Methylation of the 2‐OH group and reduction of the azide group led to the β‐tyrosine derivatives 8 . Condensation with the dipeptide acid 6 furnished the tripeptide part of the chondramides. The derived acids 21 were combined with the hydroxy ester 7 to the esters 22 . Cleavage of the tert ‐butyl groups and intramolecular lactam formation gave rise to the chondramide A analogues 2 b – k . Growth inhibition assays showed most of the analogues to be biologically active. Some of them even reach the activity of jasplakinolide. It can be concluded that the 4‐position of the aryl ring in the β‐tyrosine of chondramide A tolerates structural modifications quite well. SUB ‐ units : Ten different chondramide A analogues were prepared with different substituents at the 3‐amino‐2‐methoxy‐propanoate subunit. The modified β‐tyrosines were obtained from the corresponding cinnamates. From Mitsunobu esterification, acyclic depsipeptides were obtained that were cyclized by macrolactam formation. Almost all analogues were at least as active as chondramide A itself. However, an amide group reduced the cytotoxicity significantly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88032/1/13349_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/88032/2/chem_201101978_sm_miscellaneous_information.pd

Cyclodepsipeptides from Marine Sponges: Natural Agents for Drug Research

A number of natural products from marine sponges, such as cyclodepsipeptides, have been identified. The structural characteristics of this family of cyclic peptides include various unusual amino acid residues and unique N-terminal polyketide-derived moieties. Papuamides are representatives of a class of marine sponge derived cyclic depsipeptides, including callipeltin A, celebesides A and B, homophymine A, mirabamides, microspinosamide, neamphamide A and theopapuamides. They are thought to have cytoprotective activity against HIV-1 in vitro by inhibiting viral entry. Jasplakinolide, a representative member of marine sponge-derived cyclodepsipeptides that include arenastatin A, geodiamolides, homophymines, spongidepsin and theopapuamides, is a potent inducer of actin polymerization in vitro. Although actin dynamics is essential for tumor metasasis, no actin targeting drugs have been used in clinical trials due to their severe cytotoxicity. Nonetheless, the actin cytoskeleton remains a potential target for anti-cancer drug development. These features imply the use of cyclodepsipeptides as molecular models in drug research

The Baylis-Hillman reaction: an expedient synthesis of (Z)-keto allyl bromides and chlorides

A simple and expedient synthesis of (Z)-keto allyl bromides and chlorides, from the Baylis-Hillman adducts is described

Accumulation of explosives in hair - Part II: Factors affecting sorption

This study examines the sorption of eight explosives (2,4,6-trinitrotoluene [TNT]; pentaerythritol tetranitrate [PETN]; hexahydro-1,3,5-trinitro-s-triazine [RDX]; diacetone diperoxide [DADP]; triacetone triperoxide [TATP]; ethylene glycol [EGDN], nitroglycerin [NG]; and 2,4-dinitrotoluene [DNT]) to human hair. The study uses only cut hair, which is exposed to explosive vapor. The vapor transfer studies reported herein indicated that hair did not reach saturation even after 2.5 years of exposure to TNT. While previous studies showed black hair sorbed more explosive than blond or brown, this study reports that red hair sorption is similar to black, while grey hairs, exposed along with black hair from the same individual, sorbed significantly less explosive than the same individual\u27s black hairs. In a study using only black hair, a slight racial bias was observed with sorption greater for Mongoloid hair as compared to Caucasian or Negroid. Only for Mongoloid hairs were enough samples studied to examine for a gender bias, but one was not observed. There was much variability in results in all categories (hair color, race, and gender) that trends were established only in general terms. Hair at different ages was tested for a few individuals. Detailed studies focused on the sorption of TATP and TNT as these appear to be sorbed most differently - TATP mainly on the hair surface and TNT both on the surface and in the cortex. The uptake of high vapor pressure explosives (e.g., TATP) and moderate vapor pressure explosives (e.g., TNT) by hair was rapid and could be detected within about 1 h of exposure. Both explosives were readily sorbed by pure melanin. © 2007 American Academy of Forensic Sciences