Synthesis and biological evaluation of (-)-16-normethyldictyostatin: a potent analogue of (-)-dictyostatin

[structure: see text] (-)-16-Normethyldictyostatin has been made by total synthesis and is a potent antitumor agent in cells expressing wild-type tubulin and in one mutant cell line that is resistant to paclitaxel, but it is much less active than dictyostatin in another paclitaxel-resistant cell line where Val is substituted for Phe270. This provides strong evidence that the C16 methyl group of the dictyostatins is oriented toward Phe270 in the paclitaxel-binding site on beta-tubulin.     

Observation of high mass electron-positron pairs produced in proton-proton collisions at the CERN ISR

In an experiment performed at the CERN Intersecting Storage Rings (ISR), 11 e⁺e^? pairs of high invariant mass value (> 2.5 GeV/c²) have been observed. Of these events, 9 can be interpreted as arising from the reaction p + p → J (3.1) + anything. the cross-section for this reaction is estimated and compared with the result obtained at lower centre-of-mass energies.     

Eine charakteristische Eigenschaft beschr?nkter analytischer Funktionen

Ohne ZusammenfassungDas Manuskript dieser Arbeit lief im Februar, 1917 bei der Redaktion ein. Das Juniheft des Bd. 147 von Crelles Journal brachte unter dem Titel Über Potenzreihen, die im Inneren des Einheitskreises beschränkt sind (S. 205–232) eine größere Veröffentlichung von Herrn I. Schur, die u. a. den weitaus größten Teil der Ausführungen des Herrn Hamel enthält. Zu seinem Bedauern lernte dieser die Arbeit des Herrn Schur erst nach der Korrektur seiner Arbeit kennen, sonst würde die Veröffentlichung unterblieben sein.     

Mechanism of the second sulfenylation of indole

Sulfenylation of indole using a sulfenyl chloride occurs initially at the 3-position of the ring, leading to a 3-indolyl sulfide. When an excess of sulfenyl chloride is used, a second sulfide group is introduced at the 2-position, and an indolyl 2,3-bis-sulfide results. We have demonstrated that this second sulfenylation occurs not by direct introduction of the second sulfide at the 2-position but via initial formation of an indolenium 3,3-bis-sulfide intermediate, followed by migration of one of the sulfide groups to the 2-position. This was achieved by the isolation of two examples of 3H-indole 3,3-bis-sulfides and by subsequent demonstration that they rearrange to the indolyl 2,3-bis-sulfides by treatment with sulfenyl halides.     

Hemiasterlin analogues incorporating an aromatic,and heterocyclic type C-terminus: design,synthesis and biological evaluation

A representative series of structural analogs of the antimitotic tripeptides hemiasterlins have been designed and synthesized, as potential inhibitors of tubulin polymerization. Relying also on a computational approach, we aimed to explore unknown extensive changes at the C-fragment, by incorporating the conformationally required double bond into five- and six-membered rings. Key steps of the synthetic strategy are a dynamic resolution affording the A-fragment in 97 % ee and the preparation of six new cyclic C fragments, all potentially able to interact with tubulin by means of H bonds. Unexpectedly, biological evaluation of these analogs did not provide evidences neither for cytotoxic effect nor for inhibition of tubulin polymerization.     

Bemerkung zu einer Note der Herren Berwald und Frank über die Differentialgleichungen der Bahnkurven

Ohne Zusammenfassung     

Über die Grundlagen der Mechanik

Ohne Zusammenfassung