Prätubulysin, eine potente und synthetisch leicht zugängliche Vorstufe von Tubulysin aus Angiococcus disciformis

Abstract

Einfacher geht′s auch: Prätubulysin (Formel ohne die grünen Substituenten), ein vereinfachtes Tubulysin, wurde nicht nur im Labor hergestellt, sondern auch in der natürlichen Tubulysinquelle entdeckt. Diese biosynthetische Vorstufe der Tubulysine ist zwar weniger aktiv als die Tubulysine A und D, wirkt aber immer noch im Pikomolbereich auf eine Reihe von Krebszelllinien.

Total Syntheses of Tubulysins

“…C NMR and IR spectra of this sample were identical to those described for 10. (12) and its enantiomer (ent-12): A solution of LiOH (12.6 g, 526 mmol) in H 2 O (130 mL) at 4 8C was added to a solution of 10 (63.0 g, 105 mmol) in THF (260 mL) and MeOH (130 mL), and the mixture was stirred at the same temperature for 1 h. After concentration, the mixture was poured into H 2 O (300 mL) and the pH of the mixture was adjusted to pH 9 with 10 % H 2 SO 4 aq. The mixture was extracted with AcOEt, then the aqueous layer was adjusted to pH 3 with 10 % H 2 SO 4 aq.…”

“…[4b, [7][8][9][10][11][12] However, only a few synthetic methods adaptable to analogue synthesis have been explored, probably due to the lack of stereoselectivity or efficiency for the syntheses of Tuv and Tup. [11] We have recently developed an efficient method for the synthesis of Tuv featuring the stereoselective 1,3-dipolar cycloaddition of a nitrone derived from d-gulose with N-acryloyl camphor sultam as well as a synthetic method for Tup by employing a stereoselective aldol reaction followed by Barton deoxygenation.…”

Ultrasmall tungsten carbide catalysts stabilized in graphitic layers for high-performance oxygen reduction reaction

“…However, more theoretical and experimental works are also needed to fully understand the roles of individual WC, W 2 C and graphitic phases, as well asto further optimize the catalytic performances of WC@C composite by modifying the arc-discharge approach in coming works. (8) correspond to the present WC@C complex, commercial Pt nanoparticles [40], Au clusters [21], sulfur-doped graphene [40], nitrogen-doped grapheme [40], nitrogen-doped carbon nanotubes [42], nitrogen/boron-doped carbon nanotubes [42], and nitrogen-doped mesoporous carbon [43], respectively. Noted that the J k value of BN-CNT is calculated at -0.3 V and the others are at -0.5 V.…”

“…[18,19] Although it has been well recognized that the smaller catalyst exhibits the higher catalytic activity, but the coarsening of catalysts during the reaction process, which results in undesirable chemical and structural stability, cannot be effectively resolved yet. [20][21][22][23][24][25]On the other hand, the traditional techniques for synthesizing carbide catalysts involving high-temperature annealing processes are also lack of effectiveness in controlling the size down to ~3 nm. [26][27][28][29][30][31][32][33]All these issues thus limit their practical industrial applications.…”

Synthesis and Biological Evaluation of Pretubulysin and Derivatives

“…In addition, because it lacks the configurationally labile acetoxy group, pretubulysin is an ideal lead structure for the development of tubulysin-based anticancer drugs. We therefore pursued the total synthesis of pretubulysin [9] and adapted our route to afford a range of derivatives.…”