Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
Ricardo, M. G.; Llanes, D.; Rennert, R.; Jänicke, P.; Rivera, D. G.; Wessjohann, L. A.;Improved access to potent anticancer tubulysins and linker‐functionalized payloads via an all‐on‐resin strategyChem.-Eur. J.30e202401943(2024)DOI: 10.1002/chem.202401943
Tubulysins are among the most recent antimitotic compounds to enter into antibody/peptide‐drug conjugate (ADC/PDC) development. Thus far, the design of the most promising tubulysin payloads relied on simplifying their structures, e.g., by using small tertiary amide N‐substituents (Me, Et, Pr) on tubuvaline residue. Cumbersome solution‐phase approaches are typically used for both syntheses and functionalization with cleavable linkers. p‐Aminobenzyl quaternary ammonium (PABQ) linkers were a remarkable advancement for targeted delivery, but the procedures to incorporate them into tubulysins are only of moderate efficiency. Here we describe a novel all‐on‐resin strategy permitting a loss‐free resin linkage and an improved access to super potent tubulysin analogs showing close resemblance to the natural compounds. For the first time, a protocol enables the integration of on‐resin tubulysin derivatization with, e.g., a maleimido‐Val‐Cit‐PABQ linker, which is a notable progress for the payload‐PABQ‐linker technology. The strategy also allows tubulysin diversification of the internal amide N‐substituent, thus enabling to screen a tubulysin library for the discovery of new potent analogs. This work provides ADC/PDC developers with new tools for both rapid access to new derivatives and easier linker‐attachment and functionalization.
Publikation
Ricardo, M. G.; Schwark, M.; Llanes, D.; Niedermeyer, T. H. J.; Westermann, B.;Total synthesis of Aetokthonotoxin, the cyanobacterial neurotoxin causing vacuolar myelinopathyChem.-Eur. J.2712032-12035(2021)DOI: 10.1002/chem.202101848
Aetokthonotoxin has recently been identified as the cyanobacterial neurotoxin causing Vacuolar Myelinopathy, a fatal neurologic disease, spreading through a trophic cascade and affecting birds of prey such as the bald eagle in the USA. Here, we describe the total synthesis of this specialized metabolite. The complex, highly brominated 1,2’-biindole could be synthesized via a Somei-type Michael reaction as key step. The optimised sequence yielded the natural product in five steps with an overall yield of 29 %.
Publikation
Chalo, D. M.; Kakudidi, E.; Origa-Oryem, H.; Namukobe, J.; Franke, K.; Yenesew, A.; Wessjohann, L. A.;Chemical constituents of the roots of Ormocarpum sennoides subsp. zanzibaricumBiochem. Syst. Ecol.93104142(2020)DOI: 10.1016/j.bse.2020.104142
Phytochemical investigation of the roots of O. sennoides subsp. zanzibaricum Brenan & J.B. Gillett resulted in the isolation of three biflavonoids (trime-chamaejasmin, (+)- chamaejasmin, (+)-liquiritigeninyl-(I-3,II-3)-naringenin), one bi-4-phenyldihydrocoumarin (diphysin), one isoflavan (glabridin), one triterpenoid (3-O-acetyloleanoic acid) and a phytosterol (β-sitosterol). Compounds were identified by detailed MS, 1D and 2D NMR spectroscopic analyses. Their absolute configurations were elucidated based on ECD spectra. The previously undescribed trime-chamaejasmin represents a bis-epi-chamaejasmenin C diastereomer. The chemophenetic significance is discussed in detail. The results contribute to the phytochemical characterization of the genus Ormocarpum and suggest a close chemophenetic relationship with other genera within the subfamily Papilionoideae. Furthermore, this report provides baseline data for comparing the two infraspecific taxa of O. sennoides (Willd.) DC.
Publikation
Tchatchouang Noulala, C. G.; Fotso, G. W.; Rennert, R.; Lenta, B. N.; Sewald, N.; Arnold, N.; Happi, E. N.; Ngadjui, B. T.;Mesomeric form of quaternary indoloquinazoline alkaloid and other constituents from the Cameroonian Rutaceae Araliopsis soyauxii Engl.Biochem. Syst. Ecol.91104050(2020)DOI: 10.1016/j.bse.2020.104050
A mesomeric form of quaternary indoloquinazoline alkaloid, soyauxinium chloride (1) was obtained through the chemical investigation of stem bark and roots of Araliopsis soyauxii Engl. [syn. Vepris soyauxii (Engl.) Mziray] (Rutaceae) together with fifteen known compounds, including three furoquinoline alkaloids, three 2-quinolones, two limonoids, two triterpenes, two steroids, a coumarin, an acridone alkaloid, and a flavonoid glycoside. Their structures were established by comprehensive spectroscopic and spectrometric analyses (1D and 2D NMR, ESI-HR-MS) and by comparison with previously reported data. 13C NMR data of araliopsinine are also reported here for the first time. The isolated compounds were screened in vitro for their effects on the viability of two different human cancer cell lines, namely prostate PC-3 adenocarcinoma cells and colorectal HT-29 adenocarcinoma cells. However, none of the tested compounds exhibited strong anti-proliferative or cytotoxic activities, to either prostate PC-3 cells or colon HT-29 cells. At 100 μM, the furoquinoline maculine showed a slightly increased anti-proliferative effect, however, exclusively on HT-29 cells. The chemotaxonomic significance of the isolated compounds has also been discussed.