498-36-2Relevant academic research and scientific papers
Structure revision of isocereulide A, an isoform of the food poisoning emetic Bacillus cereus toxin cereulide
Ehling-Schulz, Monika,Hofmann, Thomas F.,Kranzler, Markus,Stark, Timo D.,Walser, Veronika
supporting information, (2021/05/31)
The emetic Bacillus cereus toxin cereulide presents an enormous safety hazard in the food industry, inducing emesis and nausea after the consumption of contaminated foods. Additional to cereulide itself, seven structurally related isoforms, namely the isocereulides A-G, have already been elucidated in their chemical structure and could further be identified in B. cereus contaminated food samples. The newly performed isolation of isocereulide A allowed, for the first time, 1D- and 2D-NMR spectroscopy of a biosynthetically produced isocereulide, revealing results that contradict previous assumptions of an L-O-Leu moiety within its chemical structure. By furthermore applying posthydrolytical dipeptide analysis, amino acid and α-hydroxy acid analysis by means of UPLC-ESITOF- MS, as well as MSn sequencing, the structure of previously reported isocereulide A could be corrected. Instead of the L-O-Leu as assumed to date, one L-O-Ile unit could be verified in the cyclic dodecadepsipeptide, revising the structure of isocereulide A to [(D-O-Leu-D-Ala-L-O-Val-L-Val)2(DO- Leu-D-Ala-L-O-Ile-L-Val)].
Total synthesis of cyclohexadepsipeptides exumolides A and B
Rahmadani, Agung,Masruhim, Muhammad Amir,Rijai, Laode,Hidayat, Ace Tatang,Supratman, Unang,Maharani, Rani
supporting information, (2021/02/20)
Exumolides A and B are two cyclodepsipeptides that was previously isolated from marine fungus. Both peptides were synthesized using a combination of solid- and solution-phase method. The linear precursor was synthesized through solid-phase method on 2-chlorotrityl resin with standard Fmoc strategy. The hydroxy acid, (S)-2-hydroxy-4-methylpentanoic acid (Hmp), was prepared from its precursor L-leucine, and attached on the resin with a double-coupling protocol. The depside bond formation that was carried out at the end of the coupling process, was beneficial, particularly, in the blockage of the diketopiperazine formation during Fmoc deprotection. The cyclic product was obtained through HATU-based cyclisation. Exumolides A and B were successfully synthesized with overall yields of 4.12% and 6.39%, respectively.
Mo–Catalyzed One-Pot Synthesis of N-Polyheterocycles from Nitroarenes and Glycols with Recycling of the Waste Reduction Byproduct. Substituent-Tuned Photophysical Properties
Hernández-Ruiz, Raquel,Rubio-Presa, Rubén,Suárez-Pantiga, Samuel,Pedrosa, María R.,Fernández-Rodríguez, Manuel A.,Tapia, M. José,Sanz, Roberto
supporting information, p. 13613 - 13623 (2021/08/23)
A catalytic domino reduction–imine formation–intramolecular cyclization–oxidation for the general synthesis of a wide variety of biologically relevant N-polyheterocycles, such as quinoxaline- and quinoline-fused derivatives, and phenanthridines, is reported. A simple, easily available, and environmentally friendly dioxomolybdenum(VI) complex has proven to be a highly efficient and versatile catalyst for transforming a broad range of starting nitroarenes involving several redox processes. Not only is this a sustainable, step-economical as well as air- and moisture-tolerant method, but also it is worth highlighting that the waste byproduct generated in the first step of the sequence is recycled and incorporated in the final target molecule, improving the overall synthetic efficiency. Moreover, selected indoloquinoxalines have been photophysically characterized in cyclohexane and toluene with exceptional fluorescence quantum yields above 0.7 for the alkyl derivatives.
Efficient Synthesis of D-Phenylalanine from L-Phenylalanine via a Tri-Enzymatic Cascade Pathway
Lu, Cui,Zhang, Sheng,Song, Wei,Liu, Jia,Chen, Xiulai,Liu, Liming,Wu, Jing
, p. 3165 - 3173 (2021/06/09)
D-phenylalanine is an important intermediate in food and pharmaceutical industries. Here, to enable efficient D-phenylalanine biosynthesis from L-phenylalanine, a tri-enzymatic cascade was designed and reconstructed in vivo. The activity of Proteus vulgaris meso-diaminopimelate dehydrogenase (PvDAPDH) toward phenyl pyruvic acid was identified as the limiting step. To overcome, the tension in the phenyl pyruvic acid side-chain, PvDAPDH was engineered, generating PvDAPDHW121A/R181S/H227I, whose catalytic activity of 6.86 U mg?1 represented an 85-fold increase over PvDAPDH. Introduction of PvDAPDHW121A/R181S/H227I, P. mirabilis L-amino acid deaminase, and Bacillus megaterium glucose dehydrogenase in E. coli enabled the production of 57.8 g L?1 D-phenylalanine in 30 h, the highest titer to date using 60 g L?1 L-phenylalanine as starting substrate, which meant a 96.3 % conversion rate and >99 % enantioselectivity on a 3-L scale. The proposed tri-enzymatic cascade provides a novel potential bio-based approach for industrial production of D-phenylalanine from cheap amino acids.
Total Synthesis of the Natural Herbicide MBH-001 and Analogues
Barber, David M.,D?ller, Uwe,Dietrich, Hansj?rg,Hoffmann, Michael G.,Kocakaya, Tamer,Kuhn, Birgit,Maier, Martin E.,Morkunas, Marius,Schmutzler, Dirk,Schnatterer, Stefan
, p. 2271 - 2290 (2020/04/23)
The first total synthesis of the natural herbicide MBH-001 (1) is reported. Structurally it is a 2-methyloxazol-5(2H)-one with a (1-hydroxyethyl) substituent at the 2-position. By relying on cyclic nitrones, a flexible route to MBH-001 and relevant analogues was developed. Key steps include the reaction of a 2-hydroxyimino ester with an aldehyde to form a 5-oxo-2,5-dihydrooxazole 3-oxide. In an aldol-type reaction, the anion of these cyclic nitrones reacted with an aldehyde at the 2-position. A final reduction of the nitrone to the corresponding imine using zinc led to the target compounds. The cyclic nitrones are also accessible by reacting an α-keto acid with an oxime. These two versatile synthetic routes enabled us to prepare the first MBH-001 analogues for structure activity relationship analysis of the herbicidal efficacy. Thus, furthering our aim of developing new herbicides to tackle the ever-growing problem of weed resistance.
Learning from Peptides to Access Functional Precision Polymer Sequences
Maron, Eva,Swisher, Jordan H.,Haven, Joris J.,Meyer, Tara Y.,Junkers, Tanja,B?rner, Hans G.
supporting information, p. 10747 - 10751 (2019/07/09)
Functional precision polymers based on monodisperse oligo(N-substituted acrylamide)s and oligo(2-substituted-α-hydroxy acid)s have been synthesized. The discrete sequences originate from a direct translation of side-chain functionality sequences of a peptide with well-studied properties. The peptide was previously selected to solubilize the photosensitizer meta-tetra(hydroxyphenyl)chlorin. The resulting peptidomimetic formulation additives preserve the drug solubilization and release characteristics of the parent peptide. In some cases, superior properties are obtained, reaching up to 40 % higher payloads and 27-times faster initial drug release.
A 2 - hydroxy dissidents calcium synthetic method
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Paragraph 0020; 0023-0024; 0030; 0033-0034; 0039; 0042-0043, (2019/07/05)
The invention discloses a 2 - hydroxy dissidents calcium synthetic method: to different pentanals, sodium bisulfite, sodium cyanide as raw material through nucleophilic addition reaction in the synthesis of 2 - hydroxy different fifth heavenly stem nitrile, then in acidic conditions by the hydrolysis reaction of the 2 - hydroxy dissidents acid, the final calcium salt exchange reaction 2 - hydroxy dissidents calcium, then refined to get the pure product 2 - hydroxy dissidents acid calcium, refined pure product purity as high as 99.7%, three-step [...] yield is up to 80% or more. The method has the production cycle is short, simple and convenient operation, is suitable for industrial production.
A novel Anti-Cancer Stem Cells compound optimized from the natural symplostatin 4 scaffold inhibits Wnt/β-catenin signaling pathway
Liu, Shuangwei,Gao, Xian,Zhang, Lisong,Qin, Shuanglin,Wei, Mingming,Liu, Ning,Zhao, Rui,Li, Benlong,Meng, Ye,Lin, Gang,Lu, Cheng,Liu, Xinhua,Xie, Maodun,Liu, Tongtong,Zhou, Honggang,Qi, Min,Yang, Guang,Yang, Cheng
, p. 21 - 42 (2018/07/06)
Cancer stem cells (CSCs) are responsible for carcinogenesis, cancer progression, relapse, metastasis and drug resistance. Therefore, the development of drug molecules targeting CSCs plays a vital role in medicinal researching field. However, there are extremely rare molecules that selectively ablate CSCs. The research and development of drugs targeting CSCs is limited due to a lack of anti-CSCs lead compounds. In this study, an anti-CSCs lead compound 35b was discovered, which was derived from the natural chemical scaffold of Symplostatin 4. This compound exhibited a significantly suppressive effect on tumor growth both in vitro and in vivo. Additionally, 35b could significantly reduce the number of melanoma tumor spheres and decrease the percentage of ALDH+ melanoma cells. Further mechanism study illustrated that compound 35b could eliminate the melanoma CSCs by efficiently blocking Wnt/β-catenin signaling pathway. Collectively, our findings would provide a novel chemical scaffold and alternative idea of molecular design for development of anti-CSCs drugs.
Readily Accessible 1,2-Amino Ether Ligands for Enantioselective Intramolecular Carbolithiation
Guyon, Hélène,Boussonnière, Anne,Castanet, Anne-Sophie
, p. 4949 - 4957 (2017/05/12)
A new class of chiral 1,2-amino ether ligands, readily accessible from naturally occurring α-amino- or α-hydroxy acids, was found to provide high levels of both conversion and stereocontrol (up to 95:5 er) in intramolecular carbolithiation reactions, outperforming the benchmark ligand (?)-sparteine. The ligand could be used in a substoichiometric amount (0.25 equiv) without significant loss of enantioselectivity.
Identification of Cyclic Depsipeptides and Their Dedicated Synthetase from Hapsidospora irregularis
Zhang, Shuwei,Qiu, Yixing,Kakule, Thomas B.,Lu, Zhenyu,Xu, Fuchao,Lamb, John G.,Reilly, Christopher A.,Zheng, Yong,Sham, Shing Wo Simon,Wang, Wei,Xuan, Lijiang,Schmidt, Eric W.,Zhan, Jixun
, p. 363 - 370 (2017/03/08)
Seven cyclic depsipeptides were isolated from Hapsidospora irregularis and structurally characterized as the calcium channel blocker leualacin and six new analogues based on the NMR and HRESIMS data. These new compounds were named leualacins B-G. The absolute configurations of the amino acids and 2-hydroxyisocaproic acids were determined by recording the optical rotation values. Biological studies showed that calcium influx elicited by leualacin F in primary human lobar bronchial epithelial cells involves the TRPA1 channel. Through genome sequencing and targeted gene disruption, a noniterative nonribosomal peptide synthetase was found to be involved in the biosynthesis of leualacin. A comparison of the structures of leualacin and its analogues indicated that the A2 and A4 domains of the leualacin synthetase are substrate specific, while A1, A3, and A5 can accept alternative precursors to yield new molecules.
