80697-95-6Relevant academic research and scientific papers
Thermal proteome profiling efficiently identifies ribosome destabilizing oxazolidinones
N?cker, Christina,Kaiser, Nadine,Foley, Daniel,Sievers, Sonja,Janning, Petra,Waldmann, Herbert,Laraia, Luca
supporting information, (2021/04/22)
Identifying the targets of bioactive small molecules is a challenging endeavor for which no general solution currently exists. Classical affinity purification experiments suffer from the need to functionalise a bioactive compound and link it to a solid support, which may interfere with target binding. A modern mass spectrometry-based proteomics technique that has partially circumvented this problem is thermal proteome profiling (TPP), which determines the effect of an unmodified small molecule on the thermal stability of the whole proteome simultaneously. Here, we use TPP to identify the mode-of-action of a newly-discovered autophagy inhibitor based on oxazolidinones often employed as chiral auxiliaries. Surprisingly, a significant portion of all ribosomal proteins were found to be destabilized by the inhibitor, highlighting the utility of this technology for determining a challenging mode-of-action.
Conformational preference in bis(porphyrin) tweezer complexes: A versatile chirality sensor for α-chiral carboxylic acids
Tanasova, Marina,Borhan, Babak
supporting information; experimental part, p. 3261 - 3269 (2012/07/01)
Metallated porphyrin tweezers have demonstrated a remarkable ability to function as reporters of absolute stereochemistry for a number of different classes of organic molecules. Flexibility in binding, however, can result in an ensemble of different Exciton Coupled Circular Dichroism (ECCD) active conformations that could lead to variable results. Linker flexibility was found to be a key determinant of binding conformation. Experimental results indicate that a balance between linker flexibility and rigidity could yield an optimum porphyrin tweezer that stabilizes a common conformation for all bound chiral guests. This leads to a more simplified approach to absolute stereochemical determination of asymmetry for small organic molecules. This was demonstrated by the use of a C3-linked zincated porphyrin tweezer that yields a common conformational preference for a variety of α-chiral carboxylic acids derivatized with a diamine carrier. Copyright
SmI2-promoted intra- and intermolecular C-C bond formation with chiral N-acyl oxazolidinones
Taaning, Rolf H.,Thim, Laura,Karaffa, Jacob,Campa?a, Araceli G.,Hansen, Anna-Mette,Skrydstrup, Troels
experimental part, p. 11884 - 11895 (2009/04/07)
The suitability of chiral oxazolidinones in the SmI2-mediated C-C bond generation between the imide functionality of an N-acyl oxazolidinone unit and an olefinic radical acceptor, in both inter- and intramolecular reactions, was investigated. It was shown that the products from an Evans asymmetric alkylation can undergo direct carbon-carbon bond formation with an acrylamide providing chiral acyclic ketones in reasonable yields. These examples represent the first transformation of such N-acyl oxazolidinones where this chiral auxiliary is removed under the conditions for ketone formation. 5-exo-trig Cyclization studies were also undertaken with the same type of substrates, providing trans-2,5-disubstituted cyclopentanones in yields of approx. 50%. However, attempts to cyclize heteroatom-containing equivalents were less rewarding.
Total Syntheses of Amphidinolide T1, T3, T4, and T5
Aissa, Christophe,Riveiros, Ricardo,Ragot, Jacques,Fuerstner, Alois
, p. 15512 - 15520 (2007/10/03)
A concise, flexible, and high yielding entry into the family of amphidinolide T macrolides, a series of cytotoxic natural products of marine origin, has been developed. All individual members, except amphidinolide T3 (3), derive from compound 39 as a comm
Total synthesis of amphidinolide T4
Fuerstner, Alois,Aissa, Christophe,Riveiros, Ricardo,Ragot, Jacques
, p. 4763 - 4766 (2007/10/03)
Organometallic chemistry in general and catalysis in particular are used in the first total synthesis of amphidinolide T4 (see scheme); a prototype member of a series of macrolide antibiotics of marine origin with rings containing an odd number of carbon
Total synthesis of the polyether antibiotic X-206
Evans,Bender,Morris
, p. 2506 - 2526 (2007/10/12)
A convergent asymmetric synthesis of the polyether antibiotic X-206 has been achieved through the synthesis and coupling of the C1-C16- and C17-C37 synthons 16 and 17, respectively. All absolute stereochemical relationships within the molecule were controlled by application of recent methodological advances in asymmetric synthesis. In the synthesis of subunit 16, both the alkylation and aldol reactions of chiral imide-derived enolates were utilized to establish the five stereogenic centers at C2-C4 and C9-C10, while the stereochemistry at C14 was indirectly controlled by the Sharpless asymmetric epoxidation. The C7 and C11 stereocenters, which are situated at the two assemblage points for 16, were established through internal asymmetric induction. The synthesis of the more complex C17-C37 subunit 17 followed a similar strategy for absolute stereocontrol. Chiral enolate methodology was employed to define the stereogenic centers at C18, C22, and C23 while asymmetric epoxidation was used to create the oxygen-bearing centers at C30-C31 and C34-C35. The remaining three stereogenic centers at C20, C26, and C28 were controlled by internal asymmetric induction. The successful construction of this synthon relied upon the development of an efficient assemblage reaction in which three fragments comprising the entire carbon framework of 17 were united in a single operation. The final coupling of the two halves was achieved by a nonstereoselective aldol reaction. In supporting studies, the selective manipulation and degradation of the natural product were also investigated.
