61700-12-7Relevant academic research and scientific papers
Ring-closing metathesis approaches towards the total synthesis of rhizoxins
Altmann, Karl-Heinz,Liniger, Marc,Neuhaus, Christian M.
supporting information, (2020/10/18)
Efforts are described towards the total synthesis of the bacterial macrolide rhizoxin F, which is a potent tubulin assembly and cancer cell growth inhibitor. A significant amount of work was expanded on the construction of the rhizoxin core macrocycle by ring-closing olefin metathesis (RCM) between C(9) and C(10), either directly or by using relay substrates, but in no case was ringclosure achieved. Macrocycle formation was possible by ring-closing alkyne metathesis (RCAM) at the C(9)/C(10) site. The requisite diyne was obtained from advanced intermediates that had been prepared as part of the synthesis of the RCM substrates. While the direct conversion of the triple bond formed in the ring-closing step into the C(9)-C(10) E double bond of the rhizoxin macrocycle proved to be elusive, the corresponding Z isomer was accessible with high selectivity by reductive decomplexation of the biscobalt hexacarbonyl complex of the triple bond with ethylpiperidinium hypophosphite. Radical-induced double bond isomerization, full elaboration of the C(15) side chain, and directed epoxidation of the C(11)-C(12) double bond completed the total synthesis of rhizoxin F.
Design and synthesis of mimics of the T7-loop of FtsZ
Sorto, Nohemy A.,Painter, Phillip P.,Fettinger, James C.,Tantillo, Dean J.,Shaw, Jared T.
supporting information, p. 2700 - 2703 (2013/07/19)
Mimics of the T7-loop of the bacterial cell division protein FtsZ have been designed and synthesized. The design is based on the X-ray cocrystal structure of P. aeruginosa FtsZ:SulA. Fast Rigid Exhaustive Docking (FRED) was employed to select compounds that can mimic the key interacting residues. Bicyclic oxazolidinones 1a-d were selected for further study and synthesized from a key bicyclic aziridine intermediate, which is synthesized from a readily available unsaturated aldehyde and amides derived from α-amino acids.
Total synthesis of the tubulin inhibitor WF-1360f based on macrocycle formation through ring-closing alkyne metathesis
Neuhaus, Christian M.,Liniger, Marc,Stieger, Martin,Altmann, Karl-Heinz
supporting information, p. 5866 - 5870 (2013/07/05)
Key steps in this total synthesis of the antimitotic natural product WF-1360F (3) include the formation of the macrocycle through ring-closing alkyne metathesis and the subsequent conversion of the ensuing alkyne moiety into an E-configured double bond. As illustrated by the synthesis of 4, the macrocyclic vinyl iodide 2 can also serve as a common precursor for the synthesis of side-chain-modified rhizoxin analogues (see scheme; TIPS=triisopropylsilyl). Copyright
Dihydroxylation-based approach for the asymmetric syntheses of hydroxy-γ-butyrolactones
Peed, Jennifer,Davies, Iwan R.,Peacock, Lucy R.,Taylor, James E.,Kociok-Koehn, Gabriele,Bull, Steven D.
experimental part, p. 543 - 555 (2012/02/04)
A method of preparing enantiopure hydroxy-γ-butyrolactones containing multiple contiguous stereocenters in high yield with good diastereoselectivity has been developed. Osmium tetroxide mediated dihydroxylation of a range of β-alkenyl-β-hydroxy-N-acyloxazolidin-2-ones results in formation of triols that undergo spontaneous intramolecular 5-exo-trig cyclization reactions to provide hydroxy-γ-butyrolactones. The stereochemistry of these hydroxy-γ-butyrolactones has been established using NOE spectroscopy, which revealed that 1-substituted, 1,1-disubstituted, (E)-1,2-disubstituted, (Z)-1,2-disubstituted, and 1,1,2-trisubstituted alkenes undergo dihydroxylation with anti-diastereoselectivity, while 1,2,2-trisubstituted systems afford syn-diastereoisomers. The synthetic utility of this methodology has been demonstrated for the asymmetric synthesis of the natural product 2-deoxy-d-ribonolactone. Published 2011 by the American Chemical Society.
Exploration of conjugate addition routes to advanced tricyclic components of mangicol A
Pichlmair, Stefan,de Lera Ruiz, Manuel,Vilotijevic, Ivan,Paquette, Leo A.
, p. 5791 - 5802 (2007/10/03)
Two synthetic approaches to the cytotoxic marine natural product known as mangicol A are described. The starting material common to both pathways is the cyclopentenonecarboxylate 11. The first tactic involves the 1,4-addition to 11 of the cuprate derivable from iodide 10, while the second proceeds via base-promoted conjugate addition of the regiospecifically generated enolate anion of 41. The first strategy proceeds by a series of efficient steps to tricyclic aldol 21 and subsequently to β-diketone 7. The latter proved to be totally unresponsive to schemes aimed at introduction of a butenyl group. The second approach involves earlier introduction of this substituent as realized in stereocontrolled fashion via transition state 42. While further passage to 44 proved uneventful, this advanced intermediate and analogs thereof proved remarkably recalcitrant to cyclization in the precedented fashion. In no instance was generation of a suitable product realized. These studies serve to underscore the extent to which steric considerations can complicate matters and the extent to which they must be skirted. Finally, a direct enantioselective route to the side chain aldehyde 2 is detailed.
4-SUBSTITUTED 2-AMINOALK-3-ENOIC ACIDS
-
, (2008/06/13)
Substituted 2-aminoalk-3-enoic acid derivative of formula I STR1 wherein R 1 is an aliphatic hydrocarbon radical that is substituted by optionally acylated or aliphatically or araliphatically etherified hydroxy, by halogen, by optionally acylated and/or aliphatically substituted amino or by an aza-, diaza-, azoxa-or oxa-cycloaliphatic radical, or is an oxacycloaliphatic hydrocarbon radical bonded via a carbon atom, or is an optionally aliphatically N-substituted or N-acylated azacycloaliphatic hydrocarbon radical, and R. sub.2 is free or esterified carboxy, and their salts exhibit NMDA-antagonistic properties and are useful as active ingredients of anticonvulsive medicaments.
A (FORMAL) TOTAL SYNTHESIS OF (+)-STRIGOL, THE WITCHWEED GERMINATION FACTOR
Berlage, Ulrich,Schmidt, Juergen,Milkova, Zenka,Welzel, Peter
, p. 3095 - 3098 (2007/10/02)
A synthetic route to (+)-1 commencing from (S)-malic acid and 20 is reported.Key steps are the coupling of 20 and 15 to give 21, an intramolecular Wittig reaction (25-27), and an oxidative cyclization (28-1).
