113522-74-0Relevant articles and documents
Ring-closing metathesis approaches towards the total synthesis of rhizoxins
Altmann, Karl-Heinz,Liniger, Marc,Neuhaus, Christian M.
, (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.
Synthesis of Chiral Tertiary Boronic Esters by Oxime-Directed Catalytic Asymmetric Hydroboration
Shoba, Veronika M.,Thacker, Nathan C.,Bochat, Andrew J.,Takacs, James M.
supporting information, p. 1465 - 1469 (2016/02/12)
Chiral boronic esters are useful intermediates in asymmetric synthesis. We have previously shown that carbonyl-directed catalytic asymmetric hydroboration (CAHB) is an efficient approach to the synthesis of functionalized primary and secondary chiral boronic esters. We now report that the oxime-directed CAHB of alkyl-substituted methylidene and trisubstituted alkene substrates by pinacolborane (pinBH) affords oxime-containing chiral tertiary boronic esters with yields up to 87 % and enantiomeric ratios up to 96:4 e.r. The utility of the method is demonstrated by the formation of chiral diols and O-substituted hydroxylamines, the generation of quaternary carbon stereocenters through carbon-carbon coupling reactions, and the preparation of chiral 3,4,4-trisubstituted isoxazolines.
N,N-Dimethylaminobenzoates enable highly enantioselective Sharpless dihydroxylations of 1,1-disubstituted alkenes
Zhao, Yaohong,Xing, Xiangyou,Zhang, Shaolong,Wang, David Zhigang
supporting information, p. 4314 - 4317 (2014/06/23)
A design scenario aimed at exploring beneficial catalyst-substrate π-π stacking electronic interactions in the classical Sharpless asymmetric dihydroxylations (SAD) leads to the identification of highly polarizable allylic N,N-dimethylaminobenzoate as a remarkably efficient auxiliary for inducing high levels of enantioselectivities (up to 99% ee) in the traditionally challenging substrate class of 1,1-disubstituted aliphatic alkenes. the Partner Organisations 2014.
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
, 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
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.
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).
