55282-91-2Relevant academic research and scientific papers
Molecular simplification in bioactive molecules: Formal synthesis of (+)-muconin
Pinacho Crisostomo, Fernando R.,Carrillo, Romen,Leon, Leticia G.,Martin, Tomas,Padron, Jose M.,Martin, Victor S.
, p. 2339 - 2345 (2006)
The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to (+)-muconin, an acetogenin with remarkable cytotoxicity. A novel approa
Enantiodivergent Cyclization by Inversion of the Reactivity in Ambiphilic Molecules
Brovetto, Margarita,Martín, Tomás,Martín, Víctor S.,Rodríguez-López, Julio
, p. 17077 - 17083 (2020)
Inverting the reactivity of the functional groups in ambiphilic molecules provides a new synthetic strategy to perform late-stage enantiodivergence. Both enantiomers of the final compound can be obtained from a common chiral precursor. As a proof of concept, the synthesis of substituted five- and six-membered oxacycles is described. The key step is the cyclization of an ambiphilic linear precursor bearing a propargylic alcohol and an epoxide linked through an alkyl chain. Through a slight modification of these linear precursors and employing different reaction conditions, these functional groups can inverse their chemical reactivity, producing one enantiomer or another of the final product. This enantiodivergent cyclization involves three stereogenic centers that can undergo fully controlled retention or inversion of their configuration depending on the cyclization pathway that is activated. The cyclization provides late-stage enantiodivergence, enabling the synthesis of either enantiomers of the oxacycles from a common chiral substrate with total transfer of the enantiomeric purity.
Rhodium-Catalyzed Stereoselective Intramolecular [5 + 2] Cycloaddition of 3-Acyloxy 1,4-Enyne and Alkene
Shu, Xing-Zhong,Schienebeck, Casi M.,Li, Xiaoxun,Zhou, Xin,Song, Wangze,Chen, Lianqing,Guzei, Ilia A.,Tang, Weiping
, p. 5128 - 5131 (2015/11/03)
The first rhodium-catalyzed intramolecular [5 + 2] cycloaddition of 3-acyloxy 1,4-enyne and alkene was developed. The cycloaddition is highly diastereoselective in most cases. Various cis-fused bicyclo[5.3.0]decadienes were prepared stereoselectively. The chirality in the propargylic ester starting materials could be transferred to the bicyclic products with high efficiency. Electron-deficient phosphine ligand greatly facilitated the cycloaddition. Up to three new stereogenic centers could be generated. The resulting diene in the products could be hydrolyzed to enones, which allowed the introduction of more functional groups to the seven-membered ring.
Intramolecular 1,3-dipolar cycloaddition-mediated stereoselective synthesis of disubstituted cyclopentane: A simple model for the cyclopentane ring system of polycyclic oroidine alkaloids
Fukahori, Yusuke,Takayama, Yohei,Imaoka, Takuya,Iwamoto, Osamu,Nagasawa, Kazuo
, p. 244 - 250 (2013/02/23)
We present a diastereoselective synthesis of disubstituted cyclopentane 8 having a nitrogen-containing quaternary carbon center, which is found in axinellamine A (5) and related compounds. During this work, we found that the 1,3-dipolar cycloaddition product 24 immediately underwent intramolecular redox reaction at the newly formed morpholin-2-one moiety, thus affording disubstituted cyclopentane containing a tertiary amine (9) stereoselectively in good yield. The amine 9 was successfully converted into guanidine 31, which corresponds to 8, through iminium cation-enamine isomerization. Copyright
Stereoselective synthesis of polyhydroxylated aminocyclohexanes
Ahmad, Sajjad,Thomas, Lynne H.,Sutherland, Andrew
experimental part, p. 2801 - 2808 (2011/05/12)
The stereoselective synthesis of a series of di- and tri-hydroxylated aminocyclohexane derivatives has been developed. A one-pot, two step tandem process involving an Overman rearrangement and a ring closing metathesis reaction has been utilised for the asymmetric synthesis of (1S)-1-(2′, 2′,2′-trichloromethylcarbonylamino)cyclohexa-2-ene. Oxidation of this cyclohexene derivative was then studied leading to the preparation of two diol analogues in excellent stereoselectivity. (1S)-1-(2′,2′, 2′-trichloromethylcarbonylamino)cyclohexa-2-ene was then converted to a novel allylic alcohol via a 4,5-dihydro-1,3-oxazole. Functionalisation of this allylic alcohol by Upjohn dihydroxylation conditions or by a directed epoxidation/hydrolysis sequence of reactions allowed the synthesis of two dihydroconduramines in excellent stereoselectivity. The stereochemical assignment of all compounds prepared was confirmed by NOE experiments or X-ray structure determination.
A three-step tandem process for the synthesis of bicyclic γ-lactams
McGonagle, Fiona I.,Brown, Lindsay,Cooke, Andrew,Sutherland, Andrew
experimental part, p. 3418 - 3425 (2010/08/21)
A one-pot, three-step tandem process has been developed for the direct synthesis of functionalised bicyclic [3.3.0], [4.3.0] and [5.3.0] γ-lactams from simple allylic trichloroacetimidates. The process involves a palladium(ii) mediated Overman rearrangement followed by the use of Grubbs first generation complex which catalyzes both a ring closing metathesis reaction and a Kharasch cyclization. As well as exploring the scope of this process for the synthesis of a range of functionalised bicyclic γ-lactams, the use of chiral palladium(ii) catalysts during the Overman rearrangement for the enantioselective synthesis of the bicyclic γ-lactams is also demonstrated. The Royal Society of Chemistry 2010.
A tandem aza-claisen rearrangement and ring closing metathesis reaction for the synthesis of cyclic allylic trichloroacetamides
Swift, Michael D.,Sutherland, Andrew
, p. 5239 - 5242 (2008/09/17)
(Chemical Equation Presented) A one-pot tandem palladium(II)-catalyzed aza-Claisen rearrangement and ring closing metathesis process has been developed for the efficient synthesis of cyclic allylic trichloroacetamides. The use of chiral Pd(II) catalysts such as (S)-COP-Cl during the rearrangement stage results in the preparation of these compounds in excellent yields and in high enantiomeric excess.
Regio- and stereospecific formation of protected allylic alcohols via zirconium-mediated SN2′ substitution of allylic chlorides
Fox, Richard J.,Lalic, Gojko,Bergman, Robert G.
, p. 14144 - 14145 (2008/09/18)
A new, highly regio- and stereospecific SN2′ substitution reaction between a zirconium oxo complex and allylic chloride has been achieved. The resulting allylic alcohol or TBS-protected allylic ether products were isolated in good to excellent yields with a wide range of E-allylic chlorides. A mechanism for the SN2′ allylic substitution consistent with kinetic, stereochemical, and secondary isotope effect studies was proposed. Copyright
A convenient and chemoselective one-pot oxidation/Wittig reaction for the C2-homologation of carbohydrate-derived glycols
Crisostomo, Fernando R. Pinacho,Carrillo, Romen,Martin, Tomas,Garcia-Tellado, Fernando,Martin, Victor S.
, p. 10099 - 10101 (2007/10/03)
A simple and convenient one-pot protocol for the chemoselective C 2-homologation of carbohydrate-derived glycols is described. The method comprises the chemoselective oxidation of the glycol to the corresponding hydroxyaldehyde and the subsequent Wittig alkenylation. In addition, the method does not need selective protective group manipulation, and it is safe, economical, fast (5 to 6 h), and bench-friendly. Its general utility is discussed.
Experimental determination of the activation parameters and stereoselectivities of the intramolecular Diels-Alder reactions of 1,3,8-nonatriene, 1,3,9-decatriene, and 1,3,10-undecatriene and transition state modeling with the Monte Carlo-Jumping between Wells/molecular dynamics method
Diedrich, Matthias K.,Kl?rner, Frank-Gerrit,Beno, Brett R.,Houk,Senderowitz, Hanoch,Still, W. Clark
, p. 10255 - 10259 (2007/10/03)
Experimental activation parameters for the intramolecular Diels-Alder reactions of 1,3,8-nonatriene, 1,3,9-decatriene, and 1,3,10-undecatriene have been measured, and the Monte Carlo-Jumping between Wells/Stochastic Dynamics [MC(JBW)/SD] method, which gives relative free energies of activation, was tested as a means to predict stereoselectivities. The predictions are compared to experimental results, and to predictions from quantum and molecular mechanics methods.
