86635-91-8Relevant academic research and scientific papers
SYNTHESIS OF 6-CARBOXY-2,2-DIMETHYLCHROMANS AND CHROMENES
Ahluwalia, V. K.,Jolly, R. S.,Tehim, A. K.
, p. 3673 - 3677 (1982)
The condensation of hydroxybenzoic acids and their methyl esters with isoprene in the presence of orthophosphoric acid gives corresponding 2,2-dimethylchromans, which can be dehydrogenated with DDQ or NBS to give the corresponding 6-carboxy-2,2-dimethylch
Total synthesis of unsymmetrical benzils, scandione and calophione A
Worayuthakarn, Rattana,Boonya-Udtayan, Sasiwadee,Ruchirawat, Somsak,Thasana, Nopporn
, p. 2496 - 2507 (2014/05/06)
The synthesis of the title unsymmetrical benzils, scandione and calophione A, is described. The key processes involve intramolecular cyclization reaction of the carbanion at the benzylic position of the arylbenzyl ether to the adjacent ester group followed by oxidation. The palladium(II)-catalyzed oxidative cyclization was also used to establish the benzofuran unit of calophione A. A convergent synthesis of the title benzils, which embody the 1,2-diarylethane-1,2-dione system, is reported. Key steps involve intramolecular cyclization of the carbanion at the benzylic position of the arylbenzyl ether to the adjacent ester group followed by oxidation. The palladium(II)-catalyzed oxidative cyclization was also studied to establish the benzofuran unit of calophione A. Copyright
A concise enantioselective synthesis and cytotoxic evaluation of the anticancer rotenoid deguelin enabled by a tandem Knoevenagel/conjugate addition/decarboxylation sequence
Farmer, Rebecca L.,Scheidt, Karl A.
, p. 3304 - 3309 (2013/07/26)
(-)-Deguelin is a rotenoid natural product that possesses significant potential as a chemopreventive and chemotherapeutic agent. While several racemic syntheses of deguelin have been reported, a formal evaluation of the anticancer activity of both the natural and unnatural enantiomers remains lacking. We describe herein the successful application of a flexible and selective thiourea-catalyzed cyclization strategy toward the enantioselective total synthesis of deguelin, which allows access to either stereoisomer for biological studies. The synthesis was completed in six steps (longest linear) with no protecting groups. The evaluation of both enantiomers of the natural product demonstrated potent inhibition of several cancer cell lines by these compounds, but interestingly showed that the unnatural (+)-deguelin preferentially inhibited the growth of MCF-7 breast cancer and HepG2 liver carcinoma cells when compared to the natural product.
Mechanism and Stereochemistry of the Enzyme-catalysed Formation of a 2,2-Dimethylchromene Ring from a Prenylated Phenol: Conversion of Rot-2'-enonic Acid into Deguelin by Deguelin Cyclase
Bhandari, Prabha,Crombie, Leslie,Harper, Mark F.,Rossiter, John T.,Sanders, Mark,Whiting, Donald A.
, p. 1685 - 1698 (2007/10/02)
The stereochemistry of the enzymic conversion of rot-2'-enonic acid into deguelin, mediated by deguelin cyclase, has been studied.Using both an enzyme preparation and seedlings of Tephrosia vogellii, it is shown that (6aS,12aS,5'R/S)-5-hydroxy-4',5'-dihydrodeguelin is not an acceptable intermediate: no evidence for other oxygenated intermediates was found.The (pro-R)- and (pro-S)-6'-methyl groups of deguelin were identified by synthesis from rot-2'-enonic acid.Addition of benzeneselenenyl chloride gives two diastereoisomeric 5'-(phenylselenides) of 4',5'-dihydrodeguelin which are separated and their stereochemistry established by X-ray crystallography.Elimination of selenoxide from the (5'S)-stereoisomer then gives (6'R)-deguelin (δC 28.20): (6'S)-deguelin has δC 28.52.Although a chemical conversion of rot-2'-enonic acid into labelled deguelin produces a 1:1 distribution of label between the (pro-R)- and (pro-S)-6'-methyls, the enzyme-mediated conversion results unexpectedly in a 76percent incorporation into the (pro-R)- and 24percent into the (pro-S)-form.The stereochemistry of the removal of the key 1'-hydrogens in rot-2'-enonic acid was therefore examined.Addition of benzenesulfenyl chloride to deguelin gave a highly reactive chloro sulfide by syn-addition through attack from the less hindered β-face of the molecule.Treatment with sodium cyanoborohydride displaced the reactive chlorine with complete inversion to give (6aS,12aS,5'S)-5'-phenylthio-4',5'-dihydrodeguelin.Ring-E scission of the latter proceeded satisfactorily using sodium naphthalenide only after reduction of the 1,2-carbonyl to the alcohol: periodinane oxidation then produced rot-2'-enonic acid.Replacement of the unlabelled cyanoborohydride by cyanoborotritide gave the desired (6aS,12aS,1'S)-rot-2'-enonic acid.The (6aS,12aS,1'R)--counterpart was made by first preparing deguelin by syn-elimination from the sulfoxide formed from (6aS,12aS,4'R,5'S)-5'-phenylthio-4',5'-dihydro-deguelin.Addition of benzenesulfenyl chloride to the deguelin, followed by a sequence parallelling that above, using unlabelled sodium cyanoborohydride, gave the required (6aS,12aS,1'R)-rot-2'-enonic acid.Enzymic conversion of each -labelled rot-2'-enonic acid into deguelin along with a -labelled monitor, shows that a 73percent loss of (pro-4'S-H) in rot-2'-enonic acid correlates with a 76percent attainment of a (pro-6'R-Me) in deguelin, whilst a 27percent loss of (pro-4'R-H) in the former correlates with a 24percent attainment of a (pro-6'S-Me) in the latter.The possible enzymic mechanism of the reaction is discussed and related to a similar mechanism we have suggested for the enzymic formation of rotenone from rot-2'-enonic acid.
