121840-97-9Relevant articles and documents
Synthesis and Structure-Activity Relationship Studies of C2-Modified Analogs of the Antimycobacterial Natural Product Pyridomycin
Kienle, Maryline,Eisenring, Patrick,Stoessel, Barbara,Horlacher, Oliver P.,Hasler, Samuel,Van Colen, Gwéna?lle,Hartkoorn, Ruben C.,Vocat, Anthony,Cole, Stewart T.,Altmann, Karl-Heinz
, p. 1105 - 1131 (2020/03/10)
A series of derivatives of the antimycobacterial natural product pyridomycin have been prepared with the C2 side chain attached to the macrocyclic core structure by a C-C single bond, in place of the synthetically more demanding enol ester double bond found in the natural product. Hydrophobic C2 substituents of sufficient size generally provide for potent anti-Mtb activity of these dihydropyridomycins (minimum inhibitory concentration (MIC) values around 2.5 μM), with several analogs thus approaching the activity of natural pyridomycin. Surprisingly, some of these compounds, in contrast to pyridomycin, are insensitive to overexpression of InhA in Mycobacterium tuberculosis (Mtb). This indicates that their anti-Mtb activity does not critically depend on the inhibition of InhA and that their overall mode of action may differ from that of the original natural product lead.
First Total Synthesis of Jomthonic Acid A 1
Dumpala, Mohan,Radha Krishna, Palakodety,Srinivas, Batthula
supporting information, p. 69 - 72 (2019/12/30)
A stereoselective total synthesis of jomthonic acid A is described. The key features of the synthetic strategy are a Sharpless asymmetric epoxidation, a Gilmann reagent-induced methylation, a Mitsunobu reaction, a Yamaguchi esterification, and an O -(benzotriazol-1-yl)- N, N, N ′, N ′-tetramethyluronium tetrafluoroborate (TBTU)-mediated amide coupling. Jomthonic acid A is an architecturally rare amino acid containing a β-methylphenylalanine residue and a 4-methyl-(2 E,4 E)-hexa-2,4-dienoate moiety. It shows antidiabetic and antiatherogenic activities when tested against mouse ST-13 preadiopocytes.
A stereoselective approach for the total synthesis of [2(S)-phenyl- propionyl]-2-piperidinone-3-(R)-yl-ester and its diastereomer
Krishna, Palakodety Radha,Arun Kumar, Pendyala Venkata,Mallula, Venkata Satyanarayana,Ramakrishna, Kallaganti V.S.
, p. 2319 - 2326 (2013/03/29)
Stereoselective total synthesis of isomers of [2-phenyl-propionyl]-2- piperidinone-3(R)-yl-ester has been achieved using commercially available starting materials like trans cinnamaldehyde and 4-pentene-1-ol. The key steps are Steglich conditions for the esterification of the two crucial intermediates; reduction of the azide to amine under Staudinger reaction conditions with concomitant intramolecular amidation reaction in one pot afforded the target compound(s). However, the total syntheses revealed that the structural revision is necessary for the reported natural product.
C-O hydrogenolysis catalyzed by Pd-PMHS nanoparticles in the company of chloroarenes
Rahaim, Ronald J.,Maleczka, Robert E.
, p. 584 - 587 (2011/04/23)
Catalytic Pd(OAc)2 and polymethylhydrosiloxane (PMHS), in conjunction with aqueous KF, and a catalytic amount of an aromatic chloride, effects the chemo-, regio-, and stereoselective deoxygenation of benzylic oxygenated substrates at room temperature in THF. Preliminary mechanistic experiments suggest the process to involve palladium-nanoparticle-catalyzed hydrosilylation followed by C-O reduction. The chloroarene additive appears to facilitate the hydrogenolysis process through the slow controlled release of HCl.
[1,2]-Wittig rearrangement of (benzyloxy)acetamides
Hameury, Thomas,Guillemont, Jér?me,Van Hijfte, Luc,Bellosta, Véronique,Cossy, Janine
scheme or table, p. 2345 - 2347 (2009/05/27)
[1,2]-Wittig rearrangement of (benzyloxy)acetamides can lead to substituted α-hydroxyamides in good yields and good diastereoselectivity. Georg Thieme Verlag Stuttgart.
A Catalytic Asymmetric Synthesis of N-Boc-β-Methylphenylalanines
Pasto, Mireia,Moyano, Albert,Pericas, Miquel A.,Riera, Antoni
, p. 8425 - 8431 (2007/10/03)
An efficient, stereodivergent, and enantioselective synthesis of the syn and anti diastereomers of N-Boc-β-methylphenylalanine has been developed. Starting from enantiomerically pure (2S,3S)-2,3-epoxy-3-phenyl-1-propanol, a three-step sequence, consisting of the oxidation of the primary alcohol up to the carboxyl stage, ring opening of the epoxy acid with Me2CuCNLi2, and esterification of the resulting hydroxy acid with methyl iodide, leads to the hydroxy ester anti-W, which has been converted in a stereodivergent manner into both the (2S,3R) and the (2R,3R) diastereomers of N-Boc-β-methylphenylalanine, syn-1 and anti-1, respectively. Activation of the secondary hydroxy group in anti-10 as a mesylate, followed by nucleophilic displacement with sodium azide, hydrogenolysis with simultaneous protection of the amino group, and saponification with LiOH, affords syn-1. The same reaction sequence applied to syn-10, obtained in turn by Mitsunobu reaction of anti-10 with p-nitrobenzoic acid followed by the hydrolysis of the resulting p-nitrobenzoate, leads to anti-1. Both products have been obtained with ≥99% enantiomeric excess.
Experimental and theoretical studies of the internal stereodifferentiation occurring during the lithiation of β-stereogenic alkyl carbamates. Kinetic resolutions by (-)-sparteine-mediated deprotonation
Haller, Jan,Hense, Thomas,Hoppe, Dieter
, p. 489 - 499 (2007/10/03)
The deprotonation of β-stereogenic alkyl carbamates 8 with sec-butyllithium/TMEDA proceeds kinetically controlled with differentiation between the diastereotopic protons at the α-methylene group. The lithium intermediates 9A and 9B are trapped by electrophiles to give carboxylic acid esters 10A/ B and stannanes 11A/B, 13A/B. The diastereomeric ratio of A to B is independent of the electrophile. The highest efficiency is achieved with β-aryl-β-alkyl-substituted starting compounds 8d-f. The trends in the experimentally observed diastereoselectivities are reflected by the results of semiempirical PM3 calculations on the transition states of the deprotonation reaction. - As a result of double stereodifferentiation, application of the chiral base sec-butyllithium/(-)-sparteine gives rise to efficient kinetic resolution of racemic alkyl carbamates. VCH Verlagsgesellschaft mbH, 1996.
Enantioselective syntheses of 2-arylpropanoic acid non-steroidal antiinflammatory drugs and related compounds
Hamon, David P.G.,Massy-Westropp, Ralph A.,Newton, Josephine L.
, p. 12645 - 12660 (2007/10/02)
(S)-2-[4′-(2″-Methylpropyl)phenylpropanoic acid (ibuprofen) and (S)-2-(3′-benzoylphenyl)propanoic acid (ketoprofen) have been synthesised in high enantiomeric excess. Control of stereochemistry was achieved by a combination of Sharpless epoxidalion followed by catalytic hydrogenolysis of the introduced benzylic epoxide oxygen bond. Also, the coupling of organic compounds in the presence of palladium with enantiopure 2-(3-iodophenyl)propanoic and 2-(4-iodophenyl)propanoic acids, prepared by the methodology above, is a general method for the synthesis of optically active arylpropanoic acids.
Practical hydroxymethylation of aldehydes and ketones via pinacol cross-coupling reactions with paraformaldehyde
Park, Jeonghan,Pedersen, Steven F.
, p. 2069 - 2080 (2007/10/02)
A general and practical method for the direct hydroxymethylation of aldehydes and ketones via pinacol cross-coupling with paraformaldehyde is described. The reaction is promoted by vanadium(II) ions which are conveniently generated from the reduction of VCl3(THF)3 with zinc dust. Excellent yields of terminal diols are obtained and stereoselective coupling is observed with some chiral aldehydes and ketones.
