114127-17-2Relevant articles and documents
Evolution of concise and flexible synthetic strategies for trichostatic acid and the potent histone deacetylase inhibitor trichostatin A
Cosner, Casey C.,Bhaskara Reddy Iska, Vijaya,Chatterjee, Anamitra,Markiewicz, John T.,Corden, Steven J.,Loefstedt, Joakim,Ankner, Tobias,Richer, Joshua,Hulett, Tyler,Schauer, Douglas J.,Wiest, Olaf,Helquist, Paul
, p. 162 - 172 (2013/02/23)
(R)-(+)-Trichostatic acid and (R)-(+)-trichostatin A (TSA) are natural products that have attracted considerable attention in the field of epigenetic therapies. TSA in particular is a naturally occurring hydroxamic acid having potent activity as a histone deacetylase inhibitor (HDACi) and having significant potential for treatment of a myriad of genetically based diseases. Development of TSA and other trichostatic acid derivatives into useful small-molecule therapies has been hindered by the low natural abundance and high cost associated with these compounds. We report herein our collective efforts towards the development of concise and scalable routes for the synthesis of trichostatic acid and TSA in both racemic and enantioenriched forms. Three independent synthetic pathways were developed with varying degrees of efficiency and convergency. In the first synthesis, the key step was a vinylogous Horner-Wadsworth-Emmons condensation. A Marshall propargylation reaction was used as the key step in the second synthesis, and Pd-catalyzed α-alkenylation of a ketone zinc enolate by using various functionalized alkenyl or dienyl halides was developed for the third synthesis. The second pathway proved to be readily amenable to an enantioselective modification, and both the second and third pathways were straightforwardly adapted for the facile preparation of new analogues of trichostatic acid and TSA. Three synthetic strategies have been developed for trichostatic acid and trichostatin A. Each strategy has a different key bond-forming step; a vinylogous Horner-Wadsworth-Emmons condensation, a Marshall propargylation, and coupling of a ketone enolate with various alkenyl halides. Two of the syntheses were efficient and able to produce analogues. Two of the syntheses were enantioselective. Copyright
SYNTHESIS OF HDAC INHIBITORS: TRICHOSTATIN A AND ANALOGUES
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, (2011/10/12)
Embodiments herein relate to histone deacetylaces (HDACs) and HDAC inhibitors, such as trichostatin A (TSA) and TSA analogues. Embodiments provide simple methods of synthesizing TSA and TSA analogues. These methods provide routes of synthesis of TSA and TSA analogues that enable the production of the HDAC inhibitors at lower cost and in greater quantities than previously were available.
Concise, convergent syntheses of (±)-trichostatin a utilizing a Pd-catalyzed ketone enolate α-alkenylation reaction
Cosner, Casey C.,Helquist, Paul
, p. 3564 - 3567 (2011/09/14)
Two concise, convergent syntheses of (±)-trichostatin A (1), a potent histone deacetylase inhibitor, have been accomplished. The key step in both is a Pd-catalyzed α-alkenylation reaction between ketone 2 and either dienyl bromide 3 or alkenyl bromide 9 u
Synthesis of 4-methyldienoates using a vinylogous horner-wadsworth-emmons reagent. application to the synthesis of trichostatic acid
Markiewicz, John T.,Schauer, Douglas J.,Loefstedt, Joakim,Corden, Steven J.,Wiest, Olaf,Helquist, Paul
supporting information; experimental part, p. 2061 - 2064 (2010/06/16)
Chemical Equation Presented The utility of the unsaturated phosphonate 1 as a vinylogous Horner-Wadsworth-Emmons reagent was explored in reactions with, aldehydes affording 4-methyldienoate esters. Factors that affect E/Z selectivity were studied. A simplified synthesis of trichostatic acid 3 was accomplished, to demonstrate utility of this reagent.
An efficient synthesis of (±)-trichostatic acid and analogues: A new route to (±)-trichostatin A
Chatterjee, Anamitra,Richer, Joshua,Hulett, Tyler,Iska, Vijaya Bhaskara Reddy,Wiest, Olaf,Helquist, Paul
supporting information; experimental part, p. 832 - 834 (2010/04/06)
An efficient synthesis of rac-trichostatic acid (1) and Its analogues is reported starting from a commercially available aldehyde. Further manipulations of rac-1 led to rac-trichostatin A (TSA). Construction of the desired molecular architecture entails a two-component union, achieved through an in situ hydroboration followed by a Suzuki-Miyaura coupling with 2. The requisite homopropargyl alcohol was synthesized by exploiting allenylindium chemistry. This new protocol paved the way for the synthesis of analogues of trichostatic acid and hence TSA.
The first total synthesis of trichostatin D
Hosokawa, Seijiro,Ogura, Takashi,Togashi, Hidetaka,Tatsuta, Kuniaki
, p. 333 - 337 (2007/10/03)
Trichostatin D and 6-epi-trichostatin D have been stereoselectively synthesized through a remote stereoinduction with a chiral vinylketene silyl N,O-acetal and glycosylation of hydroxyimide under Mitsunobu conditions.
SYNTHESIS OF TRICHOSTATIN A, A POTENT DIFFERENTIATION INDUCER OF FRIEND LEUKEMIC CELLS, AND ITS ANTIPODE
Mori, Kenji,Koseki, Koshi
, p. 6013 - 6020 (2007/10/02)
Both the enantiomers of trichostatin acid (1, 98percent e.e.) and trichostatin A (2, 93percent e.e.) were synthesized employing methyl (R)- or (S)-3-hydroxy-2-methyl-propanoate as a starting material.
