114127-18-3Relevant articles and documents
Heterologous expression of the trichostatin gene cluster and functional characterization ofN-methyltransferase TsnB8
Jannu, Vinay Gopal,Jiang, Xiaodong,Liu, Wei,Liu, Zhiwen,Ma, Liang,Zhang, Changsheng,Zhang, Qingbo,Zhang, Wenjun,Zhu, Yiguang
supporting information, p. 3649 - 3653 (2020/06/03)
Trichostatins are potent inhibitors of histone deacetylase (HDAC). In this work, a new trichostatin derivative isotrichostatin RK (1) and five known compounds trichostatin RK (2), JBIR-111 (3), 9179B (4), trichostatic acid (5) and trichostatin A (6) were isolated from marine-derivedStreptomycessp. SCSIO 40028. The biosynthetic gene cluster (tsnB) for trichostatins was identified fromStreptomycessp. SCSIO 40028 and validated by heterologous expression inStreptomyces lividansTK64.N-Methyltransferase TsnB8 was demonstrated to catalyze successive methyltransfer reactions byin vivogene inactivation andin vitroenzyme assays.
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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Page/Page column 4, (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.
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.
Processes and compounds for preparing histone deacetylase inhibitors and intermediates thereof
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Page/Page column title page; 12, (2010/11/25)
Processes for preparing unsaturated esters useful as intermediates for HDAC inhibitors, by reacting an aldehyde or ketone with compounds having the following formula XX: wherein R8 is an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group; R9 and R10 are each independently hydrogen, an aliphatic group, an aromatic group, a combined aliphatic and aromatic group, or R10 forms a double bond with L2 or X3; R11 and R12 are each independently an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group; L2 is an aliphatic linking group, an aromatic linking group, or a combined aliphatic and aromatic linking group; A is P or As; L2 being selected so that the number of carbon atoms directly in the carbon chain between the R8 and R9 groups is at least 4, X1 and X2 are each independently O or a single bond, and X3 is O or forms R13 and double bond with R10, wherein R13 is an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group.
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.
