93507-06-3Relevant academic research and scientific papers
Traceless selenocarboxylates for the one-pot synthesis of amides and derivatives
Silva, Luana,Rosário, Alisson R.,Machado, Bianca M.,Lüdtke, Diogo S.
supporting information, (2020/12/25)
We have recently reported a one-pot procedure for glycosyl amides synthesis using selenocarboxylate as traceless reagent. Herein, we present a further application of selenocarboxylate-azide reaction for amide bond formation on a broader range of substrates, including heterocyclic systems and fatty acid. This method proved to be highly efficient for the synthesis of primary and secondary amides, sulfonamides, imides, phosphoramide and also carbamate.
Point mutations (Q19P and N23K) increase the operational solubility of a 2α-o-benzoyltransferase that conveys various acyl groups from CoA to a taxane acceptor
Nawarathne, Irosha N.,Walker, Kevin D.
experimental part, p. 151 - 159 (2010/07/06)
Two site-directed mutations within the wild-type 2-o-benzoyltransferase (tbf) cDNA, from Taxus cuspidata plants, yielded an encoded protein containing replacement amino acids at Q19P and N23K that map to a solvent-exposed loop region. The likely significant changes in the biophysical, properties invoked by these mutations caused the overexpressed, modified TBT (mTBT) to partition into the soluble enzyme fraction about 5-fold greater than the wild-type enzyme. Sufficient protein could now be acquired to examine the scope of the substrate specificity of mTBT by incubation with 7,13-O,O-diacetyl-2-Odebenzoylbaccatin III that was mixed individually with various substituted benzoyls, alkanoyls, and (E)-butenoyl CoA donors. The mTBT catalyzed the conversion of each 7,13-O,O-diacetyl-2-O-debenzoylbaccatin III to several 7,13-O,O-diacetyl-2O- acyl-2-O-debenzoylbaeeatin III analogues. The relative catalytic efficiency of mTBT with the 7,13-O,O-diacetyl-2-Odebenzoyl surrogate substrate and heterole carbonyl CoA substrates was slightly greater than with the natural aroyl substrate benzoyl CoA, while substituted benzoyl CoA thioesters were less productive. Short-chain hydrocarbon carbonyl and cyclohexanoyl CoA thioesters were also productive, where C4 substrates were transferred by mTBT with ～10- to 17-fold greater catalytic efficiency compared to the transfer of benzoyl. The described broad specificity of mTBT suggests that a plethora of 2-O-acyl variants of the antimitotic paclitaxel can be assembled through biocatalytic sequences.
An N-aroyltransferase of the bahd superfamily has broad aroyl CoA specificity in vitro with analogues of N-dearoylpaclitaxel
Nevarez, Danielle M.,Mengistu, Yemane A.,Nawarathne, Irosha N.,Walker, Kevin D.
supporting information; experimental part, p. 5994 - 6002 (2009/09/24)
The native N-debenzoyl-2'-deoxypaclitaxel:N-benzoyltransferase (NDTBT), from Taxus plants, transfers a benzoyl group from the corresponding CoA thioester to the amino group of the β -phenylalanine side chain of N-debenzoyl-2'-deoxypaclitaxel, which is purportedly on the paclitaxel (Taxol) biosynthetic pathway. To elucidate the substrate specificity of NDTBT overexpressed in Escherichia coli, the purified enzyme was incubated with semisynthetically derived N-debenzoyltaxoid substrates and aroyl CoA donors (benzoyl; ortho-, meta-, and para-substituted benzoyls; various heterole carbonyls; alkanoyls; and butenoyl), which were obtained from commercial sources or synthesized via a mixed anhydride method. Several unnatural N-aroyl-N-debenzoyl-2'-deoxypaclitaxel analogues were biocatalytically assembled with catalytic efficiencies (V max/Km) ranging between 0.15 and 1.74 nmol.min -1.mM -1. In addition, several N-acyl-N-debenzoylpaclitaxel variants werebiosynthesized when N-debenzoylpaclitaxel and N-de(tert-butoxycar-bonyl )docetaxel (i.e., 10-deacetyl-N-debenzoylpaclitaxel) were used as substrates. The relative velocity (v rel) for NDTBT with the lattertwo N-debenzoyl taxane substrates ranged between '1percent and 200pe rcent for the array of aroyl CoAs compared to benzoyl CoA. Interestingly, NDTBT transferred hexanoyl, acetyl, and butyryl more rapidly than butenoyl or benzoyl from the CoA donor to taxanes with isoserinoyl side chains, whereas N-debenzoyl-2'-deoxypaclitaxel was more rapidly converted toits N-benzoyl derivative than to its N-alkanoyl or N-butenoyl congeners . Biocatalytic N-acyl transfer of novel acyl groups to the amino functional group of N-debenzoylpaclitaxel and its 2'-deoxy precursor reveal thesurprisingly indiscriminate specificity of this transferase. This featu re of NDTBT potentially provides a tool for alternative biocatalytic N-aroylation/ alkanoylation to construct next generation taxanes or other novel bioactive diterpene compounds.
Synthesis and biological activity of some novel N-aryl-nprime;-[5-(pyrid-4- yl)-1,3,4-thiadiazol-2-yl]ureas
Song, Xin-Jian,Tan, Xiao-Hong,Wang, Yan-Gang
, p. 1907 - 1913 (2008/02/10)
With the aim of searching for biologically active urea compounds, a series of new N-aryl-N'-[5-(pyrid-4-yl)-1,3,4-thiadiazol-2-yl]ureas have been designed and synthesized. Their structures were confirmed by IR, 1H NMR, and elemental analysis. The crystal
