878-47-7Relevant academic research and scientific papers
Biocatalytic Approaches to the Enantiomers of Wieland–Miescher Ketone and its Derivatives
Bertuletti, Susanna,Bayout, Ikram,Bassanini, Ivan,Ferrandi, Erica E.,Bouzemi, Nassima,Monti, Daniela,Riva, Sergio
, p. 3992 - 3998 (2021/04/09)
Biocatalytic approaches have been investigated in order to isolate the enantiomers of Wieland–Miescher ketone (1) and of its alcoholic derivatives (cis-2 and trans-3). Specifically, two enzymes from our in-house metagenomic collection of oxidoreductases, IS2-SDR and Dm7α-HSDH, catalyzed the kinetic resolution of the starting racemic ketone 1 or its complete conversion into two diastereomeric products, respectively. Moreover, the kinetic resolution of the racemic cis-alcohol (2) was very efficiently obtained (E?2.000) by lipase PS catalyzed acetylation in dry acetone. All the products were isolated with ee≥95 %. Simple chemical elaborations of some of them allowed to isolate the missing enantiomers.
Discovery of New Carbonyl Reductases Using Functional Metagenomics and Applications in Biocatalysis
Newgas, Sophie A.,Jeffries, Jack W. E.,Moody, Thomas S.,Ward, John M.,Hailes, Helen C.
, p. 3044 - 3052 (2021/04/26)
Enzyme discovery for use in the manufacture of chemicals, requiring high stereoselectivities, continues to be an important avenue of research. Here, a sequence directed metagenomics approach is described to identify short chain carbonyl reductases. PCR from a metagenomic template generated 37 enzymes, with an average 25% sequence identity, twelve of which showed interesting activities in initial screens. Six of the most productive enzymes were then tested against a panel of 21 substrates, including bulkier substrates that have been noted as challenging in biocatalytic reductions. Two enzymes were selected for further studies with the Wieland Miescher ketone. Notably, enzyme SDR-17, when co-expressed with a co-factor recycling system produced the anti-(4aR,5S) isomer in excellent isolated yields of 89% and 99% e.e. These results demonstrate the viability of a sequence directed metagenomics approach for the identification of multiple homologous sequences with low similarity, that can yield highly stereoselective enzymes with applicability in industrial biocatalysis. (Figure presented.).
Total synthesis of JBIR-03 and asporyzin C
Murokawa, Tetsuro,Enomoto, Masaru,Teranishi, Takaaki,Ogura, Yusuke,Kuwahara, Shigefumi
, p. 4107 - 4109 (2018/10/15)
The first enantioselective total synthesis of JBIR-03 and asporyzin C, indole diterpenoids of fungal origin exhibiting a range of pharmacologically important biological activities, has been accomplished from a known bicyclic keto alcohol in 13 and 14 steps, respectively. A hydroxy-directed cyclopropanation and Pd(II)-mediated indole ring formation were exploited as the key steps to obtain a pivotal pentacylic intermediate, which was converted into asporyzin C via chain elongation using cross-metathesis and then into JBIR-03 by Pd(II)-catalyzed tetrahydrofuran ring formation in an exclusively diastereoselective manner.
Study of Cascade Ring-Closing Metathesis Reactions en Route to an Advanced Intermediate of Taxol
Letort, Aurélien,Long, De-Liang,Prunet, Jo?lle
, p. 12318 - 12331 (2016/12/23)
A highly functionalized intermediate in the synthesis of Taxol has been synthesized, which features the tricyclic core and the required oxygen substituents at C1, C2, C7, C10, and C13. The key step, a ring-closing dienyne metathesis (RCDEYM) reaction, has
Viridin analogs derived from steroidal building blocks
Viswanathan, Kishore,Ononye, Sophia N.,Cooper, Harold D.,Kyle Hadden, M.,Anderson, Amy C.,Wright, Dennis L.
, p. 6919 - 6922,4 (2020/09/02)
Naturally occurring furanosteroids such as viridin and wortmannin have long been known as potent inhibitors of the lipid kinase PI-3K. We have been interested in directly accessing analogs of these complex natural products from abundant steroid feedstock materials. In this communication, we describe the synthesis of viridin/wortmannin hybrid molecules from readily available building blocks that function as PI-3K inhibitors and maintain their electrophilic properties. The compounds also show anti-proliferative effects against a breast cancer line.
Enantioselective synthesis of a taxol C ring
Ma, Cong,Schiltz, Stephanie,Prunet, Joelle
experimental part, p. 1579 - 1594 (2012/05/19)
An enantioselective synthesis of a C ring of taxol has been accomplished. The key step is an oxidative cleavage of a derivative of the Wieland-Miescher ketone. A first attempt of a Shapiro reaction modelling the coupling of the C ring with the A fragment of taxol was also successful.
Synthesis of a dysidiolide-inspired compound library and discovery of acetylcholinesterase inhibitors based on protein structure similarity clustering (PSSC)
Scheck, Michael,Koch, Marcus A.,Waldmann, Herbert
, p. 4792 - 4802 (2008/09/21)
Biologically relevant compound collections are a major prerequisite for efficient protein ligand development and ultimately for drug discovery. We herein describe the development of a compound collection inspired by the decalin core motif of two natural products, dysidiolide 1 and sulfiricin 2, both inhibitors of the Cdc25A phosphatase. Several keto-functionalized decalinols were synthesized in solution, immobilized on Merrifield resin equipped with a dihydropyranyl linker, and then subjected to aldol condensation reactions with different aldehydes leading to exocyclic E-configured olefins. Further diversity-increasing transformations on the solid support included Sonogashira, Suzuki, and Heck reactions, Cu-catalyzed conjugate addition and Grignard reactions, alkylation reactions in the α-position to a ketone, Wittig reactions, and reductive animations. In total, 483 compounds were synthesized. Cdc25A and AChE exhibit structural similarity in their ligand-sensing cores and were thus grouped into a protein structure similarity cluster (PSSC). A screen for AChE inhibition of a subset of 162 compounds yielded three micromolar inhibitors of AChE with IC50 values 20 μM.
An expedient enantioselective strategy for the oxatetracyclic core of platensimycin
Kaliappan, Krishna P.,Ravikumar, Velayutham
, p. 2417 - 2419 (2008/02/07)
An enantioselective route for the synthesis of oxatetracyclic core of platensimycin is reported for the first time using a 5-exo-trig cyclization followed by intramolecular etherification as key reactions. The requisite dienynone for the radical cyclizati
Studies directed toward the synthesis of terreulactone A: Rapid construction of the A, B, C rings
Liu, Haibo,Siegel, Dionicio R.,Danishefsky, Samuel J.
, p. 423 - 425 (2007/10/03)
An efficient, rapid synthesis of the A, B, C rings of terreulactone A is described. Key steps in the synthesis include a diastereoselective benzylic acid rearrangement to create the desired quaternary center at C2 and a mild bromolactonization
The hydroxylation of the enantiomeric hexahydro-10-methylnaphthal-4-en-3- ones by Cephalosporium aphidicola
Parvez, Aslam,Hanson, James R.
, p. 647 - 648 (2007/10/03)
The enantiomeric hexahydro-10-methylnaphthal-4-en-3-ones are hydroxylated by the fungus, Cephalosporium aphidicola at C-6 and at C-9 (steroid-like enantiomer) or at C-1 (steriod enantiomer).
