2732-96-9Relevant academic research and scientific papers
Inverting the regioselectivity of the berberine bridge enzyme by employing customized fluorine-containing substrates
Resch, Verena,Lechner, Horst,Schrittwieser, Joerg H.,Wallner, Silvia,Gruber, Karl,MacHeroux, Peter,Kroutil, Wolfgang
supporting information, p. 13173 - 13179 (2013/01/15)
Fluorine is commonly applied in pharmaceuticals to block the degradation of bioactive compounds at a specific site of the molecule. Blocking of the reaction center of the enzyme-catalyzed ring closure of 1,2,3,4- tetrahydrobenzylisoquinolines by a fluoro moiety allowed redirecting the berberine bridge enzyme (BBE)-catalyzed transformation of these compounds to give the formation of an alternative regioisomeric product namely 11-hydroxy-functionalized tetrahydroprotoberberines instead of the commonly formed 9-hydroxy-functionalized products. Alternative strategies to change the regioselectivity of the enzyme, such as protein engineering, were not applicable in this special case due to missing substrate-enzyme interactions. Medium engineering, as another possible strategy, had clear influence on the regioselectivity of the reaction pathway, but did not lead to perfect selectivity. Thus, only substrate tuning by introducing a fluoro moiety at one potential reactive carbon center switched the reaction to the formation of exclusively one regioisomer with perfect enantioselectivity. Custom-made substrates: Employing customized substrates with a fluoro atom at the normally preferred reaction site switched the regioselectivity of the berberine-bridged enzyme. With this strategy, it was possible to get access to (S)-11-hydroxy-functionalized berbines in an asymmetric fashion by using the wild-type enzyme (see scheme). Copyright
Mechanistic studies on the biomimetic reduction of tetrahydroxynaphthalene, a key intermediate in melanin biosynthesis
Ichinose,Ebizuka,Sankawa
, p. 192 - 196 (2007/10/03)
1,3,6,8-Tetrahydroxynaphthalene (T4HN) is an aromatic polyketide, serving as a general precursor of fungal melanin. Melanin biosynthesis involves two consecutive deoxygenations of T4HN, consisting of the reduction of a phenolic carbon followed by dehydrat
Solid-phase synthesis using (Allyloxy)carbonyl(Alloc) chemistry of a putative heptapeptide intermediate in vancomycin biosynthesis containing m-chloro-3-hydroxytyrosine
Freund, Ernst,Vitali, Francesca,Linden, Anthony,Robinson, John A.
, p. 2572 - 2579 (2007/10/03)
A convenient method for the solid-phase synthesis of putative linear heptapeptide intermediates in vancomycin biosynthesis is described, in particular, the heptapeptide D-Leu-Cyt-L-Asn-Hpg-Hpg-Cyt'-Dhpg (Cyt = (2R,3R)-m-chloro-3-hydroxytyrosine, Hpg = (R)-2-(p-hydroxyphenyl)glycine, Cyt' = (2S,3R)-m-chloro-3-hydroxytyrosine and Dhpg = (S)-2-(3,5-dihydroxyphenyl)glycine). The synthesis was performed on chlorotrityl resin and employed the (allyloxy)carbonyl protecting group for temporary N(α) protection during peptide-chain assembly.
SUBSTITUTED MONOCYCLIC ARYL COMPOUNDS EXHIBITING SELECTIVE LEUKOTRIENE B4 ANTAGONIST ACTIVITY
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, (2008/06/13)
Monocyclic aryl compounds having selective LTB 4 antagonists properties and comprising an amido substituent, a substituent group having a terminal carboxylic acid or derivative thereof and a lipophilic substituent, therapeutic compositions and methods of treatment of disorders which result from LTB. sub.4 activity using the monocyclic aryl compounds are disclosed.
Synthesis of 3,5-dihydroxyphenylglycine derivatives and the C-terminal dipeptide of vancomycin
Stone, Martin J.,Maplestone, Rachael A.,Man, Shirley K. Rah,Williams, Dudney H.
, p. 2663 - 2666 (2007/10/02)
Syntheses of optically active 3,5-DMPG and racemic 3,5-DHPG, the latter suitably protected for incorporation into linear peptides modelled on vancomycin, are described and a synthesis of the optically pure protected C-terminal dipeptide of vancomycin is p
Depsidone synthesis. Part 24. The synthesis of epiphorellic acid 2. A pseudo-depsidone and x-ray crystal structure of a grisadienedione epoxide
Comber, Mark F.,Sargent, Melvyn V.,Skelton, Brian W.,White, Allan H.
, p. 441 - 448 (2007/10/02)
The synthesis of the unusual pseudo-depsidone epiphorellic acid 2 (2) {6-hydroxy-3-[5-hydroxy-2-methoxycarbonyl-3-(3-oxopentylphenoxy] -4-methoxy-2-pentylbenzoic acid} by a route involving grisadienedione-depsidone rearrangement and subsequent steps is de
DEOXYGENATION IN THE BIOSYNTHESIS OF POLYKETIDES: MECHANISM OF BIOMIMETIC REDUCTION OF TETRAHYDROXYNAPHTHALENE
Ichinose, Koji,Ebizuka, Yutaka,Sankawa, Ushio
, p. 2873 - 2875 (2007/10/02)
A biomimetic synthesis of scytalone, a simple derivative of tetralone, was reinvestigeted using NMR spectroscopy.Scytalone was formed from 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN) by sodium borohydride reduction only in the presence of sodium methoxi
Biosynthesis of Fungal Metabolites. Terrein, a Metabolite of Aspergillus terreus Thom
Hill, Robert A.,Carter, Rachel H.,Staunton, James
, p. 2570 - 2576 (2007/10/02)
Terrein, a metabolite of Aspergillus terreus Thom, is biosynthesised from 3,4-dihydro-6,8-dihydroxy-3-methylisocoumarin by contraction of an aryl ring.The direction of the ring contraction has been investigated using acetate as precursor.
Drugs derived from Cannabinoids. Part 8. The Synthesis of Side-chain Analogues of Δ6a,10a-Tetrahydrocannabinol
Meltzer, Peter C.,Dalzell, Haldean C.,Razdan, Raj K.
, p. 2825 - 2829 (2007/10/02)
The continuation of studies on the synthesis of side-chain analogues of Δ6a,10a-tetrahydrocannabinol as potential therapeutic agents has led to the syntheses of a possible metabolite 1-hydroxy-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzopyran-3-ylacetic acid (1) and 2-(1-hydroxy-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzopyran-3-yl)pent-4-ynoic acid (17c).The Pechmann condensation of ethyl 4-methyl-2-oxocyclohexane-1-carboxylate with methyl 3,5-dihydroxyphenylacetate (11), followed by Grignard reaction, was utilized to produce the pyran (1).The key step in the synthesis of the propargylacetic acid (17c) was propargylation of the malonate (15) under phase-transfer catalysis.
