We report two synthetic strategies for traceless solid-phase synthesis of molecular scaffolds comprising 6- to 8-membered rings fused with 5- to 7-membered rings. Traceless synthesis facilitated preparation of target molecules without any trace of polymer-supported linkers. The cyclization proceeded via acid-mediated tandem N-acylium ion formation followed by the nucleophilic addition of O- and C-nucleophiles. The presented synthetic strategy enabled, through the use of simple building blocks without any conformational preferences, the evaluation of the predisposition of different combinations of ring sizes to form fused ring molecular scaffolds. Compounds with any combination of [6,7 + 5,6,7] ring sizes were accessible with excellent crude purity. The 8-membered cyclic iminium was successfully fused only with the 5-membered cycle and larger fused ring systems were not formed, probably due to their instability.

• Klíčová slova
• bicyclic compounds, heterocycles, iminiums, scaffold, solid-phase synthesis,
• MeSH
• cyklizace MeSH
• katalýza * MeSH
• polymery chemická syntéza   chemie   MeSH
• stereoizomerie MeSH
• techniky syntézy na pevné fázi * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• polymery MeSH

A series of N-terminally Fmoc-protected linkers of the general formula Fmoc-X-CO-O-Y-COOH have been prepared, where X is -NH-CH2 -CH2 - or -p-(aminomethyl)phenyl- and Y is -(CH2 )n - (n is 1 or 4) or -p-(methyl)phenyl-. These linkers can easily be covalently attached via their C-terminal carboxyl group to a resin bearing a free amino group. After cleavage of the N-terminal Fmoc group, the linkers can be extended by standard solid-phase peptide synthesis techniques. These ester linkers are acid-stable and resistant to the base-mediated diketopiperazine formation that often occurs during the synthesis of ester-bound peptides; they are stable at neutral pH in aqueous buffers for days but can be effectively cleaved with 0.1 m NaOH or aq. ammonia within minutes or hours, respectively. These properties make these ester handles well suited for use as linkers for the solid-phase peptide synthesis of immobilized peptides when the stable on-resin immobilization of the peptides and the testing of their biological properties in aqueous buffers at neutral pH are necessary.

• Klíčová slova
• diketopiperazines, esters, peptides, protecting groups, solid-phase synthesis,
• MeSH
• estery chemická syntéza   chemie   MeSH
• imobilizované proteiny chemická syntéza   MeSH
• indikátory a reagencie chemická syntéza   chemie   MeSH
• peptidy chemická syntéza   MeSH
• techniky syntézy na pevné fázi metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• estery MeSH
• imobilizované proteiny MeSH
• indikátory a reagencie MeSH
• peptidy MeSH

The synthesis of different diketomorpholines via N-acyl-3,4-dihydro-2 H-1,4-oxazine-3-carboxylic acids is reported in this article. The key intermediates were prepared using a convenient solid-phase synthesis starting from polymer-supported Ser( tBu)-OH. After subsequent sulfonylation with 4-nitrobenzenesulfonyl chloride (4-Nos-Cl), alkylation with an α-bromoketone, cleavage of the 4-Nos group and acylation with an α-halocarboxylic acids, acid-mediated cleavage from the resin yielded dihydrooxazine-3-carboxylic acids in high crude purities. Depending on the reaction conditions, exposure to base resulted in cyclization to either oxazino[3,4- c][1,4]oxazine-diones or 3-methylidenemorpholine-2,5-diones. Further reaction with triethylsilane-trifluoroacetic acid (TES/TFA) led to olefin reduction, in the case of oxazino[3,4- c][1,4]oxazine-dione with full control of the newly formed stereocenter.

• Klíčová slova
• bromoketone, diketomorpholine, morpholine, serine, solid-phase synthesis,
• MeSH
• acylace MeSH
• alkylace MeSH
• cyklizace MeSH
• kyselina trifluoroctová chemie   MeSH
• kyseliny karboxylové chemie   MeSH
• molekulární struktura MeSH
• morfoliny chemická syntéza   MeSH
• nitrobenzeny chemie   MeSH
• oxaziny chemie   MeSH
• polymery chemie   MeSH
• silany chemie   MeSH
• stereoizomerie MeSH
• techniky syntézy na pevné fázi metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4-nitrobenzenesulfonyl chloride MeSH Prohlížeč
• kyselina trifluoroctová MeSH
• kyseliny karboxylové MeSH
• morfoliny MeSH
• nitrobenzeny MeSH
• oxaziny MeSH
• polymery MeSH
• silany MeSH
• triethylsilane MeSH Prohlížeč

Herein we report the polymer-supported synthesis of 3,4-dihydro-2H-1,4-oxazine-3-carboxylic acid derivatives using immobilized Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH as the starting materials. After the solid-phase-synthesis of N-alkyl-N-sulfonyl/acyl intermediates, the target dihydrooxazines were obtained using trifluoroacetic acid-mediated cleavage from the resin. This approach was also studied for the preparation of dihydrothiazines from immobilized Fmoc-Cys(Trt)-OH. Inclusion of triethylsilane in the cleavage cocktail resulted in the stereoselective formation of the corresponding morpholine/thiomorpholine-3-carboxylic acids. Stereochemical studies revealed the specific configuration of the newly formed stereocenter and also the formation of stable N-acylmorpholine rotamers.

• Klíčová slova
• amino acid, bromoketone, morpholine, nitrobenzenesulfonyl chloride, oxazine, solid-phase synthesis, stereoselective synthesis, thiazine, thiomorpholine,
• MeSH
• fluoreny chemie   MeSH
• kyseliny karboxylové chemická syntéza   chemie   MeSH
• morfoliny chemická syntéza   chemie   MeSH
• oxaziny chemická syntéza   chemie   MeSH
• polymery chemie   MeSH
• stereoizomerie MeSH
• techniky syntézy na pevné fázi metody   MeSH
• thiaziny chemická syntéza   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fluoreny MeSH
• kyseliny karboxylové MeSH
• morfoliny MeSH
• oxaziny MeSH
• polymery MeSH
• thiamorpholine MeSH Prohlížeč
• thiaziny MeSH

Simple solid-phase synthesis of 3,10-dihydro-2H-benzo[e]imidazo[1,2-b][1,2,4]thiadiazin-2-one 5,5-dioxides is described, with Fmoc-α-amino acids and 2-nitrobenzenesulfonyl chlorides (2-NosCls) being the key building blocks. Fmoc-α-amino acids were immobilized on Wang resin and transformed to the corresponding 2-nitrobenzenesulfonamides in two steps. After reduction of the nitro group, Fmoc-thioureas were synthesized followed by cyclization of the 1,2,4-benzothiadiazine-1,1-dioxide scaffold with diisopropylcarbodiimide (DIC). Cleavage of the Fmoc protecting group followed by spontaneous cyclative cleavage gave the target products in excellent crude purity.

• Klíčová slova
• 2-nitrobenzenesulfonyl chlorides, Fmoc-amino acids, anagrelide analogues, cyclative cleavage, cyclic guanidines, solid-phase synthesis,
• MeSH
• aminokyseliny chemie   MeSH
• chinazoliny chemická syntéza   chemie   MeSH
• cyklizace MeSH
• fibrinolytika chemická syntéza   chemie   MeSH
• fluoreny chemie   MeSH
• kyseliny sulfinové chemická syntéza   chemie   MeSH
• techniky kombinatorické chemie MeSH
• techniky syntézy na pevné fázi MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• anagrelide MeSH Prohlížeč
• chinazoliny MeSH
• fibrinolytika MeSH
• fluoreny MeSH
• kyseliny sulfinové MeSH
• N(alpha)-fluorenylmethyloxycarbonylamino acids MeSH Prohlížeč
• sulfonyl chloride MeSH Prohlížeč

Herein, we report the stereoselective synthesis of trisubstituted benzoxazino[4,3-b][1,2,5]thiadiazepinone 6,6-dioxides from polymer-supported Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH. After the solid-phase synthesis of N-alkylated-N-sulfonylated intermediates using various 2-nitrobenzenesulfonyl chlorides and bromoketones, the target compounds were obtained via trifluoroacetic acid (TFA)-mediated cleavage from the resin, followed by cyclization of the diazepinone scaffold. Except for the threonine-based intermediates, the inclusion of triethylsilane (TES) in the cleavage cocktail yielded a specific configuration of the newly formed C3 chiral center. The final cyclization resulted in minor or no inversion of the C12a stereocenter configuration.

• Klíčová slova
• benzoxazinothiadiazepinone, bromoketone, cysteine, morpholine, nitrobenzenesulfonyl chloride, serine, solid-phase synthesis, stereoselective synthesis, thiomorpholine, threonine, triethylsilane,
• MeSH
• alkylace MeSH
• cyklické S-oxidy chemická syntéza   MeSH
• cyklizace MeSH
• knihovny malých molekul chemická syntéza   MeSH
• polymery chemie   MeSH
• stereoizomerie MeSH
• techniky syntézy na pevné fázi MeSH
• thiadiazoly chemická syntéza   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cyklické S-oxidy MeSH
• knihovny malých molekul MeSH
• polymery MeSH
• thiadiazoly MeSH

Laccases (Lac) and tyrosinases (TYR) are mild oxidants with a great potential in research and industry. In this work, we review recent advances in their use in organic synthesis. We summarize recent examples of Lac-catalyzed oxidation, homocoupling and heterocoupling, and TYR-catalyzed ortho-hydroxylation of phenols. We highlight the combination of Lac and TYR with other enzymes or chemical catalysts. We also point out the biological and pharmaceutical potential of the products, such as dimers of piceid, lignols, isorhamnetin, rutin, caffeic acid, 4-hydroxychalcones, thiols, hybrid antibiotics, benzimidazoles, benzothiazoles, pyrimidine derivatives, hydroxytyrosols, alkylcatechols, halocatechols, or dihydrocaffeoyl esters, etc. These products include radical scavengers; antibacterial, antiviral, and antitumor compounds; and building blocks for bioactive compounds and drugs. We summarize the available enzyme sources and discuss the scalability of their use in organic synthesis. In conclusion, we assume that the intensive use of laccases and tyrosinases in organic synthesis will yield new bioactive compounds and, in the long-term, reduce the environmental impact of industrial organic chemistry.

• Klíčová slova
• bioactive compound, catechol, dimer, heterocoupling, homocoupling, laccase, oligomer, organic synthesis, oxidation, tyrosinase,
• MeSH
• fenoly chemie   MeSH
• lakasa * metabolismus   MeSH
• oxidace-redukce MeSH
• techniky syntetické chemie MeSH
• tyrosinasa * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fenoly MeSH
• lakasa * MeSH
• tyrosinasa * MeSH

Convenient and straightforward synthesis of ibrutinib labeled by carbon-13 isotope is reported. Isotopically labeled building block is introduced in the last step of reaction sequence affording sufficient isolated yield (7%) of [13 C6 ]-ibrutinib calculated towards starting commercially available [13 C6 ]-bromobenzene.

• Klíčová slova
• [13C6]-ibrutinib, carbon-13, cost-effective synthesis, stable isotope labeling,
• MeSH
• adenin analogy a deriváty   chemie   MeSH
• brombenzeny chemie   MeSH
• inhibitory proteinkinas chemie   MeSH
• izotopy uhlíku chemie   MeSH
• piperidiny chemie   MeSH
• techniky syntetické chemie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenin MeSH
• brombenzeny MeSH
• bromobenzene MeSH Prohlížeč
• ibrutinib MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• izotopy uhlíku MeSH
• piperidiny MeSH

An efficient and high-yielding solid phase synthesis of a small library of imidazolidin-2-ones and imidazol-2-ones was carried out employing a high chemo- and regioselective gold-catalyzed cycloisomerization as a key step. Polymer-supported amino acids derivatized with several alkyne functionalities combined with tosyl- and phenylureas have been subjected to gold-catalysis exhibiting exclusively C-N bond formation. The present work proves the potential of solid phase synthesis and homogeneous gold catalysis as an efficient and powerful synthetic tool for the generation of drug-like heterocycles.

• Klíčová slova
• C−N bond formation, gold catalysis, imidazolidin-2-ones, propargylureas, solid-phase synthesis,
• MeSH
• alkyny chemie   MeSH
• cyklizace MeSH
• imidazolidiny chemická syntéza   MeSH
• katalýza MeSH
• knihovny malých molekul chemická syntéza   MeSH
• molekulární struktura MeSH
• techniky kombinatorické chemie MeSH
• techniky syntézy na pevné fázi MeSH
• zlato chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkyny MeSH
• ethylene urea MeSH Prohlížeč
• imidazolidiny MeSH
• knihovny malých molekul MeSH
• zlato MeSH

Solid phase synthesis of phosphonate-modified oligoribonucleotides using 2'-O-benzoyloxymethoxymethyl protected monomers is presented in both 3'→5' and 5'→3' directions. Hybridisation properties and enzymatic stability of oligoribonucleotides modified by regioisomeric 3'- and 5'-phosphonate linkages are evaluated. The introduction of the 5'-phosphonate units resulted in moderate destabilisation of the RNA/RNA duplexes (ΔT(m)-1.8 °C/mod.), whereas the introduction of the 3'-phosphonate units resulted in considerable destabilisation of the duplexes (ΔT(m)-5.7 °C/mod.). Molecular dynamics simulations have been used to explain this behaviour. Both types of phosphonate linkages exhibited remarkable resistance in the presence of ribonuclease A, phosphodiesterase I and phosphodiesterase II.

• MeSH
• exonukleasy metabolismus   MeSH
• fosfodiesterasa I metabolismus   MeSH
• oligoribonukleotidy chemická syntéza   chemie   metabolismus   MeSH
• organofosfonáty chemická syntéza   chemie   metabolismus   MeSH
• pankreatická ribonukleasa metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• techniky syntézy na pevné fázi * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• exonukleasy MeSH
• fosfodiesterasa I MeSH
• oligoribonukleotidy MeSH
• organofosfonáty MeSH
• pankreatická ribonukleasa MeSH
• spleen exonuclease MeSH Prohlížeč