Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• silyl ether-protected 2-hydroxypropanals 15a and 15b via literature procedures [10], followed by the application of the Still–Gennari Z-selective Horner–Wadsworth–Emmons olefination [11]. Koide’s group [12][13] reported that the asymmetric addition of the enyne 16 to acetaldehyde in the presence of zinc

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• prepared from the common building block 15 through multiple protecting group manipulations (Scheme 2). The N-Troc group in 15 was removed by treatment with zinc in a mixture of acetic acid and CH2Cl2. The resulting amine 16 was protected immediately as fluorenylmethylenoxy (Fmoc) carbamate by reaction with

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• -bonding interactions, the narrow π–π stacking provides a sufficient π orbital overlap to produce semiconductor-type electronic band structures and an efficient interplanar charge transport similar to g-C3N4 [192]. Duan and co-workers reported the synthesis of a zinc PDI assembly as a heterogeneous

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• combined with a solution-phase reagent, including: (1) copper(I) oxide to produce N-heterocyclic carbene–Cu(I) complexes for use as catalysts [13]; (2) proline to perform proline-based catalytic reactions [14]; (3) zinc powder to produce organozinc halides in tandem with Negishi couplings [15]; (4) zinc

• advantages allow a more straightforward production and use of these critical reagents. The preparation of organozinc species using zinc packed-bed columns [15][33][34][35] provides examples for the progression toward the on-demand synthesis of other organometallic reagents. While the concept of a reactive

• construction, pressure tolerance, heat conduction, and diameter/particle size matching; (3) the column orientation and setup–filters, etc.; (4) activation of the solid phase. The activation issue is one of the most important factors when considering the metal packing. Although our team had success with zinc

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• identified as a readily oxidizable polar component by permanganate detection even at room temperature. The prior attempts to cleave the Troc group by zinc dust in acetic acid [42] failed due to the reduction of the N–O bond. Conclusion In summary, we have developed a new synthetic approach towards 3

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• are well known. For example, the coordination of the P=O oxygen atom in bisphosphonates with a zinc cation in the catalytic site of the MMPs has been characterized, both through X-ray diffraction and molecular docking studies [11][36][37]. Consequently, we propose MMP-8 and MMP-9 as potential

• expected, 4–6 could bind the Zn2+ ion in a monodentate fashion through the oxygen atom double bonded to the phosphorus atom (P=O) of one of the phosphonate moieties, as reported in the literature for other structures [38][39]. Only for 3, zinc chelation was observed through the oxygen atom double bonded to

• the carbon atom (C=O) of the ester group (Figure 3). In all cases, a distorted tetrahedral coordination geometry was observed for the zinc ion, caused by the chelation with His197, Glu198, and His207 residues. His201 was far apart from the catalytic site, and the basic nitrogen atom in this residue

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• zinc chloride at the same temperature [30]. Chemical activation Chemical activation is a one-step method. Impregnation or mixing of the carbon precursor with the activating agent and subsequent carbonization of that mixture leads to highly porous activated carbon materials [8][92]. The activation

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• procedure reported in literature [27]. OLED fabrication and characterization was carried out according to the procedure reported earlier [28]. Materials 2-Aminobenzophenone, 3,5-difluorobenzaldehyde, ammonium acetate, phenothiazine, sodium hydride, sodium sulfate, tert-butyl chloride, zinc chloride

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• chromatography (TLC) was performed on Macherey-Nagel Polygram® SIL G/UV254 silica gel on polyester sheets, with manganese-activated zinc silicate with green fluorescence for short-wave UV (254 nm) and special inorganic fluorescent pigment with blue fluorescence for long-wave UV (366 nm) as indicators. Fluka

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• -tetrafluorocyclohexylphenyliodide 4 and 5 were subjected to Jackson’s methodology for the synthesis of the appropriate amino acid products. Thus, the coupling of the zinc homoenolate of (R)-iodoalanine 2 with a mixture of 4 and 5 in the presence of Pd(dba)3 and SPhos resulted in an excellent conversion to the fully protected amino

• , m, or p-fluoro or (trifluoromethyl)phenylpyruvic acids 97a–f. The reaction was carried out in presence of 0.5 equiv of zinc(II) acetate in the presence of NaOMe. The initially formed complexes 98a–f underwent isomerization to 99a–f. Acid hydrolysis then gave the FPhe derivatives 53a,b, 53i, 81, and

• synthesis from ethyl trifluoropyruvate hemiketal The reaction of ethyl trifluoropyruvate hemiketal 130 with thionyl chloride in pyridine afforded the chlorinated derivative 131, which upon treatment with zinc powder in DMF, afforded the dihalogenated olefin 132. The substitution of one fluorine atom in 132

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• (TMG), also known as Barton's base, in excellent yields (Figure 2A) [24]. Recently, Liu and co-workers reported this reaction in the presence of cesium carbonate in acetonitrile (Figure 2B) [25]. Dinuclear zinc [26], cinchonidine catalysts, and solvent-free conditions [27] have been also utilized for

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• . In an effort to synthesize an unsymmetrically substituted porphyrin dimer, triptycene 12 was utilized (Scheme 2). Firstly, the zinc porphyrin 13 [41] was coupled to triptycene 12 using Sonogashira methods that were previously successfully employed with compound 11. The desired compound 14 could be

• bromination of 17a [42] (Scheme 3). The coupling reaction was initially carried out with (5,15-dibromo-10,20-dihexyl/diphenyl)porphyrinato)zinc(II) but both porphyrins had extremely low solubility. Using the more soluble 17c gave access to the triptycene–porphyrin–triptycene complex 18. The reaction was

• band positions were seen for the symmetric zinc dimer 9, the unsymmetrical dimer 16 and the zinc monomer 14 at 431 (23202), 432 (23149) and 433 (23095) nm (cm−1) in CHCl3, respectively (Figure 6). A similar Soret band for both the dimer and monomer 9 and 14 suggested that the two subunits in the dimer

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• ]. Following this report, Oestreich and co-workers examined asymmetric additions of silicon to unsaturated ketones 113 using P–N-type ligand L13. However, the background reaction of the silyl–zinc reagent was predominant leading to poor chirality transfer from the phosphine ligand L13, giving essentially the

• . This same research group recently reported on the addition of silyl Grignard reagents to aziridines under copper catalysis [83]. While the use of RMgX led to high chemical yields of the desired products, the corresponding catalytic Cu/zinc reagents gave poor yields (ca. 20%; Scheme 45). A library of

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• [3]. Among these drugs, panobinostat (Farydak, Novartis) an FDA approved drug, has been recognized as a pan-deacetylase inhibitor [9][10]. As a hydroxamic acid pan-HDACi, it is zinc-dependent, capable of binding in a bidentate fashion to the zinc-containing catalytic domain of the HDACs, and

• building blocks for TOI1, TOI2, TOI3-rev and TOI4 were selected based on their ability to tether the indole amine and the zinc binding group in a para-relationship to each other. Initial efforts focused on synthesizing analogue TOI1 (Scheme 1). Acid 1 was converted to the corresponding methyl ester 5 via

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• presence of zinc(II) triflate as an activator of TIPS-EBX at 100 °C [41]. In contrast to the reaction of dipyrromethane 2, the double C–H activation at the 2,6-positions of 1a required harsh conditions (Table S1, Supporting Information File 1). The representative procedure of the reaction with EBX/gold(I

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• were induced by reacting with zinc iodide and they could exist in the complexed state as structures 115 and 116. The substituents on the amine nitrogen affect the reaction conditions as well as the stability of the P–N bond. Wassenaar et al. [22] reported on a flexible click-phosphine ligand (120

• synthesis of phosphinooxazoline (PHOX) ligands (Scheme 28) [48][117]. The 2-bromobenzonitrile (145) was treated with an in situ-generated phosphide reagent to obtain the 2-(diphenylphosphine)benzonitrile (146). This was then reacted with zinc chloride and aminoalkyl alcohol 147 in chlorobenzene to generate

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• interesting to note that the nitro group remained intact under the reaction conditions. Usually, this group is sensitive to reduction when alternative methods involving zinc or tin are used [33]. In addition, aldehydes containing halogens also gave the corresponding products 2j–l in moderate yields. These

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• involved in hydrogen bonding were His380, Asn277, Ser378, Ser381, Tyr382, Lys391, Ser387 and Ser386. In addition, the study also showed binding with the zinc ion and π-interactions, in particular, π–π T-shaped and amide–π shaped coupling with Ser377 and Tyr382. The molecular docking study of compound 5c

• exhibited π–π T-shaped interactions connecting the indole and furan rings with Tyr340. However, π–alkyl linkage was observed between the benzofuran moiety of compound 5c and amino acid Lys295. The fluorine atom of the 4-fluorophenyl group was involved in the binding with the zinc ion and Ser377. Hydrogen

• . However, the zinc–metal interaction was exhibited by the substituted phenyl moiety on the indole ring. The oxygen atom of the furan ring of dual inhibitor 6e showed a single hydrogen bond with Phe548. Asp423 was found to be involved in two π–cation bindings with the indole ring, whereas π–π stacked, π–π T

Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (1) [35] was used as starting compound. The synthesis includes the metallation of the free base porphyrin 1 with an excess of zinc acetate or nickel acetate resulting in the corresponding porphyrin Zn(II) and Ni(II) complexes 2a [36] and 2b [37], respectively

• zinc from the coordination sphere of the porphyrin macrocycle and gave the free base maleimide porphyrin 6 in a quantitative yield. A successful formation of the fluorinated porphyrin azides 3a and 3b allowed their utility as intermediates in the further porphyrin core functionalisation especially with

• zinc in porphyrin 7a under the action of CF3COOH in CHCl3 resulted in porphyrin 8 in a quantitative yield (Scheme 1). Synthesis of maleimide-substituted chlorins Following the developed procedure, maleimide-substituted chlorins were also prepared. Chlorins reveal a number of applications in the

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• employment of isoxazole nucleophiles in gold-catalyzed formal [3 + 2] cycloaddition reaction of ynamides [31][32], and zinc-catalyzed the reaction of ynol ethers [33], giving the respective multi-substituted pyrrole derivatives efficiently (Scheme 2a) [34][35]. The reaction proceeds via an α-imino gold

Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• ]+ calcd for C30H38O4, 463; found, 463; HRMS (CI) m/z: [M + H]+ calcd for C30H38O4, 463.2843; found, 463.2836; UV–vis (CH2Cl2) λmax: 320, 248 nm. General procedure B: McMurry coupling Zinc powder previously grinded (12 equiv) was suspended in dry THF (30 mL). The suspension was cooled to 0 °C in an ice

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• for the difluoromethylation of aryl-substituted acrylic acids was also achieved by Liu and co-workers. The HCF2-substituted E-alkenes were finally obtained with iron catalysis and zinc difluoromethanesulfinate ((CF2HSO2)2Zn, Baran reagent). Also, the authors proved that the formation of the Cvinyl–CF3

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• synthesized the novel tetra-1,2,3-triazolium zinc porphyrin cage 3 (Figure 4) and have probed its characteristics by using UV–visible spectroscopy, determining the association constants for complex formation in 5% water/acetone. This receptor has shown affinity toward all of the halide ions and especially

• triazole containing dialdehyde and binaphthyl with dipyrromethene, followed by zinc metalation and subsequent reaction with MeI resulted in the synthesis of the two-component catalytic system 16 (Figure 13). Here, the cooperative effect of nucleophilic triazolium moieties, their counter ion near the

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• peracetylated mannose 8 was performed using the mild acidic catalyst, zinc acetate hydrate [33]. The reaction progress was monitored by thin-layer chromatography. Within the first 20 hours compound 9 was the only product and further progress resulted in gradual removal of the remaining acetate groups. The SN2

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• activity. It is revealed from the literature that next to the copper, palladium catalysts in the form of salts (with or without ligands), complexes, NPs, etc. find their usage on mass scale syntheses of IPs. The role of zinc in synthetic chemistry Zinc salts being inexpensive, environmentally benign, low

• in toxicity and fits to the tenets of green chemistry. Zinc in the form of its salts, complexes (chelated by mono/di/tri/tetradentate ligands), oxides and sulfides proved to be a promising and active catalyst for organic chemists in both homogeneous as well as heterogeneous reaction systems [23][59

• systems based on zinc with excellent activity has been designed and used. The role of iron in synthetic chemistry Iron being the most abundant heavy element on earth with low biological toxicity along with cost economy and high reactivity was explored by Kharasch and Fields in the 1940s and Tamura and