Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• , non-proteinogenic amino acid (2S,9S)-2-amino-9,10-epoxy-8-oxodecanoic acid (Aoe) as a zinc-binding group. Interestingly, Aoe with its α-epoxyketone motif is wide-spread among this compound class as it is present in other natural products such as Cyl-1 and Cyl-2 [16][17], chlamydocin [18], and many

• ozonide formed during the reaction [57]. Consequently, no PPh3 or Me2S was required to obtain the crude aldehyde. Subsequent addition of a Wittig ylide gave access to a cyclopeptide with an α,β-unsaturated ester side chain as a (E/Z) mixture. Unfortunately, this compound contained triphenylphosphine oxide

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• ], which further increases the importance of this compound class. Much work has been dedicated to the synthesis of 1,4-DHPs, but in most of these reports, the DHP ring is fully substituted. There are only few methods available for the synthesis of C5–C6-unsubstituted 1,4-DHPs. The presence of an

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• -naphthoquinone-4-sulfonic acid sodium salt (β-NQSNa, 18) was very effective as a colorimetric indicator of blood amino acids. This compound came to be called Folin's reagent. To achieve 18 with adequate purity to be used in the tests, an elaborate large-scale synthetic route was developed. β-Naphthol (20) was

• enzyme human carboxylesterase (hCE1) that cleaves carboxylic esters. This enzyme functions in the detoxification metabolism of carcinogenic and mutagenic organic compounds, converting them into nontoxic metabolites. This compound served as inspiration for Hatfield and co-workers [84], who proposed the

• acid at room temperature produces azepinedione 40 in an 82% yield. This compound can be transformed into several 3-substituted and 4-hydroxy derivatives. However, an interesting transformation results from the treatment of 40 with hot aqueous sodium hydroxide, resulting in 2-oxoquinoline 41 in an 80

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• of this compound, (4S,5S,7R,10R)-18, was reported before from Hyptis suaveolens [30] and has been obtained by synthesis from α-bulnesene (6) with an optical rotation of [α]D29 = −79.2 (c 0.25, CHCl3) [31][32]. The negative optical rotation of 17 ([α]D25 = −7.7 (c 0.26, C6D6)) in comparison to the

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• -trimethyl-2,4-octadienoic acid. The same strain also produced another new compound, 6-(3,3-dimethylallyl)-N-acetyl-ʟ-tryptophan (6), when fermented in modified V22, a different medium. This compound was isolated by the same sequence of chromatographies as above, yielding 45 mg from a 6 L culture. The

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• irradiation, the product 11 was isolated in 28% yield, the modest yield reflecting the instability in water and on silica of this compound. The purified N-formyl 11 was then dissolved in buffer (pH 8), and its hydrolysis to amide 12 was assessed (Figure 4, inset). We observed clean first-order kinetics to

Effect of a twin-emitter design strategy on a previously reported thermally activated delayed fluorescence organic light-emitting diode

• Ettore Crovini,
• Zhen Zhang,
• Yu Kusakabe,
• Yongxia Ren,
• Yoshimasa Wada,
• Bilal A. Naqvi,
• Prakhar Sahay,
• Tomas Matulaitis,
• Stefan Diesing,
• Ifor D. W. Samuel,
• Wolfgang Brütting,
• Katsuaki Suzuki,
• Hironori Kaji,
• Stefan Bräse and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 2894–2905, doi:10.3762/bjoc.17.197

• incorporating DICzTRZ as the emitter in a solution-processed OLED, we next investigated the photophysical behavior of this compound in solid host matrices. We began with 10 wt % doped film of DICzTRZ in PMMA as the polarity of PMMA emulates well that of toluene [36]. The emission maximum in PMMA is 514 nm

• calculations showed a much larger density of triplet states, which suggests that RISC will be faster in this compound compared to its parent. The twin design strategy leads to an enhancement in the molar extinction coefficient of the low-lying CT states, accompanied by a red-shift in the emission. The 20 wt

• . DICzTRZ is less emissive than ICzTRZ (ΦPL of 72% [14]), with ΦPL in degassed toluene of 60% that decreases to 44% once exposed to oxygen. This reduction in ΦPL is in part due to the decrease in the radiative decay rate given the smaller calculated oscillator strength for the emissive S1 state for this

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• evaluated using several cell line models. Keywords: alkaloids; antiproliferative effect; codonopsinol B; diastereoselectivity; pyrrolidines; Introduction Codonopsinol B (1) is a polyhydroxylated pyrrolidine alkaloid isolated from the roots of the plant Codonopsis pilosula (Figure 1) [1]. This compound was

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• the mixture of 38 and 39 induced a second α-ketol rearrangement to 40 as a tautomeric mixture. The same research group later utilized the same [3 + 2] cycloaddition and α-ketol rearrangement approach to prepare the 2′′′-epimer of 35, which bears an inverted methyl acetal in the dioxane ring, but this

• compound was less active at inhibiting protein translation [14]. Triumphalone (41) and isotriumphalone (42) represent a class of oxidized phloroglucinol natural products isolated from the Australian plant Melaleuca triumphalis. In their total synthesis of these two compounds in racemic form, Nishimura et

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• described in this article. Results and Discussion The benzoyl-containing enaminone 15a (Ar = Ph) was selected as a model for investigating conditions for the cyclization. This compound was conveniently prepared by Eschenmoser sulfide contraction [29][30], as shown in Scheme 2. The route entailed initial

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• this compound. Thus, the isomers 3a and 3b are diastereoisomers. It is known that the starting chalcones usually have E-configuration. The phenyl group and p-chlorobenzoyl group still exist in the trans-position in both diastereoisomers 3a and 3b as in the starting chalcone. This result clearly showed

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• all the centers of the stereochemical brevipolides but in the mirror image of the natural configuration. After sequential ring-closing metathesis, base-promoted olefin migration, and MEM removal, the ent-brevipolide H (ent-8) was obtained. This compound showed inhibition activity in the preliminary

• -metathesis reaction between 83 and 84 was successfully achieved utilizing Grubbs II catalyst to give the adduct 82 in 76% yield. The E/Z ratio for this compound was determined from the 1H NMR spectral analysis as >20:1. After protection of the secondary alcohol as MEM ether 88 (83%), the epoxide ring was

• opened with vinylmagnesium bromide to give the allylic alcohol 89 (92%). The acrylate ester 90 was smoothly obtained from this molecule in 95% yield and deprotected using TMSBr to give the allylic alcohol 81. Subjection of this compound to a system containing Et2Zn/CH2I2 successfully furnished the

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• . Thus, further work is needed to develop a novel strategy for an efficient synthesis of such a versatile synthon. On the other hand, diethyl (2-oxoindolin-3-yl) phosphates 2 were easily prepared by the base-catalyzed phospha-Brook rearrangement of isatins 1 with diethyl phosphite [28][29]. This compound

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• scaffold. Keywords: deazapurines; heterocycles; pyrrolopyrimidines; queuosine; RNA cofactors; RNA methylation; Introduction Methylated preQ1 has attracted much attention recently because this compound has been found to function as cofactor for the conserved fold of a non-coding RNA, namely the preQ1

• % (Scheme 2) which is significantly lower compared to the cyclocondensations with 2,6-diamino-4-pyrimidin-4-one mentioned above [23][24][25][26][27]. We therefore envisaged a path involving 6-chloro-7-deazapurine derivative 3 (Scheme 3) as this compound is readily available from cheap starting materials

• -deazaguanine failed in our hands. The 6-chloro atom of compound 3 was substituted using sodium methoxide under concomitant cleavage of the pivaloyl group to yield the desired O6-methylated compound 1, m6preQ0 (Scheme 4). After dissolving this compound under strong silylating conditions in the presence of N,O

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• deactivate the ring in the transition state. The lowest yield was observed for compound 5j to which a cyclopentyl group is attached. Since the cyclopentyl group in this compound is directly attached to the carbon from which the carbocation is formed, byproducts are formed and the yield is reduced since

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• . However, when dyes with already existing substitutions were reproduced in this work, original substitutions are also described, as exemplified with compound CI6. Indeed, for this compound, use of a central part derived from 1-benzylpiperidin-4-one is unprecedented in the literature. Similarly, among the

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• digestion. This compound was then chemically transformed to the corresponding glycosyl donors (4-methoxyphenyl- or fluoro-glycoside) to chemoenzymatically produce complex XGs. Compounds with different substitution patterns were obtained using a glycosynthase from Humicola insolens [105][106]. This approach

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• ) emitted by Cladosporium sp. (Table 2) is known to act as a signal cue for the planthopper Sogatella furcifera [15], while this compound also attracts nematodes that feed on attacking insect herbivores [79]. Nearly all of the endophytic fungi isolated in this study were able to produce at least some

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• archetypal cyclophane, with a strong interaction between the two aromatic rings, but it is readily available, being a ‘dimer’ for the polymer parylene [6][7]. Over the last twenty years, there has been a resurgence in interest in this compound as a scaffold for the synthesis of asymmetric catalysts, energy

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• constitutive activity [41]. Compound 3e reduced the basal activity of CB1 receptors (Supporting Information File 1, Figure S2A) but not that of CB2 receptors indicating that this compound acts as an inverse agonist (EC50 0.786 ± 0.233 µM) at CB1 receptors (Supporting Information File 1, Figure S2B). This

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• close to the OTBS center. At this point, it was crucial to conclusively characterize the unexpected product 9. Fortuitously, we were able to obtain crystals for this compound after several recrystallization attempts. The crystal structure for 9 (Figure 2) very surprisingly showed the OTBS group on the

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• in the synthesis of (–)-batzelladine D 61 and (–)-13-epi-batzelladine D 62. The reaction of (SS)-58 with methyl bromoacetate in the presence on Zn and CuCl in THF, left, after removal of the sulfinyl group under acidic conditions, to β-amino ester ammonium chloride 59 in high yield. This compound was

• compound (+)-L-733,060 (140), a potent neurokinin substance P receptor antagonist. This compound displays a wide variety of biological activities, including inhibition of neurogenic inflammation, blocking of pain transmission and regulation of immune response (Scheme 38). A stereoselective synthesis of ʟ

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• 1,6-anhydro derivative 10, we were able to isolate one of the side-products in sufficient purity and quantity to assign the structure of C-furanoside 20 (Scheme 2). This compound resulted from pyranose ring contraction probably caused by intramolecular displacement of the C2 azide aided by

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• of biguanides was reported for metformin (N,N-dimethylbiguanide) in 1929. The hypoglycemic activity of this compound brought real fame to biguanides [9]. The two decades following the Second World War saw the emergence of almost all famous biguanide drugs, with activity in various therapeutic fields