Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• as a pro-nucleophile in an enantioselective addition reaction. The mild reaction conditions allow the use of various functionalized malonamates. Given the importance of highly functionalized α-amino acid derivatives, the present strategy could be useful in generating a wide range of α-oxyamino

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

• direct access to cyclopeptides related to naturally occurring histone deacetylase (HDAC) inhibitors Cyl-1 and Cyl-2. Late stage modifications on the unsaturated amino acid side chain allow the introduction of functionalities which might coordinate to metal ions in the active center of metalloproteins

• , 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

• (apicidin [19], microsporin A [20]), carboxylic acids (azumamides [21]), α-hydroxy ketones (FR235222 [22]) or thioesters (largazole [23]). These cyclopeptides mainly differ in the amino acid sequence of the peptide backbone, which causes selectivity towards the different HDAC isoforms. In fact, many

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• Department of Organic Chemistry, Kaunas University of Technology, Radvilėnų pl. 19, Kaunas LT-50254, Lithuania Vipergen ApS, Gammel Kongevej 23A, DK-1610 Copenhagen V, Denmark 10.3762/bjoc.18.11 Abstract A convenient and efficient synthesis of novel achiral and chiral heterocyclic amino acid-like building

• nonproteinogenic α-amino acids, have been used as excitatory amino acid receptor agonists [10][11][12][13]. For example, (S)-AMPA (III) and (S)-ACPA (IV) are specific agonists of an AMPA receptor that mimic the effects of the neurotransmitter glutamate [14][15][16]. Unnatural heteroarene amino acids have also been

• widely used as building blocks to prepare various heterocyclic peptides [17][18][19][20][21][22]. In particular, 1,2-oxazole amino acid derivatives, such as compounds V [20], VI [21], and VII, VIII [22], can be easily synthesized and are suitable for insertion with the corresponding heterocycle into a

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• -en-10-one is described. cis-9-Azabicyclo[6.2.0]dec-6-en-10-one was transformed into the corresponding amino ester and its protected amine. Oxidation of the double bond in the N-Boc-protected methyl 2-aminocyclooct-3-ene-1-carboxylate then delivered the targeted amino acid and its derivatives. Density

• β-amino acid derivatives have antibiotic (oryzoxymycin) and antifungal activities (Figure 1) [12][13]. Among the cyclic β-amino acids, the most widely investigated derivatives are the five- and six-membered derivatives [8][9][10][14][15], but only a few synthetic methods are available for the

• -hydroxylated cyclooctane amino acids [14][18]. Also in other ring systems, only non-hydroxylated cyclic amino acids and derivatives were synthesized [8][9][10][15][16]. Therefore, we were inspired to develop new methods for the synthesis of hydroxylated β-amino acid derivatives containing eight-membered rings

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

• signal. Danielson [48] found some errors in Folin’s analytical method and optimized it for better amino acid determination. Martin and Fieser [49] described an optimized method, analogous to Folin’s procedures, with temperature control, producing β-NQSNH4 16 and β-NQSK 20 in high yields (Scheme 2). It is

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• given next to the respective structure and backbone-atoms root mean square deviation with respect to the active conformation are indicated in parenthesis. RMSD reported and used in clustering were calculated from Pro to Met only. A schematic representation of the secondary structure of each amino acid

• , 1 h. In panel C), amino acids in R1 and R2 are with protecting groups and R2 is resin-bound (Rink amide resin); R3 = 4-phenylboronic acid or (4-ethylphenyl)boronic acid (P2–P5). Supporting Information Supporting Information File 6: Details on the amino acid and peptide synthesis, analytical data of

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• -Val5 and N-Me-ᴅ/ʟ-Phe2. Hoshinoamide C includes two N-methyl amino acids: N-Me-ᴅ-Phe2 and N-Me-ᴅ-IIe5. The C-terminal Pro is functionalized as methyl ester, while the N-terminal polypeptide is linked to the long alkyl chain amino acid Aha8/Ana8/Ama7 and p-hydroxybenzoic acid Hba9/Hba8. Hoshinoamides

GlycoBioinformatics

• Kiyoko F. Aoki-Kinoshita,
• Frédérique Lisacek,
• Niclas Karlsson,
• Daniel Kolarich and
• Nicolle H. Packer

Beilstein J. Org. Chem. 2021, 17, 2726–2728, doi:10.3762/bjoc.17.184

• ” is described by the National Human Genome Research Institute as “a subdiscipline of biology and computer science concerned with the acquisition, storage, analysis, and dissemination of biological data, most often DNA and amino acid sequences”. Adding the prefix “glyco-“ is about placing genomic and

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• ; separation of racemic nucleosides; stereoselectivity; Introduction Among all the biomolecules in an organism, nucleic acids, namely DNA and RNA, have the unique role of storing the genetic code – the nucleotide sequence that specifies the amino acid sequence of proteins that is essential for life on Earth

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• different approach for the use of cinchona-based organocatalysts. Instead of using the cinchona derivative alone, they employed a mixture of cinchona derivative and amino acid such as ᴅ-proline, termed as the modularly designed organocatalyst (MDO) for the synthesis of bridged tetrahydroisoquinoline

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• aliphatic alcohols. In 2015, Ackermann’s group [88] disclosed the visible light-induced copper-catalyzed arylation of azoles. In this case, the mechanistic studies revealed that amino acid ligands accelerated the cross-coupling (Scheme 22). In 2020, a visible-light-induced copper-catalyzed arylation of C

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• amino acid 6a was subjected to cyclization under different acidic conditions (not shown). The reaction of 6a with TiCl4 or SnCl4 in DCM at 0 °C led exclusively to the formation of 7a (TLC analysis) but it was impossible to isolate the product in a pure form probably due to the formation of the salts

• the desired dihydromethanodibenzoazocine-5-carboxylic acids 7d and 7e with yields of 52% and 96%, respectively. The overall yields of 7d and 7e (from 3d and 3e, respectively) were 37% and 91%, respectively (Scheme 5). In the case of the amino acid 6f, containing insufficiently activated phenyl rings

• with 67% yield (53% overall yield from 3d), while the reaction carried out in 20% HCl led to a mixture of products, among which 7f was not detected (Scheme 5). It should be also mentioned that the amino acid 6g with a benzyloxy-substituted aromatic ring, obtained in the Petasis reaction of boronic acid

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• motifs (Supporting Information File 1, Figure S1), composed in bacterial and non-plant eukaryotic enzymes of the aspartate-rich motif DDXX(X)D around position 90 and the NSE triad ND(L,I,V)XSXX(K,R)E near position 230 (Figure 1) [9]. While the amino acid sequences of two TPSs can strongly deviate, their

• of the pyrophosphate sensor) that form a salt bridge between helices F and G [12][13][14], and a conserved Asn (8 or 9 residues downstream of the NSE triad) that hydrogen bridges to the Mg2+ binding Glu of the NSE triad [15]. In between these structural anchors the amino acid sequences of terpene

• ). SmTS1 has a low amino acid sequence identity to other characterised TPSs, with the diterpene synthase (DTS) for cattleyene from Streptomyces cattleya as one of the closest relatives, which shows only 29% sequence identity [17]. We have recently shown that the sum of the calculated van der Waals volumina

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• compounds 1–5 was assigned as ʟ, based on the derivatization with Marfey’s reagent of compound 2 and 4 hydrolysates, which represented the two distinctive structural scaffolds and chemical shifts followed by HPLC analysis of the derivatized amino acid residuals in the hydrolysate and threonine standards

• standard amino acid derivatized solution (5 µL), compound 2 (5 µL) and 4 (5 µL) hydrolysates were analyzed by injecting into an HPLC Agilent 1260 Infinity instrument coupled with a Phenomenex C18 analytical column (5 µm, 4.6 × 150 mm) maintained at 40 °C. The mobile phase solvents comprised a mixture of A

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• with Hg(OAc)2 affording the corresponding cyclized pyanosylmethylmercuric chloride derivatives 12 (Scheme 5). This methodology can be used to synthesize rare C-glycosyl carbohydrates from easily available sugars. In a similar manner, stereoselective cyclization of C-glycosyl amino acid derivative 13

• using mercuric trifluoroacetate Hg(TFA)2 at room temperature was performed. The reaction proceeds primarily through stereoselective cyclization to give α-ᴅ-C-glycopyranosyl amino acid derivative 14 as the major product [43]. Nevertheless, C-mannopyranosyl derivatives cannot be achieved in a similar

• catalytic Hg(II)-salt-induced cyclization. Yamamoto and co-workers published the intermolecular cyclization of alkynyl-carboxylic acid 153 to produce 6-membered morpholine type ring compound 154 and compound 155 [103]. The stereochemistry of the chiral amino acid was not conserved in the cyclized product

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• proton of the enolizable β-ketoester 49 and thus activating the nucleophilic species. This enolate then adds to the cationic substrate from in situ upon halide abstraction of α-chloro amino acid derivatives 48 by the thiourea moiety of the bifunctional catalyst (Scheme 10c, key intermediate), leading to

• have been provided by the group of Jacobsen in the nucleophilic addition of indoles 17 to pyranones 62 (Scheme 14a) [71], as well as in the enantioselective synthesis of α-allyl amino esters 67 by the reaction of α-chloro amino acid derivatives 65 with allyltin and allylsilane 66 nucleophiles [72

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• strategy for the enanantioselective conjugate addition of amino acid derivatives for this reaction remains an unmet goal. Our group previously described a chiral cyclopropenimine catalyst that displayed outstanding reactivity for addition reactions of glycine imines [40][41]. We hypothesized that this

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

•  2 (A and B) [44][48][49][50][51][52][53][54]. Interestingly, when ONs were modified with C-5 amino acid-functionalized LNA nucleotides 20–22, significant increases in the melting temperatures (Tm) were measured with up to 14 °C for modification 22 towards complementary RNA, relative to the

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

• phylogenetic tree, we used the MUSCLE algorithm (gap open, −2.9; gap extend, 0; hydrophobicity multiplier, 1.2; max. iterations, 8; clustering method, upgmb) implemented in MEGA7 [89] to compute an amino acid alignment. Based on the MUSCLE alignment, the tree was constructed with MEGA7 using a Maximum

• amino acid substitutions per site. The alpha-domain of maize TPS4 [62] was chosen as an outgroup. TPS proteins from different Ascomycota are highlighted according to their different lifestyle: endophytic (purple), pathogenic (orange) and saprophytic (green). Fungal endophytes identified from leaves of

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• phosphono-PNAs retained the stability against nucleases. In another study, conjugation with glutamine phosphonate or lysine bis-phosphonate amino acid derivatives introduced up to twelve negative charges (phosphonate moieties) into PNAs [91]. The negative charges allowed cationic lipid-mediated delivery of

• conjugate approach involved the conjugation of PNA to (ᴅ)-insulin-like growth factor 1 peptide (IGF1) that enabled the delivery to cells expressing the IGF1 receptor [166]. Later developments adopted CPPs derived from natural proteins (Figure 12A), such as penetratin (16-amino acid peptide from the third

• helix of the Antennapedia homeodomain) [167], Tat (14-amino acid peptide from HIV-1 TAT protein) [168], and transportan (chimeric 27-amino acid peptide derived from galanin and mastoparan) [169]. Corey and co-workers were the first to demonstrate that conjugation of an 11-mer PNA to penetratin peptide

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

• the synthesis of (–)-AG-041R, a gastrin/cholecyctokinin-B receptor antagonist. In addition, amino ester 55 was transformed into the fully unprotected amino acid 56 under basic conditions in MeOH, and after that, further treatment with of MsCl and NaHCO3 in MeCN at 80 °C led to spiro-β-lactam

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• columns. Initially, fluorenylmethyloxycarbonyl (Fmoc) group removal from the Rink linker was achieved by applying 20% piperidine in DMF (2 × 30 min). Preactivation of Fmoc amino acid (4 equiv) prior each coupling was performed with 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide

• hexafluorophosphate (HATU, 4 equiv) and N,N-diisopropylethylamine (DIPEA, 6 equiv) in DMF. Then, the activated mixture was added to the resin swollen in DMF, and manual stirring was applied approximately every 15 min over a total reaction time of 2 h. The first amino acid was installed via double coupling. Fmoc

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• plausible mechanism shown in Scheme 14 explains the formation of azomethine ylide B by condensation of isatin with amino acid followed by release of a molecule of CO2 via A. The imine B undergoes 1,3-dipolar cycloaddition with the dipolarophiles 39. The cyclization yields the desired product 40 of the three

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• synthesis of unnatural α-amino acids 129 and precise alkylation modification of peptides in the later stage (Scheme 45). Even in the presence of other amino acid residues, this protocol has excellent regio- and chemoselectivity, providing a sequence of novel corresponding dipeptides with good yield. The

• acylation product 123 initiated by an EDA complex. Mechanism of the synthesis of acylation product 123. Synthesis of trifluoromethylation product 126 initiated by an EDA complex. Synthesis of unnatural α-amino acid 129 initiated by an EDA complex. Synthesis of thioether derivative 132 initiated by an EDA