Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• , a universal naming system is crucial to group related CYPs and to facilitate functional predictions. Hence, CYPs from all kingdoms are systematically named according to their amino acid identity by the cytochrome P450 nomenclature committee (David Nelson: dnelson@uthsc.edu). CYPs are grouped into

• subfamily [14]. Typically, all CYPs in the same subfamily share more than 55% amino acid sequence identity, and all CYPs in the same family more than 40%, although exceptions exist [15][16]. These thresholds also underline the remarkable sequence variety of CYPs, as even enzymes with only 60–70% amino acid

• on triterpenoids and steroids. Amino acid sequences (149 triterpenoid CYPs, 266 non-triterpenoid CYPs) were aligned using MUSCLE [92], and a neighbour-joining consensus tree of 1,000 bootstrap replicates was generated using the Jukes–Cantor model. The final tree was visualised in Python using the

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• reaction where the terminal phosphate dissociates from the polyP chain before being attacked by the nucleotide [18]. Both mechanisms could proceed without a phosphate group transfer onto an amino acid side chain of the enzyme as in PPK1: here, the enzyme structure generates proximity and polarisation of

• parameters KM and vmax of selected enzymes (Table S6, Supporting Information File 1) [5][10][11][15][19][20][21]. A sequence-based classification of PPKs is in most cases straightforward and unambiguous. Nevertheless, there seem to be exceptions: regarding the amino acid sequence, the PPK1 from Vibrio

• cholerae is very similar to the one from E. coli with 82% similarity (64% identity) on the amino acid level; however, it was described to show kinetic preferences of a PPK2 [20]. While the PPK2 from P. aeruginosa catalyses both synthesis and usage of ATP with kinetic preference for ATP synthesis, the

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• ) should be a key intermediate for this tandem reaction. On the basis of the above mechanistic studies and the previous works on iodide-mediated electrochemical transformation [37][38][39][40], a possible mechanism for this electrochemical reaction was proposed (Scheme 5). It is well known that amino acid

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• isolated. Moreover, the coupling of benzothiazines with amino acids was realized. In doing so, an enantioselective synthesis of the nonproteinogenic amino acid 2-amino-3-propylhexanoic acid was accomplished. Keywords: amino acid; benzothiazine; oxidative dimerization; peptide coupling; stereoselective

• our work, we aimed to utilize the carboxylic acid function of the prepared 4H-benzo-1,4-thiazines 10 by attaching them to nonproteinogenic amino acid 16a and ʟ-phenylalanine. Preparation of 3-propylnorleucin methyl ester (16a) started with the condensation reaction of heptan-4-one (12) and methyl

• isocyanoacetate (13). The palladium-catalyzed hydrogenation of intermediate 14 gave the racemic N-formyl-protected amino acid methyl ester 15 in good yield. Using either concentrated HCl (aq) or in situ-formed HCl from the reaction of MeOH and acetyl chloride, compound 15 could easily be deprotected to gain

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• Oleg A. Levitskiy Olga I. Aglamazova Yuri K. Grishin Tatiana V. Magdesieva Lomonosov Moscow State University, Dept. of Chemistry, Leninskie Gory 1/3, Moscow 119991, Russian Federation 10.3762/bjoc.18.121 Abstract The involvement of an α,α-cyclopropanated amino acid in the chiral Ni(II

• radical anions influenced by substituents in the cyclopropane ring are discussed. Optimization of the reaction conditions opens a route to the non-proteinogenic amino acid derivatives containing an α–β or β–γ double C=C bond in the side chain; the regioselectivity can be tuned by the addition of Lewis

• -activity and chirality provided by the Ni–Schiff base template, supported with the protection from redox-destruction of the amino acid skeleton, makes the suggested approach a convenient route to various types of non-proteinogenic amino acids [9][10][12][13]. Recently, several practical approaches to α,α

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• the unique methyl ester in azodyrecin The structural diversity of aliphatic azoxy natural products can be attributed to variations in the alkyl side chains and the amino acid-derived counterparts. The variation in the amino acid-derived units is considerably large, as it includes primary and secondary

• stepwise HMM-based search using models for “VlmA'' (PF09924: LPG_synthase_C) and the amino acid sequence of VlmH identified 179 pairs of VlmA/VlmH, indicating that approximately 5.7% of the actinobacteria present in the NCBI Refseq database are potential producers of aliphatic azoxy natural products. The

• . Biosynthetic gene clusters of aliphatic azoxy natural products. Conserved proteins are colored according to their functional annotations. Genes encoding homologous proteins with more than 30% amino acid sequence identities are linked. Structures of azodyrecins (a) and new azodyrecin derivatives, azodyrecins D

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• , calculated mass of 31.9 kDa) (Figure 2) caught our attention due to its low sequence identity on the amino acid sequence level (coverage below 50%) with other characterized Ptases. To further explore the putative function of UbiA-297, we generated a phylogenetic tree using 444 Ptase sequences with already

• , Belgium). Bioinformatic analysis: Amino acid sequences of all described prenyltransferases were retrieved from the UniProtKB/Swiss-Prot database. Other Ptase amino acid sequences of marine Flavobacteria and Saccharomonopora strains were obtained using Blast searches against defined genome groups within

• . machipongonensis PR1 (NZ_CM001023), Saccharomonospora sp. CNQ490 (NZ_AZUM01000003), S. viridis DSM 43017 (NC_013159), and Nostoc punctiforme PCC 73102 (NC_010628). Percentage identities of homologous genes are given in the same colored arrow boxes (Maribacter sp. MS6 was set as reference). A) Amino acid alignment

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• ], which share ≈60% amino acid identity [33]. Both isoforms catalyze the incorporation of two oxygen atoms into arachidonic acid (AA) to form an endoperoxide between C9 and C11 and a peroxide at C15 to generate prostaglandin G2 (PGG2) (Scheme 1) [24][34]. Subsequently, the 15-hydroperoxide in PGG2 is

• endoperoxidase, NvfI shares a low amino acid sequence similarity with FtmOx1 (only 17%) and a phylogenetic analysis indicated that it is located in a different clade from FtmOx1. Prior to the structure–function analysis of NvfI, four pathways were proposed for the formation of fumigatonoid A from asnovolin A

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• moderate yields (37–63%), and a decreased yield was observed with an increase of the aliphatic chain length, which was more accentuated for the diacid derivatives, and more subtle for the amino acid derivatives (Scheme 30). The same methodology was applied during the synthesis of oligopeptides linked to 10

• (Scheme 30) [132][133][134]. In detailed studies, initiated by Commandeur and co-workers [135] and expanded by Naturale and co-workers [139], the alkylation capabilities of menadione (10) were evaluated, exclusively, with several amino acid types by Kochi–Anderson radical decarboxylation [76]. In the

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• the end product of the pathway in N. altamirensis DSM 44997. Previous studies have demonstrated that, in nature, hydroxamates arise from the oxidation of terminal amino groups in amino acid side chains, followed by formylation or acylation of the resulting hydroxylamines. While the oxidations are

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• the active site of the enzyme. Once bound, substrate activation is carried out by specific amino acid side chains that adorn the inner surface of the cavity by means of a combination of covalent and/or weak intermolecular interactions leading to the stabilization of intermediate species and transition

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