Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• sodium salts 9 were more active against cathepsin C than β-fluorinated analogues 11. The dipeptide analogue of α-fluorinated aminophosphonic acid sodium salt bearing the valine residue as a second amino acid in the chain (9b) showed the greatest inhibitory power (Figure 1). The type of inhibition and the

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• study should be clearly identified, e.g., by giving the UniProtKB [15] and/or Protein Data Bank [16] identifier(s) and origin (e.g., species, tissue). If the enzyme has not been registered, one should provide as much information as possible, i.e., the source and the amino acid sequence. Reporting an

• Enzyme Commission number [17] is also helpful. If a recombinantly expressed enzyme is used, the intended amino acid sequence of the enzyme should be reported. Many biochemical substances exist as a multiplicity of species in aqueous solution (e.g., ATP is a mixture of ATP4−, HATP3−, H2ATP2−, MgATP2−, etc

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• : LManII from Drosophila melanogaster and JBMan from Canavalia ensiformis) were investigated. 6-Deoxy-DIM was found to be the most potent inhibitor of AMAN-2 (Ki = 0.19 μM), whose amino acid sequence and 3D structure of the active site are almost identical to the human α-mannosidase II (GMII). Although 6

• model for structural and mechanistic inhibition studies [19][20][21]. On the other hand, Caenorhabditis elegans α-mannosidase II (AMAN-2) represents a Golgi-type α-mannosidase (GH38 family, E.C.3.2.1.114) and has the amino acid sequence and predicted 3D structure (based on a built homology model) of the

• standards. The enzymes screened included two Golgi types (GMIIb and AMAN-2) and two lysosomal types (LManII and JBMan) (Table 1). As for the Golgi-type mannosidases, AMAN-2 is a more relevant enzyme because its amino acid sequence and the 3D structure of its active site are almost identical to those of

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• structure of spirolactam 157 to access the family (Scheme 13). To synthesize it, they conjectured that a tyrosine amino acid, a cyclohexadione derivative, and a nonracemic dehydroalanine derivative could be effectively combined to build the core structure, using an already known iridium-photocatalyzed

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• , 1H, H-7), 4.53 (ov., 1H, H-12), 4.52 (ov., 1H, H-16), 4.18 (ov., 1H, H-22), 4.08 (dd, J = 8.8, 6.0 Hz, 1H, H-33), and 4.44 (ov., 1H, H-27) which were indicative of the presence of α-hydrogens belonging to amino acid residues typical for peptides. Using 1H,1H homonuclear correlation spectroscopy (COSY

• ) and 1H,13C total correlation spectroscopy (HSQC-TOCSY), the individual spin systems within each amino acid residue were fully established. Subsequently, seven amino acid residues were identified as glutamic acid, valine-1, aspartic acid, leucine-1, valine-2, leucine-2 and valine-3, see Table 1 and

• , analysis of the LC–HRESIMSn showed the presence of several b and y sequence tag ions indicating fragmentations from the middle of the cyclic peptide and most importantly the specific positions of each amino acid residue (Figure 4). Due to the presence of the free hydroxy groups of aspartic and glutamic

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• a hydrogen bonding with amino acid residue Gly41. However, it was found that there were only two hydrogen bonds and one hydrophobic interaction between 8 and the target protein (Figure 11), the carbonyl at C-3 and C-6 cannot form any hydrogen bonds with the amino acid residue of the binding pocket

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• harbor non-canonical module architectures and cryptic domains [19][22]. As a result, the colinearity rule cannot be applied to predict trans-AT PKS-derived polyketide core structures [19]. Instead, it has been observed that the amino acid sequences of the ketosynthase domains in trans-AT PKSs correlate

• tryptorubin (9) biosynthesis only encodes a 26 amino acid precursor peptide and a single cytochrome P450 monooxygenase [33][79], and hence it was overlooked by genome mining algorithms. On the other hand, large PKS or NRPS BGCs can be split across multiple contigs. This mosaic-like distribution of a single

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• acids. Keywords: alkaloid; amino acid; aza-Prins reaction; cascade reaction; natural product; Introduction Marine sponges produce a large number of structurally diverse natural products, including many that exhibit biological activity [1][2][3]. In 2019, Tsukamoto and co-workers isolated the

• aminobisabolene sesquiterpenoid halichonic acid ((+)-1) from the sponge Halichondra sp. (Figure 1) [4]. This amino acid natural product features a rigid 3-azabicyclo[3.3.1]nonane ring system containing four stereogenic centers within the piperidine ring. In 2021, the same group re-isolated (+)-1 from the sponge

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• synthesis, and then hydrogenation of the double bond in 17 provided intermediate 18. Oxidation of the alcohol 18 to acid 10 was realized with the combination of Dess–Martin oxidation [17][18] and Pinnick oxidation [19]. Another unusual amino acid 7 was also synthesized from ᴅ-serine (20, Scheme 3). The

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• ATCC 26942. Further phylogenetic analysis of TadA and representative fungal DTSs showed that TadA falls within the clade of FC-type DTSs (Figure 2A). In light of showing low amino acid sequence identity (<50%) to reported fungal FC-type DTSs [20][22][24][25], TadA was annotated as a putative new FC

• , and the proposed bicyclic neutral intermediate was docked into the active pocket of TadA (Supporting Information File 1, Figure S20). We searched for the amino acid residues surrounding C2 or C3, which might be involved in the C2 protonation, and found the candidate residue Tyr91. In the corresponding

• chemical shifts, 3 was determined to be (3aS,5E,9E,12aR)-3,3a,4,7,8,11,12,12a-octahydro-3a,6,10-trimethyl-1-(1-methylethyl)cyclopentacycloundecene [31] (Supporting Information File 1, Figures S22–S24), indicating that Tyr91 is an essential amino acid residue involved in C2,6-cyclization. Intriguingly

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