Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• retaining mechanism). In the case of O-GTs, the nucleophile is an alcohol or a phenol (carbohydrates, serine, threonine, …), whereas in N-GTs, the nature of the nitrogen-containing group is more diverse (amines, amides, guanidine or even indoles) [12]. S- and C-GTs follow a similar mechanism with the

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• recently investigated the resilience of enzymes under ball milling conditions. The results from these studies have shown that biocatalysts such as cysteine and serine proteases tolerated the milling conditions and catalyzed the mechanoenzymatic peptide and amide bond formation after short milling times

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• different downstream signaling cascades. As the core component of these complexes, mTOR exhibits protein kinase activity and phosphorylates a variety of downstream meditators. One of the principal substrates of the mTORC2 complex is the serine/threonine kinase Akt, which gets activated upon phosphorylation

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• molecular target of PMA was identified in a series of isoforms of PKC, a family of serine/threonine kinases involved in a host of cellular activities [9]. Because of its kinase-activating properties, PMA has become an indispensable tool in the study of cell function, with a single vendor claiming to have

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• which ACP was found in contact with the KS domain [31]. In fungal FAS, ACP is an extended fold comprised of a bacterial-like core fold and a 4-helical extender fold, rendering ACP about twice the size of ACP occurring in mammalian FAS and PKS. The active serine, which is post-translationally

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• attachment groups and first units involved in energy exchanges [26]. Alternating drying steps followed by rains or floods resulted in the condensation of phosphate moieties on many primeval compounds. These include serine as serine phosphate and aspartate protected against cyclisation as aspartyl phosphate

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• . GPCRs are normally deactivated by β-arrestin, as shown in Figure 4. After activation and dissociation of the β/γ subunit, IL3 and the C-terminus of the GPCR are phosphorylated at serine and threonine residues (Figure 4a). This phosphorylation allows the recruitment of β-arrestin (Figure 4b), which can

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• numbering) capable of forming salt bridges with the carboxyl group of the building block, while these are non-polar amino acids in starter-unit specific ATs. The choice of methylmalonyl-CoA over malonyl-CoA is correlated with a YASH motif some 100 residues downstream of the active site serine, whereas

• extension. Based on the presumed biosynthetic origin of these extender units (from L-serine and from a glycolytic intermediate (in all likelihood 1,3-biphospho-D-glycerate), respectively), it was initially proposed that the (2S)-isomer of aminomalonyl-ACP and the (2R)-isomers of hydroxyl-/methoxymalonyl-ACP

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• has occurred at an internal tryptophan residue of the precursor peptide. Kawaguchipeptin A Apart from the ComX pheromones, post-translational dimethylallylations of the tyrosine, threonine, serine, and tryptophan residues of cyclic peptides from cyanobacteria were reported [49][50][51]. The RiPPs

Solution-phase automated synthesis of an α-amino aldehyde as a versatile intermediate

• Hisashi Masui,
• Sae Yosugi,
• Shinichiro Fuse and
• Takashi Takahashi

Beilstein J. Org. Chem. 2017, 13, 106–110, doi:10.3762/bjoc.13.13

• serine, and the subsequent reduction of carboxylic acid derivatives such as ester [20][21][22][23][24][25][26][27], thioester [28], or Weinreb amide [29][30] to the aldehyde. In addition, Burke and co-workers reported an asymmetric hydroformylation of 2,2-dimethyl-2,3-dihydrooxazole for the synthesis of

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• glycosylation with a TES-protected glycosyl donor has also been performed in a case where the target contained a 6-O-acylglucoside and hence protective groups that could be removed under mild acidic conditions were needed [9]. This was for example used for the synthesis of the serine protease inhibitor

Phosphated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds

• Cira Mollings Puentes and
• Thomas J. Wenzel

Beilstein J. Org. Chem. 2017, 13, 43–53, doi:10.3762/bjoc.13.6

• )cyclohexanemethanol (13), alanine methyl ester (14), 2-phenylglycine methyl ester (15), phenylalanine methyl ester (16), tyrosine (17), 4-chlorophenylalanine methyl ester (18), 4-chlorophenylalanine ethyl ester (19), carbobenzyloxy serine (20), 2-methylindoline (21), trans-1-amino-2-indanol (22), cis-1-amino-2

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• have been exploited as valuable building blocks in natural product syntheses, e.g., calyculins A and B as potent serine-threonine protein phosphatase inhibitors [6], as well as ligands in enantioselective reactions [7]. Furthermore, allylphosphonates are important bioactive compounds that exhibit

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• serine residue of the PCP-domain using the R4-4 mutant of the promiscuous phosphopantetheinyl transferase Sfp. The substrate peptide is attached to the PCP-domain via a coenzyme A-derived phosphopantetheine moiety. Excess of substrate is removed via centrifugation using centrifugal filter units with an

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• group. We explored a 26-residue coiled-coil peptide which undergoes a conformational transition to amyloid fibrils in 24 hours under physiological conditions [41], but remains random coil if one of three serine residues carries a phosphate group [27]. The aggregation process could be restored by

• between glutamates and lysines. Intermolecular coulombic interactions between e and g direct the monomers into a parallel dimeric orientation. The solvent-exposed position f is occupied by serine for better solubility. One site of each position b, c, and f contains valine, making the system prone to

• cells [50]. The serine/threonine kinase PKA uses ATP as phosphate donor. It has to be activated from its natural species with cAMP which leads to dissociation of PKA in two regular and two catalytic subunits [51]. We used the preactivated catalytic subunit of PKA to perform the reactions. The structural

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• synthetically broken down into tripeptides 78 and 79 (Scheme 15). Tripeptide 78 was further disconnected into protected serine 80 and protected β-hydroxyenduracididine residues 81 and 82. The synthesis of key amino acids 81 and 82 was based on an aldol reaction between protected aldehyde 83 and glycine 84

p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates

• Madhuri Vangala and
• Ganesh P Shinde

Beilstein J. Org. Chem. 2016, 12, 2086–2092, doi:10.3762/bjoc.12.197

• containing substrates such as the p-nitrophenyl carbonate of 9-fluorenemethanol 16a and N-Cbz-L-serine methyl ester 17a, resulted in the dibenzofulvene product 16b in the former, and a mixture of products in the latter, with DBN acting as a base. Even though the γ-lactam products were the only major

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• D-serine as a starting material [6]. In this regard, our group has recently reported the synthesis of the C3’-branched carbohydrate core of amipurimycin starting from D-glucose [15]. In the continuation of this area, we now report the synthesis of the amipurimycin pyranose core comprising of (a) a

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• -butanol (16), 5-azidopentanol (17), cyclohexanol (18) and 2-adamantanol (19), to give O-2-deoxyglucosides in high yields (74–90%) and α-selectivities (α:β = 7–10:1, Table 3, entries 2–8). Regarding the glycosylation with amino acid derivatives, L-serine 20 and threonine derivative 21, increased ratio of β

• -Serine and threonine derivatives 20 and 21 reacted with galactal 4 to give the glycosylated amino acids 59 and 60 (Table 4, entries 9 and 10) in excellent selectivities (59, α only; 60, α:β = 9:1) but in different yields (59, 50%; 60, 97%). In Table 4, entry 11, disaccharide 61 was acquired in the

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• -translationally modified into the final product, and a heterotrimeric complex that is responsible for both heterocyclisation of serine and cysteine residues, and subsequent oxidation of (ox/thi)azolines into (ox/thi)azoles (Figure 3A). This catalytic complex consists of “C” and “D” proteins (annotated as McbB and

• McbD, respectively, for microcin B17) that cooperate to catalyse heterocyclisation of specific serine and cysteine residues in McbA, and a flavin-dependent dehydrogenase (the “B-protein”, McbC for microcin B17) that oxidises these heterocycles. These early in vitro studies indicated that the “C-protein

• then be attacked by an adjacent serine or cysteine side chain, thus releasing phosphate/AMP and generating the heterocycle. This order of steps was not advocated by either the Naismith or Mitchell groups as it requires a disfavoured 5-endo-trig cyclisation, although this mode of cyclisation is

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• Jaroslav Padevet Marcus G. Schrems Robin Scheil Andreas Pfaltz Department of Chemistry, University of Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland 10.3762/bjoc.12.114 Abstract A synthesis of new NeoPHOX ligands derived from serine or threonine has been developed. The central

• the substantially higher ee values induced by the analogous catalyst Ir-1a [28] lacking substituents at C(5). Based on these negative results we chose a new approach based on serine or threonine as starting materials (Figure 4). The carboxyl group of these amino acids serves as surrogate for the tert

• protecting group, the steric properties of the ligand can be optimized for a specific application. PHOX ligands of this type have been previously prepared from serine and successfully used in iridium-catalyzed hydrogenation [29][30]. Synthesis of serine- and threonine-derived NeoPHOX ligands The synthesis

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• better Z-(dia)stereoselectivity was observed when compared to the previous one-pot method. The (dia)stereoselectivity of the process was affected neither by the reaction solvent nor by the amount of DIBAL-H employed. The method is compatible with the presence of free hydroxy groups as shown with serine

• -protected α-amino esters requires three chemical steps, i.e. reduction, oxidation and olefination (Figure 1) [9][10]. When the benzyl group is used as protecting group for the nitrogen functionality, the method represents a variation of the well-known Reetz protocol [11]. In the particular case of serine

• aldehydes. It comprises the one-pot sequential reduction to aldehyde with DIBAL-H at −78 °C and subsequent in situ addition of Grignard reagents. Remarkably, our method is friendly with serine and threonine derivatives without the requisite to protect the β-hydroxy group. With this tool in hand, we thought

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• . synthesised the hydroxyleucine moiety found in naturally occurring muraymycins of classes A to C (Scheme 8) [107]. Adapting a strategy developed by Zhu et al., D-serine (59) was stereoselectively converted into the protected amino alcohol 60 [108]. Key intermediate 60 was then Cbz- and acetonide protected to