Natural products in synthesis and biosynthesis II
Universität Bonn
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Natural products in synthesis and biosynthesis
Biosynthesis and function of secondary metabolites
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Natural products in synthesis and biosynthesis II
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2016, 12, 413–414, doi:10.3762/bjoc.12.44
Recent highlights in biosynthesis research using stable isotopes
- Jan Rinkel and
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271
Graphical Abstract
Figure 1: Structures of lovastatin (1), aflatoxin B1 (2) and amphotericin B (3).
Scheme 1: a) Structure of rhizoxin (4). b) Two possible mechanisms of chain branching catalysed by a branchin...
Scheme 2: Structure of coelimycin P1 (8) and proposed biosynthetic formation from the putative PKS produced a...
Scheme 3: Structure of trioxacarcin A (9) with highlighted carbon origins of the polyketide core from acetate...
Scheme 4: Proposed biosynthetic assembly of clostrubin A (12). Bold bonds show intact acetate units.
Figure 2: Structure of forazoline A (13).
Figure 3: Structures of tyrocidine A (14) and teixobactin (15).
Figure 4: Top: Structure of the NRPS product kollosin A (16) with the sequence N-formyl-D-Leu-L-Ala-D-Leu-L-V...
Scheme 5: Proposed biosynthesis of aspirochlorine (20) via 18 and 19.
Scheme 6: Two different macrocyclization mechanisms in the biosynthesis of pyrrocidine A (24).
Figure 5: Structure of thiomarinol A (27). Bold bonds indicate carbon atoms derived from 4-hydroxybutyrate.
Figure 6: Structures of artemisinin (28), ingenol (29) and paclitaxel (30).
Figure 7: The revised (31) and the previously suggested (32) structure of hypodoratoxide and the structure of...
Figure 8: Structure of the two interconvertible conformers of (1(10)E,4E)-germacradien-6-ol (34) studied with...
Scheme 7: Proposed cyclization mechanism of corvol ethers A (42) and B (43) with the investigated reprotonati...
Scheme 8: Predicted (top) and observed (bottom) 13C-labeling pattern in cyclooctatin (45) after feeding of [U-...
Scheme 9: Proposed mechanism of the cyclooctat-9-en-7-ol (52) biosynthesis catalysed by CotB2. Annotated hydr...
Scheme 10: Cyclization mechanism of sesterfisherol (59). Bold lines indicate acetate units; black circles repr...
Scheme 11: Cyclization mechanisms to pentalenene (65) and protoillud-6-ene (67).
Scheme 12: Reactions of chorismate catalyzed by three different enzyme subfamilies. Oxygen atoms originating f...
Scheme 13: Incorporation of sulfur into tropodithietic acid (72) via cysteine.
Scheme 14: Biosynthetic proposal for the starter unit of antimycin biosynthesis. The hydrogens at positions R1...
Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms
- Tatjana Huber,
- Lara Weisheit and
- Thomas Magauer
Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273
Graphical Abstract
Figure 1: a) Structure of xenicin (1) and b) numbering of the xenicane skeleton according to Schmitz and van ...
Figure 2: Overview of selected Xenia diterpenoids according to the four subclasses [2-20]. The nine-membered carboc...
Figure 3: Representative members of the caryophyllenes, azamilides and Dictyota diterpenes.
Scheme 1: Proposed biosynthesis of Xenia diterpenoids (OPP = pyrophosphate, GGPP = geranylgeranyl pyrophospha...
Scheme 2: Direct synthesis of the nine-membered carbocycle as proposed by Schmitz and van der Helm (E = elect...
Scheme 3: The construction of E- or Z-cyclononenes.
Scheme 4: Total synthesis of racemic β-caryophyllene (22) by Corey.
Scheme 5: Total synthesis of racemic β-caryophyllene (22) by Oishi.
Scheme 6: Total synthesis of coraxeniolide A (10) by Leumann.
Scheme 7: Total synthesis of antheliolide A (18) by Corey.
Scheme 8: a) Synthesis of enantiomer 80, b) total syntheses of coraxeniolide A (10) and c) β-caryophyllene (22...
Scheme 9: Total synthesis of blumiolide C (11) by Altmann.
Scheme 10: Synthesis of a xeniolide F precursor by Hiersemann.
Scheme 11: Synthesis of the xenibellol (15) and the umbellacetal (114) core by Danishefsky.
Scheme 12: Proposed biosynthesis of plumisclerin A (118).
Scheme 13: Synthesis of the tricyclic core structure of plumisclerin A by Yao.
Scheme 14: Total synthesis of 4-hydroxydictyolactone (137) by Williams.
Scheme 15: Photoisomerization of 4-hydroxydictyolactone (137) to 4-hydroxycrenulide (138).
Scheme 16: The total synthesis of (+)-acetoxycrenulide (151) by Paquette.
Natural products from microbes associated with insects
- Christine Beemelmanns,
- Huijuan Guo,
- Maja Rischer and
- Michael Poulsen
Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34
Graphical Abstract
Figure 1: Flow chart of the typical characterization of chemical signals from microbial interactions. (1) Che...
Figure 2: Multilateral microbe–insect interactions. (1) Insect–symbiont interactions with both partners benef...
Figure 3: a) Interactions between bacterial (endo)symbionts and insects with both partners benefiting from th...
Figure 4: Multilateral microbial interactions in fungus-growing insects. (1) Insect cultivar: protects and sh...
Figure 5: Small molecules (chemical mediators) play key roles in maintaining garden homeostasis in fungus-gro...
Figure 6: Secondary metabolites isolated from Actinobacteria from fungus-growing termites. Microtermolide A (...
Figure 7: Secondary metabolites from bacterial mutualists of solitary insects. Bafilomycin A1 (21), bafilomyc...
Figure 8: Beneficial interactions (1) between fungal symbionts and insects.
Figure 9: Secondary metabolites isolated from fungal symbionts. Cerulenin (30), helvolic acid (31), lepiochlo...
Figure 10: Predatory interactions, (1) entomopathogenic fungi use insect as prey.
Figure 11: Entomopathogenic fungi use secondary metabolites as insecticidal compounds to kill their prey. Dest...
Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis
- Stephanie R. Hare and
- Dean J. Tantillo
Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41
Graphical Abstract
Figure 1: Representative terpenes.
Figure 2: Two different models showing how energy evolves throughout the course of a reaction: (a) a two-dime...
Figure 3: A depiction of the “snowboarder” analogy for reactions displaying non-statistical dynamic effects. ...
Figure 4: The tetramethylbromonium ion system [14].
Figure 5: The reaction mechanisms of interest in the PES and dynamics studies of Dupuis and co-workers (R = CH...
Figure 6: The portion of the norborn-2-en-7-ylmethyl cation PES examined by Ghigo et al. [60]. Energies reported ...
Figure 7: The transformation of 2-norbornyl cation to 1,3-dimethylcyclopentyl cation.
Figure 8: Carbocation rearrangements for which trajectory calculations were used to estimate lifetimes of sec...
Figure 9: Carbocation rearrangements involved in abietadiene formation.
Figure 10: Carbocation rearrangements involved in miltiradiene formation.
Figure 11: Top: carbocation rearrangements involved in epi-isozizaene formation. Bottom: reaction coordinate d...
Biosynthesis of α-pyrones
- Till F. Schäberle
Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56
Graphical Abstract
Figure 1: Selected monocyclic and monobenzo α-pyrone structures.
Figure 2: The basic core structure of dibenzo-α-pyrones.
Figure 3: Selected dibenzo-α-pyrones.
Figure 4: Structure of ellagic acid and of the urolithins, the latter metabolized from ellagic acid by intest...
Figure 5: Structure of murayalactone, the only dibenzo-α-pyrone described from bacteria.
Figure 6: Structures of the 6-pentyl-2-pyrone (29) and of trichopyrone (30). Only 29 showed antifungal activi...
Figure 7: Selected monocyclic α-pyrones.
Figure 8: Structures of the gibepyrones A–F.
Figure 9: Structures of the phomenins A and B.
Figure 10: Structures of monocyclic α-pyrones showing pheromone (47) and antitumor activity (48), respectively....
Figure 11: Structures of 6-alkyl (alkoxy or alkylthio)-4-aryl-3-(4-methanesulfonylphenyl)pyrones.
Figure 12: Structures of kavalactones.
Figure 13: Strutures of germicins.
Figure 14: Structures of the pseudopyronines.
Figure 15: The structures of the monobenzo-α-pyrone anticoagulant drugs warfarin and phenprocoumon.
Figure 16: Structures of selected monobenzo-α-pyrones.
Figure 17: Hypothetical pathway of 29 generation from linoleic acid [34].
Figure 18: Proposed biosynthetic pathway of alternariol (modified from [77]). Malonyl-CoA building blocks are appl...
Figure 19: Structures of phenylnannolones and of enterocin, both biosynthesized via polyketide synthase system...
Figure 20: Pyrone ring formation. Examples for the three types of PKS systems are shown in A–C. In D the mecha...
Figure 21: Structures of csypyrones.
Figure 22: Schematic drawing of the T-shaped catalytic cavities of the related enzymes CorB and MxnB. The two ...
Figure 23: Stereo representation of the CorB binding situation (modified from [89]). The substrate mimic (dark vio...
Figure 24: Proposed mechanism for the CsyB enzymatic reaction. A) Coupling reaction of the β-keto fatty acyl i...
Figure 25: Proposed biosynthesis of photopyrone D (37) by the enzyme PpyS from P. luminescens (modified from [63])...
Antibiotics from predatory bacteria
- Juliane Korp,
- María S. Vela Gurovic and
- Markus Nett
Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58
Graphical Abstract
Figure 1: Natural products isolated from M. xanthus DK1622. DKxanthene-534 (1); myxalamid B (2); myxovirescin...
Figure 2: Vegetative cells of P. fallax HKI 727 under a phase-contrast microscope (K. Martin, unpublished). B...
Figure 3: Structures of myxopyronins A (11) and B (12), corallopyronins A (13), B (14) and C (15), as well as...
Figure 4: Structure of althiomycin (17).
Figure 5: Structures of cystobactamids 919-1 (18), 919-2 (19), and 507 (20).
Figure 6: Structures of natural products isolated from Herpetosiphon spp.: siphonazole (21); auriculamide (22...
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
Graphical Abstract
Figure 1: Structures of the naturally occurring muraymycins isolated by McDonald et al. [22].
Figure 2: Structures of selected classes of nucleoside antibiotics. Similarities to the muraymycins are highl...
Figure 3: Structure of peptidoglycan. Long chains of glycosides (alternating GlcNAc (green) and MurNAc (blue)...
Figure 4: Schematic representation of bacterial cell wall biosynthesis.
Figure 5: Translocase I (MraY) catalyses the reaction of UDP-MurNAc-pentapeptide with undecaprenyl phosphate ...
Figure 6: Proposed mechanisms for the MraY-catalysed reaction. A: Two-step mechanism postulated by Heydanek e...
Scheme 1: First synthetic access towards simplified muraymycin analogues as reported by Yamashita et al. [76].
Scheme 2: Synthesis of (+)-caprazol (19) reported by Ichikawa, Matsuda et al. [92].
Scheme 3: Synthesis of the epicapreomycidine-containing urea dipeptide via C–H activation [96,97].
Scheme 4: Synthesis of muraymycin D2 and its epimer reported by Ichikawa, Matsuda et al. [96,97].
Scheme 5: Synthesis of the urea tripeptide unit as a building block for muraymycins reported by Kurosu et al. ...
Scheme 6: Synthesis of the uridine-derived core structure of naturally occuring muraymycins reported by Ducho...
Scheme 7: Synthesis of the epicapreomycidine-containing urea dipeptide from Garner's aldehyde reported by Duc...
Scheme 8: Synthesis of a hydroxyleucine-derived aldehyde building block reported by Ducho et al. [107].
Scheme 9: Synthesis of 5'-deoxy muraymycin C4 (65) as a closely related natural product analogue [78,109,110].
Figure 7: Summary of modifications on semisynthetic muraymycin analogues tested by Lin et al. [86]. Most active c...
Figure 8: Bioactive muraymycin analogues identified by Yamashita et al. [76].
Figure 9: Muraymycin D2 and several non-natural lipidated analogues 91a–d [77,114].
Figure 10: Non-natural muraymycin analogues with varying peptide structures [77,114].
Figure 11: SAR results for several structural variations of the muraymycin scaffold.
Figure 12: Muraymycin analogues designed for potential anti-Pseudomonas activity (most active analogues are hi...
Scheme 10: Proposed outline pathway for muraymycin biosynthesis based on the analysis of the biosynthetic gene...
Scheme 11: Biosynthesis of the nucleoside core structure of A-90289 antibiotics (which is identical to the mur...
Scheme 12: Transaldolase-catalysed formation of the key intermediate GlyU 101 in the biosynthesis of muraymyci...
Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites
- Antonio Dávila-Céspedes,
- Peter Hufendiek,
- Max Crüsemann,
- Till F. Schäberle and
- Gabriele M. König
Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96
Graphical Abstract
Figure 1: Structures of cystobactamids 507, 919-1 and 919-2.
Figure 2: Structures of aurafuron A and corallopyronin A.
Figure 3: Structures of ixabepilone and capecitabine.
Figure 4: Structures of DKxanthene-534 and myxochelin A.
Figure 5: Phylogenetic tree of halotolerant and halophilic myxobacteria. The neighbor-joining tree is based o...
Figure 6: Structure of nannocystin A.
Figure 7: Structure of phenylnannolones A–C.
Figure 8: Structures of the pyrronazols, dihydroxyphenazin and 1-hydroxyphenazin-6-yl-α-D-arabinofuranoside.
Figure 9: Structures of nannozinones A + B and nannochelin A from N. pusilla strain MNa10913.
Figure 10: Structure of haliangicin from H. ochraceum.
Figure 11: Structure of haliamide from H. ochraceum SMP-2.
Figure 12: Structures of salimabromide, enhygrolides A + B and salimyxins A + B.
Figure 13: Structures of miuraenamides A–F from P. miuraensis.
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
Graphical Abstract
Figure 1: Schematic of RiPP biosynthesis. Thiazole/oxazole formation is represented by the blue heterocycle (...
Figure 2: Examples of heterocycles in RiPPs alongside the precursor peptides that these molecules derive from...
Figure 3: Formation of thiazoles and oxazoles in RiPPs. A) Biosynthesis of microcin B17. B) Mechanistic model...
Figure 4: Lanthionine bond formation. A) Nisin and its precursor peptide. B) Mechanism of lanthionine bond fo...
Figure 5: S-[(Z)-2-Aminovinyl]-D-cysteine (AviCys) formation in the epidermin pathway. A) Mechanisms for deca...
Figure 6: Cyclisation in the biosynthesis of thiopeptides. A) Mechanism of TclM-catalysed heterocyclisation i...
Figure 7: ATP-dependent macrocyclisation. A) General mechanism for ATP-dependent macrolactonisation or macrol...
Figure 8: Peptidase-like macrolactam formation. A) General mechanism. B) Examples of RiPPs cyclised by serine...
Figure 9: Structure of autoinducing peptide AIP-I from Staphylococcus aureus and the sequence of the correspo...
Figure 10: Radical cyclisation in RiPP biosynthesis. A) AlbA-catalysed formation of thioethers in the biosynth...
Figure 11: RiPPs with uncharacterised mechanisms of cyclisation. Unusual heterocycles in ComX and methanobacti...
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
Graphical Abstract
Scheme 1: Schematic description of the cyclisation reaction catalysed by TE domains. In most cases, the nucle...
Scheme 2: Mechanisms for the formation of oxygen heterocycles. The degree of substitution can differ from tha...
Scheme 3: Pyran-ring formation in pederin (24) biosynthesis. Incubation of recombinant PedPS7 with substrate ...
Scheme 4: The domain AmbDH3 from ambruticin biosynthesis catalyses the dehydration of 25 and subsequent cycli...
Scheme 5: SalBIII catalyses dehydration of 29 and subsequent cyclisation to tetrahydropyran 30 [18].
Figure 1: All pyranonaphtoquinones contain either the naphtha[2,3-c]pyran-5,10-dione (32) or the regioisomeri...
Scheme 6: Pyran-ring formation in actinorhodin (34) biosynthesis. DNPA: 4-dihydro-9-hydroxy-1-methyl-10-oxo-3H...
Scheme 7: Pyran formation in granaticin (36) biosynthesis. DNPA: 4-dihydro-9-hydroxy-1-methyl-10-oxo-3H-napht...
Scheme 8: Pyran formation in alnumycin (37) biosynthesis. Adapted from [21].
Scheme 9: Biosynthesis of pseudomonic acid A (61). The pyran ring is initially formed in 57 after dehydrogena...
Scheme 10: Epoxidation–cyclisation leads to the formation of the tetrahydropyran ring in the western part of t...
Scheme 11: a) Nonactin (70) is formed from heterodimers of (−)(+)-dimeric nonactic acid and (+)(−)-dimeric non...
Figure 2: Pamamycins (73) are macrodiolide antibiotics containing three tetrahydrofuran moieties, which are a...
Scheme 12: A PS domain homolog in oocydin A (76) biosynthesis is proposed to catalyse furan formation via an o...
Scheme 13: Mechanism of oxidation–furan cyclisation by AurH, which converts (+)-deoxyaureothin (77) into (+)-a...
Scheme 14: Leupyrrin A2 (80) and the proposed biosynthesis of its furylidene moiety [69,70].
Scheme 15: Asperfuranone (93) biosynthesis, adapted from [75].
Figure 3: The four major aflatoxins produced by Aspergilli are the types B1, B2, G1 and G2 (94–97). In the di...
Scheme 16: Overview on aflatoxin B1 (94) biosynthesis. HOMST = 11-hydroxy-O-methylsterigmatocystin [78,79,82-106].
Scheme 17: A zipper mechanism leads to the formation of oxygen heterocycles in monensin biosynthesis [109-111].
Scheme 18: Formation of the 2,6-dioxabicyclo[3.2.1]octane (DBO) ring system in aurovertin B (118) biosynthesis ...
Figure 4: Structures of the epoxide-containing polyketides epothilone A (119) and oleandomycin (120) [123-125].
Scheme 19: Structures of phoslactomycin B (121) (a) and jerangolid A (122) (b). The heterocycle-forming steps ...
Scheme 20: a) Structures of rhizoxin (130) and cycloheximide (131). Model for the formation of δ-lactones (b) ...
Scheme 21: EncM catalyses a dual oxidation sequence and following processing of the highly reactive intermedia...
Figure 5: Mesomeric structures of tetronates [138,139].
Figure 6: Structures of tetronates for which gene clusters have been sequenced. The tetronate moiety is shown...
Scheme 22: Conserved steps for formation and processing in several 3-acyl-tetronate biosynthetic pathways were...
Scheme 23: In versipelostatin A (153) biosynthesis, VstJ is a candidate enzyme for catalysing the [4 + 2] cycl...
Scheme 24: a) Structures of some thiotetronate antibiotics. b) Biosynthesis of thiolactomycin (165) as propose...
Scheme 25: Aureusidine synthase (AS) catalyses phenolic oxidation and conjugate addition of chalcones leading ...
Scheme 26: a) Oxidative cyclisation is a key step in the biosynthesis of spirobenzofuranes 189, 192 and 193. b...
Scheme 27: A bicyclisation mechanism forms a β-lactone and a pyrrolidinone and removes the precursor from the ...
Scheme 28: Spontaneous cyclisation leads to off-loading of ebelactone A (201) from the PKS machinery [163].
Scheme 29: Mechanisms for the formation of nitrogen heterocycles.
Scheme 30: Biosynthesis of highly substituted α-pyridinones. a) Feeding experiments confirmed the polyketide o...
Scheme 31: Acridone synthase (ACS) catalyses the formation of 1,3-dihydroxy-N-methylacridone (224) by condensa...
Scheme 32: A Dieckmann condensation leads to the formation of a 3-acyl-4-hydroxypyridin-2-one 227 and removes ...
Scheme 33: a) Biosynthesis of the pyridinone tenellin (234). b) A radical mechanism was proposed for the ring-...
Scheme 34: a) Oxazole-containing PKS–NRPS-derived natural products oxazolomycin (244) and conglobatin (245). b...
Scheme 35: Structure of tetramic acids 251 (a) and major tautomers of 3-acyltetramic acids 252a–d (b). Adapted...
Scheme 36: Equisetin biosynthesis. R*: terminal reductive domain. Adapted from [202].
Scheme 37: a) Polyketides for which a similar biosynthetic logic was suggested. b) Pseurotin A (256) biosynthe...
Figure 7: Representative examples of PTMs with varying ring sizes and oxidation patterns [205,206].
Scheme 38: Ikarugamycin biosynthesis. Adapted from [209-211].
Scheme 39: Tetramate formation in pyrroindomycin aglycone (279) biosynthesis [213-215].
Scheme 40: Dieckmann cyclases catalyse tetramate or 2-pyridone formation in the biosynthesis of, for example, ...
The direct oxidative diene cyclization and related reactions in natural product synthesis
- Juliane Adrian,
- Leona J. Gross and
- Christian B. W. Stark
Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200
Graphical Abstract
Scheme 1: Putative structures of geraniol 1a (R = H) or 1b (R = H) (in 1924), their expected dihydroxylation ...
Scheme 2: Correlation between the substrate double bond geometry and relative stereochemistry of the correspo...
Scheme 3: Mechanisms and classification for the metal-mediated oxidative cyclizations to form 2,5-disubstitut...
Scheme 4: Synthesis of (+)-anhydro-D-glucitol and (+)-D-chitaric acid using an OsO4-mediated oxidative cycliz...
Scheme 5: Total synthesis of neodysiherbaine A via a Ru(VIII)- and an Os(VI)-catalyzed oxidative cyclization,...
Scheme 6: Formal synthesis of ionomycin by Kocienski and co-workers.
Scheme 7: Total synthesis of amphidinolide F by Fürstner and co-workers.
Scheme 8: Brown`s and Donohoe`s oxidative cyclization approach to cis-solamin A.
Scheme 9: Total synthesis of cis-solamin A using a Ru(VIII)-catalyzed oxidative cyclization and enzymatic des...
Scheme 10: Donohoe´s double oxidative cyclization approach to cis-sylvaticin.
Scheme 11: Permanganate-mediated approach to cis-sylvaticin by Brown and co-workers.
Scheme 12: Total synthesis of membranacin using a KMnO4-mediated oxidative cyclization.
Scheme 13: Total synthesis of membrarollin and its analogue 21,22-diepi-membrarollin.
Scheme 14: Total synthesis of rollidecin C and D using a late stage Re(VII)-catalyzed oxidative polycyclizatio...
Scheme 15: Co(II)-catalyzed oxidative cyclization in the total synthesis of asimilobin and gigantetrocin A.
Scheme 16: Mn(VII)-catalyzed oxidative cyclization of a 1,5-diene in the synthesis of trans-(+)-linalool oxide....
Scheme 17: Re(VII)-catalyzed oxidative cyclization in the total synthesis of teurilene.
Scheme 18: Total synthesis of (+)-eurylene via Re(VII)- and Cr(VI)-mediated oxidative cyclizations.
Scheme 19: Synthesis of cis- and trans-THF Rings of eurylene via Mn(VII)-mediated oxidative cyclizations.
Scheme 20: Cr(VI)-catalyzed oxidative cyclization in the total synthesis of venustatriol by Corey et al.
Scheme 21: Ru(VIII)-catalyzed oxidative cyclization of a 1,5-diene in the synthesis and evaluation of its ster...
Scheme 22: Ru(VII)-catalyzed oxidative cyclization of a 5,6-dihydroxy alkene in the synthesis of the core stru...
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
Graphical Abstract
Figure 1: Structures of the enduracididine family of amino acids (1–6).
Figure 2: Enduracidin A (7) and B (8).
Figure 3: Minosaminomycin (9) and related antibiotic kasugamycin (10).
Figure 4: Enduracididine-containing compound 11 identified in a cytotoxic extract of Leptoclinides dubius [32].
Figure 5: Mannopeptimycins α–ε (12–16).
Figure 6: Regions of the mannopeptimycin structure investigated in structure–activity relationship investigat...
Figure 7: Teixobactin (17).
Scheme 1: Proposed biosynthesis of L-enduracididine (1) and L-β-hydroxyenduracididine (5).
Scheme 2: Synthesis of enduracididine (1) by Shiba et al.
Scheme 3: Synthesis of protected enduracididine diastereomers 31 and 32.
Scheme 4: Synthesis of the C-2 azido diastereomers 36 and 37.
Scheme 5: Synthesis of 2-azido-β-hydroxyenduracididine derivatives 38 and 39.
Scheme 6: Synthesis of protected β-hydroxyenduracididine derivatives 40 and 41.
Scheme 7: Synthesis of C-2 diastereomeric amino acids 46 and 47.
Scheme 8: Synthesis of protected β-hydroxyenduracididines 51 and 52.
Scheme 9: General transformation of alkenes to cyclic sulfonamide 54 via aziridine intermediate 53.
Scheme 10: Synthesis of (±)-enduracididine (1) and (±)-allo-enduracididine (3).
Scheme 11: Synthesis of L-allo-enduracididine (3).
Scheme 12: Synthesis of protected L-allo-enduracididine 63.
Scheme 13: Synthesis of β-hydroxyenduracididine derivative 69.
Scheme 14: Synthesis of minosaminomycin (9).
Scheme 15: Retrosynthetic analysis of mannopeptimycin aglycone (77).
Scheme 16: Synthesis of protected amino acids 87 and 88.
Scheme 17: Synthesis of mannopeptimycin aglycone (77).
Scheme 18: Synthesis of N-mannosylation model guanidine 92 and attempted synthesis of benzyl protected mannosy...
Scheme 19: Synthesis of benzyl protected mannosyl D-β-hydroxyenduracididine 97.
Scheme 20: Synthesis of L-β-hydroxyenduracididine 98.
Scheme 21: Total synthesis of mannopeptimycin α (12) and β (13).
Scheme 22: Synthesis of protected L-allo-enduracididine 102.
Scheme 23: The solid phase synthesis of teixobactin (17).
Scheme 24: Retrosynthesis of the macrocyclic core 109 of teixobactin (17).
Scheme 25: Synthesis of macrocycle 117.
