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Search for "depsipeptide" in Full Text gives 16 result(s) in Beilstein Journal of Organic Chemistry.
Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization
- Senze Qiao,
- Zhongyu Cheng and
- Fuzhuo Li
Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66
- type B streptogramin variants [41], including pristinamycin IE (8), which belongs to the class of depsipeptide antibiotics. Similarly, the linear peptide-SNAC was prepared through the SPPS method on 2-chlorotrityl resin, and macrolactonization was catalyzed by SnbDE TE, a thioesterase from
- cyclization process. Most recently, the synthesis of monocyclic depsipeptide, seongsanamide E (10), was reported by Boddy and co-workers via two different strategies [43]. On the one hand, the regular chemical approach, attempting Yonemitsu’s conditions to macrolactonize the seco-acid, was unsuccessful. On
- demonstrated that some of them exhibit comparable activities to the clinically approved antibiotics against Gram-positive strains while also enhancing activities against Gram-negative pathogens. The cryptophycins The cryptophycins are a large family of 16-membered ring depsipeptide natural products, which
Graphical Abstract
Scheme 1: Brief introduction of thioesterase (TE) domain. (a) NRPS and PKS assembly lines. (b) Mechanism of T...
Scheme 2: Chemoenzymatic synthesis of tyrocidine A and its analogs. (a) First-gen chemoenzymatic synthesis of...
Scheme 3: Representative examples of NAC-activated thioesters-mediated biocatalytic macrolactamization.
Scheme 4: Chemoenzymatic synthesis of CDA, daptomycin and their analogs. (a) Biocatalytic macrocyclization of...
Scheme 5: Chemoenzymatic synthesis of surugamide B and related natural products. (a) Three synthetic strategi...
Scheme 6: Chemoenzymatic synthesis of the pikromycins. (a) Macrocyclization of 10-deoxymethynolide catalyzed ...
Scheme 7: Chemoenzymatic synthesis of the juevnimicins.
Scheme 8: Chemoenzymatic synthesis of the cryptophycins.
Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines
- Yelong Lei and
- Jiaxi Xu
Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6
- some natural products [2] and pharmaceuticals [3], such as in the antitumor epi-oxazoline halipeptin D isolated from marine organisms [4], in the cytotoxic natural depsipeptide brasilibactin A [5], and cyclohexapeptide bistratamide A [6] (Figure 1). Oxazoline is also one of the crucial coordinating
Graphical Abstract
Figure 1: Oxazoline-containing bioactive natural products.
Scheme 1: Synthetic methods of oxazoline derivatives.
Scheme 2: Scopes of aziridines and diazo esters.
Scheme 3: Proposed reaction mechanism.
Scheme 4: Direction of tautomerization.
Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions
- Angélica de Fátima S. Barreto and
- Carlos Kleber Z. Andrade
Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88
- methodology was used in the synthesis of six cyclic depsipeptoids inspired by the structure of the natural depsipeptide sansalvamide A, which involved five steps (Scheme 19). In the first step, formation of the peptoid was achieved via the first Ugi reaction. Then, subsequent hydrolysis of the ester was
Graphical Abstract
Scheme 1: Comparison between a normal sequential reaction and an MCR.
Scheme 2: Synthesis of tetrazoles and hydantoinimide derivatives by consecutive Ugi reactions [17].
Scheme 3: Synthesis of tetrazole-ketopiperazines by two consecutive Ugi reactions [19].
Scheme 4: Synthesis of acylhydrazino bis(1,5-disubstituted tetrazoles) through two hydrazine-Ugi-azide reacti...
Scheme 5: Synthesis of substituted α-aminomethyltetrazoles through two consecutive Ugi reactions (U-4CR and U...
Scheme 6: Synthesis of tetrazole peptidomimetics by direct use of amino acids in two consecutive Ugi reaction...
Scheme 7: One-pot 8CR based on 3 sequential IMCRs [25].
Scheme 8: Combination of IMCRs for the synthesis of substituted 2H-imidazolines [25].
Scheme 9: 6CR involving a tandem combination of Groebke–Blackburn–Bienaymé and Ugi reaction for the synthesis...
Scheme 10: 5CR involving a tandem combination of Groebke–Blackburn–Bienaymé and Passerini reaction for the syn...
Scheme 11: Synthesis of tubugis via three consecutive IMCRs [27].
Scheme 12: Synthesis of telaprevir through consecutive IMCRs [28].
Scheme 13: Another synthesis of telaprevir through consecutive IMCRs [29].
Scheme 14: a) Synthetic sequence for accessing diverse macrocycles containing the tetrazole nucleus by the uni...
Scheme 15: a) Synthetic sequence for the tetrazolic macrocyclic depsipeptides using a combination of two IMCRs...
Scheme 16: Synthesis of cyclic pentapeptoids by consecutive Ugi reactions [32].
Scheme 17: Synthesis of a cyclic pentapeptoid by consecutive Ugi reactions [32].
Scheme 18: MW-mediated synthesis of a cyclopeptoid by consecutive Ugi reactions [33].
Scheme 19: Synthesis of six cyclic pentadepsipeptoids via consecutive isocyanide-based IMCRs [34].
Scheme 20: Microwave-mediated synthesis of a cyclic heptapeptoid through four consecutive IMCRs [35].
Scheme 21: Macrocyclization of bifunctional building blocks containing diacid/diisonitrile and diamine/diisoni...
Scheme 22: Synthesis of steroid-biaryl ether hybrid macrocycles by MiBs [38].
Scheme 23: Synthesis of biaryl ether-containing macrocycles by MiBs [39].
Scheme 24: Synthesis of natural product-inspired biaryl ether-cyclopeptoid macrocycles [40].
Scheme 25: Synthesis of cholane-based hybrid macrolactams by MiBs [41].
Scheme 26: Synthesis of macrocyclic oligoimine-based DCL using the Ugi-4CR-based quenching approach [42].
Scheme 27: Dye-modified and photoswitchable macrocycles by MiBs [43].
Scheme 28: Synthesis of nonsymmetric cryptands by two sequential double Ugi-4CR-based macrocyclizations [44].
Scheme 29: Synthesis of steroid–aryl hybrid cages by sequential 2- and 3-fold Ugi-4CR-based macrocyclizations [46]....
Scheme 30: Ugi-MiBs approach towards natural product-like macrocycles [47].
Scheme 31: a) Bidirectional macrocyclization of peptides by double Ugi reaction. b) Ugi-4CR for the generation...
Scheme 32: MiBs based on the Passerini-3CR for the synthesis of macrolactones [49].
Scheme 33: Template-driven approach for the synthesis of macrotricycles 170 [50].
A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E
- Marcel Reimann,
- Louis P. Sandjo,
- Luis Antelo,
- Eckhard Thines,
- Isabella Siepe and
- Till Opatz
Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140
- natural fusaricidin by the Jolliffe group employed a ring closure via a lactonization in solution and subsequent attachment of the side chain to the cyclized depsipeptide [10]. Since the macrolactonization approach suffered from diastereoselectivity issues and low yield, it was decided to perform an on
- of the respective products. Structure of fusaricidins E (1) and F (2). NOESY /COSY and HMBC correlations of compound 1. Fragmentation pattern of compounds 1 and 2. Byproducts from removal of Cbz group in THF and DMF. Retrosynthetic plan for the depsipeptide and GHPD side chain. a) LiAlH4, THF, reflux
- °C, 2: PPh3, –78 °C → rt, 77%; i) NaClO2, NaH2PO4, amylene, t-BuOH, H2O, rt, 80%. Ester bond formation with 2,2-dimethylated pseudoproline including peptide 16. Cyclization with 2,2-dimethylated pseudoproline including peptide 16. Depsipeptide cyclization and coupling with GHPD side chain
Graphical Abstract
Figure 1: Structure of fusaricidins E (1) and F (2).
Figure 2: NOESY /COSY and HMBC correlations of compound 1.
Figure 3: Fragmentation pattern of compounds 1 and 2.
Scheme 1: Retrosynthetic plan for the depsipeptide and GHPD side chain.
Scheme 2: a) LiAlH4, THF, reflux, 12 h, quant.; b) Fmoc-OSu, NaHCO3, 1,4-dioxane, H2O, 0 °C to rt, 87%; c) 1:...
Scheme 3: Ester bond formation with 2,2-dimethylated pseudoproline including peptide 16.
Scheme 4: Cyclization with 2,2-dimethylated pseudoproline including peptide 16.
Scheme 5: Depsipeptide cyclization and coupling with GHPD side chain.
Figure 4: Byproducts from removal of Cbz group in THF and DMF.
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
- (1–6) are a rare structural class of amino acids that contain a unique five-membered cyclic guanidine moiety (blue, Figure 1). L-Enduracididine (1) and D-allo-enduracididine (4) were the first identified as amino acid components of potent depsipeptide antibiotics [1][2]. Free enduracididine (1) was
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.
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
- (33–36) [66]. The cyclic core structure of this compound class represents a halogenated depsipeptide with an additional polyketide-derived moiety. As in haliangicin, all miuraenamides, except E, contain a methoxyacrylate structural motif, which surely is important for the biological activity. For
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.
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
- associated with protective Actinobacteria belonging in most attine ant genera to the genus Pseudonocardia, which grow on species-specific areas of the cuticle [73][74][75][76]. In vitro bioassay-guided screening of one of the Pseudonocardia symbionts afforded the antimicrobial cyclic depsipeptide
- D-serine. Due to the presence in conidia, serinocyclines have also been hypothesized to play a role in the virulence of M. anisopliae. Chemical analysis of the entomopathogenic fungus B. bassiana yielded beauvericin (43), a depsipeptide with alternating methylphenylalanyl and hydroxyisovaleryl
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...
Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids
- Angélica de Fátima S. Barreto,
- Otilie E. Vercillo,
- Ludger A. Wessjohann and
- Carlos Kleber Z. Andrade
Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101
- Nossa Senhora de Fátima, Planaltina, 73300-000, Brasília, DF, Brazil Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany 10.3762/bjoc.10.101 Abstract The synthesis of six cyclic depsipeptoids inspired by the natural depsipeptide
- cyclic depsipeptide is sansalvamide A (San A, Figure 1) [20][21][22][23][24][25][26][27][28][29], which was isolated from a marine fungus (Fusarium spp.) [20] and exhibits antitumor activity against multiple cancer cell lines. It is cytotoxic against colon (HCT-116) [20][23][25][26], pancreatic (S2-013
- in combinatorial synthesis [40][41][42][43] and can be used strategically for the synthesis of depsipeptoids. By analogy to peptides and peptoids, a depsipeptoid would be a peptoid bearing an ester group instead of an amide group. Differences between peptide, peptoid, depsipeptide and depsipeptoid
Graphical Abstract
Figure 1: Sansalvamide A (1) and its depsipeptoid analogues (2).
Figure 2: Generic structures of (a) peptide, (b) peptoid, (c) depsipeptide and (d) depsipeptoid.
Figure 3: Structures of six pentadepsipeptoid analogues of San A.
Scheme 1: Retrosynthetic analysis of the cyclic depsipeptoids.
Scheme 2: Synthesis of acyclic depsipeptoids 11a,b.
Scheme 3: Synthesis of macrocycles 2a-f.
Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
- Gijs Koopmanschap,
- Eelco Ruijter and
- Romano V.A. Orru
Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50
Graphical Abstract
Scheme 1: The proposed mechanism of the Passerini reaction.
Scheme 2: The PADAM-strategy to α-hydroxy-β-amino amide derivatives 7. An additional oxidation provides α-ket...
Scheme 3: The general accepted Ugi-mechanism.
Scheme 4: Three commonly applied Ugi/cyclization approaches. a) UDC-process, b) UAC-sequence, c) UDAC-combina...
Scheme 5: Ugi reaction that involves the condensation of Armstrong’s convertible isocyanide.
Scheme 6: Mechanism of the U-4C-3CR towards bicyclic β-lactams.
Scheme 7: The Ugi 4C-3CR towards oxabicyclo β-lactams.
Scheme 8: Ugi MCR between an enantiopure monoterpene based β-amino acid, aldehyde and isocyanide resulting in...
Scheme 9: General MCR for β-lactams in water.
Scheme 10: a) Ugi reaction for β-lactam-linked peptidomimetics. b) Varying the β-amino acid resulted in β-lact...
Scheme 11: Ugi-4CR followed by a Pd-catalyzed Sn2 cyclization.
Scheme 12: Ugi-3CR of dipeptide mimics from 2-substituted pyrrolines.
Scheme 13: Joullié–Ugi reaction towards 2,5-disubstituted pyrrolidines.
Scheme 14: Further elaboration of the Ugi-scaffold towards bicyclic systems.
Scheme 15: Dihydroxyproline derivatives from an Ugi reaction.
Scheme 16: Diastereoselective Ugi reaction described by Banfi and co-workers.
Scheme 17: Similar Ugi reaction as in Scheme 16 but with different acids and two chiral isocyanides.
Scheme 18: Highly diastereoselective synthesis of pyrrolidine-dipeptoids via a MAO-N/MCR-procedure.
Scheme 19: MAO-N/MCR-approach towards the hepatitis C drug telaprevir.
Scheme 20: Enantioselective MAO-U-3CR procedure starting from chiral pyrroline 64.
Scheme 21: Synthesis of γ-lactams via an UDC-sequence.
Scheme 22: Utilizing bifunctional groups to provide bicyclic γ-lactam-ketopiperazines.
Scheme 23: The Ugi reaction provided both γ- as δ-lactams depending on which inputs were used.
Scheme 24: The sequential Ugi/RCM with olefinic substrates provided bicyclic lactams.
Scheme 25: a) The structural and dipole similarities of the triazole unit with the amide bond. b) The copper-c...
Scheme 26: The Ugi/Click sequence provided triazole based peptidomimetics.
Scheme 27: The Ugi/Click reaction as described by Nanajdenko.
Scheme 28: The Ugi/Click-approach by Pramitha and Bahulayan.
Scheme 29: The Ugi/Click-combination by Niu et al.
Scheme 30: Triazole linked peptidomimetics obtained from two separate MCRs and a sequential Click reaction.
Scheme 31: Copper-free synthesis of triazoles via two MCRs in one-pot.
Scheme 32: The sequential Ugi/Paal–Knorr reaction to afford pyrazoles.
Scheme 33: An intramolecular Paal–Knorr condensation provided under basic conditions pyrazolones.
Scheme 34: Similar cyclization performed under acidic conditions provided pyrazolones without the trifluoroace...
Scheme 35: The Ugi-4CR towards 2,4-disubstituted thiazoles.
Scheme 36: Solid phase approach towards thiazoles.
Scheme 37: Reaction mechanism of formation of thiazole peptidomimetics containing an additional β-lactam moiet...
Scheme 38: The synthesis of the trisubstituted thiazoles could be either performed via an Ugi reaction with pr...
Scheme 39: Performing the Ugi reaction with DMB-protected isocyanide gave access to either oxazoles or thiazol...
Scheme 40: Ugi/cyclization-approach towards 2,5-disubstituted thiazoles. The Ugi reaction was performed with d...
Scheme 41: Further derivatization of the thiazole scaffold.
Scheme 42: Three-step procedure towards the natural product bacillamide C.
Scheme 43: Ugi-4CR to oxazoles reported by Zhu and co-workers.
Scheme 44: Ugi-based synthesis of oxazole-containing peptidomimetics.
Scheme 45: TMNS3 based Ugi reaction for peptidomimics containing a tetrazole.
Scheme 46: Catalytic cycle of the enantioselective Passerini reaction towards tetrazole-based peptidomimetics.
Scheme 47: Tetrazole-based peptidomimetics via an Ugi reaction and a subsequent sigmatropic rearrangement.
Scheme 48: Resin-bound Ugi-approach towards tetrazole-based peptidomimetics.
Scheme 49: Ugi/cyclization approach towards γ/δ/ε-lactam tetrazoles.
Scheme 50: Ugi-3CR to pipecolic acid-based peptidomimetics.
Scheme 51: Staudinger–Aza-Wittig/Ugi-approach towards pipecolic acid peptidomimetics.
Figure 1: The three structural isomers of diketopiperazines. The 2,5-DKP isomer is most common.
Scheme 52: UDC-approach to obtain 2,5-DKPs, either using Armstrong’s isocyanide or via ethylglyoxalate.
Scheme 53: a) Ugi reaction in water gave either 2,5-DKP structures or spiro compounds. b) The Ugi reaction in ...
Scheme 54: Solid-phase approach towards diketopiperazines.
Scheme 55: UDAC-approach towards DKPs.
Scheme 56: The intermediate amide is activated as leaving group by acid and microwave assisted organic synthes...
Scheme 57: UDC-procedure towards active oxytocin inhibitors.
Scheme 58: An improved stereoselective MCR-approach towards the oxytocin inhibitor.
Scheme 59: The less common Ugi reaction towards DKPs, involving a Sn2-substitution.
Figure 2: Spatial similarities between a natural β-turn conformation and a DKP based β-turn mimetic [158].
Scheme 60: Ugi-based syntheses of bicyclic DKPs. The amine component is derived from a coupling between (R)-N-...
Scheme 61: Ugi-based synthesis of β-turn and γ-turn mimetics.
Figure 3: Isocyanide substituted 3,4-dihydropyridin-2-ones, dihydropyridines and the Freidinger lactams. Bio-...
Scheme 62: The mechanism of the 4-CR towards 3,4-dihydropyridine-2-ones 212.
Scheme 63: a) Multiple MCR-approach to provide DHP-peptidomimetic in two-steps. b) A one-pot 6-CR providing th...
Scheme 64: The MCR–alkylation–MCR procedure to obtain either tetrapeptoids or depsipeptides.
Scheme 65: U-3CR/cyclization employing semicarbazone as imine component gave triazine based peptidomimetics.
Scheme 66: 4CR towards triazinane-diones.
Scheme 67: The MCR–alkylation–IMCR-sequence described by our group towards triazinane dione-based peptidomimet...
Scheme 68: Ugi-4CR approaches followed by a cyclization to thiomorpholin-ones (a) and pyrrolidines (b).
Scheme 69: UDC-approach for benzodiazepinones.
Scheme 70: Ugi/Mitsunobu sequence to BDPs.
Scheme 71: A UDAC-approach to BDPs with convertible isocyanides. The corresponding amide is cleaved by microwa...
Scheme 72: microwave assisted post condensation Ugi reaction.
Scheme 73: Benzodiazepinones synthesized via the post-condensation Ugi/ Staudinger–Aza-Wittig cyclization.
Scheme 74: Two Ugi/cyclization approaches utilizing chiral carboxylic acids. Reaction (a) provided the product...
Scheme 75: The mechanism of the Gewald-3CR includes three base-catalysed steps involving first a Knoevnagel–Co...
Scheme 76: Two structural 1,4-thienodiazepine-2,5-dione isomers by U-4CR/cyclization.
Scheme 77: Tetrazole-based diazepinones by UDC-procedure.
Scheme 78: Tetrazole-based BDPs via a sequential Ugi/hydrolysis/coupling.
Scheme 79: MCR synthesis of three different tricyclic BPDs.
Scheme 80: Two similar approaches both involving an Ugi reaction and a Mitsunobu cyclization.
Scheme 81: Mitsunobu–Ugi-approach towards dihydro-1,4-benzoxazepines.
Scheme 82: Ugi reaction towards hetero-aryl fused 5-oxo-1,4-oxazepines.
Scheme 83: a) Ugi/RCM-approach towards nine-membered peptidomimetics b) Sequential peptide-coupling, deprotect...
Scheme 84: Ugi-based synthesis towards cyclic RGD-pentapeptides.
Scheme 85: Ugi/MCR-approach towards 12–15 membered macrocycles.
Scheme 86: Stereoselective Ugi/RCM approach towards 16-membered macrocycles.
Scheme 87: Passerini/RCM-sequence to 22-membered macrocycles.
Scheme 88: UDAC-approach towards 12–18-membered depsipeptides.
Figure 4: Enopeptin A with its more active derivative ADEP-4.
Scheme 89: a) The Joullié–Ugi-approach towards ADEP-4 derivatives b) Ugi-approach for the α,α-dimethylated der...
Scheme 90: Ugi–Click-strategy for 15-membered macrocyclic glyco-peptidomimetics.
Scheme 91: Ugi/Click combinations provided macrocycles containing both a triazole and an oxazole moiety.
Scheme 92: a) A solution-phase procedure towards macrocycles. b) Alternative solid-phase synthesis as was repo...
Scheme 93: Ugi/cyclization towards cyclophane based macrocycles.
Scheme 94: PADAM-strategy towards eurystatin A.
Scheme 95: PADAM-approach for cyclotheanamide.
Scheme 96: A triple MCR-approach affording RGD-pentapeptoids.
Scheme 97: Ugi-MiBs-approach towards peptoid macrocycles.
Scheme 98: Passerini-based MiB approaches towards macrocycles 345 and 346.
Scheme 99: Macrocyclic peptide formation by the use of amphoteric aziridine-based aldehydes.
Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog
- Werner Telle,
- Gerhard Kelter,
- Heinz-Herbert Fiebig,
- Peter G. Jones and
- Thomas Lindel
Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29
- depsipeptide malevamide D (1, Figure 1) belongs to the dolastatin class of marine natural products and has been isolated from the cyanobacterium Symploca hydnoides by Scheuer and co-workers in 2002 (7.5 mg, 0.014% of the dry weight) [1]. Malevamide D (1) was reported to exhibit in vitro cytotoxicity in the
Graphical Abstract
Figure 1: Structures of the strongly cytotoxic marine natural products malevamide D (1), isodolastatin H (2),...
Scheme 1: Total synthesis of malevamide D (1). a) DMSO (16 equiv), NEt3 (5 equiv), pyridine·SO3 (5 equiv), 0 ...
Scheme 2: Formation of oxazolylphosphate 18 on attempted DEPC-mediated coupling of dipeptide 15.
Scheme 3: Synthesis of tosyloximes (Z)-22 and (E)-22, X-ray structure of (E)-22. a) NH2OH·HCl (1.5 equiv), py...
Scheme 4: Synthesis of photo malevamide D 30. a) NH3(l), t-BuOMe, −40 °C, 2 h, rt, 16 h, quant. b) I2 (1.2 eq...
Figure 2: DSC curve of diazirine 25, heating rate 5 °C/min.
The regulation and biosynthesis of antimycins
- Ryan F. Seipke and
- Matthew I. Hutchings
Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290
- machinery suggest it is possible to use synthetic biology to bioengineer non-natural analogues in large enough quantity to test their efficacies in the clinic. In line with that view, generating a chemistry-dereplicated culture collection of antimycin-type depsipeptide producers to build a library of
Graphical Abstract
Figure 1: Antimycins: Antimycins A1, A2, A3, and A4 and non-natural antimycins referenced in the text. Antimy...
Figure 2: Schematic representation of ant biosynthetic gene clusters. L-form ant gene clusters are encoded by...
Figure 3: Proposed biosynthetic pathway for antimycins. The antimycin biosynthetic pathway is described in de...
Figure 4: σAntA comprises a new subfamily of ECF RNA polymerase σ factors. σAntA amino acid sequences were al...
Total synthesis and biological evaluation of fluorinated cryptophycins
- Christine Weiß,
- Tobias Bogner,
- Benedikt Sammet and
- Norbert Sewald
Beilstein J. Org. Chem. 2012, 8, 2060–2066, doi:10.3762/bjoc.8.231
- highly active against KB-3-1 cells and exhibited an IC50 value in the low picomolar range. However, the replacement of the 3-chloro-4-methoxyphenyl-substituent in unit B by a pentafluorophenyl moiety resulted in a significant loss of activity. Keywords: antimitotic drug; cytotoxicity; depsipeptide
- , but did not interfere with the subsequent Yamaguchi esterification of 18 with the unit C–D segment 19 and was removed on this stage [33]. Fmoc cleavage of the seco-depsipeptide 20 liberated the free amino group of unit C, which under the reaction conditions displaced the trichloroethylester of unit B
Graphical Abstract
Figure 1: Structures of cryptophycin-1 (1) and -52 (2).
Figure 2: Fluorinated derivatives of cryptophycin-1 and -52 [20-22].
Scheme 1: Access to the trifluoromethyl substituted unit A-building block 16. Reagents and conditions: (a) SO...
Scheme 2: Assembly of units A–D and macrocyclization, followed by diol-epoxide transformation to give the tri...
Scheme 3: Synthesis of the pentafluorophenylalanine building block 26. Reagents and conditions: (a) pyridine,...
Scheme 4: Convergent synthesis of the pentafluorinated cryptophycin 31. Reagents and conditions: (a) Grubbs I...
A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues
- James R. Cochrane,
- Dong Hee Yoon,
- Christopher S. P. McErlean and
- Katrina A. Jolliffe
Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154
- James R. Cochrane Dong Hee Yoon Christopher S. P. McErlean Katrina A. Jolliffe School of Chemistry, The University of Sydney, 2006, NSW, Australia; Tel: +61-2-93512297; Fax: +61-2-93513329 10.3762/bjoc.8.154 Abstract The cyclic peptide core of the antifungal and antibiotic cyclic depsipeptide LI
- naturally occurring cyclic peptide may be required for the antifungal activity of this natural product. Keywords: antifungal; cyclic depsipeptide; epimerization; lipopeptide; macrolactonization; peptides; Introduction The LI-F or fusaricidin class of cyclic depsipeptides are produced by a number of
- depsipeptide 8, in which the C-terminal Ala residue had epimerized (Figure 1). Since the Yamaguchi conditions gave improved ratios of the desired/epimerized cyclic depsipeptides, subsequent optimization of the macrolactonization conditions focussed on this and related procedures (Table 1). The best yields of
Graphical Abstract
Scheme 1: Retrosynthetic strategy.
Scheme 2: Macrolactonization reactions of seco acids 5 and 6 (for reagents and yields see Table 1 and Table 2).
Figure 1: Analytical HPLC traces of linear peptides. (a) Compound 9 (retention time = 31.5 min); (b) Compound ...
Scheme 3: Synthesis of the dehydroxy side chain 12.
Scheme 4: Synthesis of LI-F04a (1) and analogues 20–23.
Figure 2: Structures and lowest-energy conformers of 24 (left) and 25 (right) obtained using Macromodel. Hydr...
Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum
- Friederike I. Nollmann,
- Andrea Dowling,
- Marcel Kaiser,
- Klaus Deckmann,
- Sabine Grösch,
- Richard ffrench-Constant and
- Helge B. Bode
Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60
- -60590 Frankfurt a. M., Germany 10.3762/bjoc.8.60 Abstract The synthesis of the recently characterized depsipeptide szentiamide (1), which is produced by the entomopathogenic bacterium Xenorhabdus szentirmaii, is described. Whereas no biological activity was previously identified for 1, the material
- derived from the efficient synthesis enabled additional bioactivity tests leading to the identification of a notable activity against insect cells and Plasmodium falciparum, the causative agent of malaria. Keywords: cyclic depsipeptide; esterification; natural product; szentiamide; Xenorhabdus
- been isolated, representing only the second depsipeptide (Figure 1) from these bacteria [12]. It is composed of six amino acids having a formylated N-terminus and raised our interest as it is produced by X. szentirmaii, whose crude extract shows a very high biological activity in several different
Graphical Abstract
Figure 1: Structure of depsipeptides szentiamide (1) [12] and xenematide (2) [8] identified in Xenorhabdus strains.
Scheme 1: Overview of the synthetic strategy.
Scheme 2: Synthesis of compound 1.
Figure 2: HPLC–MS data of an XAD-extract of X. szentirmaii (a; base-peak chromatogram), the natural 1 (b; ext...
Molecular recognition of organic ammonium ions in solution using synthetic receptors
- Andreas Späth and
- Burkhard König
Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32
Graphical Abstract
Figure 1: Biologically important amines and quaternary ammonium salts: histamine (1), dopamine (2) and acetyl...
Figure 2: Crown ether 18-crown-6.
Figure 3: Conformations of 18-crown-6 (4) in solvents of different polarity.
Figure 4: Binding topologies of the ammonium ion depending on the crown ring size.
Figure 5: A “pseudorotaxane” structure consisting of 24-crown-8 and a secondary ammonium ion (5); R = Ph.
Figure 6: Typical examples of azacrown ethers, cryptands and related aza macrocycles.
Figure 7: Binding of ammonium to azacrown ethers and cryptands [111-113].
Figure 8: A 19-crown-6-ether with decalino blocking groups (11) and a thiazole-dibenzo-18-crown-6-ether (12).
Figure 9: 1,3-Bis(6-oxopyridazin-1-yl)propane derivatives 13 and 14 by Campayo et al.
Figure 10: Fluorescent azacrown-PET-sensors based on coumarin.
Figure 11: Two different pyridino-cryptands (17 and 18) compared to a pyridino-crown (19); chiral ammonium ion...
Figure 12: Pyridino-18-crown-6 ligand (21), a similar acridino-18-crown-6 ligand (22) and a structurally relat...
Figure 13: Ciral pyridine-azacrown ether receptors 24.
Figure 14: Chiral 15-crown-5 receptors 26 and an analogue 18-crown-6 ligand 27 derived from amino alcohols.
Figure 15: C2-symmetric chiral 18-crown-6 amino alcohol derivatives 28 and related macrocycles.
Figure 16: Macrocycles with diamide-diester groups (30).
Figure 17: C2-symmetric chiral aza-18-crown-6 ethers (31) with phenethylamine residues.
Figure 18: Chiral C-pivot p-methoxy-phenoxy-lariat ethers.
Figure 19: Chiral lariat crown ether 34.
Figure 20: Sucrose-based chiral crown ether receptors 36.
Figure 21: Permethylated fructooligosaccharide 37 showing induced-fit chiral recognition.
Figure 22: Biphenanthryl-18-crown-6 derivative 38.
Figure 23: Chiral lariat crown ethers derived from binol by Fuji et al.
Figure 24: Chiral phenolic crown ether 41 with “aryl chiral barriers” and guest amines.
Figure 25: Chiral bis-crown receptor 43 with a meso-ternaphthalene backbone.
Figure 26: Chromogenic pH-dependent bis-crown chemosensor 44 for diamines.
Figure 27: Triamine guests for binding to receptor 44.
Figure 28: Chiral bis-crown phenolphthalein chemosensors 46.
Figure 29: Crown ether amino acid 47.
Figure 30: Luminescent receptor 48 for bis-alkylammonium guests.
Figure 31: Luminescent CEAA (49a), a bis-CEAA receptor for amino acids (49b) and the structure of lysine bindi...
Figure 32: Luminescent CEAA tripeptide for binding small peptides.
Figure 33: Bis crown ether 51a self assembles co-operatively with C60-ammonium ion 51b.
Figure 34: Triptycene-based macrotricyclic dibenzo-[24]-crown-8 ether host 52 and guests.
Figure 35: Copper imido diacetic acid azacrown receptor 53a and the suggested His-Lys binding motif; a copper ...
Figure 36: Urea (54) and thiourea (55) benzo crown receptor for transport and extraction of amino acids.
Figure 37: Crown pyryliums ion receptors 56 for amino acids.
Figure 38: Ditopic sulfonamide bridged crown ether receptor 57.
Figure 39: Luminescent peptide receptor 58.
Figure 40: Luminescent receptor 59 for the detection of D-glucosamine hydrochloride in water/ethanol and lumin...
Figure 41: Guanidinium azacrown receptor 61 for simple amino acids and ditopic receptor 62 with crown ether an...
Figure 42: Chiral bicyclic guanidinium azacrown receptor 63 and similar receptor 64 for the enantioselective t...
Figure 43: Receptors for zwitterionic species based on luminescent CEAAs.
Figure 44: 1,10-Azacrown ethers with sugar podand arms and the anticancer agent busulfan.
Figure 45: Benzo-18-crown-6 modified β-cyclodextrin 69 and β-cyclodextrin functionalized with diaza-18-crown-6...
Figure 46: Receptors for colorimetric detection of primary and secondary ammonium ions.
Figure 47: Porphyrine-crown-receptors 72.
Figure 48: Porphyrin-crown ether conjugate 73 and fullerene-ammonium ion guest 74.
Figure 49: Calix[4]arene (75a), homooxocalix[4]arene (75b) and resorcin[4]arene (75c) compared (R = H, alkyl c...
Figure 50: Calix[4]arene and ammonium ion guest (R = H, alkyl, OAcyl etc.), possible binding sites; A: co-ordi...
Figure 51: Typical guests for studies with calixarenes and related molecules.
Figure 52: Lower rim modified p-tert-butylcalix[5]arenes 82.
Figure 53: The first example of a water soluble calixarene.
Figure 54: Sulfonated water soluble calix[n]arenes that bind ammonium ions.
Figure 55: Displacement assay for acetylcholine (3) with a sulfonato-calix[6]arene (84b).
Figure 56: Amino acid inclusion in p-sulfonatocalix[4]arene (84a).
Figure 57: Calixarene receptor family 86 with upper and lower rim functionalization.
Figure 58: Calix[6]arenes 87 with one carboxylic acid functionality.
Figure 59: Sulfonated calix[n]arenes with mono-substitution at the lower rim systematically studied on their r...
Figure 60: Cyclotetrachromotropylene host (91) and its binding to lysine (81c).
Figure 61: Calixarenes 92 and 93 with phosphonic acids groups.
Figure 62: Calix[4]arene tetraphosphonic acid (94a) and a double bridged analogue (94b).
Figure 63: Calix[4]arene tetraphosphonic acid ester (92c) for surface recognition experiments.
Figure 64: Calixarene receptors 95 with α-aminophosphonate groups.
Figure 65: A bridged homocalix[3]arene 95 and a distally bridged homocalix[4]crown 96.
Figure 66: Homocalix[3]arene ammonium ion receptor 97a and the Reichardt’s dye (97b) for colorimetric assays.
Figure 67: Chromogenic diazo-bridged calix[4]arene 98.
Figure 68: Calixarene receptor 99 by Huang et al.
Figure 69: Calixarenes 100 reported by Parisi et al.
Figure 70: Guest molecules for inclusion in calixarenes 100: DAP × 2 HCl (101a), APA (101b) and Lys-OMe × 2 HC...
Figure 71: Different N-linked peptido-calixarenes open and with glycol chain bridges.
Figure 72: (S)-1,1′-Bi-2-naphthol calixarene derivative 104 published by Kubo et al.
Figure 73: A chiral ammonium-ion receptor 105 based on the calix[4]arene skeleton.
Figure 74: R-/S-phenylalaninol functionalized calix[6]arenes 106a and 106b.
Figure 75: Capped homocalix[3]arene ammonium ion receptor 107.
Figure 76: Two C3 symmetric capped calix[6]arenes 108 and 109.
Figure 77: Phosphorous-containing rigidified calix[6]arene 110.
Figure 78: Calix[6]azacryptand 111.
Figure 79: Further substituted calix[6]azacryptands 112.
Figure 80: Resorcin[4]arene (75c) and the cavitands (113).
Figure 81: Tetrasulfonatomethylcalix[4]resorcinarene (114).
Figure 82: Resorcin[4]arenes (115a/b) and pyrogallo[4]arenes (115c, 116).
Figure 83: Displacement assay for acetylcholine (3) with tetracyanoresorcin[4]arene (117).
Figure 84: Tetramethoxy resorcinarene mono-crown-5 (118).
Figure 85: Components of a resorcinarene based displacement assay for ammonium ions.
Figure 86: Chiral basket resorcin[4]arenas 121.
Figure 87: Resorcinarenes with deeper cavitand structure (122).
Figure 88: Resorcinarene with partially open deeper cavitand structure (123).
Figure 89: Water-stabilized deep cavitands with partially structure (124, 125).
Figure 90: Charged cavitands 126 for tetralkylammonium ions.
Figure 91: Ditopic calix[4]arene receptor 127 capped with glycol chains.
Figure 92: A calix[5]arene dimer for diammonium salt recognition.
Figure 93: Calixarene parts 92c and 129 for the formation molecular capsules.
Figure 94: Encapsulation of a quaternary ammonium cation by two resorcin[4]arene molecules (NMe4+@[75c]2 × Cl−...
Figure 95: Encapsulation of a quaternary ammonium cation by six resorcin[4]arene molecules (NMe3D+@[130]6 × Cl−...
Figure 96: Structure and schematic of cucurbit[6]uril (CB[6], 131a).
Figure 97: Cyclohexanocucurbit[6]uril (CB′[6], 132) and the guest molecule spermine (133).
Figure 98: α,α,δ,δ-Tetramethylcucurbit[6]uril (134).
Figure 99: Structure of the cucurbituril-phthalhydrazide analogue 135.
Figure 100: Organic cavities for the displacement assay for amine differentiation.
Figure 101: Displacement assay methodology for diammonium- and related guests involving cucurbiturils and some ...
Figure 102: Nor-seco-Cucurbituril (±)-bis-ns-CB[6] (140) and guest molecules.
Figure 103: The cucurbit[6]uril based complexes 141 for chiral discrimination.
Figure 104: Cucurbit[7]uril (131c) and its ferrocene guests (142) opposed.
Figure 105: Cucurbit[7]uril (131c) guest inclusion and representative guests.
Figure 106: Cucurbit[7]uril (131c) binding to succinylcholine (145) and different bis-ammonium and bis-phosphon...
Figure 107: Paraquat-cucurbit[8]uril complex 149.
Figure 108: Gluconuril-based ammonium receptors 150.
Figure 109: Examples of clefts (151a), tweezers (151b, 151c, 151d) and clips (151e).
Figure 110: Kemp’s triacid (152a), on example of Rebek’s receptors (152b) and guests.
Figure 111: Amino acid receptor (154) by Rebek et al.
Figure 112: Hexagonal lattice designed hosts by Bell et al.
Figure 113: Bell’s amidinium receptor (156) and the amidinium ion (157).
Figure 114: Aromatic phosphonic acids.
Figure 115: Xylene phosphonates 159 and 160a/b for recognition of amines and amino alcohols.
Figure 116: Bisphosphonate recognition motif 161 for a colorimetric assay with alizarin complexone (163) for ca...
Figure 117: Bisphosphonate/phosphate clip 164 and bisphosphonate cleft 165.
Figure 118: N-Methylpyrazine 166a, N-methylnicotinamide iodide (166b) and NAD+ (166c).
Figure 119: Bisphosphate cavitands.
Figure 120: Bisphosphonate 167 of Schrader and Finocchiaro.
Figure 121: Tweezer 168 for noradrenaline (80b).
Figure 122: Different tripods and heparin (170).
Figure 123: Squaramide based receptors 172.
Figure 124: Cage like NH4+ receptor 173 of Kim et al.
Figure 125: Ammonium receptors 174 of Chin et al.
Figure 126: 2-Oxazolin-based ammonium receptors 175a–d and 176 by Ahn et al.
Figure 127: Racemic guest molecules 177.
Figure 128: Tripods based on a imidazole containing macrocycle (178) and the guest molecules employed in the st...
Figure 129: Ammonium ion receptor 180.
Figure 130: Tetraoxa[3.3.3.3]paracyclophanes 181 and a cyclophanic tetraester (182).
Figure 131: Peptidic bridged paraquat-cyclophane.
Figure 132: Shape-selective noradrenaline host.
Figure 133: Receptor 185 for binding of noradrenaline on surface layers from Schrader et al.
Figure 134: Tetraphosphonate receptor for binding of noradrenaline.
Figure 135: Tetraphosphonate 187 of Schrader and Finocchiaro.
Figure 136: Zinc-Porphyrin ammonium-ion receptors 188 and 189 of Mizutani et al.
Figure 137: Zinc porphyrin receptor 190.
Figure 138: Zinc porphyrin receptors 191 capable of amino acid binding.
Figure 139: Zinc-porphyrins with amino acid side chains for stereoinduction.
Figure 140: Bis-zinc-bis-porphyrin based on Tröger’s base 193.
Figure 141: BINAP-zinc-prophyrin derivative 194 and it’s guests.
Figure 142: Bisaryl-linked-zinc-porphyrin receptors.
Figure 143: Bis-zinc-porphyrin 199 for diamine recognition and guests.
Figure 144: Bis-zinc-porphyrin crown ether 201.
Figure 145: Bis-zinc-porphyrin 202 for stereodiscrimination (L = large substituent; S = small substituent).
Figure 146: Bis-zinc-porphyrin[3]rotaxane and its copper complex and guests.
Figure 147: Dien-bipyridyl ligand 206 for co-ordination of two metal atoms.
Figure 148: The ligand and corresponding tetradentate co-complex 207 serving as enantioselective receptor for a...
Figure 149: Bis(oxazoline)–copper(II) complex 208 for the recognition of amino acids in aqueous solution.
Figure 150: Zinc-salen-complexes 209 for the recognition tertiary amines.
Figure 151: Bis(oxazoline)–copper(II) 211 for the recognition of amino acids in aqueous solution.
Figure 152: Zn(II)-complex of a C2 terpyridine crown ether.
Figure 153: Displacement assay and receptor for aspartate over glutamate.
Figure 154: Chiral complex 214 for a colorimetric displacement assay for amino acids.
Figure 155: Metal complex receptor 215 with tripeptide side arms.
Figure 156: A sandwich complex 216 and its displaceable dye 217.
Figure 157: Lanthanide complexes 218–220 for amino acid recognition.
Figure 158: Nonactin (221), valinomycin (222) and vancomycin (223).
Figure 159: Monesin (224a) and a chiral analogue for enantiodiscrimination of ammonium guests (224b).
Figure 160: Chiral podands (226) compared to pentaglyme-dimethylether (225) and 18-crown-6 (4).
Figure 161: Lasalocid A (228).
Figure 162: Lasalocid derivatives (230) of Sessler et al.
Figure 163: The Coporphyrin I tetraanion (231).
Figure 164: Linear and cyclic peptides for ammonium ion recognition.
Figure 165: Cyclic and bicyclic depsipeptides for ammonium ion recognition.
Figure 166: α-Cyclodextrin (136a) and novocaine (236).
Figure 167: Helical diol receptor 237 by Reetz and Sostmann.
Figure 168: Ammonium binding spherand by Cram et al. (238a) and the cyclic[6]metaphenylacetylene 238b in compar...
Figure 169: Receptor for peptide backbone and ammonium binding (239).
Figure 170: Anion sensor principle with 3-hydroxy-2-naphthanilide of Jiang et al.
Figure 171: 7-bromo-3-hydroxy-N-(2-hydroxyphenyl)naphthalene 2-carboxamide (241) and its amine binding.
Figure 172: Naturally occurring catechins with affinity to quaternary ammonium ions.
Figure 173: Spiropyran (244) and merocyanine form (244a) of the amino acid receptors of Fuji et al.
Figure 174: Coumarin aldehyde (245) and its iminium species with amino acid bound (245a) by Glass et al.
Figure 175: Coumarin aldehyde appended with boronic acid.
Figure 176: Quinolone aldehyde dimers by Glass et al.
Figure 177: Chromogenic ammonium ion receptors with trifluoroacetophenone recognition motifs.
Figure 178: Chromogenic ammonium ion receptor with trifluoroacetophenone recognition motif bound on different m...
2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β2-amino acids
- Markus Nahrwold,
- Arvydas Stončius,
- Anna Penner,
- Beate Neumann,
- Hans-Georg Stammler and
- Norbert Sewald
Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43
- ]. Examples are cryptophycin-1 (a highly cytotoxic depsipeptide produced by cyanobacteria Nostoc sp. GSV224 and ATCC53789) [11][12][13][14] as well as a class of lipopeptides isolated from various fungi, comprising topostatin (a topoisomerase I and II inhibitor) [15], YM-170320 (an inhibitor of ergosterol
Graphical Abstract
Scheme 1: Selectively cleavable β2-amino acid precursors: Structures and reactivities of 2-tert-butyl-tetrahy...
Scheme 2: Cyclocondensation of Cbz-βAla-NH2 (3) and benzaldehyde. a) [p-TsOH], toluene, reflux, Dean–Stark tr...
Scheme 3: Protection and deprotection of 4. a) Boc2O, DMAP, CH3CN, 16 h, rt; b) 1. n-BuLi, THF, −78 °C, 30 mi...
Scheme 4: Synthesis of enantiopure 2-phenyl-tetrahydropyrimidine-4(1H)-ones. a) PhCH(OMe)2, BF3·Et2O (6.0 equ...
Figure 1: X-ray crystal structure of 10 [44].
Scheme 5: Diastereoselective alkylation of 5.
Figure 2: Comparison of coupling constants (C5–C6-ABX system) within the 1H-NMR spectra of literature known c...
Figure 3: Supposed enolate conformations.
Scheme 6: Selective ring opening of the heterocycle 11d and isolation of orthogonally protected β2-homoaspart...
