- Beyond the Diketopiperazine Family with Alternatively Bridged Brevianamide F Analogues
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A method for the preparation of 3,5-bridged piperazin-2-ones from a tryptophan-proline-based diketopiperazine is described using diphosgene to induce the ring closure. Density functional theory calculations were conducted to study the mechanism of this C-C bond formation. Several derivatives of the thus obtained α-chloroamine were synthesized by substitution of the chlorine atom using a range of O-, N-, S-, and C-nucleophiles. This novel class of brevianamide F analogues possess interesting breast cancer resistance protein inhibitory activity.
- Wauters,Goossens,Delbeke,Muylaert,Roman,Van Hecke,Van Speybroeck,Stevens
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p. 8046 - 8054
(2015/09/02)
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- Synergism between genome sequencing, tandem mass spectrometry and bio-inspired synthesis reveals insights into nocardioazine B biogenesis
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Marine actinomycete-derived natural products continue to inspire chemical and biological investigations. Nocardioazines A and B (3 and 4), from Nocardiopsis sp. CMB-M0232, are structurally unique alkaloids featuring a 2,5-diketopiperazine (DKP) core functionalized with indole C3-prenyl as well as indole C3- and N-methyl groups. The logic of their assembly remains cryptic. Bioinformatics analyses of the Nocardiopsis sp. CMB-M0232 draft genome afforded the noz cluster, split across two regions of the genome, and encoding putative open reading frames with roles in nocardioazine biosynthesis, including cyclodipeptide synthase (CDPS), prenyltransferase, methyltransferase, and cytochrome P450 homologs. Heterologous expression of a twelve gene contig from the noz cluster in Streptomyces coelicolor resulted in accumulation of cyclo-l-Trp-l-Trp DKP (5). This experimentally connected the noz cluster to indole alkaloid natural product biosynthesis. Results from bioinformatics analyses of the noz pathway along with challenges in actinomycete genetics prompted us to use asymmetric synthesis and mass spectrometry to determine biosynthetic intermediates in the noz pathway. The structures of hypothesized biosynthetic intermediates 5 and 12-17 were firmly established through chemical synthesis. LC-MS and MS-MS comparison of these synthetic compounds with metabolites present in chemical extracts from Nocardiopsis sp. CMB-M0232 revealed which of these hypothesized intermediates were relevant in the nocardioazine biosynthetic pathway. This established the early and mid-stages of the biosynthetic pathway, demonstrating that Nocardiopsis performs indole C3-methylation prior to indole C3-normal prenylation and indole N1′-methylation in nocardioazine B assembly. These results highlight the utility of merging bioinformatics analyses, asymmetric synthetic approaches, and mass spectrometric metabolite profiling in probing natural product biosynthesis.
- Alqahtani, Norah,Porwal, Suheel K.,James, Elle D.,Bis, Dana M.,Karty, Jonathan A.,Lane, Amy L.,Viswanathan, Rajesh
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supporting information
p. 7177 - 7192
(2015/07/01)
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- A concise preparation of the non-proteinogenic amino acid l-kynurenine
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A concise and practical preparation of the non-proteinogenic amino acid l-kynurenine is reported. The synthetic approach is scalable and provides ready access to this valuable amino acid in either l- or d-stereochemistry starting from l- or d-tryptophan, respectively. In the optimized procedure, two discreet oxidation steps are applied sequentially to convert the tryptophan indole ring into the keto-aniline moiety contained within the kynurenine side chain.
- Kleijn, Laurens H.J.,Müskens, Frederike M.,Oppedijk, Sabine F.,De Bruin, Gerjan,Martin, Nathaniel I.
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supporting information
p. 6430 - 6432
(2013/01/15)
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- A concise total synthesis of (+)-okaramine C
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The first total synthesis of (+)-okaramine C is described. Our previously described selenocyclisation-oxidative deselenation sequence was used to establish a 3a-hydroxy-pyrrolo[2,3-b]-indole core, which was modified by selective epimerisation to the commo
- Hewitt, Peter R.,Cleator, Ed,Ley, Steven V.
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p. 2415 - 2417
(2007/10/03)
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- Cyclodextrin-mediated deacylation of amino acid esters with marked stereoselectivity.
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With respect to the hydrolysis (deacylation) of Z-D(L)-amino acid esters (N-(benzyloxycarbonyl)-D(L)-amino acid p-nitrophenyl esters) mediated by alpha-, beta- and gamma-cyclodextrins (CyDs), a remarkably high enantioselectivity (L/D=9.0) was observed for the deacylation of Ala substrate with gamma-CyD. The kinetic results on the basis of the Michaelis-Menten principle indicate that the enantioselectivity should be mainly originated in the deacylation process of substrates following the formation of gamma-CyD-substrate (1 : 1) complexes. The computer modeling (molecular mechanics) studies on the inclusion complexes are also described.
- Goto, Koichi,Nakashima, Kentaro,Tanoue, Osamu,Nukushina, Satoshi,Toudo, Isao,Imamura, Chikara,Ihara, Yasuji,Matsumoto, Yoko,Ueoka, Ryuichi
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p. 1283 - 1285
(2007/10/03)
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- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
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A variety of racemic carboxylic acids have been for the first time directly resolved by normal-phase, high-performance liquid chromatography using a hexane-2-propanol eluting system containing a small amount (ca. 1percent) of a strong carboxylic acid, like formic acid, trichloroacetic acid, and trifluoroacetic acid.
- Okamoto, Yoshio,Aburatani, Ryo,Kaida, Yuriko,Hatada, Koichi
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p. 1125 - 1128
(2007/10/02)
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- PAPAIN-ASSISTED RESOLUTION OF NATURAL AND XENOBIOTIC α-AMINO ACIDS
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A new and convenient method for the preparation of pure enantiomers of α-amino acids is described.Industrial papain, catalyzes the synthesis of L-Z-amino acid ethyl esters in ethanolic medium, with good yields.These esters are obtained from DL-Z-amino acids with 100percent optical purity.Unreactive D-Z-amino acids are readily isolated from reaction medium.Physical constants of natural and xenobiotic L-Z-amino acid esters and D-Z-amino acids are described.
- Moriniere, J. L.,Danree, B.,Lemoine, J.,Guy, A.
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p. 441 - 444
(2007/10/02)
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- Origins of Micellar Diastereoselectivity
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Thiol-functionalized surfactant micelles (n-C12H25N+Me2CH2CH2SH,Cl-) were used to cleave Z-Trp-Pro p-nitrophenyl dipeptide esters.Marked kinetic diastereoselectivity was observed in these reactions.For example at pH 8 and concentrations (ca.6-7)x1E-3 M, the micellar thiol cleaved the LL substrate 5-6 times more rapidly than its DL diastereomer.This kinetic diastereoselectivity was shown to develop at surfactant concentrations ca.5x1E-3 M, considerably above the cmc (ca.1x1E-3 M), i.e., at a second "critical concentration".Dynamic light-scattering measurements showed that micelles which had reacted with the LL (but not the DL) substrate underwent a marked increase in apparent hydrodynamic diameter (from ca. 15 to 26 nm) near this second critical concentration.Similar phenomena could be induced upon addition of 2x1E-5 M LL dipeptide surfactant reaction product to the thiol micelles.Micelles of n-C12H25N+Me2CH2CH2OH,Cl- or n-C12H25N+Me3,Cl- were unresponsive to such additions (light scattering).The results are discussed in terms of molecular and supramolecular interactions between surfactant and solubilizate molecules.
- Moss, Robert A.,Chiang, Yuan-Ching P.,Hui, Yongzheng
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p. 7506 - 7513
(2007/10/02)
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- 3-ACYL- AND 3-ALKOXYCARBONYL-2-OXAZOLONES AND THEIR HOMOPOLYMERS AS AMINO-PROTECTING REAGENTS
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3-Acyl and 3-alkoxycarbonyl-2-oxazolones as well as their homopolymers serve as practically usefull N-protecting reagents of amines including α-amino acids.
- Kunieda, Takehisa,Higuchi, Tsunehiko,Abe, Yoshihiro,Hirobe, Masaaki
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p. 3065 - 3066
(2007/10/02)
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