- Zelkovamycins B-E, Cyclic Octapeptides Containing Rare Amino Acid Residues from an Endophytic Kitasatospora sp
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Four unusual cyclopeptides, zelkovamycins B-E (1-4), were isolated from an endophytic Kitasatospora sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxypyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey's method, and NMR calculations. A plausible biosynthetic pathway for zelkovamycins was proposed based on gene cluster analysis. Zelkovamycin E displayed potent inhibitory activity against H1N1 influenza A virus.
- Cen, Shan,Connolly, Jack A.,Gan, Maoluo,Goss, Rebecca J. M.,Hao, Xiaomeng,Liu, Yufeng,Wang, Yujia,Yu, Jiaqing,Yu, Liyan,Zhang, Yuqin
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p. 9346 - 9350
(2020/12/21)
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- One-Pot Biocatalytic Synthesis of Substituted d -Tryptophans from Indoles Enabled by an Engineered Aminotransferase
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d-Tryptophan and its derivatives are important precursors of a wide range of indole-containing pharmaceuticals and natural products. Here, we developed a one-pot biocatalytic process enabling the synthesis of d-tryptophans from indoles in good yields and high enantiomeric excess (91% to >99%). Our method couples the synthesis of l-tryptophans catalyzed by Salmonella enterica tryptophan synthase with a stereoinversion cascade mediated by Proteus myxofaciens l-amino acid deaminase and an aminotransferase variant that we engineered to display native-like activity toward d-tryptophan. Our process is applicable to preparative-scale synthesis of a broad range of d-tryptophan derivatives containing electron-donating or -withdrawing substituents at all benzene-ring positions on the indole group.
- Parmeggiani, Fabio,Rué Casamajo, Arnau,Walton, Curtis J. W.,Galman, James L.,Turner, Nicholas J.,Chica, Roberto A.
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p. 3482 - 3486
(2019/04/13)
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- De novo Biosynthesis of “Non-Natural” Thaxtomin Phytotoxins
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Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from S. scabies, along with genes encoding a promiscuous tryptophan synthase (TrpS) from Salmonella typhimurium, were assembled in a heterologous host Streptomyces albus. Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to “non-natural” product target compounds.
- Winn, Michael,Francis, Daniel,Micklefield, Jason
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supporting information
p. 6830 - 6833
(2018/06/04)
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- Synthesis method of non-natural tryptophan derivative
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The invention relates to the field of organic synthesis, and discloses a method for synthesizing a non-natural tryptophan derivative. A derivative of indol-3-formaldehyde is adopted as a raw material. The method comprises the steps that 1, the derivative of indol-3-formaldehyde and ethyl azidoacetate are dissolved into an organic solvent, a mixed solution of sodium alkoxide and alcohol is dropwise added under protection of nitrogen or inert gas, reacting is conducted for 4 hours to 8 hours, and after reacting is completed, a coarse product-a second compound is obtained; 2, the second compound and Boc anhydride generate a hydrogenation reaction through a palladium-carbon catalyst, filtering is conducted to obtain filtrate after reacting is completed, and concentration and recrystallization are conducted to obtain a third compound; 3, the third compound is dissolved into an organic solvent, hydrogen chloride gas is introduced till no solid is separated out, filtering is conducted to obtain solids, and a fourth compound is obtained; 4, the fourth compound is dissolved into a mixed solvent of tetrahydrofuran and water, lithium hydroxide is added, the pH is regulated to be 5.8-6.0 after reacting is completed, and filtering is conducted to obtain solids. According to the method, the raw materials are easy to obtain, the reaction conditions are mild, the yield is high, production is easy to enlarge, and the cost is reduced.
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Paragraph 0030; 0032; 0042-0044
(2017/08/27)
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- Multisite prenylation of 4-substituted tryptophans by dimethylallyltryptophan synthase
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The aromatic prenyltransferase dimethylallyltryptophan synthase in Claviceps purpurea catalyzes the normal prenylation of tryptophan at C4 of the indole nucleus in the first committed step of ergot alkaloid biosynthesis. 4-Methyltryptophan is a competitive inhibitor of the enzyme that has been used in kinetic studies. Upon investigation of background activity during incubations of 4-methyltryptophan with dimethylallyl diphosphate, we found that the analogue was an alternate substrate, which gave four products. The structures of three of these compounds were established by 1H NMR and 2D NMR studies and revealed that dimethylallyltryptophan synthase catalyzed both normal and reverse prenylation at C3 of the indole ring and normal prenylation of N1. Similarly, 4-methoxytryptophan was an alternate substrate, giving normal prenylation at C5 as the major product. 4-Aminotryptophan, another alternate substrate, gave normal prenylation at C5 and C7. The ability of dimethylallyltryptophan synthase to prenylate at five different sites on the indole nucleus, with normal and reverse prenylation at one of the sites, is consistent with a dissociative electrophilic alkylation of the indole ring, where orientation of the substrates within the active site and substituent electronic effects determine the position and type of prenylation. These results suggest a common mechanism for prenylation of tryptophan by all of the members of the structurally related dimethylallyltryptophan synthase family.
- Rudolf, Jeffrey D.,Wang, Hong,Poulter, C. Dale
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p. 1895 - 1902
(2013/04/23)
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- IMPROVED METHOD FOR PRODUCING INTERMEDIATES FOR THE PRODUCTION OF MACROCYCLES THAT ARE INHIBITORS OF THE PROTEASOMIC DEGRADATION OF P27, SUCH AS ARGYRIN AND DERIVATIVES THEREOF
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The present invention relates to an improved method for the synthesis of particular macrocycles that are inhibitors of the proteasomic degradation of p27, in particular argyrin and derivatives thereof.
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Page/Page column 11-12
(2011/07/07)
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- General approach to the total synthesis of 9-methoxy-substituted indole alkaloids: Synthesis of mitragynine, as well as 9-methoxygeissoschizol and 9-methoxy-Nb-methylgeissoschizol
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(Chemical Equation Presented) Herein, the full details of the synthesis of the 9-methoxy-substituted Corynanthe indole alkaloids mitragynine (1), 9-methoxygeissoschizol (3), and 9-methoxy-Nb-methylgeissoschizol (4) are described. Initially, an efficient synthetic route to the optically active 4-methoxytryptophan ethyl ester 20 on a multigram scale was developed via a Mori-Ban-Hegedus indole synthesis. The ethyl ester of D-4-methoxytryptophan 20 was obtained with a radical-mediated regioselective bromination of indoline 12 serving as a key step. Alternatively, the key 4-methoxytryptophan intermediate 22 could be synthesized by the Larock heteroannulation of aryl iodide 10b with the internal alkyne 21a. The use of the Boc-protected aniline 10b was crucial to the success of this heteroannulation. The α,β-unsaturated ester 6 was synthesized via the Pictet-Spengler reaction as the pivotal step. This was followed by a Ni(COD)2-mediated cyclization to set up the stereocenter at C-15. The benzyloxy group in 31 was removed to provide the intermediate ester 5. This chiral tetracyclic ester 5 was employed to accomplish the first total synthesis of 9-methoxygeissoschizol (3) and 9-methoxy-N b-methylgeissoschizol (4) as well as the opioid agonistic indole alkaloid mitragynine (1).
- Ma, Jun,Yin, Wenyuan,Zhou, Hao,Liao, Xuebin,Cook, James M.
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supporting information; experimental part
p. 264 - 273
(2009/04/10)
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- Method for producing intermediates for the production of novel macrocycles that are inhibitors of the proteasomic degradation of p27, such as argyrin and derivatives thereof, and uses of said macrocycles
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The present invention relates to the use of particular macrocycles that are inhibitors of the proteasomic degradation of p27, in particular argyrin and derivatives thereof, for a treatment in a variety of conditions, such as the induction of immunotolerance, autoimmune diseases, bacterial infections, and proliferative diseases, such as cancers.
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- Total synthesis of the cyclic peptide Argyrin B
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The details of the total synthesis of Argyrin B, a natural product with immunosuppressive properties, are reported below. The two most unusual amino acid residues of this cyclic peptide are 4-methoxytryptophan and dehydroalanine, which were obtained by mo
- Ley, Steven V.,Priour, Alain
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p. 3995 - 4004
(2007/10/03)
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- Total synthesis of the cyclic heptapeptide Argyrin B: A new potent inhibitor of T-cell independent antibody formation
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(equation presented) Argyrin B (1) The total synthesis of Argyrin B (1) is presented using a synthetic plan that is convergent and flexible and conserves the stereogenic centers. The unusual amino acid 4-methoxy tryptophan (6) was obtained via an enzymati
- Ley, Steven V.,Prieur, Alain,Heusser, Christoph
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p. 711 - 714
(2007/10/03)
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