Tryprostatin B
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| Category | Bioactive by-products |
| Catalog number | BBF-02724 |
| CAS | 179936-52-8 |
| Molecular Weight | 351.44 |
| Molecular Formula | C21H25N3O2 |
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Description
Tryprostatin B is a natural compound isolated from Aspergillus fumigatus and arrests cell cycle progression at the G2/M phase.
Specification
| Synonyms | triprostatin B; (-)-Tryprostatin B; (3S,8aS)-3-{[2-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyl}hexahydropyrrolo[1,2-a]pyrazine-1,4-dione |
| IUPAC Name | (3S,8aS)-3-[[2-(3-methylbut-2-enyl)-1H-indol-3-yl]methyl]-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione |
| Canonical SMILES | CC(=CCC1=C(C2=CC=CC=C2N1)CC3C(=O)N4CCCC4C(=O)N3)C |
| InChI | InChI=1S/C21H25N3O2/c1-13(2)9-10-17-15(14-6-3-4-7-16(14)22-17)12-18-21(26)24-11-5-8-19(24)20(25)23-18/h3-4,6-7,9,18-19,22H,5,8,10-12H2,1-2H3,(H,23,25)/t18-,19-/m0/s1 |
| InChI Key | GLWYBXPXOSKQAW-OALUTQOASA-N |
Properties
| Appearance | Pale Yellow Crystalline Solid |
| Melting Point | 102-105°C |
Reference Reading
1. Indole C6 Functionalization of Tryprostatin B Using Prenyltransferase CdpNPT
Eric D Gardner, Dustin A Dimas, Matthew C Finneran, Sara M Brown, Anthony W Burgett, Shanteri Singh Catalysts. 2020 Nov;10(11):1247. doi: 10.3390/catal10111247. Epub 2020 Oct 28.
Tryprostatin A and B are prenylated, tryptophan-containing, diketopiperazine natural products, displaying cytotoxic activity through different mechanisms of action. The presence of the 6-methoxy substituent on the indole moiety of tryprostatin A was shown to be essential for the dual inhibition of topoisomerase II and tubulin polymerization. However, the inability to perform late-stage modification of the indole ring has limited the structure-activity relationship studies of this class of natural products. Herein, we describe an efficient chemoenzymatic approach for the late-stage modification of tryprostatin B using a cyclic dipeptide N-prenyltransferase (CdpNPT) from Aspergillus fumigatus, which generates novel analogs functionalized with allylic, benzylic, heterocyclic, and diene moieties. Notably, this biocatalytic functionalizational study revealed high selectivity for the indole C6 position. Seven of the 11 structurally characterized analogs were exclusively C6-alkylated, and the remaining four contained predominant C6-regioisomers. Of the 24 accepted substrates, 10 provided >50% conversion and eight provided 20-50% conversion, with the remaining six giving <20% conversion under standard conditions. This study demonstrates that prenyltransferase-based late-stage diversification enables direct access to previously inaccessible natural product analogs.
2. Total Synthesis of Tryprostatin B: Synthesis and Asymmetric Phase-Transfer-Catalyzed Reaction of Prenylated Gramine Salt
Matthew Huisman, Mizzanoor Rahaman, Sharif Asad, Sarah Oehm, Sherwin Novin, Arnold L Rheingold, M Mahmun Hossain Org Lett. 2019 Jan 4;21(1):134-137. doi: 10.1021/acs.orglett.8b03593. Epub 2018 Dec 18.
A concise and efficient total synthesis of microtubule inhibitor tryprostatin B (1) is described. The key step is the preparation of a diprenylated gramine salt 9a. In this step, the prenyl group is incorporated at the 2-position of the indole moiety by direct lithiation of the Boc-protected gramine. We also developed and optimized the asymmetric phase-transfer-catalyzed reaction with salt 9a to provide the C2-prenyl tryptophan intermediate 2 resulting in 93% enantiomeric excess (ee) and 65% yield. The total synthesis of 1 is done in six steps with 35% overall yield.
3. Bioinspired Brønsted Acid-Promoted Regioselective Tryptophan Isoprenylations
Tushar M Khopade, Kalyani Ajayan, Swapnil S Joshi, Amy L Lane, Rajesh Viswanathan ACS Omega. 2021 Apr 12;6(16):10840-10858. doi: 10.1021/acsomega.1c00515. eCollection 2021 Apr 27.
Tryptophan-containing isoprenoid indole alkaloid natural products are well known for their intricate structural architectures and significant biological activities. Nature employs dimethylallyl tryptophan synthases (DMATSs) or aromatic indole prenyltransferases (iPTs) to catalyze regio- and stereoselective prenylation of l-Trp. Regioselective synthetic routes that isoprenylate cyclo-Trp-Trp in a 2,5-diketopiperazine (DKP) core, in a desymmetrizing manner, are nonexistent and are highly desirable. Herein, we present an elaborate report on Brønsted acid-promoted regioselective tryptophan isoprenylation strategy, applicable to both the monomeric amino acid and its dimeric l-Trp DKP. This report outlines a method that regio- and stereoselectively increases sp3 centers of a privileged bioactive core. We report on conditions involving screening of Brønsted acids, their conjugate base as salt, solvent, temperature, and various substrates with diverse side chains. Furthermore, we extensively delineate effects on regio- and stereoselection of isoprenylation and their stereochemical confirmation via NMR experiments. Regioselectively, the C3-position undergoes normal-isoprenylation or benzylation and forms exo-ring-fused pyrroloindolines selectively. Through appropriate prenyl group migrations, we report access to the bioactive tryprostatin alkaloids, and by C3-normal-farnesylation, we access anticancer drimentines as direct targets of this method. The optimized strategy affords iso-tryprostatin B-type products and predrimentine C with 58 and 55% yields, respectively. The current work has several similarities to biosynthesis, such as-reactions can be performed on unprotected substrates, conditions that enable Brønsted acid promotion, and they are easy to perform under ambient conditions, without the need for stoichiometric levels of any transition metal or expensive ligands.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
