102396-24-7

Basic information

• Product Name: JASPLAKINOLIDE
• Synonyms: JASPLAKINOLIDE;JASPLAKINOLIDE, JASPIS JOHNSTONI;(3S,6R,9R,13S,15R,16E,19S)-3,5,13,15,17,19-Hexamethyl-6-[(2-bromo-1H-indole-3-yl)methyl]-9-(4-hydroxyphenyl)-12-oxa-2,5,8-triazacyclononadeca-16-ene-1,4,7,11-tetraone;[3S,6R,9R,13S,15R,19S,16E,(+)]-6-[(2-Bromo-1H-indol-3-yl)methyl]-9-(4-hydroxyphenyl)-3,5,13,15,17,19-hexamethyl-2,5,8-triaza-12-oxacyclononadecan-16-ene-1,4,7,11-tetrone;NSC 613009;GQWYWHOHRVVHAP-DHKPLNAMSA-N
• CAS NO: 102396-24-7
• Molecular Formula: C₃₆H₄₅BrN₄O₆
• Molecular Weight: 709.67
• Product Categories: Amines, Aromatics, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 102396-24-7.mol
• Article Data: 8

Chemical Properties

• Melting Point: 110℃ (decomposition)
• Boiling Point: 968.3°Cat760mmHg
• Flash Point: 539.4°C
• Appearance: off white to beige/
• Density: 1.227g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.553
• Storage Temp.: ?20°C
• Solubility: DMSO: >2mg/mL
• CAS DataBase Reference: JASPLAKINOLIDE(CAS DataBase Reference)
• NIST Chemistry Reference: JASPLAKINOLIDE(102396-24-7)
• EPA Substance Registry System: JASPLAKINOLIDE(102396-24-7)

Safety Data

• RIDADR: 3172
• WGK Germany: 3
• RTECS: GX7000000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 102396-24-7(Hazardous Substances Data)

Usage

Description

Jasplakinolide is a natural macrocyclic peptide first isolated from a marine sponge, Jaspis splendens. It exhibits antineoplastic activity and potently inhibits the proliferation of PC3 prostate carcinoma cells by binding to F-actin. This binding stabilizes actin filaments in vitro but disrupts them and induces irregular polymerization of monomeric actin in vivo. Jasplakinolide is used to investigate the role of actin in various cellular functions, such as motility, transport, and development.

Uses

1. Used in Anticancer Applications:
Jasplakinolide is used as an anticancer agent, particularly against prostate and breast carcinoma cell proliferation. It modulates the actin cytoskeleton, which plays a crucial role in cell division and migration, thereby inhibiting tumor growth and progression.
2. Used in Cellular Research:
Jasplakinolide is used as an actin stabilizing agent for studying the role of actin in diverse cellular roles, such as motility, transport, and development. Its ability to stabilize actin filaments in vitro and disrupt them in vivo makes it a valuable tool for understanding actin dynamics and its impact on cellular processes.
3. Used in Nerve Guidance Studies:
Jasplakinolide has been used to analyze its influence on sciatic nerve guidance effect in vivo in chicken embryos. It is applied on control cells for the treatment of blocking actin dynamics, which helps in understanding the role of actin in nerve development and guidance.
4. Used in Drug Development:
As a potent inhibitor of cancer cell proliferation, jasplakinolide serves as a starting point for the development of new drugs targeting actin-related pathways in cancer therapy. Its unique mechanism of action and ability to disrupt actin filaments make it a promising candidate for further research and potential therapeutic applications.

Biochem/physiol Actions

Jasplakinolide is an actin-specific reagent that promotes actin polymerization and stabilizes actin filaments. In vitro, Jasplakinolidet potently induces actin polymerization by stimulating actin filament nucleation and competes with phalloidin for actin binding (Kd = 15 nM). In vivo, Jasplakinolide has been found to disrupt actin filaments and induce polymerization of monomeric actin into amorphous masses, the exact mechanism of which has not been determined yet. Jasplakinolide differs from other actin stabilizers in that it is cell permeable. This peptide has fungicidal, insecticidal and antiproliferative activity, and is useful for investigating cell processes mediated by actin polymerization and depolymerization, such as cell adhesion, locomotion, endocytosis, and vesicle sorting and release.

InChI:InChI=1/C36H45BrN4O6/c1-20-15-21(2)17-23(4)47-32(43)19-30(25-11-13-26(42)14-12-25)40-35(45)31(18-28-27-9-7-8-10-29(27)39-33(28)37)41(6)36(46)24(5)38-34(44)22(3)16-20/h7-15,21-24,30-31,39,42H,16-19H2,1-6H3,(H,38,44)(H,40,45)/b20-15+/t21-,22-,23-,24-,30+,31+/m0/s1

Upstream product

• 112896-93-2 O-tert-butyldimethylsilyl-(R)-β-tyrosine tert-but 
• 112896-90-9 N-tert-butoxycarbonyl-O-tert-butyldimethylsilyl-(S)-4-hydroxyphenylglycine 
• 112896-92-1 N-tert-butoxycarbonyl-O-tert-butyldimethylsilyl-(R)-β-tyrosine tert-butyl ester 
• 112896-87-4 methyl (R)-3-<1-(tert-butyldimethylsilyl)indol-3-yl>-2-(N-tert-butoxycarbonyl-N-methylamino)propanoate 
• 112896-91-0 (S)-N-tert-butoxycarbonyl-4-tert-butyldimethylsilyloxy-α-diazoacetylbenzylamine 
• 112896-83-0 N-methyl-2-bromo-(R)-tryptophanyl-O-tert-butyldimethylsilyl-(R)-β-tyrosine tert-butyl ester 
• 112896-94-3 N-tert-butyoxycarbonyl-N-methyl-2-bromo-(R)-tryptophanyl-O-tert-butyldimethylsilyl-(R)-β-tyrosine tert-butyl ester 
• 134781-83-2 (2S,4R)-4,6-Dimethyl-hept-6-ene-2,5-diol 
• 154140-42-8 (R)-3-{(R)-3-(2-Bromo-1H-indol-3-yl)-2-[((S)-2-tert-butoxycarbonylamino-propionyl)-methyl-amino]-propionylamino}-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionic acid ethyl ester 
• 1026064-42-5 (R)-3-[(R)-2-[((S)-2-Amino-propionyl)-methyl-amino]-3-(2-bromo-1H-indol-3-yl)-propionylamino]-3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-propionic acid ethyl ester 
• 154140-39-3 (R)-3-Azido-3-(4-benzyloxy-phenyl)-propionic acid ethyl ester 
• 131791-78-1 (R)-methyl-2-((S)-2-((tert-butoxycarbonyl)amino)-N-methylpropanamido)-3-(1H-indol-3-yl) propanoate 
• 53090-45-2 ethyl 3-[4-(benzyloxy)phenyl]-3-oxopropanoate 
• 4397-53-9 p-benzyloxybenzaldehyde 

Downstream Products

• 161925-59-3 jaspamide Z₁ 
• 103848-63-1 (E)-8-Hydroxy-2,4,6-trimethyl-non-4-enoic acid [1-({2-(2-bromo-1H-indol-3-yl)-1-[3-hydroxy-1-(4-hydroxy-phenyl)-propylcarbamoyl]-ethyl}-methyl-carbamoyl)-ethyl]-amide 
• 102396-25-8 Acetic acid 4-[(E)-7-(2-bromo-1H-indol-3-ylmethyl)-8,10,13,15,17,19-hexamethyl-2,6,9,12-tetraoxo-1-oxa-5,8,11-triaza-cyclononadec-15-en-4-yl]-phenyl ester 

Relevant articles and documents

Synthesis and structure-activity correlation of natural-product inspired cyclodepsipeptides stabilizing F-actin

The fundamental role played by actin In the regulation of eukaryotic cell maintenance and motility renders it a primary target for small-molecule intervention. in this arena, a class of potent cytotoxic cyclodepsipeptide natural products has emerged over the last quarter-century to stimulate the fields of biology and chemistry with their unique actin-stabilizing properties and complex peptide-polyketide hybrid structures. Despite considerable research effort, a structural basis for the activity of these secondary metabolites remains elusive, not least for the lack of high-resolution structural data and a reliable synthetic route to diverse compound libraries. in response to this, an efficient solid-phase approach has been developed and successfully applied to the total synthesis of Jasplakinolide and chondramide C and diverse analogues. The key macrocylization step was realized using ruthenium-catalyzed ring-closing metathesis (RCM) that in the course of a library synthesis produced discernible trends in metathesis reactivity and E/Z-selectivity, After optimization, the RCM step could be operated under mild conditions, a result that promises to facilitate the synthesis of more extensive analogue libraries for structure-function studies. The growth inhibitory effects of the synthesized compounds were quantified and structure-activity correlations established which appear to be in good alignment with relevant biological data from natural products. in this way a number of potent unnatural and simplified analogues have been found. Furthermore, potentially important stereochemical and structural components of a common pharmacophore have been identified and rationalized using molecular modeling. These data will guide in-depth mode-of-action studies, especially into the relationship between the cytotoxicity of these compounds and their actin-perturbing properties, and should inform the future design of simplified and functionalized actln stabilizers as well.

Enantioselective total synthesis of (+)-jasplakinolide

An enantioselective total synthesis of (+)-jasplakinolide is described. The synthesis of the polyketide template utilized a diastereoselective syn-aldol, ortho-ester Claisen rearrangement followed by efficient conversion to a cyanide. The β-amino acid uni

Studies on the Novel Cyclodepsipeptides. A Total Synthesis of (+)-Jasplakinolide (Jaspamide)

Diastereocontrolled total synthesis of (+)-jasplakinolide (1) has been accomplished via coupling of the tetrapropionate-derived segment (9) with the tripeptide (10) followed by trichlorobenzoyl chloride-mediated macrolactonization.