1426953-21-0

Basic information

• Product Name: [(3R,5S,7R,8R)-7-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6-di-methyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-8-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]acetic acid
• Synonyms: [(3R,5S,7R,8R)-7-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6-di-methyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-8-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]acetic acid
• CAS NO: 1426953-21-0
• Molecular Weight: 535.635
• Mol File: 1426953-21-0.mol
• Article Data: 0

Chemical Properties

• CAS DataBase Reference: [(3R,5S,7R,8R)-7-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6-di-methyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-8-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]acetic acid(CAS DataBase Reference)
• NIST Chemistry Reference: [(3R,5S,7R,8R)-7-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6-di-methyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-8-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]acetic acid(1426953-21-0)
• EPA Substance Registry System: [(3R,5S,7R,8R)-7-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6-di-methyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-8-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]acetic acid(1426953-21-0)

Safety Data

• Hazardous Substances Data: 1426953-21-0(Hazardous Substances Data)

Usage

Description

Thailanstatin A, a promising lead compound for drug discovery and development efforts, is derived from Thailandensis burkholderia MSMB43. It reveals low nanomolar to subnanomolar cytotoxicity against a variety of human cancer cell lines.

Mechanism of action

The mechanism of action (MOA) of thailanstatin A is the inhibition of spliceosome assembly. Thailanstatin A binds firmly to the SF3b subunit of the U2 snRNA sub-complex, a crucial component of the spliceosome. Since the spliceosomes of cancer cells are more active and exhibits higher mutation rates than those of normal cells, this sub-cellular component is by far the most well-established anti-tumor target in novel drug discoveries.

Synthesis

Thailanstatin A (1): To a stirred solution of epoxide 6 (4.0 mg, 0.012 mmol, 1.0 equiv) and boronate 5 (5.8 mg, 13 μmol, 1.1 equiv) in rigorously degassed (freeze-pump-thaw technique3) 3:1:1 1,4-dioxane/MeCN/H2O (0.64 mL,) at 25°C. was added tripotassium phosphate monohydrate (2.8 mg, 0.012 mmol, 1.0 equiv) followed by Pd(dppf)Cl2.CH2Cl2 (0.1 mg, 0.125 μmol, 0.025 equiv). After 10 min, the reaction mixture was neutralized with phosphate buffer (NaH2PO4, 1.0 M, 2.5 mL), filtered through a layer of Celite, and rinsed thoroughly with ethyl acetate (20 mL). Then the organic layer was dried with anhydrous sodium sulfate and concentrated in vacuo. The obtained residue was purified by reversed-phase HPLC (C18, φ19150 mm, Atlantis, 40→50% aqueous MeCN containing 0.03% TFA) to afford thailanstatin A (1) (ca. 3.0 mg, 6.0 μmol, 52%) as a white foam.

Downstream Products

• 1609108-86-2 (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,5R,7S)-7-{2-[(4-carbamoylphenyl)amino]-2-oxoethyl}-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate 
• 1609106-20-8 (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-(2-{(2E)-2-[1-(4-{4-[(2,5-dioxopyrrolidin-1-yl)oxy]-4-oxobutoxy}phenyl)ethylidene]hydrazinyl}-2-oxoethyl)-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate 
• 1609106-19-5 4-{4-[(1E)-1-(2-{[(3R,5S,7R,8R)-7-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6-dimethyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-8-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]acetyl}hydrazinylidene)ethyl]phenoxy}butanoic acid 
• 1609108-98-6 (1S,5R)-5-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6-dimethyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-1,5-anhydro-3-C-(chloromethyl)-2-deoxy-1-[2-oxo-2-(pentafluorophenoxy)ethyl]-D-erythro-pentitol 
• 1609108-85-1 (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-{2-[(4-carbamoylbenzyl)amino]-2-oxoethyl}-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate 
• 1609106-08-2 (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-{2-[(4-aminobenzyl)amino]-2-oxoethyl}-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate 
• 1609107-56-3 (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-4-hydroxy-7-{2-[(trans-4-hydroxycyclohexyl)amino]-2-oxoethyl}-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate 
• 1609107-19-8 (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-{2-[(4-{[({4-[(N-{6-[(bromoacetyl)amino]hexanoyl}glycyl)amino]benzyl}oxy)carbonyl]amino}benzyl)amino]-2-oxoethyl}-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate 
• 1609106-00-4 pentafluorophenyl [(3R,5S,7R,8R)-7-{(1E,3E)-5-[(2S,3S,5R,6R)-5-{[(2Z,4S)-4-(acetyloxy)pent-2-enoyl]amino}-3,6-dimethyltetrahydro-2H-pyran-2-yl]-3-methylpenta-1,3-dien-1-yl}-8-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]acetate 
• 1609106-72-0 (2S,3Z)-5-{[(2R,3R,5S,6S)-6-{(2E,4E)-5-[(3R,4R,5R,7S)-7-{2-[(trans-4-aminocyclohexyl)amino]-2-oxoethyl}-4-hydroxy-1,6-dioxaspiro[2.5]oct-5-yl]-3-methylpenta-2,4-dien-1-yl}-2,5-dimethyltetrahydro-2H-pyran-3-yl]amino}-5-oxopent-3-en-2-yl acetate