Trabectedin (also known as ecteinascidin 743 or by the brand name Yondelis) is a experimental anti-tumor drug. First isolated from aqueous ethanol extract of tunicates in 1969, the complex molecule was found to have impressive cytotoxic activities in the pico- to nanomolar range. It is composed of 3 tetrahydroquinoline moieties, 8 rings including one 10-membered heteocyclic ring containing a cystine residue, and 7 chiral centers. This structure was not determined until 1984, and was first totally synthesized by Elias James Corey in 1996. The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... Grain alcohol redirects here. ... Classes Ascidiacea (2,300 species) Thaliacea Appendicularia Sorberacea Urochordata (sometimes known as tunicata and commonly called urochordates, tunicates, sea squirts) is the subphylum of saclike filter feeders with incurrent and excurrent siphons. ... Cytotoxicity is the quality of being poisonous to cells. ... In organic chemistry, functional groups (or moieties) are specific groups of atoms within molecules, that are responsible for the characteristic chemical reactions of those molecules. ... Chemical structure of cystine formed from L-cysteine (under biological conditions) 3D representation of cystine with the disulfide bond shown in yellow Cystine is a conditionally non-essential crystalline, sulfur-containing amino acid. ... Elias James Corey (born July 12, 1928) is an American organic chemist. ...

The biological mechanism of action is believed to involve the production of superoxide near the DNA strand, resulting in DNA backbone cleavage and cell apoptosis. The actual mechanism is not yet known, but is believed to proceed from reduction of molecular oxygen into superoxide via an unusual auto-redox reaction on a hydroxyquinone moiety of the compound following. There is also some speculation the compound becomes 'activated' into its reactive oxazolidine form. Wikipedia does not yet have an article with this exact name. ... Lewis electron configuration of superoxide. ... A section of mouse liver showing an apoptotic cell indicated by an arrow Apoptosis (pronounced apo tō sis) is a process of suicide by a cell in a multicellular organism. ... Oxazolidines consist of one or more five-membered heterocyclic rings containing oxygen and nitrogen. ...

Biosynthesis is also beleieved to involve the dimerization of two tyrosine residues to form the pentacyclic core of the molecule. The total synthesis by E.J. Corey used this proposed biosynthesis in their attempt at the compounds synthetic creation. Their synthesis utilized such reactions as the Mannich reaction, Pictet-Spengler reaction, the Curtius rearrangement, and chiral rhodium-based diphosphine catalized enantioselective hydrogenation. A separate synthetic process also involved the Ugi reaction to assist in the formation of the pentacyclic core. This reaction was unprecedented for using such a one pot multi-component reaction in the synthesis of such a complex molecule. Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese[1][2]), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells... The Mannich reaction is a chemical reaction in organic chemistry and is a amino alkylation of an acidic proton placed next to a carbonyl functional group with formaldehyde and ammonia or any primary or secondary amine. ... The Pictet-Spengler reaction is a chemical reaction in which a β-arylethylamine such as tryptamine undergoes ringclosure after condensation with an aldehyde. ... The Curtius rearrangement, as first defined by Theodor Curtius, is a chemical reaction that involves the rearrangement of an acyl azide to a isocyanate. ... In chemistry two stereoisomers are said to be enantiomers if one can be superimposed on the mirror image of the other. ... Hydrogenation is a class of chemical reactions which result an addition of hydrogen (H2) usually to unsaturated organic compounds. ... The Ugi reaction is a multi-component reaction in organic chemistry involving a ketone or aldehyde, an amine, an isocyanide and a carboxylic acid to form a bis-amide. ...

External links

• Yondelis at PharmaMar.com