Biomaterial Database

Total synthesis of the Hsp90 inhibitor geldanamycin. 2008

Hua-Li Qin, and James S Panek

Department of Chemistry and Center for Chemical Methodology and Library Development, Metcalf Center for Science and Engineering, Boston University, Boston, MA 02215, USA.

An enantioselective synthesis of the Hsp90 inhibitor geldanamycin was achieved in 20 linear steps and 2.0% overall yield from 2-methoxyhydroquinone. The synthesis is highlighted by a regio- and stereoselective hydroboration reaction; a Sc(OTf)(3)/Et(3)SiH-mediated pyran ring-opening reaction; an enantioselective crotylation to simultaneously install the C8-C9 (E) -trisubstituted olefin, the C10 and C11 stereocenters; a chelation-controlled asymmetric metallated acetylide addition; and an intramolecular copper(I)-mediated aryl amidation reaction to close the 19-membered macrolactam.

UI	MeSH Term	Description	Entries
D002384	Catalysis	The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.	Catalyses
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D006873	Hydroquinones	Derivatives of hydroquinone (1,4-dihydrobenzene) made by reduction of BENZOQUINONES.	Quinol,p-Dihydroxybenzenes,para-Dihydroxybenzenes,Quinols,p Dihydroxybenzenes,para Dihydroxybenzenes
D013237	Stereoisomerism	The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)	Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D016227	Benzoquinones	Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.	1,2-Benzoquinones,1,4-Benzoquinones,Benzodiones,2,5-Cyclohexadiene-1,4-Diones,o-Benzoquinones,p-Benzoquinones
D047029	Lactams, Macrocyclic	LACTAM-forming compounds with a ring size of approximately 1-3 dozen atoms.	Ansamycins,Macrocyclic Lactams
D018841	HSP90 Heat-Shock Proteins	A class of MOLECULAR CHAPERONES whose members act in the mechanism of SIGNAL TRANSDUCTION by STEROID RECEPTORS.	Heat-Shock Proteins 90,HSP90 Heat Shock Proteins,Heat Shock Proteins 90,Heat-Shock Proteins, HSP90