title: Total synthesis of five thapsigargins: guaianolide natural products exhibiting sub-nanomolar SERCA inhibition.
abstract: Herein we describe the total synthesis of five guaianolide natural products: thapsigargin, thapsivillosin C, thapsivillosin F, trilobolide and nortrilobolide. Prodrug derivatives of thapsigargin have shown selective in vivo cytotoxicity against prostate tumours and the need for further investigation of this phenomenon highlights the importance of these total syntheses. The first absolute stereochemical assignment of thapsivillosin C is also delineated.
authors.affiliation: University Chemical Laboratory, Lensifield Road, Cambridge, CB2 1EW, UK.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Andrews
authors.forename: Matthew
authors.initials: M
authors.lastname: Ball
authors.forename: Frank
authors.initials: F
authors.lastname: Wierschem
authors.forename: Ed
authors.initials: E
authors.lastname: Cleator
authors.forename: Steven
authors.initials: S
authors.lastname: Oliver
authors.forename: Klemens
authors.initials: K
authors.lastname: Högenauer
authors.forename: Oliver
authors.initials: O
authors.lastname: Simic
authors.forename: Alessandra
authors.initials: A
authors.lastname: Antonello
authors.forename: Udo
authors.initials: U
authors.lastname: Hünger
authors.forename: Martin D
authors.initials: MD
authors.lastname: Smith
authors.forename: Steven V
authors.initials: SV
authors.lastname: Ley
mesh_terms: D000475:Alkenes / Q000737:chemistry; D001685:Biological Factors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D036103:Nanotechnology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D045789:Sesquiterpenes, Guaiane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D019284:Thapsigargin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000475:Alkenes; D001685:Biological Factors; D004791:Enzyme Inhibitors; D045789:Sesquiterpenes, Guaiane; D019284:Thapsigargin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases