Modern synthetic efforts toward biologically active terpenes.
Terpenes represent one of the largest and most diverse classes of secondary metabolites, with over 55,000 members isolated to date. The terpene cyclase enzymes used in nature convert simple, linear hydrocarbon phosphates into an exotic array of chiral, carbocyclic skeletons. Further oxidation and rearrangement results in an almost endless number of conceivable structures. The enormous structural diversity presented by this class of natural products ensures a broad range of biological properties-ranging from anti-cancer and anti-malarial activities to tumor promotion and ion-channel binding. The marked structural differences of terpenes also largely thwart the development of any truly general strategies for their synthetic construction. This review focuses on synthetic strategies directed toward some of the most complex, biologically relevant terpenes prepared by total synthesis within the past decade. Of crucial importance are both the obstacles that modern synthetic chemists must confront when trying to construct such natural products and the key chemical transformations and strategies that have been developed to meet these challenges.
Maimone
Thomas J
TJ
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.
Baran
Phil S
PS
D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry
D000962:Antimalarials; D000970:Antineoplastic Agents; D001643:Bridged Bicyclo Compounds; D004224:Diterpenes; D006576:Heterocyclic Compounds, 4 or More Rings; D013729:Terpenes; C109551:eleutherobin; C409194:guanacastepene; C097941:neotripterifordin; C450680:saudin; C413206:phomactin A; C080890:terpestacin; C024353:resiniferatoxin; C008125:ingenol