A biomimetically inspired, efficient synthesis of the South 7 hemisphere of cephalostatin 7.
Synthesis of the South 7 hemisphere of cephalostatin 7 is described applying a second-generation synthetic strategy, which retains all the existing carbons in hecogenin acetate 1. TFAT (trifluoroacetyl trifluoromethanesulfonate)-assisted E-ring opening yields the key D-ring cyclopentadiene. A facially selective [4 + 2] cycloaddition between a series of steroidal D-ring dienes and singlet oxygen was conformationally directed by the C21-Me stereochemistry of the side chain. Sharpless asymmetric dihydroxylation of the terminal olefin provides (S)-C25-OH. An acid-catalyzed SN2' intramolecular alkylation of an acetal oxygen was followed by a one-pot sequence of beta-elimination and spiroketalization. The new route provides a practical 16-operation synthesis of the South 7 hemisphere (20% overall), as well as a model for construction of the crucial North 1 hemisphere.
Lee
Jong Seok
JS
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
Fuchs
Philip L
PL
D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D008958:Models, Molecular; D008968:Molecular Conformation; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry; D026082:Singlet Oxygen / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry
D006571:Heterocyclic Compounds; D010619:Phenazines; D013141:Spiro Compounds; D013256:Steroids; C409226:cephalostatin 7; C505700:south 7; D026082:Singlet Oxygen; C505698:hecogenin acetate