Chemical synthesis of febrifugine and analogues. Issue 9 (15th May 2018)

• Record Type: Journal Article
• Authors: Smullen, Shaun; McLaughlin, Noel P.; Evans, Paul
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 9(2018)
• Page Start: 2199
• Page End: 2220
• Publication Date: 2018-05-15
• Subjects: Ac acetyl -- AD-mix asymmetric dihydroxylation mix -- ATP adenosine triphosphate -- Bn benzyl -- Boc tert-butyloxycarbonyl -- Bu butyl (n-Bu, n-butyl -- I isobutyl -- sec-Bu sec-butyl -- t-Bu tert-butyl) -- Bz benzoyl -- CAL-B Candida antartcia lipase-B -- CAN ceric ammonium nitrate -- Cat. catalytic -- Cbz carboxybenzyl (benzyloxycarbonyl) -- DBU 1, 8-diazobicylco[5.4.0]undec-7-ene -- de diastereomeric excess -- DEAD diethylazodicarboxylate -- DIBAL diisobutylaluminium hydride -- DIPEA N, N-diisopropylethylamine (Hünig's base) -- DMAP 4-(N, N-dimethylamino)pyridine -- DMP Dess-Martin periodinane -- DMSO dimethyl sulfoxide -- DPPA diphenylphosphoryl azide -- ee enantiomeric excess -- Et ethyl -- Grubbs catalyst 1st gen. dichloro(benzylidene)bis(tricyclohexylphosphine)ruthenium(II) -- Grubbs catalyst 2nd gen. dichloro[1, 3-bis(2, 4, 6-trimethylphenyl)-2-imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II) -- h hours -- HMBC heteronuclear multiple bond correlation -- IFN interferon -- Ig immunoglobulin -- IL interleukin -- LiHMDS lithium bis(trimethylsilyl)amide -- MCPBA meta-chloroperbenzoic acid -- Me methyl -- MOM methoxymethyl -- Ms methanesulfonate -- NBS N-bromosuccinimide -- NMM N-methylmorpholine -- NMO N-methylmorpholine N-oxide -- NOESY nuclear Overhauser effect spectroscopy -- Ph phenyl -- PMB para-methoxybenzyl -- PPTS pyridiumium para-toluenesulfonate -- Red-Al sodium bis(2-methoxyethoxy)aluminium hydride -- RNA ribonucleic acid -- TBAF tetra-n-butylammonium fluoride -- TBDPS tert-butyldiphenylsilyl -- TBS tert-butyldimethylsilyl -- Tf trifluoromethanesulfonate -- TFA trifluoromethane sulfonic acid -- TGF transforming growth factor -- TH T helper cell -- TIPS triisopropylsilyl -- TMS trimethylsilyl -- Tp hydridotrispyrazolylborato -- Ts toluenesulfonate; Febrifugine -- Isofebrifugine -- Dichroine A and B -- Quinazolinone -- 3-hydroxypiperidine -- Isomerization -- Halofuginone -- Anti-protozoal -- Anti-angiogenic -- Anti-fibrotic; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.04.027
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: The quinazolinone-containing 2, 3-disubstituted piperidines febrifugine and isofebrifugine have been the subject of significant research efforts since their occurrence in Dichroa febrifuga and their anti-malarial actions were first described in the late 1940s. Subsequently they have also been shown to be present in other plants belonging to the hydrangea family and various analogues of febrifugine have been prepared in attempts to tune biological properties. The most notable analogue is termed halofuginone and a substantial body of work now demonstrates that this compound possesses potent human disease relevant activities. This review focuses on the literature associated with efforts dedicated towards uncovering the structures of febrifugine and isofebrifugine, the development of practical methods for their synthesis and the syntheses of structural analogues.