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https://hdl.handle.net/1959.11/22865
Title: | Efficient Synthesis of an Indinavir Precursor from Biomass-Derived (-)-Levoglucosenone | Contributor(s): | Ledingham, Edward (author); Stockton, Kieran (author); Greatrex, Ben (author) | Publication Date: | 2017 | DOI: | 10.1071/ch17227 | Handle Link: | https://hdl.handle.net/1959.11/22865 | Abstract: | Lignocellulosic biomass pyrolysis with acid catalysis selectively produces the useful chiral synthon 6,8-dioxabicyclo[3.2.1]oct-2-ene-4-one ((-)-levoglucosenone,LGO). In this report, LGO was used to prepare (3R,5S)-3-benzyl-5-(hydroxymethyl)-4,5-dihydrofuran-2(3H)-one, which is an intermediate used in the construction of antivirals including the protease inhibitor indinavir. To achieve the synthesis, the hydrogenated derivative of LGO was functionalised using aldol chemistry and various aromatic aldehydes were used to show the scope of the reaction. Choice of base affected reaction times and the best yields were obtained using 1,1,3,3-tetramethylguanidine. Hydrogenation of the α-benzylidene-substituted bicyclic system afforded a 4:3 equatorial/axial mixture of isomers, which was equilibrated to a 97:3 mixture under basic conditions. Subsequent Baeyer-Villiger reaction afforded the target lactone in 57 % overall yield for four steps,a route that avoids the protection and strong base required in the traditional approach. The aldol route is contrasted with the α-alkylation and a Baylis-Hillman approach that also both start with LGO. | Publication Type: | Journal Article | Source of Publication: | Australian Journal of Chemistry, 70(10), p. 1146-1150 | Publisher: | CSIRO Publishing | Place of Publication: | Australia | ISSN: | 1445-0038 0004-9425 |
Fields of Research (FoR) 2008: | 030503 Organic Chemical Synthesis 030504 Organic Green Chemistry 030401 Biologically Active Molecules |
Fields of Research (FoR) 2020: | 340503 Organic chemical synthesis 340504 Organic green chemistry 340401 Biologically active molecules |
Socio-Economic Objective (SEO) 2008: | 860803 Human Pharmaceutical Treatments (e.g. Antibiotics) 970103 Expanding Knowledge in the Chemical Sciences 860604 Organic Industrial Chemicals (excl. Resins, Rubber and Plastics) |
Socio-Economic Objective (SEO) 2020: | 240803 Human pharmaceutical treatments 280105 Expanding knowledge in the chemical sciences 240908 Organic industrial chemicals (excl. resins, rubber and plastics) |
Peer Reviewed: | Yes | HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
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Appears in Collections: | Journal Article School of Rural Medicine School of Science and Technology |
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