Efficient Synthesis of an Indinavir Precursor from Biomass-Derived (-)-Levoglucosenone

Title
Efficient Synthesis of an Indinavir Precursor from Biomass-Derived (-)-Levoglucosenone
Publication Date
2017
Author(s)
Ledingham, Edward
Stockton, Kieran
Greatrex, Ben
( author )
OrcID: https://orcid.org/0000-0002-0356-4966
Email: bgreatre@une.edu.au
UNE Id une-id:bgreatre
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
CSIRO Publishing
Place of publication
Australia
DOI
10.1071/ch17227
UNE publication id
une:23049
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.
Link
Citation
Australian Journal of Chemistry, 70(10), p. 1146-1150
ISSN
1445-0038
0004-9425
Start page
1146
End page
1150

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