- Synthesis of Podophyllotoxin
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(CAS NO.: ), with other names as (5R,5aR,8aR,9R)-9-Hydroxy-5-(3,4,5-trimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3,4:6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one, could be produced through the following synthetic routes.

The oxidation of the aldehyde group of (XVI) with NaClO2 in tert-butanol affords the corresponding carboxylic acid (XVII), which is condensed with 2-oxazolidinone (XVIII) by means of carbonyldiimidazole (CDI) in THF to give the acyl imidazolide (XIX). The arylation of (XIX) with 3,4,5-trimethoxyphenylmagnesium bromide (XX) in THF yields the expected addition product (XXI), which is cyclized by means of TBAF in hot THF to afford the tetracyclic intermediate (XXII).Isomerization of the cis-lactone ring of (XXII) with LDA in THF affords intermediate (XXIII) with its lactone ring with the correct trans-conformation. Finally, this compound is deprotected with ethyl mercaptane and MgBr2 in ethyl ether to provide the target compound.
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