AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |
Back to Blog
48.2 psi to atm12/11/2023 ![]() Fortunately, the presence of a 3-hydroxycyclohexanone suggests that this ring might be formed by an aldol or Prins reaction. The bridgehead hydroxy group of sauroine ( 4) and 7-hydroxylycopodine ( 5) is not compatible with most of the approaches that have been used for the synthesis of lycopodine ( 2) and clavolonine ( 3). 5j,k 8-Hydroxylycopodine ( 3, clavolonine) was synthesized in racemic form in 1984 by Wenkert 6a and more recently in optically pure form by Evans, 6b Breit, 6c and Fujikoka. 5l The first synthesis of lycopodine in optically pure form was recently reported by Carter in 2008. Racemic lycopodine ( 2) was first synthesized by Stork 5a and Ayer 5b in 1968, with additional syntheses by Kim, 5c Heathcock, 5d Schumann, 5e Wenkert, 6a Kraus, 5f Grieco, 5g Padwa 5h, and Mori 5i over the next 30 years. Structures of huperzine A ( 1), lycopodine ( 2), clavolonine ( 3), sauroine ( 4), and 7-hydroxylycopodine ( 5). In attempts to hydroxylate the starting material so that we could adapt this synthesis to the preparation of (±)-7,8-dihydroxylycopodine (sauroine) we observed the novel oxidation of a bicyclic vinylogous amide to a keto pyridine with Mn(OAc) 3 and to an amino phenol with KHMDS and oxygen. ![]() During unsuccessful attempts to make optically pure starting material, we observed the selective Pt-catalyzed hydrogenation of the 5-phenyl group of a 4,5-diphenyloxazolidine under acidic conditions and the Pt-catalyzed isomerization of the oxazolidine to an amide under neutral conditions. ![]() The resulting product was converted to 7-hydroxydehydrolycopodine by heating with KO- t-Bu and benzophenone in benzene followed by acidic workup. A one-pot procedure orthogonally protected the primary alcohol as an acetate and the tertiary alcohol as a methylthiomethyl ether. The key step is a Prins reaction in 60% sulfuric acid that gave the key tricyclic intermediate with complete control of the ring fusion stereochemistry. A seven-step synthesis of (±)-7-hydroxylycopodine that proceeds in 5% overall yield has been achieved. ![]()
0 Comments
Read More
Leave a Reply. |