Total synthesis of +/--hyphodermins A and D.
An efficient formal synthesis of (+/-)-hyphodermins A and D, metabolites of Hyphoderma radula, has been completed in 12 and 11 steps, respectively. The tricyclic carbon skeleton of enone 6 was rapidly assembled from diester 11 via an alpha brominationn-elimination sequence followed by anhydride formation. Regioselective reduction of the lactone group of enone 6 with LiAlH(t-BuO) 3 gave lactol 15. Lactol 15 was converted in two steps to (+/-)-hyphodermin D, without the need for complex protection-deprotection strategies. Lactol 15 was converted in three steps to (+/-)-hyphodermin A, via the key step of epoxidation of an enone in the presence of a THP lactol. A combination of NMR and ab initio studies suggests that the structures of hyphodermin C and D should be interchanged.
Loughlin
Wendy A
WA
School of Biomolecular and Physical Sciences, Griffith University, Brisbane, QLD, 4111, Australia. w.loughlin@griffith.edu.au
Jenkins
Ian D
ID
Henderson
Luke C
LC
Campitelli
Marc R
MR
Healy
Peter C
PC
D000080:Acetals / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D008745:Methylation; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry
D000080:Acetals; D005663:Furans; D009281:Naphthalenes; C529501:hyphodermin A; C529502:hyphodermin D