A concise total synthesis of saliniketal B.
We report a concise, enantioselective, and highly efficient synthesis of the marine actinomycete-derived natural product saliniketal B. Our approach was motivated with an eye toward future structure-function studies of this inhibitor of phorbol ester-mediated ornithine decarboxylase induction via an unknown mechanism. Our strategy highlights the utility of Pt(II)-mediated cycloisomerization of alkynediols developed in our laboratory to construct the dioxabicyclo[3.2.1]octane ring system, a highly selective aldol fragment coupling whose stereochemical outcome is influenced by a gamma-stereogenic methyl group, and an interesting one-pot desilylation/dihydropyranone fragmentation/amidation sequence. As such, saliniketal B was obtained in 11 steps and 23% overall yield from commercially available starting material via a convergent coupling of two equally complex fragments assembled in seven and eight steps (39 and 45%), respectively.
Liu
Jun
J
Department of Biochemistry and Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, USA.
De Brabander
Jef K
JK
D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D001688:Biological Products; D019086:Bridged Bicyclo Compounds, Heterocyclic; C517708:saliniketal B; D009955:Ornithine Decarboxylase