A synthetic approach toward nitiol: construction of two 1,22-dihydroxynitianes.
Synthetic work toward the total synthesis of nitiol has culminated in the construction of two epimeric hydroxylated derivatives, the 1,22-dihydroxynitianes. Key stereodefining steps in the construction of the A-ring fragment (13) were the use of a siloxy-epoxide rearrangement reaction, a Pauson-Khand reaction, a Norrish 1 photochemical cleavage reaction, and a highly regio- and stereoselective hydrostannylation reaction of an ynoate. The stereochemistry of the synthetically challenging C-ring fragment (20) was established using an Ireland-Claisen reaction and a Grubbs ring-closing metathesis process as key steps. The 12-membered B-ring of the nitiane skeleton was constructed using a copper-promoted Stille cross-coupling and a Kishi-Hiyama-Nozaki carbonyl addition reaction. Unfortunately, the carbonyl addition reaction produced hydroxyl functionality that could not be selectively removed. Consequently, a synthesis of epimeric 1,22-dihydroxynitianes, which are compounds that are structural hybrids of two natural products, nitiol and variculanol, was completed.
Wilson
Michael S
MS
Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver, B.C., Canada V6T 1Z1.
Woo
Jacqueline C S
JC
Dake
Gregory R
GR
D031313:Gentianella / Q000737:chemistry; D015394:Molecular Structure; D013729:Terpenes / Q000138:chemical synthesis*
D013729:Terpenes; C401231:nitiol