Date of Graduation
The enantioselective synthesis of anamarine has been achieved in 21 steps. The route relies upon an enantio- and regioselective Sharpless dihydroxylation of dienoate ester and zinc borohydride reduction to establish the C-8 to C-11 stereochemistry. A diastereoselective Leighton allylation established the desired C-5 stereochemistry. The route has also been used to prepare two diastereoisomers. The de novo synthesis of fostriecin has been achieved in 27 steps. The route relies upon an enantio- and regioselective Sharpless dihydroxylation of trienyne ester and Pd-catalyzed asymmetric hydration to set up the C-8, C-9 and C-11 stereocenters. A diastereoselective Leighton allylation established the desired C-5 stereochemistry and a ring closing metathesis to build the lactone moiety. Rhodium-catalyzed trans-hydroboration reaction followed by a Suzuki-Miyaura crossing-coupling at late stage set up the unstable Z,Z,E-triene fragment. Selective deprotection of the TES group, followed by install of the phosphate group finished the total synthesis.
Gao, Dong, "Syntheses of polyoxygenated α,β-unsaturated lactone natural products: Anamarine and fostriecin." (2006). Graduate Theses, Dissertations, and Problem Reports. 8888.