Convergent Total Synthesis of (+)‐TMC‐151C by a Vinylogous Mukaiyama Aldol Reaction and Ring‐Closing Metathesis

Abstract

Two key reaction types were used for the total synthesis of the antibiotic agent (+)‐TMC‐151C: the vinylogous Mukaiyama aldol reaction and silicon‐tethered ring‐closing metathesis (RCM; see scheme). This strategy should provide efficient access to a range of related natural polyketides containing pent‐2‐ene‐1,5‐diol units.

Temporary Silicon‐Tethered Ring‐Closing Metathesis: Recent Advances in Methodology Development and Natural Product Synthesis

“…Finally, the global silyl deprotection of silacycle 111 , provided the natural product 112 in good yield with the spectroscopic data in agreement with those obtained from the naturally derived 112 . This highly convergent synthesis accentuates two pivotal strategies: 1) the iterative application of vinyloguous Mukayama aldol reaction and 2) the powerful TST‐RCM reaction utilized for the union of advanced synthetic intermediates 108 and 109 through the stereoselective construction of ( E )‐olefin 41…”

“…[21] In a subsequent study, Kobayashi and co-workers applied this fruitful strategy to the total synthesis of potent anticancer agent (+)-TMC-151C (112). [41] The TST-RCM strategy was utilized in the final stage of the synthesis to join the left-and right-hand fragments through the formation of (E)olefin between C6 and C7. The finalization of the total synthesis of (+)-TMC-151C (112) is described in Scheme 17.…”

“…This highly convergent synthesis accentuates two pivotal strategies: 1) the iterative application of vinyloguous Mukayama aldol reaction and 2) the powerful TST-RCM reaction utilized for the union of advanced synthetic intermediates 108 and 109 through the stereoselective construction of (E)-olefin. [41]…”