Total Synthesis of Natural Products via Strategic Use of Claisen Rearrangement and Ring-Closing Metathesis
소속 :
연사 : 김상희 교수 (서울대학교 약대)
일시 : 2012-09-20 17:00 ~
장소 : 500동 목암홀
일 시 : 2012년 9월 20일, 5:00 PM
장 소 : 500동 목암홀
-Abstract-
The advent of olefin metathesis, one of the most powerful tools for the C-C bond formation,has changed the retrosynthetic analysis of molecular frameworks.1Claisenrearrangementisalsoanuseful tool for retrosynthetic analysis in that the stereochemical outcome of the product can be easily predictable and can be controlled.2AcombinationofClaisenRearrangementandring-closing olefin metathesis can provide an efficient synthetic route to many polycyclic natural products. We have achieved a number of total syntheses, such as (-)-lepadiformine (1), (-)-fasicularin (2), (+)-pancratistatin (3), (+)-trans-dihydronarciclasine (4), (-)-perhydrohistrionicotoxin, and (-)-perrottetinene by the strategic use of these two reactions. Pancratistatin (3) and trans-dihydronarciclasine (4) are representative members of Amaryllidaceae isocarbostyril alkaloids. They have been an attractive synthetic target for the last two decades due to their potent and selective anticancer activity as well as their unique structural features. We have achieved the highly stereoselective and efficient total synthesis of these isocarbostyril alkaloids from a readily available chiral intermediate. The stereoselectivity for introducing all of the stereogenic reactions was excellent, with only a single diastereomer of each product being observed. The concise nature of this total synthesis hinges in part on the demonstration of the successful conversion of a Claisen rearrangement product into a six-membered cyclic intermediate via a RCM reaction or a regioselective Wacker oxidation and Dieckmann condensation based sequence. The successful B-ring formation with high regioselectivity from an N-Boc substrate via an isocyanate intermediate is also quite noteworthy, and the present transformation is a useful complement to Banwell’s variant of the Bischler-Napieralski reaction in the synthesis of dihydroisocarbostyrils from β-arylethylcarbamates.
장 소 : 500동 목암홀
-Abstract-
The advent of olefin metathesis, one of the most powerful tools for the C-C bond formation,has changed the retrosynthetic analysis of molecular frameworks.1Claisenrearrangementisalsoanuseful tool for retrosynthetic analysis in that the stereochemical outcome of the product can be easily predictable and can be controlled.2AcombinationofClaisenRearrangementandring-closing olefin metathesis can provide an efficient synthetic route to many polycyclic natural products. We have achieved a number of total syntheses, such as (-)-lepadiformine (1), (-)-fasicularin (2), (+)-pancratistatin (3), (+)-trans-dihydronarciclasine (4), (-)-perhydrohistrionicotoxin, and (-)-perrottetinene by the strategic use of these two reactions. Pancratistatin (3) and trans-dihydronarciclasine (4) are representative members of Amaryllidaceae isocarbostyril alkaloids. They have been an attractive synthetic target for the last two decades due to their potent and selective anticancer activity as well as their unique structural features. We have achieved the highly stereoselective and efficient total synthesis of these isocarbostyril alkaloids from a readily available chiral intermediate. The stereoselectivity for introducing all of the stereogenic reactions was excellent, with only a single diastereomer of each product being observed. The concise nature of this total synthesis hinges in part on the demonstration of the successful conversion of a Claisen rearrangement product into a six-membered cyclic intermediate via a RCM reaction or a regioselective Wacker oxidation and Dieckmann condensation based sequence. The successful B-ring formation with high regioselectivity from an N-Boc substrate via an isocyanate intermediate is also quite noteworthy, and the present transformation is a useful complement to Banwell’s variant of the Bischler-Napieralski reaction in the synthesis of dihydroisocarbostyrils from β-arylethylcarbamates.
