Detailed Information

Enantioselective Total Synthesis of Nitraria Alkaloids: (+)-Nitramine, (+)-Isonitramine, (−)-Isonitramine, and (−)-Sibirine via Asymmetric Phase-Transfer Catalytic α-Allylations of α-Carboxylactams : Enantioselective Total Synthesis of Nitraria Alkaloids: (+)-Nitramine, (+)-Isonitramine, (-)-Isonitramine, and (-)-Sibirine via Asymmetric Phase-Transfer Catalytic alpha-Allylations of alpha-Carboxylactams

Cited 6 time in Web of Science Cited 6 time in Scopus

Yang, Jewon; Park, Yohan; Yang, Sehun; Lee, Geumwoo; Ha, Min Woo; Kim, Mi-hyun; Hong, Suckchang; Park, Hyeung-geun

Issue Date
American Chemical Society
Journal of Organic Chemistry, Vol.86 No.6, pp.4375-4390
Many optically active 2-azaspirocyclic structures have frequently been found in biologically active natural products. In particular, Nitraria alkaloids, (+)-nitramine, (+)-isonitramine, (-)-isonitramine, and (-)-sibirine, have stereo H genicity on their quaternary carbon of the 2-azaspiro[S,S]undecane-7- of structure. To synthesize Nitraria alkaloids, we developed a new enantioselective synthetic method for chiral alpha-quaternary lactams via the alpha- kylation of alpha-tert-butoxycarbonyl lactams. alpha-Alkylation of alpha-tert-butoxycarbox- ylactams in the circumstances of phase-transfer catalytic (PTC) system (solid KOH, toluene, and -40 degrees C) by virtue of the catalytic action of (S,S)-NAS bromide (5 mol %) furnished the corresponding alpha-alkyl-alpha-tert-butoxycarbonyl lactams in very high chemical (<99%) and enantioselectivity (<98% ee). Our catalytic methodology was successfully applied for the enantioselective total synthesis of Nitraria alkaloids. (+)-Isonitramine was obtained in 12 steps (98% ee, 43% yield) from delta-valerolactam through enantioselective phase-transfer catalytic allylation, Dieckmann condensation, and diastereoselective reduction as the key reactions. (-)-Sibirine and (+)-nitramine were prepared from (-)-isonitramine or its intermediate. Switching the phase-transfer catalyst from (S,S)-NAS bromide to (R,R)-NAS bromide afforded (-)-isonitramine (98% ee, 41% yield). (-)-Sibirine was synthesized by N-ethoxycarbonylation of (-)-isonitramine followed by reduction (98% ee, 14 steps, 32% yield). Furthermore, the diastereoselective reduction of (R)-2-benzhydry1-2-azaspiro[5.5]undecane-1,7-dione [(R)-15] followed by reductive removal of the diphenylmethyl group successfully gave (+)-nitramine (98% ee, 11 steps, 40% yield).
Files in This Item:
There are no files associated with this item.
Appears in Collections:

Related Researcher

  • College of Pharmacy
  • Department of Manufacturing Pharmacy
Research Area Development of methodologies using metal catalyst, Total synthesis of natural products


Item View & Download Count

  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.