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Efficient Asymmetric Synthesis of Pumiliotoxin C via Intramolecular [4+2] Cycloaddition
Author(s) -
Oppolzer Wolfgang,
Flaskamp Elmar,
Bieber Lothar W.
Publication year - 2001
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20010131)84:1<141::aid-hlca141>3.0.co;2-r
Subject(s) - chemistry , intramolecular force , imine , cycloaddition , amide , medicinal chemistry , stereochemistry , enantioselective synthesis , amine gas treating , organic chemistry , catalysis
An efficient asymmetric synthesis in nine steps of natural (−)‐pumiliotoxin C ( 1 ), a decahydroquinoline alkaloid found in the skin of Central American frog species, is presented. The enantiomerically pure starting material ( S )‐norvalinol ( 3 ), obtained from commercial ( S )‐norvaline, was cyclized in a one‐pot procedure to the tosylated aziridine 5 . Ring opening with propargylmagnesium bromide led to the acetylenic sulfonamide tosylamide 6 , free of the allenic isomer. Compound 6 was methylated on the acetylenic C‐atom, reduced, and deprotected with Na in liquid NH 3 to give the ( E )‐configured unsaturated amine 8 , which was condensed with crotonaldehyde to the imine 9 and N ‐acylated with isobutanoyl chloride to the key intermediate 2 . Intramolecular Diels‐Alder reaction furnished a diastereoisomeric mixture of N ‐protected octahydroquinolines 10 . After catalytic hydrogenation and cleavage of the amide, natural 1 was obtained as the main product in 25% overall yield; 3.2% of its isomer 11 with the inverse configurations in position 4a, 5, and 8a was also isolated.