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Total Syntheses of (+)‐Grandilodine C and (+)‐Lapidilectine B and Determination of their Absolute Stereochemistry
Author(s) -
Nakajima Masaya,
Arai Shigeru,
Nishida Atsushi
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201510561
Subject(s) - chemistry , enantioselective synthesis , total synthesis , ozonolysis , stereochemistry , stereoselectivity , absolute configuration , ring closing metathesis , metathesis , amination , intramolecular force , allylic rearrangement , lactone , enone , reductive amination , organic chemistry , catalysis , polymerization , polymer
Enantioselective total syntheses of the Kopsia alkaloids (+)‐grandilodine C and (+)‐lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee . Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)‐grandilodine C was achieved by palladium‐catalyzed intramolecular allylic amination and ring‐closing metathesis to give 8‐ and 5‐membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)‐lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies.