518-99-0Relevant articles and documents
Synthesis and affinity studies of himbacine derived muscarinic receptor antagonists.
Gao, Ling-Jie,Waelbroeck, Magali,Hofman, Sven,Van Haver, Dirk,Milanesio, Marco,Viterbo, Davide,De Clercq, Pierre J
, p. 1909 - 1912 (2002)
A series of himbacine (1)-related analogues has been prepared featuring three different isomeric configurations with respect to the B-ring (a, b and natural c) and three different interconnecting two-carbon unsaturated units [natural (E)-ene, (Z)-ene, and yne]. The study of the binding affinities of the nine resulting compounds, including synthetic (+)-himbacine (3c), towards the M(1)-M(4) muscarine receptor subtypes revealed that analogues 3a and 5c display a promising 10-fold selectivity for the M(2) receptor as compared to the M(1) receptor.
Biomimetic total synthesis of (+)-himbacine
Tchabanenko, Kirill,Adlington, Robert M.,Cowley, Andrew R.,Baldwin, Jack E.
, p. 585 - 588 (2007/10/03)
(Chemical Equation Presented) On treatment with trifluoroacetic acid butenolide 14 undergoes N-Boc deprotection and condensation followed by an iminium ion activated intramolecular Diels-Alder cycloaddition to give the (+)-himbacine precursor 11 on reduct
Total synthesis of (+)-himbacine and (+)-himbeline
Chackalamannil, Samuel,Davies, Robert J.,Wang, Yuguang,Asberom, Theodros,Doller, Dario,Wong, Jesse,Leone, Daria,McPhail, Andrew T.
, p. 1932 - 1940 (2007/10/03)
Himbacine (1), a complex piperidine alkaloid isolated from the bark of Australian magnolias, is a promising lead in Alzheimer's disease research due to its potent muscarinic receptor antagonist property. We have described here a highly efficient synthetic strategy that resulted in the total synthesis of himbacine (1) in about 10% overall yield and isohimbacine (1a), an unnatural isomer of himbacine, in 18% overall yield. The total synthesis of himbacine was initially approached using an intramolecular Diels-Alder reaction as the key step to generate intermediate 5 followed by a [3 + 2] cycloaddition with nitrone 4 to produce the isoxazolidine derivative 3. Methylation followed by catalytic reduction of 3 gave 12'-hydroxyhimbacine (20), which, upon dehydration, gave isohimbacine (1a) as the sole product. In an alternative approach, an all-encompassing intramolecular Diels-Alder reaction of an appropriately substituted tetraene derivative 31, which bears the entire latent carbon framework and functional group substitution of himbacine, gave the desired advanced tricyclic intermediate 33, which was readily converted to (+)-himbeline (2) and (+)-himbacine (1).
