518-99-0Relevant academic research and scientific papers
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 approach to Galbulimina type I alkaloids
Tchabanenko, Kirill,Chesworth, Richard,Parker, Jeremy S.,Anand, Neel K.,Russell, Andrew T.,Adlington, Robert M.,Baldwin, Jack E.
, p. 11649 - 11656 (2007/10/03)
On treatment with trifluoroacetic acid the tetraene precursor 23 underwent Boc deprotection, condensation and an iminium ion accelerated intramolecular Diels-Alder cycloaddition resulting in an iminium species 12, which was further converted into himbacin
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
Synthetic studies of himbacine, a potent antagonist of the muscarinic M2 subtype receptor 1. Stereoselective total synthesis and antagonistic activity of enantiomeric pairs of himbacine and (2′S,6′R)-diepihimbacine, 4-epihimbacine, and novel himbacine congeners
Takadoi, Masanori,Katoh, Tadashi,Ishiwata, Akihiro,Terashima, Shiro
, p. 9903 - 9923 (2007/10/03)
Total synthesis of an enantiomeric pair of himbacine 1 and ent-1 was achieved in a highly stereoselective manner by employing an intermolecular Diels-Alder reaction of tetrahydroisobenzofuran 8 with chiral furan-2(5H)-one (S)-9 and (R)-9, respectively, as a key step. An enantiomeric pair of (2′S,6′R)-diepihimbacine 24 and ent-24, 4-epihimbacine 4-epi-1, and novel himbacine congeners bearing the same tricyclic moiety as that of 1 were also successfully prepared by utilizing the key synthetic intermediates for 1, establishing the convergency and flexibility of the explored synthetic route. All of the synthesized compounds used were subjected to muscarinic M2 subtype receptor binding affinity assay, disclosing novel aspects of the structure-activity relationships for 1.
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).
Applications of organosulfur chemistry to organic synthesis: Total synthesis of (+)-himbeline and (+)-himbacine
Hart, David J.,Li, Jing,Wu, Wen-Lian,Kozikowski, Alan P.
, p. 5023 - 5033 (2007/10/03)
Total syntheses of (+)-himbacine (1) and (+)-himbeline (2) are described. The synthesis involves the preparation of sulfone 38 and aldehyde 42 as single enantiomers followed by coupling of these compounds using a Julia-Lythgoe olefination. The preparation of sulfone 38 features an acid- promoted intramolecular Diels-Alder reaction of an α,β-unsaturated thioester while the synthesis of 42 features a Beak alkylation of piperidine 39.
