192133-37-2Relevant academic research and scientific papers
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.
A novel total synthesis of (+)-himbacine, a potent antagonist of the muscarinic receptor of M2 subtype
Takadoi, Masanori,Katoh, Tadashi,Ishiwata, Akihiro,Terashima, Shiro
, p. 3399 - 3402 (2007/10/03)
The title total synthesis was achieved by a method featuring highly stereoselective intermolecular Diels-Alder reaction of the tetrahydroisobenzofuran 5 with the chiral butenolide 6 as the key step. The cycloadduct 4 was converted to the title alkaloid by way of the known sulfone 2 in 17 steps.
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.
