- Combining the [2,3] sigmatropic rearrangement and ring-closing metathesis strategies for the synthesis of spirocyclic alkaloids. A short and efficient route to (±)-perhydrohistrionicotoxin
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This paper describes the use of selenium-based [2,3] sigmatropic rearrangement in combination with ruthenium-catalyzed ring-closing metathesis (RCM) for the synthesis of azaspiro ring systems, as exemplified by the reactions of model substrates 5 and 6. T
- Tanner, David,Hagberg, Lars,Poulsen, Anders
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p. 1427 - 1440
(2007/10/03)
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- A Stereoselective Organopalladium Route toward Perhydrohistrionicotoxin
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An efficient stereocontrolled route to the spirocyclic alkaloid perhydrohistrionicotoxin (2) is described.The readily available 2-substituted 1,3-cyclohexadiene 4 was converted regio- and stereoselectively to the chloro acetate 5 by using organopalladium methodology.Chemoselective SN2' displacement of the chloride via a copper-catalyzed Grignard reaction furnished 6, thus establishing the correct relative configuration at two adjacent centers.Further elaboration to the δ-amino alkene 10 was followed by a completely stereoselective iodocyclization reaction which yielded azaspirocycle 11.This compound was transformed to depentylperhydrohistrionicotoxin (3) in essentially one operation, thus completing a formal total synthesis of the title alkaloid.The overall yield of 3 from 4 was 23percent for nine operations.An alternative route to advanced intermediate 8 was also developed, the key step being the coupling of enol triflate 15 with the appropriate lithium organocuprate reagent.
- Tanner, David,Sellen, Mikael,Baeckvall, Jan-E.
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p. 3374 - 3378
(2007/10/02)
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- Flexible Synthetic Approach to Histrionicotoxin Congeners. Formal Total Synthesis of (+/-)-Perhydrohistrionicotoxin
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Conversion of 1-benzyl-1-azaspiroundec-7-en-9-one (7), readily available using simple organoiron chemistry, in six steps into (+/-)-depentylperhydrohistrionicotoxin (3) is reported.This compound has been previously reported as an intermediate for syn
- Pearson, Anthony J.,Ham, Peter
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p. 1421 - 1425
(2007/10/02)
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- Synthesis of (+/-)-Depentylperhydrohistrionicotoxin
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Palladium(0)-catalysed cyclisation of 3-acetoxy-1-(4-aminoalkyl)cyclohexenes provides convenient access to the 1-azaspiroundecane ring system found in the histrionicotoxins.Hydroboration of the 7-butyl derivative (4; R1 = Bun, R
- Carruthers, William,Cumming, S. Andrew
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p. 2383 - 2386
(2007/10/02)
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- Trimethylsilyl Iodide Catalyzed Spirocyclization of Amines. Synthesis of Perhydrohistrionicotoxin
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A trimethylsilyl iodide catalyzed Michael reaction of an enone amine and a trimethylsilyl iodide catalyzed SN2' spirocyclization of an allylic alcohol amine are the crucial reactions in two new syntheses of perhydrohistrionicotoxin.
- Godleski, Stephen A.,Heacock, Deborah J.
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p. 4820 - 4822
(2007/10/02)
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- (+/-)-2-Depentylperhydrohistrionicotoxin: A New Probe for a Regulatory Site on the Nicotinic Acetylcholine Receptor-Channel
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(+/-)-2-Depentylperhydrohistrionicotoxin (4), several of its analogues, and N- and O-substituted derivatives were prepared and tested for their effects on the neuromuscular transmission of the frog sartorius muscle.Compound 4, its N-methyl derivative 5, the O-acetyl derivative 9, an the quaternary methiodides 19 and 20 blocked the indirectly elicited twich.The oxidation of 4 and 5 to ketones 12 and 14 and their reduction to the epimeric alcohols 17 and 18 afforded materials with substantially reduced activity.N-Acetylation of 4 to 11 changed the course of the activity to a transient potentiation of muscle twich.Both 4 and 5 were not very toxic to mice after subcutaneous administration. (+/-)-7-n-Butyl-1-azaspiroundecan-8-one (12) epimerized readily at room temperature to afford the epimer 13, and preparation of the hydrochloride of its N-methylated derivative 14 was accompanied by the 2-n-butyl-3-cyclohexene-2-one (22).The strongly hydrogen-bonded alcohol 4 was analyzed as the hydrobromide by a single-crystal X-ray analysis, confirming its structure.
- Takahashi, Kimio,Jacobson, Arthur E.,Mak, Chin-Pong,Witkop, Bernhard,Brossi, Arnold,et al.
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p. 919 - 925
(2007/10/02)
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