Azaspiro- -undecan

Histrionicotoxins represent a unique structural class of alkaloids found only in dendrobatid frogs (see below). Somewhat similar hydroxy-azaspiro-undecanes, namely, sibirine, nitramine, and isonitramine, occur in certain plants of the genus Nitraria (cf. Ref. 70). 

For 5-(2-diazo-l,3-dioxobutyl)-l-oxa-5-azaspiro[5,5]undecane (313), intramolecular carbenoid insertion into a (N)C—H bond represents quite an unusual way of constructing a P-laetam ring 285). 

Heteroatom Oxidation, Dehydrogenation Electrooxidative kinetic resolution of rac alcohols mediated with a catalytic amount of an optically active A-oxyl was performed in an undivided cell at constant current conditions. A high enantiomeric purity for the recovered alcohol was found, which could be increased by electrolysis at lower temperatures. The optically active A-oxyl was recovered and used repeatedly without change in efficiency and selectivity [368]. Cyclovoltammetry with the A-oxyl (GR, 7S, 10/f)-4-oxo-2,2,7-trimethyl-10-isopropyl-l-azaspiro[5.5]undecane-A-oxyl as catalyst showed for rac-1-phenylethanol a highly enhanced catalytic... 

The 2-azaspiro[5.5]undecane group of alkaloids occur in certain plants of the genus Nitraria. There has been some interest in the biological activity of these alkaloids because their structures are similar to the histrionicotoxins, a group of... 

Further comparative studies77-79 have been carried out with N<3-dimethyl-aminopropyl)-8,8-dimethyl-2-azaspiro[4.5]decane 101a) and N-(3-dimethylamino-propyl)-9,9-dimethyl-3-azaspiro[5.5]undecane 102a) and their sila-analogues 101b and 102b, respectively. 

Tetranitro-2,4,8,10-tetra-azaspiro(5.5)undecane (TNSU) (KEMTIF)... 

Anodic oxidation in the synthesis of piperidine alkaloids 90YGK814. Antitumor sesbanimides, total synthesis of 87YGK983. l-Azaspiro[5.5]undecane system of histrionicotoxines, syntheses of 89BSF370. 

Cumulative Index of Heterocyclic Systems 2-Oxa-7-azaspiro[4.6]undecane (1311)... 

Hbtrionlcotoxins. Alkaloids from arrow poison frogs (Dendrobatidae) of the genera Dendrobates, Epipedo-bates, and Phyllobates with a l-azaspiro[5.5]undecane ring system. The 16 presently known H. have unsatu-... 

The synthesis of the natural product (-)-sibirine (72), a compound containing an unusual 2-azaspiro[5,5]undecane skeleton, was described by Iwata [53], The method involved initial attack of allylmagnesium bromide on the non-racemic vinylic sulfoxide (73) (Scheme 4.38), followed by a Pummerer-type reaction (or isomerization) of the double bond as illustrated in Scheme 4.39 [54]. 

Kashiwagi Y, Kurashima F, Chiba S.Anzai J, Osa T, Bobbitt TM (2003) Asymmetric electrochemical lactonization of diols on a chiral l-azaspiro[5.5] undecane Al-oxyl radical mediator-modified graphite felt electrode. Chem Conununll4-115. doi 10.1039/ B209871G... 

Cl9H23CI2N5O, 2- 3-[4-(m-Chlorophenyl)-1-piperazinyl]propyl -s-tri-azolo-[4,3-a]-pyridin-3(2H)-one hydrochloride, 45B, 279 Cl9H24CINO5 H2O, 1-(3,4,5-Trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate, 45B, 279 C19H2 eClNO, 7-(cis-1-Buten-3-yny1)-8-hydroxy-2-(3,4-pentadienyl)-1 -azaspiro[5.5]undecane hydrochloride, 39B, 203 C19H28N4O7, 8a-t-Butyl-trans-decahydroquinoline picrate, 46B, 260 C19H28N4O7, 8 -t-Butyl-trans-decahydroquinoline hydrogen picrate, 45B, 280 46B, 260... 

Y. Inubushi and T. Ibuka, Synthesis of l-Azaspiro[5,5]undecanes Stereoselective Synthesis of Perhydro- and Octahydrohistrionicotoxin , Heterocycles, 1982, 17, 507. 

Diene)Fe(GO)3 complexes have been used to construct 2-azaspiro[5.5]undecane and tricyclic ring systems. Intramolecular coupling reactions between diene-Fe(GO)3 complexes and a pendant olefinic group or pendant alcohols have been studied.The cyclization of allylic thioester-functionalized cyclohexadiene iron tricarbonyl... 

A synthesis of the azaspiro-[5.5]-undecan-8-ol ring system characteristic of the histrionicotoxins was first reported in 1975 in 30% overall yield by Gossinger etal. (SchemeXXI) (11. The carbon-13 magnetic resonance spectral peaks for azaspiro-[5.5]-undecan-8-ol were as follows 67.5 (C-8), 52.0 (C-6), 40.8 (C-2), 40.0,38.5,37.4,33.7,27.5,20.0,15.9. The base peak in the mass spectra was at m/z 126. No major ion at m/z 96 was included in the mass spectral tabulation. Infrared and proton magnetic resonance data were reported. The synthetic approach was not successful for the synthesis of 7-n-butylazaspiro-[5.5]-undecan-8-ol, a desamyl-analog of perhydro-histrionicotoxin. This compound has now been synthesized by Takahashi etal. (246). 

SchemeXXL Synthesis of azaspiro-[5.5]-undecan-8-ol (115). The route proved unsuccessful for synthesis of 7-butylazaspiro-[5.5]-undecan 8-ol (see reaction IX). A i) HgO. B i) 5-Pentenyl MgBr, ii) HgO. C i) 110". D i) 190". E i) Raney nickel, H2...

Scheme XXII. Synthesis of precursors for the elaboration of histrionicotoxins (reaction ABC, 28 DEFG, 166 HI, 44 JKL, 205). For further references to syntheses related to the azaspiro-[5.5]-undecane system see 147). A i) HOCH2CH2OH, H, ii) CH2 = CHCO2CH3, iii) NaOH, iv)SOCl2, v)CH2N2, vi)a. (C2H5)3N, b. AgBF4, CH3OH. B i) Raney nickel, H2,...

Scheme XXXII. Cyclizations leading to hexahydroquinolines rather than the desired azaspiro-[5.5]-undecan-8-ones (70). A i) B i) Methylfluorosulphonate, ii) NaHCOa...

Scheme XXXVI. Cyclization leading to an azaspiro-[4.5]-decane system rather than the desired azaspiro-[5.5]-undecane (259). A i) SOCb, pyridine, ii) NaNHi, NH3. B i) Dihydropyran, ii) n-ButylLi, methyl chloroformate, iii) Toluenesulphonic acid, iv) Lindlar s Pd, H2, v) CrOa, vi) Oxalyl chloride. C i) Cul, hexamethylphosphoric triamide, ethyl 4-lithiobutylacetaldehyde acetal. D i) HCl, ii) CH3SO2CI, (C2H5)3N, iii) LiBr, iv) NaN02. E i) Zn, NH4CI. F i) Heat...

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