Rearrangement alkaloids

R = H) undergoes a variety of enzyme-catalyzed free-radical intramolecular cyclization reactions, followed by late-stage oxidations, eliminations, rearrangements, and O- and N-alkylations. Working from this generalization as an organizing principle, the majority of known AmaryUidaceae alkaloids can be divided into eight stmctural classes (47). 

Reactions at the aromatic nucleus that are quite different from the usual mild condensations and rearrangements which apparendy generate the typical alkaloids already discussed must be iavolved. Securinine (137) is reported to stimulate respiration and increase cardiac output, as do many other alkaloids, but it also appears generally to be less toxic (98). 

The principal steps in the mechanism of polyisoprene formation in plants are known and should help to improve the natural production of hydrocarbons. Mevalonic acid, a key intermediate derived from plant carbohydrate via acetylcoen2yme A, is transformed into isopentenyl pyrophosphate (IPP) via phosphorylation, dehydration, and decarboxylation (see Alkaloids). IPP then rearranges to dimethylaHyl pyrophosphate (DMAPP). DMAPP and... 

Chemical Properties. Reactions of quaternaries can be categorized iato three types (169) Hoffman eliminations, displacements, and rearrangements. Thermal decomposition of a quaternary ammonium hydroxide to an alkene, tertiary amine, and water is known as the Hoffman elimination (eq. la) (170). This reaction has not been used extensively to prepare olefins. Some cycHc olefins, however, are best prepared this way (171). Exhaustive methylation, followed by elimination, is known as the Hoffman degradation and is important ia the stmctural determination of unknown amines, especially for alkaloids (qv) (172). 

H-Indole, 3,3-dichloro-synthesis, 4, 369 3H-Indole, 3,3-dimethyl-synthesis, 4, 224 3H-Indole, 3-hydroperoxy-autoxidation, 4, 247 rearrangement, 4, 249 3H-Indole, 3-oximino-synthesis, 4, 209, 210 3H-Indole, 3-oximino-2-phenyl Beckmann rearrangement, 4, 210 Indoleacetic acid synthesis, 4, 337 Indole-3-acetic acid as growth regulator, 4, 372 synthesis, 4, 346 Indole alkaloids, 4, 373 synthesis, 4, 276... 

The C-nor-D-homosteroid rearrangement was discovered by Hirschmann and co-workers at the time that Wintersteiner and his collaborators established that the steroid alkaloids jervine and veratramine incorporate a 14 (1312) abeo-nng system. This was the predecessor of the family of simultaneous ring contraction-expansion reactions. Solvolysis of the 12j5-methanesulfonate (144a) gives mainly the kinetic reaction product, the C-nor-D-homo exocyclic olefin (145) along with some 13(17)-ene (146a). 

The enamine-imine tautomerism of the indolenine system gives rise to rearrangement reactions of interest in indole alkaloid chemistry. Thus the synthesis of dihydroburnamicine (625) utilized the rearrangement of an acetoxyindolenine to an a-hydroxyalkyl indole, presumably through an intermediate enamine. Similarly 2,3-dialkyl indoles undergo oxidations to 2-acyl indoles (626-631). 

Scheme 2.52 Aza-[2,3]-Wittig rearrangements of vinylaziridines 213 and alkaloid syntheses.

Blechert s synthesis of the piperidine alkaloid (-)-halosaline (387) by Ru-catalyzed RRM is outlined in Scheme 76 [160]. In the presence of 5 mol% of catalyst A, the ring rearrangement of metathesis precursor 385 proceeded cleanly with formation of both heterocyclic rings in 386. In situ deprotection of the cyclic silyl ether in 386, followed by selective reduction and removal of the to-syl group led to 387. 

Aziridinocyclopropanes 163 derived from 2-phenylsulfonyl-l,3-dienes undergo BF3-induced rearrangement to bicyclic amines 165, which feature the skeleton of the tropane alkaloids. The reaction proceeds via cyclopropyl carbinyl cation 164, an intermediate also invoked in the analogous epoxide rearrangements. Trapping by fluoride ion is a competing pathway <96TL3371>. 

The xanthene unit of the dibenzopyranoazepine alkaloid, clavizepine, has been obtained from a dibenzoxepinediol by a pinacol rearrangement <96JOC5818>. 

Wiesler U-M, WeU T, Mullen K (2001) Nanosized Polyphenylene Dendrimers. 2/2 1 - 40 WUliams RM, Stocking EM, Sanz-Cervera JF (2000) Biosynthesis of Prenylated Alkaloids Derived from Tryptophan. 209 97-173 Wirth T (2000) Introduction and General Aspects. 208 1-5 Wirth T (2003) Introduction and General Aspects. 224 1-4 Wirth T (2003) Oxidations and Rearrangements. 224 185-208... 

Likewise, treatment of sulfoxide 1254 with Me3CSi(Me)20Tf 987/NEt3 induces rearrangement via 1255 to give 30% of the aspidosperma alkaloid 1256 and 25% starting material 1254 [51] (Scheme 8.20). 

Scheme 6.17 gives some examples of the orthoamide and imidate versions of the Claisen rearrangement. Entry 1 applied the reaction in the synthesis of a portion of the alkaloid tabersonine. The reaction in Entry 2 was used in an enantiospecific synthesis of pravastatin, one of a family of drugs used to lower cholesterol levels. The product from the reaction in Entry 3 was used in a synthesis of a portion of the antibiotic rampamycin. Entries 4 and 5 were used in the synthesis of polycyclic natural products. Note that the reaction in Entry 4 also leads to isomerization of the double bond into conjugation with the ester group. Entries 1 to 5 all involve cyclic reactants, and the concerted TS ensures that the substituent is introduced syn to the original hydroxy substituent. 

Biosynthesis of the spirobenzylisoquinoline alkaloid ochotensimine (282) via the quinomethide intermediate (Scheme 49) was proposed by Shamma and Jones (7J0). On the basis of this hypothesis, several biomimetic transformations of phenolic protoberberines to spirobenzylisoquinolines have been realized by the base-induced rearrangement via the quinomethide. 

In conclusion, although the Stevens rearrangement of a tetrahydroproto-berberine metho salt readily afforded a spirobenzylisoquinoline skeleton, there exist no reports on synthesis of functionalized spirobenzylisoquinolines or related alkaloids using this method. 

Bentley and Murray (201) reported another method for synthesis of protopine alkaloids allocryptopine (392) and cryptopalmatine (395) from tetrahydroprotoberberine /V-oxides (35a and 400) through oxidative rearrangement with potassium chromate (Scheme 73). 

Rearrangement of spirobenzylisoquinolines, having a hydroxyl group on ring C trans to the nitrogen, to indenobenzazepines was first reported by Irie et al. (209,210) in their synthesis of rhoeadine alkaloids (Section V,G,1). This... 

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