Alkaloids formation, scheme

The reaction of 2-(a-pyridyl)alkylmalonic acid with J -piperideine leading to formation of 3-((x-pyridyl)quinolizidine-l-carboxylic acid on decarboxylation, has been used by Van Tamelen and Foltz (316) for the syntheis of the alkaloid lupanine (Scheme 20). A very elegant synthesis of matrine has been accomplished by Bohlmann et al. (317). 

The heteroatom version of the vinylcyclopropane rearrangement serves to facilitate alkaloid construction. Scheme 13 outlines a strategy for the pyrrolizidine alkaloid isoretronecanol 211 90). Use of a carboxaldehyde (i.e. 213) as a synthon for the primary alcohol provides an ability to adjust stereochemistry. It also sets up formation of the pyrrolidine ring bearing the aldehyde by an aldol-type condensation of an enol of the aldehyde onto an imine derived from 214. Because of the lability of such systems, introduction of X=PhS imparts stability. The resultant azacyclopentene translates to an imine 215 using the iminocyclopropane rearrangement methodology. Simple condensation of the primary amine 216 with aldehyde 37a then initiates this... 

As indicated previously, amides (carbamates) (120) are susceptible to oxidation at an alkyl center adjacent to nitrogen. The resulting acyl imminium ion (121) can be intercepted by a variety of nucleophiles in a process that sets the stage for subsequent carbon-carbon formation (Scheme 30). As the following discussion illustrates, the creative utilization of this protocol provides an exceptionally useful entry to a host of alkaloids. 

About the same time a number of publications appeared on the complete synthesis of 7a, 7b, 30 and 31 using a different approach to build the alkaloid framework (Scheme 5 68M1364, 68M1584, 69JCA(C)2738). Phenylhydrazone 34 under Fischer reaction conditions was converted into indole 34a with subsequent successive transformations to pentacyclic derivative 35. Its acid-initiated rearrangement led to the formation of 7b and 30 in a ratio of 1 5. While 7b and... 

The formation of the tricyclic 9a-arylhydrolilolidine ring system is exemplified in the conversion of (154) to (155). Wolff ring contraction of the ketonic ring of (155) and further functional group modifications provided the Melodinus alkaloid ( )-meIoscine. (Scheme 55). 

Intramolecular photocyclization of an isonitrile onto an indole ring has been proposed to explain the formation of the dimer 90 upon photolysis of the novel isonitrile containing indole alkaloids 91 (Scheme 51) [101]. 

The formation of benzofuranoid and analogous ring systems seems to follow a common pathway. In the rotenoid amorphigenin (25) the sequence is shown in Scheme 3. Here all five carbon atoms are retained. With the furanocoumarins there is a loss of three carbon atoms but the initial stages are probably analogous. Several studies on these sequences are summarized in Scheme 4. A similar process occurs in the biosynthesis of furanoquinoline alkaloids (see Scheme 5). 

The first naphthyl isoquinoline alkaloid to be synthesized in optically active form was ancistrocladine (1) itself, the most important and widespread of all the Ancistrocladus alkaloids (see Scheme 31). The effectivity of the ester bridge assisted aryl coupling method (as presented in Section V.D.) was demonstrated by the regioselective formation of the highly strained lactone 124, which— different from the corresponding triphyophylline precursor 108 (see Scheme... 

The acid-catalysed rearrangement of thevinols has been shown to proceed with retention of configuration at C(7) and therefore not via an -hybridised centre at C(7) as had been previously proposed. A proposed mechanism for the rearrangement is shown in Scheme 100. Cathovaline-like compounds have been prepared from the rearrangement of vindoline derivatives in superacidic media,and the observed formation of the bridged 16-spiro compound (350) upon acetic anhydride-pyridine treatment of the hydroxyindolenine (349) represents a new rearrangement in iboga alkaloids see Scheme 101. 

In studies devoted to the synthesis of the alkaloid (+)-montabuphine (Scheme 25.50), the octahydroindole moiety was assembled by a radical addition/elimination process from 104, which embodies a sulfide as the proradical and a vinylhaUde as the radical acceptor. After the formation of the C C bond, the resulting cyclohexyl radical underwent a fragmentation process with the adjacent chlorine atom to diastereoselectively give 105. ... 

During studies on the acid-induced formation of the alkaloid yuehchukene and related structures from pienylindoles, it was discovered that treatment of indole 173 with p-toluenesulfonic acid and silica gel leads to the formation of indolo-[3,2-b]carbazole 174 and the indole derivative 175 (Scheme 21). Similarly, the disubstituted product 176 could be isolated after TFA treatment of the substrate 177. Detailed mechanistic explanations have also been provided in this work (96T9455). 

Leptopinine 82 possesses the 3,4-dihydro-isoquinolin-7-ol moiety without further conjugation and was isolated as yellow powder from Hypecoum leptocarpum after several extractions with hydrochloric acid so that this alkaloid was finally isolated as a chloride (Scheme 29). The formation of a mesomeric betaine from this dihydroisoquinoline derivative is unlikely because on addition of base no significant changes of the UV spectra were observed (99P339). A similar structure is Pycnarrhine Pycnarrhena longifolia), which was isolated as a hydroxide (81P323). 

Oxidation of the alkaloid Glaucin (136) resulted in the formation of a yellow alkaloid 137, which seemingly is contained in Glaucium flavum var. vestitum (Scheme 48). Addition of methyl iodide converted this compound via a methylation/ether cleavage sequence into Corunnine (127) and small amounts of Pontevedrine (138) which is not a mesomeric betaine (71TL3093). 

Quaternization of harman (235) with ethyl bromoacetate, followed by cyclization of the pyridinium salt 236 with 1,2-cyclohexane-dione in refluxing ethanol yielded an ester which on hydrolysis gave the pseudo-cross-conjugated mesomeric betaine 237. Decarboxylation resulted in the formation of the alkaloid Sempervirine (238). The PCCMB 237 is isoconjugate with the 11/7-benzo[u]fluorene anion—an odd nonalternant hydrocarbon anion—and belongs to class 14 of heterocyclic mesomeric betaines (Scheme 78). 

The papaver alkaloid Narcotoline (265) can be converted into the yellow colored Cotarnoline (267) on hydrolysis which adopts a zwitterionic ground state (56MI1, 57MI1) (Scheme 87). The corresponding dihydro derivative was also identified in nature. The UV spectrum of the zwitterionic Tarkonine (268), which forms red crystals from acetone, is shifted bathochromically in comparison to the chloride. Tarkonine is a very weak base (pA b = 9.58), which is well in accord with the formation of an inner salt, and Cotarnoline (267) is a stronger base than Tarkonine (268) (pA b = 9.15). The pK values are larger than 13 (66MI3). The methylated derivative of Narcotoline is Narcotine (266). 

Hudlicky and coworkers also reported a related 2-pyrroline formation from viny-laziridines [81], which are extremely useful for the synthesis of pyrrolizidine alkaloids such as the protected (+)-trihydroxyheliotridane 210 (Scheme 2.51). Since the pyrolysis of either diastereomer of 208 furnished the cyclized product 209 as a... 

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