Synthesis of Nuphar Alkaloids

Scheme 9. Routes for the synthesis of Nuphar alkaloids from nitrones.

Quinolizidines 965 and 966, potentially useful intermediates for the synthesis of Nuphar alkaloids, have been prepared by reducing the quinolizinium salt precursor 967 with sodium cyanoborohydride in ethanol-acetic acid (616). Compound 967 was itself prepared by Hantzch condensation of ethyl (5-benzoyloxy-2-pyridyl)acetate with the ethyl enol ether of 3-furoylacetaldehyde. 

In a projected synthesis of Nuphar quinolizidine alkaloids, it was shown by X tay analysis that the reaction of the pyridine... 

Valenta and Liu have given an account of the structure and synthesis of Ormosia alkaloids, and a review of the Nuphar alkaloids has been published. Carbon-13 n.m.r. and mass spectroscopy of quinoiizidine alkaloids have been reviewed. 

An optically active piperidine ring has been constructed by an intramolecular aza-Wittig reaction allowing a concise enantiospecific synthesis of nuphar piperidine alkaloids, among them (-)-anhydronupharamine (118), which has a sesquiterpenoid structure... 

Although the detection and isolation of bicyclic, tricyclic, and tetracyclic quinolizidine alkaloids and stereochemical studies, increasingly aided by X-ray analysis, proceeds apace, the main emphasis this year is on synthesis of the Nuphar, azaphenalene, and phenanthroquinolizidine alkaloids. 

Alder reaction [524, 525]. Danishefsky et al. have used nitroso dienophiles for the synthesis of mitomycin K and antibiotics of the FR 900482 family, the latter ones are structurally unique aziridino-l,2-oxazine derivatives [526-529]. An approach directed to the cephalotaxus alkaloids has been worked out by Fuchs et al. [530], and several indolizidine alkaloids have been prepared by Keck s [531] and Kibayashi s groups [532,533]. Kibayashi et al. also synthesised Nuphar piperidine alkaloids in enantiomerically pure form by means of an asymmetric nitroso Diels-Alder reaction [534]. 

Once again the azaphenalene, Nuphar, and Lythraceae alkaloids are included in this Chapter. Perhaps the most notable achievement of the year is the synthesis of azaphenalenes of ladybird beetles by Ayer and co-workers.Amongst the new alkaloids, the novel pyridone quinoiizidine, mamanine (3) and its tetrahydro-derivative, pohakuline (5) are of special interest. ... 

A stepwise formal [3+3] cycloaddition reaction entailed the generation of the dianion of 168, transmetalation with MgBr2, and addition of aziridine 169 to give intermediate 170. A Mitsunobu reaction to give 171 completed the sequence with an overall yield of >90% <05OL2993> (Scheme 48). This strategy was applied to other aziridines in the preparation of 3-methylenepiperidine intermediates for the total synthesis of several Nuphar alkaloids <05JOC207>. 

Cycloadditions. Harrity and co-workers have explored Pd-TMM reactions with activated aziridines, which generate [3 +3]-cycloadducts. They have used this reaction in their synthesis of (—)-Castoramine and other Nuphar alkaloids. In this particular case, the reaction of 18 gave only a modest yield of the desired product 19 along with other substances arising form aziridine ring opening (eq 35). 

Harrity and coworkers approached the enantioselective synthesis of three Nuphar alkaloids by using a formal [3 - - 3] cycloaddition to construct the C-6/C-9 piperidine ring (Scheme xhe ester groups of the... 

In 2005, Honda et al. pubhshed a first total synthesis of a quinohzidine alkaloid using RCM as one of the key steps, namely, (—)-deoxynupharidine (246) [80]. The alkaloid was isolated from plants of the genus Nuphar and exhibited amongst others immunosuppressive activity. Its synthesis commenced with a stereoselective construction of the enantiopure 5,6-disubstituted piperidinone building block 244 by modification and ring expansion of the protected D-pyroglutamic acid derivative 243 (Scheme 2.53). Subsequent RCM of 244 (catalyst [Ru]-II, benzene, 60°C) afforded quinolizidinone 245 in 96% yield, whereafter three consecutive steps led to the natural product itself... 

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