Lycoricidine

The Michael addition of the copper-zinc reagent derived from ethyl 4-bromobntyrate to the plperonal-derived nitroalkene proceeds cleaniy to give the nitre ester, which is an intermediate for the synthesis of lycoricidine alkaloids fEq. 4.85. ... 

Fessner et al. have reported an elegant strategy for the stereospecific synthesis of novel pancratistatin analogs [42]. The pancratistatin alkaloid and its closely related natural congeners, including notably trans-dihydrolycoricidine and the anhydro and deoxy derivatives narciclasine and lycoricidine (Figure 4.2), have attracted considerable attention due to their biological activities [43]. 

Total synthesis of (-l-)-lycoricidine, (—)-lycoricidine and (-l-)-narciclasine via 6-exo cyclization of substituted vinyl radicals with oxime ethers has been reported . Thus, interaction of oxime ether 321 with thiophenol and then with Sml2 and TFA afforded (-l-)-lycoricidine 322 in good overall yield (equation 139). 

Lycoris aura (L Her.) Herb. L. longituba Y. Han et Fan L. radiata (L Her.) Herb. Shi Suan (Amaryllis) (rhizome) Galanthamine, lycoremine, lycorine, lycoramine, lycorenine, tazettine, pseudolycorine, dihydrolycorine, homolycorine, lycoricidine, lycoricidinol.33 As a cholinesterase inhibitor, lower blood pressure, stimulate secretion from the pituitary gland, increase natidiuretic hormone secretion. 

Whereas narciclasine (215) had been previously shown to be identical with lycoricidinol, the mutual identity of lycoricidine (214) and margetine has now also been established by a comparison of the H-NMR spectra of the derived triacetates (141). Although the names narciclasine and margetine have chronological priority, common usage appears to have, established narciclasine and lycoricidine as the preferred names. In agreement with a previous recommendation (141), and to avoid any further confusion in the literature, this nomenclature should be maintained. 

The majority of the approaches that have been adopted for the synthesis of narciclasine (215), lycoricidine (214), and related alkaloids have involved the strategy of constructing the ring system in the order A — C —> B. There have also been examples of the A — BC and C —> A —> B type. 

The total synthesis of ( )-lycoricidine (214) from the aryl cyclohexene 272, which was accessed by a Diels-Alder reaction of the carbinol 46, has been... 

Narciclasine has been detected along with traces of lycoricidine in Qalanthus nivalis L. 

Hymenocallis hybr. var. Advance contains only lycoricidine (101). 

Nearly equal amounts of narciclasine and lycoricidine have been detected in Lycoris radiata Herb. (78). 

Independently, lycoricidine and lycoricidinol, two lactams which presented physical and chemical properties identical with those of margetine and narciclasine, respectively, were isolated from Lycoris radiata. A different interpretation of the physical and chemical data... 

Several syntheses of phenanthridone derivatives related to the aromatization products of narciclasine and lycoricidine and apparently designed to further support the structural revision have been completed. In a photochemical synthesis starting from 368 the compound 360 was obtained yielding on debenzylation narciprimine (356), whereas from 369 in an analogous way arolycoricidine (361) was prepared. Also, starting from the amide 370 through photocyclization to 362 via 363 a compound identical with natural permethylisonarciprimine (357) was obtained (81). 

In efforts aimed at delving into structure-activity relationships, the lycoricidine-type compound (27), lacking two hydroxy-groups of the parent alkaloid, has been synthesized (Scheme 3).10 The known carboxylic acid (25) (see Vol. 7 of these... 

Many further important natural product syntheses are covered by the aforementioned review. Particularly noteworthy amongst them are Hudlicky s syntheses of conduramines [522] and (+)-lycoricidine [523] since they employ enantioselective microbial oxidations of halobenzenes as source of chirality. Racemic lycoricidine has also been prepared by Martin et al. this synthesis exhibits an interesting Heck cyclisation as key step in addition to the hetero Diels-... 

C2 epimer failed [309]. Inversion of configuration at C2 was thus performed and final deprotection gave enantiomerically pure lycoricidine 402. 

Chida, N, Ohtsuka, M, Ogawa, S, Stereoselective total synthesis of (+)-lycoricidine. Tetrahedron Lett., 32, 4525-4528, 1991. 

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