Applications lycorine

The first asymmetric total synthesis of (+)-lycorine is outlined in Scheme 15. While our earlier applications of the Birch reduction-alkylation of chiral benzamide 5 were focused on target structures with a quaternary stereocenter derived from C(l) of the starting benzoic acid derivative, the synthesis of 64 demonstrates that the method also is applicable to the construction of chiral six-membered rings containing only tertiary and trigonal carbon atoms. s... 

A comparison of the molecular rotations of lycorine and 2-epilycorine provided the first evidence for the absolute configuration of alkaloids of the lycorine type by the application of Mills rule. The development of suitable chemical methods of interconversion between the lycorine- and lycorenine-type alkaloids permitted an additional correlation between the two types by the Hudson-Klyne lactone rule. These assignments have recently been shown to be correct by X-ray crystallographic methods (65). With these findings the structure and absolute configuration of lycorine is described by I (R, Ri = H). The absolute configurations of many of the alkaloids discussed in Section III also are secure because these alkaloids have been interrelated and converted to known compounds of the lycorine series. 

Application of Mills rule (7) to the pairs lycorine-epilycorine and 0,0-diacetyIlycorine-0,0-diacetyl-2-epiIycorine showed that the epi series was more negative in molecular rotation, and hence the configuration at C-2 should be as in I (R, Ri = H) for lycorine (71). The absolute configuration shown for lycorine has been confirmed by X-ray methods (65). Supplementary evidence for the structures of lycorine and several derivatives has been obtained from detailed CD-, ORD-, and NMR-studies (72). 

Because pluviine and methylpseudolycorine are less abundant than their methylenedioxy analogs, caranine and lycorine, it was desirable to find methods of interconversion between the two series of alkaloids so that observations in the methylenedioxy (lycorine) series would also be applicable to the dimethoxy (methylpseudolycorine) series. Ethanolic potassium hydroxide cleaved a-dihydrocaranine (XIV R = H) to an ethoxy methyl ether (XXXVI) which was converted to a-dihydropluviine (XXXVII) by acid hydrolysis and methylation with diazomethane (77). 

Absolute configurations were first assigned to alkaloids of this section both by chemical transformations to compounds in the lycorine series where Mills rule had been applied and by Klyne s modification of the Hudson lactone rule. This extension states that lactones possessing the absolute configuration of XLVII are more positive in molecular rotation than derivatives in which the lactone ring is opened. If this rule is applicable to the alkaloids of this section, the conversion of homolycorine (XLVIII [M]d -f-268°) to tetrahydrohomolycorine (XLIX [M]d —322°) requires that homolycorine and tetrahydrohomolycorine have the absolute configurations shown in XLVIII and XLIX. These assign-... 

Full details are now available of Torssell s synthesis of l-desoxylycorin-7-one (15) (cf. Vol. 5, p. 172). ° Application of the phenylselenium bromide procedure to the lactam (12) led to an improved synthesis of the enol (13), which by acid-catalysed allylic rearrangement was converted into the allylic acetate (14) (Scheme 1) lycorine (16) has already been prepared from the latter compound. 

Galanthamine also blocks acetylcholine estaase activity. One of the new applicaticms of galanthamine is in a treatment of Alzheimer s disease (AD). Moreover, this natural (and presently also synthetically driven) alkaloid can be used in decreasing negative side effects caused by applications of nondepolarizing alkaloids, for example, those of tubocurarine. Acetylcholinesterase activity is reported to depress and inhibit by lycorine and its derivatives. Lycorine is an object of therapeutic approaches to cure AD and decrease a level of esterase activity, Other alkaloids from the Amaiyllidaceae plant family are probably useful for these purposes and are being researched. 

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