Necine

The Necines. The most important of these substances and their near derivatives are the following —... 

The Necic Acids. There appears to be much more variety among the necic acids than among the necines, possibly because so little is known about them. Most of them are described briefly under their appropriate alkaloids, but there are at least four which need more detailed description. 

On the evidence available there is no reason to doubt that the necyl-necines or parent alkaloids of this group are constituted normally, in which case (VI p. 613) probably represents a typical retronecine ester. 

Ill spite of their importance, basicity constants rarely figure in descriptions of alkaloids. Figures for a series of alkaloids and related substances were published by Kolthoff in 1925 and have been extensively used. Recently a few more have been added by Schoorl, and Adams and Mahan have provided figures for the whole group of necines, the amino-alcohols resulting from the hydrolysis of the pyrrolizidine group of alkaloids. ... 

The tandem [4+2 /[3+2 cycloaddidon of uitroalkenes is an extremely flexible method for the synthesis of necins. Ail of the stereochemicid artiibutes are subject to a high level of... 

The strategy based on tandem cycloaddition leads to a short and efficient asymmetric synthesis of the pyrrolizidine necine base (-)-hastanecine, as shown in Scheme 8.32.163 Pyrrolizidine alkaloids have a long history for attracting the interest of synthetic chemists because of their physiological properties. The method of Denmark shown in this scheme is very simple and applied to synthesis of various alkaloids. The Lewis acid-promoted [4+2] cycloaddition between 2-acyloxy nitroalkene and chiral vinyl ether gives a nitronate that... 

The development of a new route to allylzirconocene derivatives has prompted further investigations in this area [76—79]. Its elegant application to the synthesis of (—)-macro-necine is noteworthy [116]. More recent investigations have led to an assortment of interesting transformations, as shown in Scheme 1.28 [117,118],... 

Scheme 11.14 The synthesis of building block 44 in the total synthesis of (+)-heliotridine, a necine base present in a large diversity of pyrrolizidine alkaloids [69], a)78 22 mixture of diastereomers.

Highly efficient and stereoselective addition of tertiary amines to electron-deficient alkenes is used by Pete et al. for the synthesis of necine bases [26,27], The photoinduced electron transfer of tertiary amines like Af-methylpyrrolidine to aromatic ketone sensitizers yield regiospecifically only one of the possible radical species which then adds diastereospecifically to (5I )-5-menthyloxy-2-(5//)-furanone as an electron-poor alkene. For the synthesis of pyrrazolidine alkaloids in approximately 30% overall yield, the group uses a second PET step for the oxidative demethylation of the pyrrolidine. The resulting secondary amine react spontaneously to the lactam by intramolecular aminolysis of the lactone (Scheme 20) [26,27]. 

Cbz-4-hydroxy-L-proline was used in the preparation of 72 (the Geissman-Waiss lactone), which is a synthon for necines (82H23). This compound was prepared in eight steps (62JOC139). The alkaloids retronecine, platy-necine, and croalbinecine were prepared from the lactone (83H1331). 

We have extended our work on a new synthesis of the antiprotozoal antibiotic anisomycin to the necine bases of the pyrrolizidine alkaloids, in particular retronecine and crotanecine. The key intermediate, (2R,3S,4R)-2-(alkoxy-carbonylmethyl)-3,4—isopropylidenedioxypyrrolidine, has been prepared by three distinct routes from D-ribose and g-erythrose, using reactions of high stereoselectivity. 

The Geissman-Waiss lactone (7)( ) is a well-known precursor of (+)- retronecine ( ) ( -y-), one of the most common necine bases... 

The dipolar cycloaddition of nitronates has been applied to the synthesis of several natural products in the context of the tandem [4+2] / [3 + 2] nitroalkene cycloaddition process. All of these syntheses have focused on the construction of pyrrolidine, pyrrolizidine, and indolizidine alkaloids. For example, the synthesis of ( )-hastanecine (316), a necine alkaloid, involves the elaboration of a p-benzoy-loxynitroalkene 311 via [4 + 2] cycloaddition with a chiral vinyl ether (312) in the presence of a titanium based Lewis acid, to provide the nitronate 313 with high diastereo- and facial selectivity (Scheme 2.30) (69). The dipolar cycloaddition of... 

The position was resolved by Adams and Van Duuren.79 Platy-necine, when treated with thionyl chloride under mild conditions, yields the cyclic sulfite 128, whereas no analogous compound can be obtained by similar treatment of dihydroxyheliotridane. The sulfite... 

The Lewis acid-promoted tandem inter[4 + 2]/intra[3 + 2]-cycloaddition of the (fumaroyloxy)nitroalkene (124) with the chiral /i-silylvinyl ether (125) is the key step in the total synthesis of (+)-crotanecine (126), the necine base of a number of pyrrolizidine alkaloids (Scheme 46).237 The tandem inter[4 + 2]/intra[3 + 2]-cycload-ditions of nitroalkenes (127) with dipolarophiles attached to the /f-carbon of a vinyl ether (128) provides a method of asymmetric synthesis of highly functionalized aminocyclopentanes (129) (Scheme 47).238 trans-2-( 1 -Methyl-phenylethyl)cyclohex-anol has been developed as a new auxiliary in tandem 4 + 2/3 + 2-cycloadditions of nitroalkenes.239 The scope and limitations of the bridged mode tandem inter-[4 + 2]/intra[3 + 2]-cycloadditions involving simple penta-1,4-dienes are described in detail.240 A tandem intermolecular/intramolecular Diels-Alder cycloaddition was successfiilly used to synthesize a B/C cA-fused taxane nucleus (130) in 50% overall... 

The number of synthetic routes to the natural 1-hydroxymethyl-pyrrolizidines continues to increase. Robins and Sakdarat have achieved the first synthesis of these necines in optically active form, using natural (-)-4-hydroxy-L-proline as a chiral template.2 The dihydropyrrolizine ester (2) was prepared by regiospecific 1,3-dipolar cycloaddition of ethyl propiolate to the N,0-diformyl derivative (1) of (-)-4-hydroxy-L-proline, followed by deformylation (Scheme 1). Addition... 

Tufariello has reviewed his strategy for the synthesis of alkaloids (including necine bases) using the 1,3-dipolar cycloaddition of nitrones to alkenes.5 This work began with the synthesis of ( )-supinidine (7) from 1-pyrroline 1-oxide (see these Reports, Vol. 2, Ch. 4). A related approach has been used by Iwashita et al. in their synthesis of ( )-isoretronecanol (5).6 The stereochemistry of the exo-product (8), formed by regiospecific 1,3-dipolar cycloaddition of 1-pyrroline 1-oxide to dihydrofuran (Scheme 2), was confirmed by its conversion into... 

A phytochemical study of Crotalaria species has revealed the presence of 1-methylenepyrrolizidine (68) in four new species, namely C. grandistipulata Harms, C. lachnophora A. Rich, C. natalitia Meissner, and C. stolzii (Baker fil.) Milne-Redh. ex Polhill.38 The necine (69) is probably present in C. cylindrocarpa DC and C. podocarpa DC.38... 

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