Pyrrolizidine 3.5- dimethyl

Note It is reported that the use of chlorobenzene as solvent is essential when the reagent is to be used to detect aromatic amines [1]. In the case of steroids, penicillins, diuretics and alkaloids the reaction should be accelerated and intensified by spraying afterwards with dimethylsulfoxide (DMSO) or dimethylformamide (DMF), indeed this step makes it possible to detect some substances when this would not otherwise be possible [5,9-11] this latter treatment can, like heating, cause color changes [5,9]. Penicillins and diuretics only exhibit weak reactions if not treated afterwards with DMF [10, 11]. Steroids alone also yield colored derivatives with DMSO [9]. Tlreatment afterwards with diluted sulfuric acid (c = 2 mol/L) also leads to an improvement in detection sensitivity in the case of a range of alkaloids. In the case of pyrrolizidine alkaloids it is possible to use o-chloranil as an alternative detection reagent however, in this case it is recommended that the plate be treated afterwards with a solution of 2 g 4-(dimethyl-amino)-benzaldehyde and 2 ml boron trifluoride etherate in 100 ml anhydrous ethanol because otherwise the colors initially produced with o-chloranil rapidly fade [12]. 

Dipolarophiles D14. The 1,3-dipolar cycloaddition of nitrones to dimethyl maleate and dimethyl fumarate is widely used in the synthesis of polyhydroxy alkaloid derivatives of dihydroindolizidinone (81), pyrrolizidine (119), (—)-codonopsinine, and (+ )-hyacinthacines Ai and A2 (312). In cases of unstable nitrones, syntheses of cycloadducts are performed in situ (81). 

Cycloaddition reaction of nitrone (—)-(394) with dimethyl maleate D14 has been used for the synthesis of two new polyhydroxyl pyrrolizidines (687) and (688) (Schemes 2.293, 2.294). These compounds are analogs of alkaloids ros-marinecine and crotanecine, which were assayed for their inhibitory activities toward 22 commercially available glycosidase enzymes. One of them ((-)- a-epi-crotanecine) (—)-(688) is a potent and selective inhibitor of a-mannosidases (310). The reaction of (—)-(394) with dimethyl maleate gave a 9.6 6 1 mixture of cycloadducts (—)-(680), (+ )-(680), and (—)-(681), which arise from anti-exo,... 

A new synthesis of pyrrolizidine, which is based on the reaction of bis-tertiary glycols with co-chloronitriles, was reported by Meyers and Libano.28 The method involves three steps (a) condensation of 2,5-dimethyl-2,5-hexanediol (48) with 4-chlorobutyronitrile in the presence of sulfuric acid to give a derivative of A 1-pyrroline (49), (6) reduction of 49 with sodium borohydride to give the corresponding pyrrolidine (50), and (c) intramolecular cyclization of the pyrrolidine in the presence of alkali to give the pyrrolizidine derivative 51. The three-step synthesis was performed without isolation of the intermediate products. 

Scheme 9.8 The hydrogenation pathway of dimethyl y-nitropimelate leading to pyrrolizidine.

The lactams, which may be formed from the intermediate amino diesters, should be the intermediates leading to the pyrrolizidines. The lactam 18 was isolated on distillation of the product of hydrogenation of dimethyl y-nitropimelate (16 R = H, R = Me) over platinum oxide in methanol at 25°C and 0.2-0.3 MPa H2. When the lactam... 

Application of the dimethyl acetylenedicarboxylate reaction to enamines of cyclic ketones gave similar results the pyrrolidine enamines of cyclopentanone and a-tetralone gave the ring-expanded products (60 and 62, respectively) in toluene, and pyrrolizidines (61 and 63, respectively) in methanol (equation 32)53. 

Consider now the cw-2,8-dimethyl-frawi-pyrrolizidine (13, X = N), with its trans-ring fusion and its gas-phase enthalpy of formation of —66.7 2.6 kJmoU. The enthalpy of formation of the corresponding hydrocarbon, 2,8-dimethyl-frawi-bicyclo[3.3.0]octane (13, X = CH) is estimated to be —126 kJ moU by assuming thermoneutrality of reaction 11. 

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