Dolichothele sphaerica

L-histidine-derived Cactaceae Dolichothele sphaerica Dolichotheline... 

Histidine is a proven precursor of dolichothe-line (Figure 6.111) in Dolichothele sphaerica (Cactaceae), the remaining carbon atoms originating from leucine via isovaleric acid (see page 197). The imidazole alkaloids found in... 

Cactaceae Rutaceae Coryphantha cornifera Coryphantha cornifera var. echinus Coryphantha greenwoodii Coryphantha pectinata Coryphantha ramillosa Dolichothele sphaerica Mamillaria elongata Dancy mandarin 129 129 128, 146 54, 129 133 51 151 218... 

Dolichotheline (111) is a histamine-derived alkaloid produced by the cactus Dolichothele sphaerica Britton and Rose (Cactaceae) native to southern Texas and northern Mexico. The alkaloid was first isolated in 1969 by Rosenberg and Paul (160). Spectroscopic data suggested structure 111, 4(5)-(iV-isovalerylaminoethyl)imidazole or 7V -isovalerylhistamine. The structure was proved by synthesis. Refluxing of histamine with isovaleric anhydride yielded 111, identical to the natural product (160). In addition to the major alkaloid dolichotheline, five minor alkaloids have been isolated (161). These were identified as A-methylphenethylamine, /i-O-methylsyn-ephrine, vV-methyltyramine, synephrine, and / -0-ethylsynephrine by IR, NMR, and comparison to authentic materials / -0-ethylsynephrine was probably an artifact of synephrine, since it was not found in a second extraction attempt when no ethanol was used. 

It was possible also to incorporate unnatural precursors into the alkaloids of Dolichothele sphaerica (164,165,168,169). On feeding of 3-aminoethyl-pyrazole, the alkaloid 3-(Ar-isovalerylaminoethyl)pyrazole (112) was produced, and A -isocaproylhistamine was obtained by the simultaneous feeding of 4-methylpentanoic acid (isocaproic acid) and of 4(5)-aminoethy-... 

Dolichotheline.—The biosynthesis of dolichotheline (120) in intact Dolichothele sphaerica cacti plants is straightforward.79 An experiment with DL-[2-14C]hista-mine (123) showed that the histamine residue arises specifically from this precursor. The isovaleryl unit incorporated activity efficiently from dl-[2-14C]-leucine (121) and [l-14C]isovalerate (122) to label in each case the carbonyl group of (120) (Scheme 28) mevalonic acid was a specific but less efficient precursor of this residue. 

An imidazole alkaloid has been isolated for the first time from a cactus species.10 Dolichotheline (7 R = COCH2CH2CHMe2) has been obtained from Dolichothele sphaerica and its structure has been established on the basis of spectral and degradative evidence and confirmed by synthesis from histamine (7 R = H) and isovaleric anhydride. This represents only the second report of a chemical investigation in the genus Dolichothele. 

Dolichotheline.—Dolichotheline (202) is an unusual imidazole alkaloid produced by the cactus Dolichothele sphaerica along a pathway which involves condensation of histamine with isovaleric acid. Administration of isocaproic acid and 4(5)-aminomethylimidazole led to the production of the unnatural alkaloids (203) and (204), respectively. ... 

Positively inotropic histamine-derived compounds have been isolated from members of the Cactaceae. V, V -Dimeth-ylhistamine (6) from Echinocereus blanckii and dolicothe-line (7) from Dolichothele sphaerica have been studied. Dol-ichotheline has an ED50 of 1.6 X 10" mol/L (Figure 37.3) (Wagner, 1988). 

Only the biosynthesis of Pilocarpus alkaloids and dolichotheline, from Dolichothele sphaerica, were reported in literature as described below. 

DolichotheUne is an amide derivative from histamine of Dolichothele sphaerica (Cactaceae) whose structure suggests the cOTidensatiOTi of the imidazole unit with isovaleric acid [14, 15]. Its biosynthesis was evaluated by means of radiolabeled tracers such as DL-[2- " C]histidine, DL-[2- " C]leucine, DL-[2- " C]mevalonic acid lactone, and sodiiun [l- " C]isovalerate [42]. The extension of radioactivity... 

Rosenberg H, Paul AG (1969) Dolichotheline, a novel imidazole alkaloid fiom Dolichothele sphaerica. Tefrahedron Lett 13 1039-1042. doi 10.1016/80040-4039(01)97731-7... 

Rosenberg H, Stohs SJ, Paul AG (1974) Directed biosynthesis of mmatural alkaloids in Dolichothele sphaerica. Phytochemistry 13 823-827. doi 10.1016/S0031-9422(00)91146-4... 

---