Homotropane

Hyperaspine (23) is the first 3-oxaquinolizidine alkaloid reported so far from ladybird beetles. Its skeleton, however, which is based on a chain of 13 carbon atoms, is biosynthetically related to those of the homotropane and perhydroazaphenalene alkaloid already isolated from ladybirds [38]. 

Homologues of tropane and granatane can be prepared by starting with alkyl derivatives of cyclohexenone and heptanone, respectively. Full details13 of the synthesis7 of adaline (30), a homotropane, using the nitrone route,14 have now been given. 

Anatoxin-a is a naturally occurring homotropane alkaloid produced by freshwater cyanobacteria of the genera Anabama (A. flos-ctquae and A. circinalis), Aphanizome-non, Cylindrospermum, Planktothrix, Microcystis aeruginosa [5-7], and Phormidium favosum [8]. Fatal intoxications have typically included cattle and birds [9], and, more recently, dogs [8] and flamingos [10]. 

Anatoxin-a, the first highly potent cyanotoxin to have its structure and absolute stereochemistry elucidated, was originally isolated from a unialgal clone of Anabaena Jlos-aquae (NRC-44h) [5]. The structure was confirmed by X-ray crystallographic data for the N-acetyl derivative [11] and additional studies have since provided further proof for the structure and stereochemistry (for example, [12]). Anatoxin-a is an unsymmetrical bicyclic secondary amine, and was the first naturally occurring alkaloid discovered to contain a 9-azabicyclo[4,2,l]nonane (homotropane) skeleton. Homotropanes are one-carbon analogs of the tropanes and, as such, are structurally closely related to the well-known alkaloid cocaine. 

The simple alkyl derivatives such homo-, propyl-, and /Ao-propylanatoxin-a (Fig. 7.4A) are all potent nicotinic ligands (Wonnacott et al. 1992). Most of the efforts to determine the precise stmc-tural requirements of the receptor have resulted in the synthesis of conformationally restricted derivatives (Hernandez and Rapoport 1994 Brough et al. 1992). The first bioisosteric and conformationally constrained variation of (+)-anatoxin-a found to retain mnch of the potency of the natn-ral compound was racemic ( )-pyrido[3,4-b]homotropane (PHT) (Fig. 7.4B), representing the... 

Giindisch, D., Kampchen, T, Schwarz, S., Seitz, G., Siegl, I, and Wegge, T. 2002. Syntheses and evaluation of pyridazine and pyrimidine containing bioisosteres of ( )-pyrido[3.4-b]homotropane and pyrido-[3.4-b]tropane as novel nAChR ligands. 5 oorgATerf C/2em 10, 1-9. 

Cocaine served as an intermediate in the synthesis of the homotropane anatoxin-a (13b). Anhydroecgonine was converted into the methylketone (11), which was treated with trimethylsulphoxonium methylide the resultant endo cyclopropane (12b) was subsequently photolysed. Ring cleavage could also be... 

This reaction type is useful for the synthesis of tropane-like azabicycles (equations 94 and 95). Allyl-and propargyl-silanes are excellent nucleophiles in this process.Enone (125) is probably first transformed into an enol ether (c/. equation 70) before it cyclizes to the homotropane skeleton, which is eventually isolated as a mixture of enone (126) and chloride (127). 

The Katritzky reaction of 3-pyridinols has been applied to the synthesis of homotropanes. ... 

Wonnacott S, Gallagher T (2006) The chemistry and pharmacology of anatoxin-a and related homotropanes with respect to nicotinic acetylcholine receptors. Mar Drugs 4 228-254. doi 10.3390/md403228... 

Homobrassinolide (28-homoBL), 3862 Homocamptothecin, 652, 657, 666 Homocysteine (Hey), 3681-3683 Homoeostrichus sinclairii, 2895 Homoharringtonine, 1453 Homoisoflavonoids, 2163 Homologous genes, 686 Homomeric prenyltransferases, 2709 Homospermidine, 365 Homospermidine synthase (HSS), 365 Homoterpenes, 2915 Homotropane alkaloid, 43 Homovanillic, 2476... 

Anatoxin-a is a bicyclic amine alkaloid (Figure 31.3). It contains a homotropane scaffold that is derived from glutamic acid. It is chiral, with two S5unmetric centers (Wonnacott and Gallagher, 2006). Only the (-l-)-anatoxin-a enantiomeric form is naturally produced, and the pKg of this form, at 9.4, indicates that it is mostly in the pro-tonated form under typical environmental pH conditions... 

In most cases of secondary protection of insect herbivores by alkaloids the source of the alkaloid is the herbivore diet, i.e. the plant host. There have been several interesting reports on the occurrence of chemical defenses of insects based on alkaloids actively synthesized or at least chemically modified by the insect. One such report showed that deterrence to predation by ants and spiders was afibrded to the Mexican bean beetle Epilachna varivestis) by the production of the homotropane alkaloid euphococcinine (66). This compound which actually may be a polyketide, is not present in the body of larvae or newly hatched adults but is accumulated in the beetles blood within one week of emergence. When attacked, the beetle reflex-bleeds emitting droplets of blood containing as much as 5 pg of euphococcinine. 

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