Benzylisoquinoline derivatives

Benzylisoquinoline Derivatives. Papaverine, C20H21O4N Xanthaline, C20H19O5N dZ-Laudanine, C20H25O4N Laudanidine, C20H25O4N Codamine, C20H25O4N Laudanosine, C21H27O4N... 

Reticuline (38), one of the most important intermediates in the biosynthesis of opium alkaloids, has been synthesized in racemic form (Scheme 7) (78). 6-Methoxy-7-benzyloxyisoquinoline (39), prepared from O-benzylisovanillin via a modified Pomeranz-Fritsch isoquinoline synthesis, was treated with benzoyl chloride and potassium cyanide to obtain Reissert compound 40. Alkylation of the anion generated from 40 with 3-benzyloxy-4-methoxybenzyl chloride gave the corresponding 1-substituted Reissert compound 41 which was hydrolyzed in alkaline medium to 1-benzylisoquinoline derivative 42. Quatemarization of 42 with methyl iodide followed by sodium borohydride reduction and debenzylation led to ( )-reticuline (38) in about 25% overall yield from 39. 

The total synthesis of pavinane alkaloid platycerine (89) (Scheme 14) has been accomplished successfully (26) via 1-benzylisoquinoline derivative 91 obtained from Reissert intermediate 90. Quatemarization of 91 with methyl iodide followed by lithium aluminum hydride reduction supplied 1,2-dihydroisoquinoline 92, which on treatment with a 7 5 mixture of formic acid and phosphorous acid gave ( )-platycerine (89) in 60-70% yield. 

This section considers in vivo transformations other than those involved in biosynthesis, which forms the subject of Section VII. At present, tetrandrine (48) and thalicarpine (94) are the only bisbenzylisoquinoline alkaloids whose microbial transformations have been studied. In work that is apparently the first such investigation of any benzylisoquinoline-derived alkaloids, likely organisms were selected by their ability to metabolize monomeric benzylisoquinoline alkaloids... 

Bobbitt et al.113 reported that when benzylaminoacetaldehyde dialkyl acetals (18) are heated under reflux with concentrated hydrochloric acid and ethanol, in the presence of benzaldehyde, good yields of the 4-benzylisoquinoline derivatives (85), via the 1,2-dihydroisoquinoline (82), can be isolated. A mechanism for this reaction114 is summarized in Scheme VI. With cyclohexanone enamine and aldehydes, the intermediate has been formulated115 as 86. It was originally reported114 that an intermediate of the... 

Amona muricata L. -graviola Tranquilizer No information Caboclos [59] Acetogenins [86,87] neurotoxic benzylisoquinoline derivatives [88] essential oil [89,90] alkaloids [91,92] flavonoids and terpenoids [93] striatal neurodegeneration [252] atypical parkinsonism [253] anti leishmanial activity [254] antidepressive activity [91]... 

Alternative approaches to aporphine alkaloids using benzyne intermediates have been reported.113-118 For example, treatment of the readily available bromo-benzylisoquinoline derivative (98 X = Br, Y = H) with potassium amide gave the corresponding amino-compound (98 X = H, Y = NH2), which upon... 

Total syntheses of ( )-capaurine (194 R1 = R2 = R4 = R5 = Me, R3 = OH),209 ( )-isocorybulbine (195 R1 = Me, R2 = R3 = H, R4 = R5 = OMe),202 ( )-kikemanine (194 R1 = R2 = R4 = Me, R3 = R5 = H),210 and ( )-0-methylcaseadine (202)211 have been reported. In all cases, conventional routes involving Bischler-Napieralski cyclization to form benzylisoquinoline derivatives and subsequent insertion of the C(8)-carbon by reaction with formaldehyde were adopted. A further example of para-activation by an ethoxycarbonyl-amino-function for the Bischler-Napieralski reaction may be noted.211 In the synthesis of capaurine, the presence of the bromo-function in compound (203) forced the Mannich reaction with formaldehyde to produce the tetracyclic derivative (204) rather than the normally more favourable mode of cyclization para to the hydroxy-group. Debromination was effected at a later stage with zinc powder in 50 % acetic acid solution.209... 

In an eady attempt to understand the genesis of alkaloids from amino acids it was postulated (56) that intramolecular phenolic coupling should lead from benzylisoquinoline bases such as laudanosine (77, R = CH3), before it was completely methylated, to aporphine bases such as isothebaine (81). For example, between a benzylisoquinoline derived from laudanosoline (77, R = H), such as orientaline (82), and an aporphine alkaloid such as isothebaine (81), there should be a proaporphine alkaloid such as orientalinone (83) (56). The isolation of 83 lent credence to the hypothesis. Indeed, the fragile nature of 83 (it readily undeigoes the dienone—phenol rearrangement on acid treatment) required unusual skill in obtaining it from total plant extract. 

The increasing demand of the pharmaceutical industry for various isoquinoline and benzylisoquinoline derivatives with different electron-donating substituents led to a thorough study of the problem of selective... 

The isoquinoline alkaloids constitute perhaps the largest single group of alkaloids known. Generally speaking, they exert their most pronounced pharmacological actions on the central nervous system and on smooth muscle. With respect to the latter, the benzylisoquinoline derivatives... 

Corydalis aurea Willd. contains several alkaloids, from which a protober-berine-type base, capaurine (112), as well as a benzylisoquinoline derivative, corpaverine (previously labeled F24), have been isolated (113). Cor-... 

Cabedo N, Berenguer I, Figadere B, Cortes D (2009) An overview on benzylisoquinoline derivatives with dopaminergic and serotonergic activities. Curr Med Chem 16 2441-2467... 

The idea that the opium alkaloid morphine is a modified benzyliso-quinoline provided the key to the structure 6.152) for the alkaloid twisting of the benzylisoquinoline skeleton into that shown for reticuline (6.127) in (6.148) illustrates this relationship and suggests a possible biogenesis. This was later proved correct in the course of a study which is one of the classics of alkaloid biosynthesis. In the first experiments ever to be carried out with complex plant-alkaloid precursors, [1- C]- and [S- Cj-norlaudanosoline [as (6.123) were fed to opium poppies [99, 100]. They were found to label morphine (6.152), codeine (6.153) and thebaine (6.151) specifically, thus establishing that these alkaloids are indeed benzylisoquinoline derivatives. The key intermediate [101] proved to be reticuline (6.148). Both (R) and (5)-isomers were utilized, the latter by way of (6.155) [101, 102] which allowed its conversion into (i )-reticuline (6.148), the correct intermediate, with the same configuration as the three opium alkaloids [as (6.151). ... 

Figure 1.23. Explanation of possible ways of the origin of plants containing two types of alkaloids, in this case furoquinolines (derivatives of anthranilic acid) and benzylisoquinolines (derivatives of tyrosine), in the closely related genera Fagara and Zanthoxylum. According to the hypotheses the alkaloid character originated independently in two separate postulations. By means of introgression it spread over the whole unit. In some cases the two alkaloid-bearing types met and both characters were retained in the offspring (crosshatched circles). The horizontal lines in circles are species with benzylisoquinoline alkaloids, and the vertical lines are species with furoquinoline alkaloids. Data on alkaloids are from Boit (1961) and Vaquette et al (1974).

Benzylisoquinoline Derivatives. Papaverine, C2oHg 04N Xanthaline, CgoHigOgN dZ-Laudanine, C20H2BO4N... 

A.C. Smith has furnished a number of imino-bis-benzylisoquinoline derivatives, with the two parts arranged in a head-to-tail fashion in addition, isochondrodendrine (21) is present in the plant (Takahashi and Cava 1976, Takahashi et al. 1976, Galeffi et al. 1978). 

Bick IRC, Bremner JB, Wiriyachitra P (1971) Photo-oxidation of some benzylisoquinoline-derived alkaloids. Tetrahedron Lett 4795-4797... 

Grewe R, Fischer H, Friederichsen W (1967) Partial Birch reduction of 1-benzylisoquinoline derivatives. Chem Ber 100 1-8... 

---