Alkaloids homoaporphine

The c-ring expansion of aporphines via the dichlorocyclopropane ring opening238 induced by LAH has been utilized in a synthesis of homoaporphine alkaloids (equation 93). Reductive cleavage of 2-silyloxy-dibromocyclopropanes gives a,(3-unsaturated ketones directly (equation 96).239... 

Barolo, S.M., Teng, X., Cuny, G.D. and Rossi, R.A. (2006) Syntheses of aporphine and homoaporphine alkaloids by intramolecular ortho-arylation of phenols with aryl halides via SRn1 reactions in liquid ammonia. Journal of Organic Chemistry, 71, 8493—8499. 

The oxidation of phenolic phenethylisoquinolines has been studied in some detail. With iron(iii) chloride the bases (68 R = H and R = OMe) have been oxidised to the homoproaporphine bases (69 R = H and OMe), and the base (70) has been oxidised to the homoproaporphine (71), which yielded the homoaporphine alkaloid multifloramine when subjected to dienone-phenol rearrangement. In this last process, when the dienone (71) was treated with concentrated hydrochloric acid in glacial acetic acid, the mixed acetal (72 R = Me), convertible into the hemiacetal (72 R = H), was isolated. ... 

Homoaporphine Alkaloids.—Full details of the research on the biosynthesis of the homoaporphine alkaloids of Kreysigia multiflora have been published. In essence there is no information additional to that published in preliminary form and reviewed. ... 

An intramolecular SrnI reaction was used as key step in the synthesis of the alkaloid 0-demethyleupoularamine 3. The intermediately formed SrnI product is readily transformed by photochemical oxidative biaryl formation and subsequent methylation to the target compound 3 in good yield (Equation 13.7) [23]. The SrnI cyclization of l-(2-bromobenzyl)-l,2,3,4-tetrahydroisoquinolin-7-ol derivatives 4 was recently applied to the synthesis of aporphine alkaloids 5 (Equation 13.8) [24] and, by using the same approach, homoaporphine alkaloids can also be synthesized. 

Like carbanions and anions from aryl amines, the anions from phenols have been used in intramolecular to obtain heterocycles by C—C bond formation [87]. One example of this approach is the photostimulated reaction of the phenoxide ion linked with a pendant bromoarene by Al-substi-tuted tetrahydroisoquinoline bridge such as 122. Under this reaction condition, aporphine alkaloid derivatives 123a,b (n=1) were obtained in good yields (Eq. 10.42). This approach was extended for the first time to the synthesis of a homoaporphine alkaloid 123c (w=2) [88]. 

An elegant synthesis of the neurotoxic alkaloid anatoxin has exploited the electrocyclic opening of the dibromobicyclo[5.1.0]octane followed by transannular cyclization (Scheme 13).238 Similarly, the thermal electrocyclic opening of the dichlorocyclopropane followed by intramolecular trapping of the developing allylic cation by a suitably positioned amine has been used in a homoaporphine synthesis.238... 

Phenethylisoquinoline alkaloids are classified into seven major alkaloid groups based on structural differences simple 1-phenethylisoquinolines (1), homomorphinanedienones (2), bisphenethylisoquinolines (3), homoproaporphines (4), homoaporphines (5), homoerythrines (6), and dibenz[benzylisoquinoline alkaloids. Although tropolone and Cephalotaxus alkaloids also belong to the... 

Although biosynthesis of the phenethylisoquinoline alkaloids has not yet been studied in full, that of androcymbines, homoaporphines, and homoerythrinans has been examined by work with radioactive tracers. In this section tracer experiments as well as hypothetical biogenetic routes in the synthesis of the phenethylisoquinoline alkaloids are discussed. 

Specifically C-labeled 1 -phenethylisoquinolines were administered to Kreysigia multiflora plants, and the alkaloids were isolated and degraded to unambiguous sequences. The results show that the C-homoaporphine... 

One-electron withdrawing inorganic reagents have been used to perform biomimetic syntheses of phenolic phenethylisoquinoline alkaloids. In order to obtain androcymbine compounds of type 85, the diphenolic isoquinoline 82a was subjected to phenol oxidation with manganese dioxide. The homoaporphine 83a coupled at the ortho-ortho position to the hydroxy group was the only product formed under these reaction... 

Since the total synthesis of O-methylandrocymbine (17) was accomplished via a photolytic cyclodehydrobromination reaction of a l-(2-bromophenethyl)-7-hydroxyisoquinoline (67), many phenethylisoquinoline alkaloids have been synthesized by this reaction. Irradiation of the bromoisoquinoline 113a,b with a Hanovia 450-W mercury lamp, using a Pyrex filter, in the presence of an excess of sodium hydroxide and sodium hydrogen sulfite gave alkaloid CC-24 (83a) (68) and the homoaporphine 114 (69), respectively. 

Phenethylisoquinoline alkaloids are classified into six major alkaloid groups based on structural differences, namely, simple 1-phenethyliso-quinoline (1), homomorphinandienone (2), bisphenethylisoquinoline (3), homoproaporphine (4), homoaporphine (5), and homoerythrina alkaloids (6). These alkaloids are related to the benzylisoquinoline alkaloids such as morphinandienone, bisbenzylisoquinoline, proaporphine, apor-phine, and erythrina alkaloids. Although colchicine and its derivatives also belong to the phenethylisoquinoline alkaloids group, these alkaloids are not included in this review as they have been reviewed earlier 1). 

By analogy with the biosynthesis of several aporphine alkaloids (33-35) the homoaporphines could arise naturally by way of homoproaporphines 78a and 78b or by direct coupling of the diphenolic isoquinoline 77a. 

Base-catalyzed photolyses of 2 -bromo-7-hydroxytetrahydrophenethyl-isoquinolines have resulted in the synthesis of the homoaporphines kreysigine " and alkaloid CC-24. ... 

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