Rhoeadines

Methods of synthesis of rhoeadines have been reviewed.120 

The alkaloids of the rhoeadine group are benzazepines and essentially bear the same relationship to the indanobenzazepines as do the secoberberines (section 10) to the spirobenzylisoquinolines (section 13). 

Alpenigenine (339) has been converted into is-alpinigen-ine by hydrochloric acid (A. Guggisberg, M. Hesse and H. Schmid, Helv. 1977, 2402). 0-Methyla1pinigenine has been 

A positional isomer of xylopinine of structure (345), prepared by synthesis, has been subjected to Hofmann degradation to the olefin (346), which on oxidation with osmium tetroxide gives the diol (347). Cleavage of the diol gave the dialdehyde (348), photolysis of which yields a mixture of cis-alpen-igenine (30%) and alpenigenine (339) (1%) (S.B. Prabhakar, et al., J.Chem.Soc., Perkin I 1981, 1273). The 7,8,13,14-tetra- 

Reduction of the lactone (351) with di-isobutyl-aluminium hydride gives the related hemi-acetal, cyclodehydration of which gives cis-deoxyalpenigenine (352). Oxidation of this gives the lactone (352) which may be reduced to eis-alp-enigenine (I. Ahmad and V. Sniekus, Canad.J.Chem., 1982, 60, 2678). 

Bicuculline (354) has been rearranged to the lactone (355, R=Me) and conversion of this into the secondary base (355, R= H) and the urethane (355, R=C0NHTol) followed by reduction to the hemi-acetal and 0-methylation of this with methyl orthoformate and final hydrolysis to the secondary base yields papaverrubine-E (356) (R. Hohlbrugger and W. Kloetzer, Ber., 1979, 112, 849). 

Rhoeadine has been isolated from Bocconia frutescens,110 alpinigenine from Papaver bracteatum,146 and rhoeadine, rhoeagenine, glaucamine, glaudine, epi-glaudine, oreodine, and oreogenine from P. tauricola.108 

Alkaloids of this group have been isolated from the following  

14-dioxo-2-hydroxy-7,8-methylene-dioxy-12,13-diraethoxyaporhoeadane rhoeadine, papaverrubines A, C, and E 

---

Rhoeadine crystallises from a mixture of chloroform and ether, sublimes at 215-25" /0-02 mm., and then melts at 256-57-5° (vac.), and has [a] / ° -f 232° (CHClj). According to Awe it has m.p. 272-4° (Kofler s micro-apparatus), and [a]] ° -f 243° (CHClj). A crystalline liydriodide, B. HI. 2H2O, was prepared by the addition of potassium iodide to a solution of the alkaloid in acetic acid. Rhoeadine contains one methoxyl group and a dioxymethylene group, but no reactive hydrogen (Zerewitinoff). 

Opium (Papaver somniferum) Benzylfsoquinolines Phthalide isoquinolines Morphine Sub-group, Sinomenium acutum Other Papaver spp. Rhoeadine, etc.. ... 

The protoberberine alkaloids (5-75) play important roles as precursors in the biosynthesis of a variety of related isoquinoline alkaloids such as protopine, phthalideisoquinoline, spirobenzylisoquinoline, rhoeadine, inde-nobenzazepine, secoberbine, and benzo[c]phenanthridine alkaloids. Chemical transformations of protoberberines to these alkaloids are particularly interesting and exciting from the biogenetic viewpoint and further from ready availability of starting protoberberines in nature or synthesis. 

Analogous results were obtained from the reaction of another cycloberbine (183), as depicted in Scheme 33 (102-104). These reactions were applied to synthesis of indenobenzazepine (Section V,F,5) and rhoeadine alkaloids (Section V,G,2). 

Indenobenzazepines have been used as key intermediates for synthesis of rhoeadine, protopine, phthalideisoquinoline, and spirobenzylisoquinoline alkaloids. Several new alkaloids possessing an indenobenzazepine skeleton have been isolated, and they are presumably biosynthesized from proto-berberine alkaloids. 

Rearrangement of spirobenzylisoquinolines, having a hydroxyl group on ring C trans to the nitrogen, to indenobenzazepines was first reported by Irie et al. (209,210) in their synthesis of rhoeadine alkaloids (Section V,G,1). This... 

Rhoeadine alkaloids have been reviewed (1,2,7-10,217) and compiled (218). Only a few transformations have been developed despite the interesting structural features of these alkaloids. 

The first synthesis of a rhoeadine alkaloid was achieved by Irie et al. (209,210) through skeletal rearrangement of a spirobenzylisoquinoline to an indenobenzazepine. The trans-alcohols 434 and 329 were treated with methanesulfonyl chloride and rearranged to the indenobenzazepine 435,... 

Another interesting conversion of a protoberberine to a rhoeadine skeleton was developed by Murugesan et al. (100). The ketol 176 obtained easily from berberine (15) (Section IV,A,2) was oxidized with sodium periodate to the keto lactone 451, which was transformed to the rhoeadine analogs 452 and 453 by known methods (Scheme 91). Their stereochemistry at the anomeric carbon was not fully clarified. 

Scheme 91. Synthesis of rhoeadine analogs via indenobenzazepines. Reagents a, NaI04 b, NaBH4 c, HC1 d, DIBAL e, HC(OMe)3. ...

Ring D inversion seems to be a crucial step in biogenetic transformations of protoberberines to related alkaloids such as rhoeadine, retroprotoberberine, spirobenzylisoquinoline, and indenobenzazepine alkaloids. 8,14-Cyclober-bin-13-ol 478 derived from berberine (15) was successively treated with ethyl chloroformate, silver nitrate, and pyridinium dichromate (PDC) in dimethyl-formamide to give the keto oxazolidinone 479 (Scheme 98). Heating of 479 with 10% aqueous sodium hydroxide in ethanol effected hydrolysis, retro-aldol reaction, cyclization, and dehydration to provide successfully the... 

Acid-catalyzed hydrolysis of the latter followed by Jones oxidation furnished racemic peshawarine (43) (Scheme 12). Simanek et al. (59) transformed the same amino acetal 47, obtained in optically active form from the Emde degradation of rhoeadine methiodide (48), to ( )-43, also by hydrolysis and oxidation. However, the optical activity was lost during hydrolysis (Scheme 12). 

Secophthalideisoquinoline enol lactones of type 128 were used by Klotzer et al. (95,103-105) for the synthesis of benzazepine system 129 which was further transformed to alkaloids of rhoeadine type. 

Ronsch (129,130) described the synthesis of ene lactam 152, formally belonging to cordrastine series, from the rhoeadine alkaloid, alpinigenine (150), by Hofmann degradation of its derivative 151 (Scheme 26). Treatment of the nitrile 151 with methyl iodide and then with potassium hydroxide gave ene lactam 152, for which the Z configuration could be deduced on the grounds of UV (365 nm) and H-NMR (57.09 and 7.39, J = 8 Hz) spectral data. 

Rhodium compounds, 19 644-648 synthesis of, 19 646 uses for, 19 646-648 Rhodium oxide, 10 42 Rhodium plating, 9 822 19 648 Rhodium-platinum alloys, 19 602 Rhodochrosite, 15 540 Rhodochrosite ore, 15 589 Rhodococcus, as a host system for gene expression, 12 478 Rhodonite, 15 540 color, 7 331 Rhodopsin, 9 512 Rhoeadine, 2 90 Rhoedales... 

Papaver rhoeaes L. Li Chun Hua (Corn poppy) (flower, root) Rhoeadine, rhoeagenine.72 For jaundice, as a gargle or ingested as bechic. 

Papaver somniferum L. Yu Mei Ku (Opium poppy) (whole plant) Berberine, codeine, papaverine, isocorypalmine, laudanine, magnoflorine, meconine, 6-methylocodine, morphine, narcotine, pseudomorphine, rhoeadine, sanguinarine, beta-sitosterol, stigmasterol, thebaine, zanthaline.50 Antitussive, antispasmodic, analgesic, astringent, narcotic, treat chronic enteritis, diarrhea, enterorrhagia, headache, toothache, asthma. 

Other alkaloids are codamine, cryptopine, gnoscopine, hydrocotarnine, lanthopine, lauda-nine, laudanosine, meconidine, oxynarcotine, papaveramine, protopine, pseudomorphine, rhoeadine, and tritopine. Many of them occur only in traces, and some are regarded as probable derivatives of morphine. Porphyroxin is said to be a complex combination of several of the alkaloids, and not a proximate principle (Potter, 1910). 

---