Sinactine

Sinactine, C20H21O4N, is of interest in that the dZ-form had been obtained by Perkin (234) from cryptopine before it was discovered by Goto and Sudzuki (161) as the levorotatory form in Sinomenium aculum. It has since been isolated from Fumaria officinalis (77), where it occurs as a mixture of the I- and dU forms. It crystallizes from hot methanol in stout prisms which have [ ]d —312° (chloroform) and melt at 176°. Its hydrochloride (m.p. 272°) is sparingly soluble in water and serves as a convenient compound for isolation and purification. The alkaloid is readily oxidized by air, but the dehydro compound has not been recognized as a naturally occurring alkaloid. 

Structure and Synthesis. When Buck and Perkin (228) attempted to apply the Pictet and Gams synthesis (220) of berberine to epiberberine they obtained an isomer, tetrahydro- -epiberberine (XXXIII). Subsequently, Haworth and Perkin achieved a total synthesis which is detailed in connection with the synthesis of cryptopine. Oxidation of sinactine with iodine in boiling alcohol yields epiberberinium iodide, from which the chloride was prepared by treatment with silver chloride, and this was identical with epiberberinium chloride prepared from cryptopine (235). Finaly, Spath and Mosettig (236) resolved the dZ-tetrahydroepiberberine (m.p. 170°) (XLIII) from cryptopine by means of d- and Z-tartaric acids in succession and showed that the Z-form, [a] —302° (chloroform), was identical with the natural alkaloid. The cZ-form had the same numerical value for its optical rotation and melted at 178-179°. 

It should be added that oxidation of sinactine with permanganate in neutral solution has yielded 6,7-dimethoxy-l-keto-l,2,3,4-tetrahydro-isoquinoline, but 3,4-methylenedioxyphthalic acid could not be obtained by this method (34). 

Cheilanthifoline, C19H19O4N, has been isolated in small amounts by one of the writers from Corydalis cheilantheifolia (34), C. scouleri (47), and C. sibirica (49). It crystallizes in stout plates from methanol, in which it is moderately soluble [a]n — 311° (methanol), m.p. 184°. 

Its structure (XLIV) follows in part from the fact that its 0-methyl 

---

Other members of this sub-group, usually more closely associated with berberine in distribution, or in structure, or both, and therefore dealt with in the Berberis group, are canadine (p. 338), capaurine (p. 339), cheilanthifoline (p. 339), ophiocarpine (p. 338), sinactine (p. 338), tetra-hydroshobakunine (p. 340) and tetrahydroworenine (p. 344). 

Sinomenium acutum Rehd and Wils. Sinactine (Z-tetrahydro-epiberberine) and other alkaloids (p. 268). 

The tested isoquinolines were observed to display a selective inhibition against PI-3 as seen in Table 4, except for (-t-)-isoboldine, (-)-stylopine, and ( )-corydalidzine, that were totally ineffective against both viruses. Protopine, b-allocryptopine, chelidimerine, fumarophycine, a-hydrastine, (-t-)-bulbocapnine, (+)-isoboldine, (-)-sinactine, palmatine, dehydrocoryda-... 

Tetrahydropalmatine and Sinactine. Irradiation of the enamide 133 afforded a mixture of two lactams 162 and 163 in 20 and 8% yields, respectively, as a result of cyclization to the roots of each one of two o-methoxyl... 

Cavidine. As in the case of the synthesis of tetrahydropalmatine (23) and sinactine (22,23), the 13-methylprotoberberine alkaloid cavidine (170) was synthesized via the dehydrolactam 169, which was readily prepared from the enamide 136 on irradiation (22,24). Since cavidine (170) had been converted (114) to thalictrifoline, this synthesis formally completed the first total synthesis of thalictrifoline (171) (Scheme 68). 

Isochromanones on condensation with p-phenylethyl amines, followed by Bischler-Napieralski cyclisation and NaBH reduction furnish berbine alkaloids in good to excellent yields. The 7,8-dimethoxy and mcthylenedioxy isochromanones prepared by lithiation methods provide the 9,10-oxygenated berbine alkaloids, such as tetra-hydropalmatine 51a canadine stylopine 57c , sinactine... 

Fumarophycine, C22H28O6N (mp 107°-109° [a] -67.5°) which on alkaline hydrolysis gave fumarophycinal (mp 128°-130°) and on methy-lation with diazomethane gave the 0-methyl ether (mp 124°-126°). Spectral examination indicated the presence of NMe, phenolic OH, OMe, O2CH2, and acetyl groups. Protopine and sinactine were also isolated (94). 

Bicuculline, cryptopine, fumaramine, fumaridine, Af-methylhydrasteine, parfumidine, parfumine, protopine, sanguinarine 111, 170-174 (+)-Adlumine, cryptopine, fumariiine, fumaritridine, fumaritrine, fumarostelline, parfumine, protopine, sinactine, stylopine 160, 175, 176... 

R = Me, R + R = OCH2O, R = were prepared by this method. The last two compounds were easily converted into (+ )-sinactine and (+)-cavidine. A number of other substituents (160 X = OAc, Cl, or Br) were also shown to be useful for the photoelimination reaction.The dealkylation of N-substituted protoberberinium salts on a semi-industrial scale has been described.( )-Mecambridine has been synthesized along conventional lines.New protoberberine derivatives of the type (162) have been synthesized (see also Vol. 3). 

Sinomenium acutum Rehder Sinactine (161), Tuduranine (162), Acutumine... 

---