The Alkaloids of Tylophora crebriflora

Tylophora crebriflora S. T. Blake (T. floribunda Benth.) occurs in North Queensland. Extraction of the plant material with hot methanol afforded the crude mixture of alkaloids which was purified by chromatography on cellulose powder using propanol-2 N acetic acid as the eluent. Further purification by repeated chromatography yielded tylophorine (Bf 0.5 in butan-l-ol-acetic acid 97 3) and tylocrebrine (R 0.2 in the same solvent system) (mp 218°-220° [a] D — 45° + 2° (c 0.1, CHCI3). (+ )-Tylocrebrine isolated from Ficus septica Forst. f. was found (4) to have mp 220°-222° and [a] f + 20.5° + 2° (c 0.8, CHCI3). 

Besides tylophorine and tylocrebrine, four additional alkaloids of the same group have been reported to be present in the plant (21). These possess either alcoholic or phenolic hydroxyl groups but details of the structural work are not available. 

Tylocrebrine, C24H27O4N (mp 218°-220°), is a tertiary base having four methoxyl groups, no N-methyl group, and no easily reducible unsaturation. Its UV-spectrum with absorption maxima at 263, 342, and 360 mp. (loge 4.81, 3.25, 3.09) is practically superposable on that of 3,4,6,7-tetramethoxy-9-methylphenanthrene. The IR-spectrum confirms the absence of OH, NH, or carbonyl functions. Since the alkaloid is isomeric and occurs jointly with tylophorine, it may be assumed to have the same phenanthroindolizidine system on the basis of the UV-spectrum two structures (XIX or XX) may be proposed. A choice between the two structures was made by synthesis as described in the next section. 

The syntheses of 9,ll,12,13,13a,14-hexahydro-2,3,5,6-tetramethoxy-dibenzo[/,A]pyrrolo[l,2-6]isoquinoline (XIX) and the 3,4,6,7-tetra-methoxy isomer (XX) were accomplished by the same sequence of reactions as employed for tylophorine,. starting from methyl-3,4,6,7-tetramethoxyphenanthrene-9-carboxylate and methyl-2,3,5,6-tetra-methoxyphenanthrene-9-carboxylate, respectively. Natural tylocre-brine was found to correspond to structure XIX. 

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