Studies related to bark extractives of some fir and spruce species, and synthesis and biosynthesis of indole alkaloids
Creators: name: Westcott, Neil Douglas
Publisher: name: University of British Columbia
Year: 2011

description: Part I of the thesis describes four investigations of some of the neutral components of bark extractives. The petroleum ether extract of grand fir [Abies grandis (Dougl.) Lindl.] was found to contain two triterpene lactones. The first compound, cyclo-grandisolide, was shown by chemical and spectroscopic considerations and confirmed by X-ray analysis to be (2 3R)-3a-methoxy-9,19-cyclo-9β-lanost-24-ene-26 ,23-lactone (38) . The second component, epi-cyclograndisolide, was isomeric with the first and was assigned as (23S)-3α-methoxy-9,19-cyclo-9 β- lanost-24-ene-26,23-lactone (43). In the second investigation, three triterpenes of the chloroform extract of Pacific silver fir [A. amabilis (Dougl.) Forbes] were examined. The main component, abieslactone, was known and had been assigned as (23R)-3α-methoxylanosta-9(11),24—diene-26,23-lactone (30). Chemical and spectroscopic evidence is considered which indicates that assignment to be incorrect and abieslactone is tentatively re-assigned as (23R)-3a-methoxy-9β-lanosta-7,24-diene-26,23-lactone (81). A minor component, AA₃ was assigned on the basis of methylation studies as 3-desmethylabieslactone or (23R)-3α-hydroxy-9β-lanosta-7,24-diene-26,23-lactone (83). Oxidation of AA₃ gave a ketone identical to the second minor component, AA₂, which is then (23R)-3-oxo-9β-lanosta-7,24-diene-26,23-lactone (82). The third investigation concerns the structure of W₄, a triterpene ketone from the petroleum ether extract of Western white spruce [Picea glauca (Moench) Voss. var. albertiana (S. Brown) Sarg.]. The structure tentatively assigned on the basis of spectroscopic evidence is 3β-methoxy-8α-serrat-13-en-21-one (91). The fourth investigation was a chemosystematic study of the petroleum ether extract of Engelmann spruce [P. engelmannii Parry]. The presence of methoxyserratene derivatives known to be present in other members of the same genus were not detected in the present investigation. Part II of the thesis describes synthetic endeavors leading to possible bio-intermediates of indole alkaloids and the biosynthetic evaluation of one synthetic compound. Condensation of 3-ethylpyridine with 2-carboethoxy-3(β-chloroethyl)indole (60) followed by reduction gave N-[β{3(2-hydroxymethylindolyl)}ethyl]-3-ethy1-1,2,5,6-tetrahydropyridine (64). The benzoxymethyl derivative 65 of compound 64 was treated with potassium cyanide to give the cyanomethyl derivative 66 which could be hydroxyzed to N-[β{3(2-carbomethoxymethylindolyl)}ethyl]-3-ethyl-1,2,5,6-tetrahydropyridine (67). Alkylation of the compound with methyl formate followed by reduction of the resulating enol, gave 16,17-dihydrosecodin-17-ol (69). This compound was shown to be not, or very slightly, incorporated into the alkaloids of Vinca rosea L. plants. Attempts to oxidize the tetrahydropyridine 64 with mercuric acetate under various conditions failed to give detectable amounts of the corresponding pyridinium salt. In another synthetic sequence, condensation of the tryptophyl derivative 60 with 3-acetylpyridine ethylene ketal followed by the same sequence of reduction and homologation as employed before gave N-[β{3(2-carbomethoxy-methylindolyl)}ethyl]-3-acetyl-l,2,5,6-tetrahydropyridine (82). Attempts to oxidize 82 with mercurous acetate followed by hydrogenation failed to give the desired N-[β{3(2-carbomethoxymethylindolyl)}ethyl]-3-acetyl-l,4,5,6-tetrahydropyridine (83). In a second attempt to synthesize 83, the pyridinium chloride salt 84 from the condensation of 3-acetylpyridine with the tryptophyl derivative 60, was hydrogenated to N-[β{3(2-carboethoxyindolyl) }ethyl]-3-acetyl-l,4,5, 6-tetrahydropyridine (85). Reduction of 85 under a variety of conditions gave major amounts of N-[β{3(2-hydroxymethylindolyl)}ethyl]-3-acetylpiperi-dine (86) with only trace amounts of N-[β{3(2-hydroxymethylindoiy 1)}ethy1]-3-acety1-1,4,5,6-tetrahydropyridine (87) containing the necessary vinylogous amide chromophore. In a third approach to the synthesis of 83, methyl indole-2-carboxylate (88) was reduced and homologated as before to give methyl indole-2-acetate (92). Treatment of 92 with ethylene oxide and stannic.chloride gave methyl 3(β.-hydroxyethyl)indole-2-acetate (93). Treatment of the tryptophyl bromide derivative 94, produced by the action of phosphorous tribromide on hydrogenated to the vinylogous amide 83. More conveniently, treatment of 93 in 3-acetylpyridine with phosphorous tribromide and immediate hydrogenation gave 83 in better yield.