Studies related to: bark extractives of western white pine; and synthesis of indole alkaloids
Creators: name: Eigendorf, Günter Klaus
Publisher: name: University of British Columbia
Year: 2010

description: Part I of this thesis describes the structural elucidation of eleven triterpenes isolated from the benzene extract of Western white pine (Pinus monticbla Dougl.) bark. Chemical and detailed spectroscopic investigations revealed the presence of a common tetracyclic A9(ll)-lanostene skeleton in all of the investigated materials. Structural variations were found at the C3 position and in the side chain at C17. The following assignments have been made: compound I, 33~methoxy-5a-lanost-9(ll)-en-24S,25-diol (43); compound II, the corresponding 33-hydroxy derivative (51); compound III, 33-methoxy-5a-lanost-9(11)-en-24-one (59); compound IV, 33-methoxy-5a-lanost-9(11),25-dien-24S-ol (65); compound V, 3a-hydroxy-5a-lanost-9(ll),25-dien-24-ol (66); compound VI, 33-methoxy-5a-lanost-9(ll)-en-22,25-diol (70); compound VII, 33-methoxy-26,27-bis nor-5a-lanost-9(ll)-en-24-one (71). Compound VIII was shown to be the ethylidene derivative of 33-methoxy-5a-lanost-9(ll)-en-24S,25-diol (76) and compounds IX and X were assigned to structures (78) and (80), respectively. A novel dimeric steroidal structure (83) has been proposed for compound XI. Part II describes synthetic investigations which lead to the development of a sequence providing a synthon [(193) and (194)] for the synthesis of vobasine (78)- and sarpagine (77)-type alkaloids. 2-Amino-3-indolyl(3a)-propanol (121), obtained by lithium aluminum hydride reduction of L-tryptophan (106), was converted to its ditosylate (150). Treatment of the latter with cyanide ion provided 3-(N~tosylamino)-4-indolyl(3a)-butanonitrile (151) which was transformed to 3-(N-tosylamino)-4-indolyl(3a)-butanoic acid (152) by means of 30% sodium hydroxide solution. 3-Amino-4-indolyl(3a)-butanoi.c acid methyl ester (155) was obtained through reductive cleavage of (152), followed by Fischer esterification. Compound (155) could then be converted to 3-CN-.formylami.no)-4- (N-benzyl-indolyl)(3a)-butanoic acid methyl ester (163) by treatment with a mixture of formic acid and acetic anhydride followed by sodium hydride and benzyl bromide. Reaction with trifluoroacetic acid converted compound (163) to the tricyclic 3-carbomethoxymethyl-N -benzyl-3,4-dihydrocarboline (173) which upon condensation with 3-methylene-pentan-2-one (126) afforded the tetracyclic 2-oxo-3-ethyl-6-carbomethoxymethyl-l,2,3,4,6,7,12,12b-octahydro-(N-benzylindolo)(2,3-a)-quinolizine (175). The ethylene ketal (177) of the latter material was treated with diisopropyllithium amide and methyl chloroformate to provide 2-oxo-3-ethyl-6-dicarbomethoxymethyl-l,2,3,4,6,7, 12,12b-octahydro-(N-benzylindolo)(2,3-a)-quinolizine ethylene ketal (178), which possesses a highly activated acidic proton (C6a) in the side chain. A suitable leaving group at the C2 position, necessary for subsequent transannular cyclisation, was available through conversion of the tetracyclic ketone (175) to the corresponding C2cx-alcohol (181) and further transformation of the latter into various derivatives such as the acetate (182), the mesylate (183) and the p-nitrobenzoate (185). In order to allow generation of an exocyclic olefin at C3, the C2-olefin, 3-ethyl-6-carbomethoxymethyl-l,4,6,7,12,12b-hexahydro-(N-benzylindolo)(2,3-a)quinolizine (184), obtained via dehydration of the alcohol (181), was converted to 2,3-a-dihydroxy-3-ethyl-6-carbomethoxymethyl-l,2,3,4,6,7,12,12b-octahydro-(N-benzylindolo) (2,3-a)-quinolizine (186) by osmium tetroxide oxidation. Treatment of (186) with acetic anhydride or p-nitrobenzoyl chloride provided the diacetate (187) or the C2 mono p-nitrobenzoate (188), respectively. The 10-membered ring system, present in the vobasine skeleton, became availahle through reductive cleavage of the C/D ring junction in the tetracyclic alcohol (181), thus, affording 2a-hydroxy-3a-ethyl-N^-methyl-6-carhomethoxymethyl-l,2,3,4,6,7,12,12b,12b-nonahydro-(N-benzyl-indolo)(2,3-a)-12b,N^-seco-quinolizine (190). Acetic anhydride treatment of the ethylene ketal (177) provided two isomeric components, 2-oxo-3-ethyl-Nb-acetyl-6-carbomethoxymethyl-1,2,3,4,6,7,12,12b-octahydro-12b-acetoxy-(N-benzylindolo)(2,3-a)-12b,Nb-seco-quinolizine ethylene ketal (191a and b), also possessing the 10-membered ring skeleton. Furthermore, the latter materials enable an entry into the family of 2-acylindole alkaloids as well as members of the dimeric alkaloids such as voacamine (75).