UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Synthetic studies directed towards the indole alkaloid (±)-aristoteline Jamieson, Patrick Robert


This thesis describes some synthetic studies directed towards (±)— aristoteline (8), a naturally occurring indole alkaloid possessing a novel molecular structure. An efficient, stereoselective synthesis of the ketal carbamate (116) and attempts to transform this material into (8) are reported. The synthesis of the intermediate diketal ether (35) was accomplished as follows. Treatment of 9-methyl-5(10)-octalin-l,6-dione with 2,2-dimethyl-l,3-propanediol in the presence of jp-toluenesulfonic acid (as catalyst) produced the corresponding diketal compound. Subjection of the latter material to a hydroboration-oxidation sequence, using borane-dimethylsulfide complex and hydrogen peroxide, afforded two alcohols in a ratio of approximately 9:1. The relative stereochemistry of these alcohols was determined by chemical correlation with compounds of known structure and stereochemistry. The preparation of the diketal ether (35) was completed by the etherification of the major product from the hydroboration-oxidation sequence with β-methoxyethoxymethyl chloride. The elaboration of the diketal ether (35) into the α,β -unsaturated ester (61) was accomplished in two steps. Thus, treatment of compound (35) with 2-methylcyclohexanone in the presence of a catalytic amount of p-toluenesulfonic acid produced a mixture of the corresponding monoketal compounds. This crude mixture was allowed to react with the potassium salt of triethyl phosphonoacetate giving the α,β-unsaturated ester (61) as a 1:1 mixture of geometric isomers. Hydrogenation of compound (61) using platinum oxide catalyst produced a mixture (64:36, respectively) of two saturated esters, the desired α-face epimer (72) and its diastereomer. The sterochemical disposition of these compounds was deduced by chemical correlation with compounds of known stereochemistry in conjunction with ¹H nmr spectral analysis. The synthesis of the ketal carbamate (116) was completed in three steps from the saturated ester (72). Treatment of the latter compound with lithium diisopropylamide and methyl iodide afforded the corresponding α,α-dimethylester. The ester functionality was then cleaved using a mixture of potassium tert-butoxide in anhydrous dimethylsulfoxide. The resulting carboxylic acid was elaborated into the ketal carbamate (116) through the use of a novel and efficient modification of the Curtius reaction. Unfortunately, the conversion of the ketal carbamate (116) into (±)-aristoteline (8), via an intramolecular cyclization, was unsuccessful. All attempts to selectively remove the methoxyethoxymethyl (MEM) ether moiety from (116) met with failure. In an attempt to circumvent this problem a modified approach for the completion of the synthesis of (8) was initiated. The ketal carbamate (116) was treated with excess titanium tetrachloride resulting in the removal of both the ketal group and the ether functionality. Oxidation of the resulting alcohol, with a chromium trioxide-pyridine complex, afforded the carbamate dione (128). Unfortunately, attempts to deprotect the amino group of (128), and subsequently elaborate the desired product into (8), via a reductive amination, were unsuccessful.

Item Media

Item Citations and Data


For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.