2, 4-Di-O-methyl-L-erythrose is thought to occur in the hydrolysis and periodate oxidation products of polysaccharides. This sugar has now been synthesized from methyl-L-arabofuranoside by tosylation, methylation, detosylation and periodate oxidation. The free sugar was obtained as a sirup and was characterized by the preparation of a crystalline phenylhydrazone and a crystalline p nitrobenzoate. / Science, Faculty of / Chemistry, Department of / Graduate

It is well established that various partially methylated tetroses and pentoses occur in periodate oxidation products of methylated polysaccharides. To provide reference compounds as a means of identifying some of these sugars 2,3 di-O-methyi-L-threose, 2,3 di-O-methyi-D-erythrose, and 3,4 di-O-methyl-L-xylose have been synthesized. The threose and xylose were synthesized from ∝-methyl-D-glucoside by benzylidene condensation, methyiation, hydrolysis, reduction and periodate oxidation, whereas the erythrose was obtained from D-mannose by a similar sequence of reactions. The sugars were obtained as syrups and were characterized by the preparation of crystalline derivatives. ii. Black Spruce hemicelluloses:- By using different concentrations of alkali three different hemiceiluloses were extracted from black spruce holocellulose. Of these two fractions, the xylan and the glucomannan were purified by fractional precipitation using barium hydroxide solution and Fehling's solution. Previous workers have observed that the xylan fraction was always contaminated by small amounts of galactose. This was also true in the present instance if barium hydroxide alone was used for purification, but when this was followed by two treatments with Fehling's solution the galactose was completely eliminated. This is believed to be the first case of the isolation of such a xylan in a pure state from the hemicelluloses of a coniferous wood. The third fraction - the galactoglucomannan was found to be quite difficult to re-dissolve in alkali and as a result its purification is not quite complete. / Science, Faculty of / Chemistry, Department of / Graduate

The possibility of using a calomel electrode as a reference standard in the polarographic comparisons in acetonitrile has been studied. The results indicate that the time required for attaining a constant potential is too long to be convenient for such use. The behaviour of some organic nitrocompounds at the dropping mercury electrode in acetonitrile containing 0.1 molar tetrabutylammonium iodide has been studied. The nitroanilines and the nitrophenols give distinct double waves on polarographic reduction. There is no formation of any maxima in the case of the nitroanilines, whereas, maxima are found to develop with time in the case of the nitrophenols. The maxima are found to be non-suppressible. The ease of reduction of the nitrophenols and the nitroanilines, as given by their half-wave potentials, is in agreement with the order expected on the basis of the previously established theories of Shikata and Astle. A possible mechanism of the reduction is given with the irreversibility of the reduction in view. / Science, Faculty of / Chemistry, Department of / Graduate

Two sequences leading to the total synthesis of several octahydrochrysene derivatives are described; in particular, the synthesis of B-nor-cis-2-methoxy-8α-acetoxy-5-keto-10a-methyl-5,6,7,8,9,10,10a-octahydrochrysene (XL) is achieved. In one sequence an olefinic bond at the 5,6 position of ring B (XXXII) was introduced by reduction of cis-2-methoxy-8α-acetoxy-5-keto-10a-methyl-5,6,6a, 7,8,9,10,lOa-octahydrochrysene (XIV) with sodium borohydride, followed by dehydration with phosphorus pentoxide.Subsequent reaction at the olefinic linkage by osmium tetroxide provided the α-diol (XXX), which upon treatment with periodic acid yielded a hemiacetal (XXXIV). Cyclization on alumina then provided the B-nor internal aldol condensation product (XXXIX). The latter readily underwent / oxidation with Jones' reagent to result in the B-nor-5-keto acetate (XL). In an alternate sequence the cis-2-methoxy-8α-acetoxy-5-keto-5,6,6a,7,8, 9,10, 10a-octahydrochrysene (XIV) is oximinated at the 6-position with isoamyl nitrite and the oxime is converted by acid hydrolysis to a 5,6-diketo-8-hydroxy compound (XLII). An attempt was made to accomplish a benzilic acid rearrangement on the α-diketo compound and the resulting product (XLVII) was subjected to lead tetra-acetate oxidation in the hope that the B-nor-5-keto system (XLVIII) could be obtained. The structures from the last two reactions were only tentatively established. A critical discussion of the n.m.r. data is reserved to a separate section of the thesis. Tentative assignments of all the aromatic protons were made. Of special note is the chemical shift dependence of the proton at C₄ on the substitution at C₅. Configurational and conformational assignments of the ring A/B system were made on the basis of angular methyl and 8β-proton frequencies. / Science, Faculty of / Chemistry, Department of / Graduate

The first part of this thesis describes a sequence which provides a total synthesis of cleavamine (23) and catharanthine (12). Dihydrocatharanthinol (76) obtained by lithium aluminum hydride reduction of dihydrocatharanthine (34) was converted to its tosylate derivative. The latter intermediate upon heating in benzene containing two equivalents of triethylamine underwent an interesting fragmentation reaction to provide a seco-diene (78) containing the cleavamine ring system. Reaction of this diene with osmium tetroxide provided a tetrol (96) which could be converted to cleavamine on the one hand and the C₄-functionalized cleavamine derivatives on the other. Thus treatment of the tetrol with sodium borohydride allowed the hydrogenolysis of the carbinol amine function and provided a triol (97). The vicinal diol present in 97 was cleaved by means of periodate and the resultant 2-acylindole chromophore was further converted by borohydride to a 4,18-dihydroxy dihydrocleavamine derivative (99). Reductive removal of the C₁₈ hydroxyl function by means of lithium aluminum hydride provided isovelbanamine (100). Acid catalyzed dehydration of the latter yielded cleavamine (23) while isomerization under aqueous acidic conditions provided velbanamine (22). To complete the total synthesis of catharanthine (12), cleavamine was reacted with t-butyl hypochlorite and the resultant chloroindolenine was then subjected to nucleophilic attack by cyanide ion to provide 18ϐ-cyanocleavamine. Basic hydrolysis of the nitrile function followed by esterification provided 18ϐ-carbomethoxycleavamine (60). This compound upon reaction with mercuric acetate was cyclized to catharanthine. The second part of this thesis establishes the utility of both the chloroindolenine and the C₁₈-hydroxy analogues of the cleavamine systems to the synthesis of dimeric compounds structurally similar to the natural dimeric alkaloids. Treatment of either of these analogues with vindoline under mild acidic conditions yielded the appropriate dimers containing the indole and dihydroindole units present in vincaleukoblastine. The dimerization reaction was shown to be stereospecific and led in each case to the same stereochemistry at C₁₈, of the resulting dimers / Science, Faculty of / Chemistry, Department of / Graduate

This thesis describes work leading to the completion of a total synthesis of the sesquiterpenoids (±)-prezizanol (188) and (±)-prezizaene (6). The known alcohol 128 was transformed, in three steps, into the endo-monochloride 156. The commercially available alcohol 129 was converted, in a two step sequence, into the vinyl iodide 127. Palladium catalyzed coupling of the vinyl iodide 127 with an organozinc compound derived from the chloride 156 provided the bicyclo[3.1.0]hexane 165. The bicyclo[3.1.0]hexane 165 was elaborated, in three steps, into the ester 172. Treatment of this ester with lithium diisopropylamide, followed by kinetic protonation of the resultant enolate anion, provided the endo-(1-alkenyl)-bicyclo[3.1.0]hex-2-ene 123, which cleanly underwent a Cope rearrangement to provide the bicyclo[3.2.1]octadiene 121. An attempt to cleanly synthesize 121 via the Cope rearrangement of the exo-(1-alkenyl)bicyclo-[3.1.0]hex-2-ene 122 was unsuccessful. A six step sequence was used to synthesize the mixture of silyl ethers 186 and 187 (88:12, respectively) from the bicyclo[3.2.1]octadiene 121. (±)-Prezizanol (188) was prepared, in a series of seven steps, from the silyl ether 186. Dehydration of (±)-prezizanol (188) provided (±)-prezizaene (6) in 2.2% overall yield from the alcohol 128. [Formula Omitted] / Science, Faculty of / Chemistry, Department of / Graduate

The major theme of the work described in this thesis is concerned with the preparation of the β-trimethylstannyl enoates 53, 54 and 55, and their utilization in annulation processes. Treatment of the enol triflates 88, 91 and 92 with the cuprate reagent 56 produces compounds 53, 54 and 55, respectively, in good yields. Base promoted alkylation of the enoates 53 and 54 with 3-iodo-1-chloropropane provides the products 111 and 119. Under similar reaction conditions, 55 was alkylated with 1,4-dibromobutane and 1,5-dibromopentane to give 132 and 136. By employing standard reactions, 111, 119, 132 and 136 were converted into 113, 123, 134 and 141, respectively. Treatment of 113, 123, 134 and 141 with methyllithium in THF, in the presence of HMPA, led to the formation of the substituted bicycle[4.3.0]nonenes 114, 124 and 128, and the bicyclo[5.3.0]decene 142, respectively. The annulation method described above was applied successfully to the synthesis of the sesquiterpenoid (±)-chiloscyphone (151) and its isomer (±)-S-epi-chilos-cyphone (203). Thus, reaction of compounds 182 and 183, which were derived from 54 and the alkylating agent 178, with methyllithium in THF-HMPA provided the key bicyclic intermediates 184 and 190, respectively. These two compounds were subsequently transformed into 151 and 203. The sesquiterpenoid eremofukinone, whose structure was proposed as 204, was synthesized by exploiting the annulation method described earlier. Treatment of compound 228, which was produced from 54 and the dibromide 223, with methyllithium in 1,2-dimethoxyethane afforded the key intermediate 229 along with the diene 230. Suitable chemical manipulations converted 229 into 204. On comparing the ¹H nmr spectra of 204 and eremofukinone, substantial differences were noticed. Since compound 204 was constructed by an unambiguous route, it was concluded that the original structural proposal for eremofukinone is in error. [Formula Omitted] / Science, Faculty of / Chemistry, Department of / Graduate

A number of conjugates of carbohydrates were prepared. Metal conjugates were synthesized in two different ways. Firstly, chelate coordination complexes were synthesized by forming salicylaldimine ligands derived from combinations of amino sugars [methyl-3,4,6-tri-0-acetyl-2-amino-2-deoxy-β-D-glucopyranoside, 1,3,4,6-tetra-0-acetyl-2-amino-2-deoxy-β-D-glucopyranose or 2-amino-2-deoxy-a,β-D-glucopyranose (glucosamine)] and either salicylaldehyde or 3-formyl-2-hydroxy-benzoic acid with subsequent complexation of these to copper (II) , cobalt (II), and zinc (II). A number of physical techniques were used to characterize these complexes including esr spectroscopy, visible absorption spectroscopy, mass spectrometry, nmr spectroscopy and magnetic susceptibility measurements. From the data provided by these techniques the copper-sugar complexes derived from salicylaldehyde were found in general to have the usual bis-bidentate structure. The copper complex derived from the amino-glycoside and 3-formyl-2-hydroxy-benzoic acid was found to be binuclear in structure containing two sugar moieties and two copper atoms. The second approach to forming metal sugar conjugates consisted of synthesizing organometallic π-complexes: ferrocenyl-sugar conjugates. A variety of organic- and water-soluble compounds were formed by reaction of amino, hydroxyl, or thio sugar groups with suitably substituted ferrocene derivatives. Thus organic soluble products were obtained from combinations of the sugars [l,3,4,6-tetra-0-acetyl-2-amino-2-deoxy- β-D-glucopyranose, l-thio-2,3,4,6-tetra-0-acetyl-β-D-glucopyranose, 1,2,5,6-di-0_-isopropylidene-α-D-glucofuranose and 1,2,3,4-di-o-isopropylidene-α-D-galactopyranose] with 1 - and 1,1'-ferrocenecarbonyl chlorides, N,N-dimethylaminomethylferrocene methiodide, (1-hydroxymethylferrocene)-p-toluenesulphonate and 2,4-dichloro-6-(1-hydroxymethylferrocene)-s-triazine. Water soluble products were prepared by deacetylation of some of the above compounds and by condensation of ferrocene carboxaldehyde with glucosamine to form the corresponding Schiff's base. Proton spin-lattice relaxation rates were used to assign the substituted cyclopentadienyl rings and to determine the relative spinning rates of the substituted and unsubstituted cyclopentadienyl rings. The chemistry of cyanuric chloride (2,4,6-trichloro-s-triazine), as a general means of derivatizing carbohydrates was also investigated. Thus, metals, hydrophobic alkyl groups and nitroxide spin labels were attached in various combinations to carbohydrates. A number of monosaccharide derivatives were formed including model glycolipids and a number of polysaccharides, cellulose, agarose, Sephadex, guar gum, xanthan gum and starch were spin labelled using this chemistry. For polysaccharides, information such as extent of derivatization, evidence for a covalent bond, environment of the triazine unit and the distance between triazine units was obtained. This chemistry was also extended to derivatize Bovine Serum Albumin, microporous glass beads and aluminum oxide. / Science, Faculty of / Chemistry, Department of / Graduate

M.Sc.

M.Sc. (Chemistry) / Palladium-mediated carbon-earbon (and carbon-heteroatom) bond formation! is to an increasing extent playing a vital role in synthetic organic chemistry. The chemistry is usually performed under mild conditions, with the organopal1adium intermediates being formed in situ from inorganic palladium salts or complexes, and has good tolerance of functionality on the substrates. The palladium mediator may be present in the reaction in amounts ranging from stoichiometric to catalytic. Reactions requiring stoichiometric amounts of palladium may appear to be inherently uneconomical. Palladium, however, may be easily recovered in most cases, and may be converted into salts useful for catalysis, effectively offsetting the initial expense. 2 The use of polymer-bound palladium catalysts! has also been shown to be a viable method of palladium recovery. Palladium may form a- or 1r-eomplexes with organic compounds and, as with many other transition-metal complexes, a-palladium complexes are generally only stable in the presence of select ligands. Arylphosphines are most commonly used, and of these triphenylphosphine is the ligand of choice for its availability and low cost...