Thesis (Ph. D.)--University of Wisconsin, 1964. / Typescript. eContent provider-neutral record in process. Description based on print version record. Bibliography: leaves 53-56.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1956. / Typescript. Abstracted in Dissertation abstracts, v.16 (1956) no. 4, p. 766. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 128-129).

Thesis--Marburg. / Vita. Includes bibliographical references.

The total synthesis of a variety of indole and dihydroindole alkaloids, is described. Mere specifically, the d1-epimers of naturally occurring vincadine, vincaminoreine, vincaminorine, minovine, vincadifformine, N-methyl-quebrachamine and vincaminoridirie have been obtained by appropriate modifications in the general synthetic scheme. This work also illustrates that the transannular cyclization reaction previously developed in our laboratories is of great versatility in the synthesis of alkaloids in the Vinca and Aspidosperma families. In essence, the synthetic sequence involves the reaction of the aldehydo-ester (118) with either tryptamine or 6-methoxytryptamine to provide in high yield, the tetracyclic lactams (119 or 166). Lithium aluminum hydride reduction of the latter, followed by hydrogenolysis of the benzyl group provided the corresponding alcohols (94 or 165). These compounds were transformed via their mesylate derivatives to the quaternary salts (95 or 187) which served as the crucial intermediates for the preparation of the nine-membered-ring alkaloids. Finally transannular cyclization of the latter substances leads to the pentacyclic Aspidosperma and Vinca alkaloids. / Science, Faculty of / Chemistry, Department of / Graduate

The condensation of a C-nor-D-homo steroidal portion with the lithium derivative of various substituted pyridines is outlined as a general method for the synthesis of Veratrun alkaloids. The application of this approach to the synthesis of verticine (138), a representative of the a-cevanine bases is described. Hecogenin acetate (180) was converted in excellent yield to 33-acetoxy-13a-acetoxymethyl~18-nor-5a,12a-spirostan (240). Performic acid degradation of the spiroketal side chain in 240 gave 38-acetoxy-13et-acetox.ymethyl-18-nor-12a-pregnajervan-20-one (260). This ketone was coupled with 2-lithio-5-methyl pyridine to give after acetylation 33,18-diacetoxy-20-hydroxy-20,23,24,25,26-N-hexadehydro-5a,136(H),17a(H)-vcratraiiine (277). The coupling product vras reduced with PtC^ in acetic acid to 33,18-diacetoxy-5ct,133(H),17a(H)-veratranine (287). The final conversion to the hexacyclic a-cevane skeleton (90) was attempted by heating 287 at 130° for 72 hours in triglyme. The above results open the possibility of the synthesis of several hypotensive Veratrum alkaloids and the access to several compounds not easily obtained from the natural products by degradation reactions. While some of the naturally occurring alkaloids are known to exhibit hypotensive activity, it is not known whether alterations in stereochemistry and structure will cause enhancement or loss of such activity. / Science, Faculty of / Chemistry, Department of / Graduate

Many naturally occurring and synthetically made azapolycyclic aromatic ring systems display important biological activities. One class of naturally occurring azapolycyclic aromatic ring systems is the dibenzopyrrocoline alkaloids, made from an indole nucleus fused to an isoquinoline system sharing the same nitrogen, i.e. the indolo[2,1-a]isoquinoline nucleus. The indolo[2,1-a]isoquinoline and its analogues have been reported to possess antileukemic, tubulin polymerization inhibitory and antitumor activity. A variety of indolo[2,1-a]isoquinolines have been synthesized in our labs. This includes, the 5,12-dimethyl-6-phenylindolo[2,1-a]isoquinoline, using the Suzuki- Miyaura cross-coupling reaction and reaction conditions for the formation of aromatic rings (KOBut in DMF) developed in our laboratories. In this dissertation, we outline the syntheses of (±)-5,6-dihydro-6-phenylindolo[2,1-a]isoquinolin-5-ol and 2-(1-benzyl-1H-benzo[d]imidazol-2-yl)benzaldehyde. We also discuss the synthesis and the modelling studies, (docked in silico) of the 3-substituted oxindoles in the X-ray crystal structure of the PfPK5 cyclin dependent kinase (CDK). The synthesis of indolo[2,1-a]isoquinolines started with N-protection of isatin and benzimidazole with a benzyl group to afford 1-benzylindoline-2,3-dione and 1- benzyl-1H-benzo[d]imidazole, respectively. The next step was the synthesis of the brominated compound, 1-benzyl-2-bromo-1H-indole, and the iodated compound, 1-benzyl-2-iodo-1H-benzo[d]imidazole. 1-Benzyl-2-bromo-1H-indole was synthesized by means of a functional group interconversion of the oxygen in the 3-position of isatin to two chlorine atoms initially, followed by removal of those chlorine atoms with activated zinc, followed by the conversion of the carbonyl of the oxindole to give a 2-bromoindole using POBr3. 1-Benzyl-2-iodo-1Hbenzo[ d]imidazole was synthesized in two ways. Firstly, 1-benzyl-1Hbenzo[ d]imidazole was exposed to LDA followed by iodinating the 2-position by 5 exposure of the intermediate to diiodoethane. The second method uses a halogenating method developed in our labs. 1-Benzyl-1H-benzo[d]imidazole was exposed to isopropylmagnesium chloride lithium chloride followed by I2. Having obtained the halogenated products, both sets of halogenated precursors were coupled with 2-formylphenylboronic acid using the Suzuki-Miyaura crosscoupling reaction to obtain the products, 2-(1-benzyl-1H-indol-2-yl)benzaldehyde and 2-(1-benzyl-1H-benzo[d]imidazol-2-yl)benzaldehyde in 98 and 67% yield, respectively. Aromatization of 2-(1-benzyl-1H-indol-2-yl)benzaldehyde occurred easily using tBuOK in DMF at room temperature to afford (±)-5,6-dihydro-6- phenylindolo[2,1-a]isoquinolin-5-ol in 75% yield (7:3 ratio of anti-: syn-) but exposing 2-(1-benzyl-1H-benzo[d]imidazol-2-yl)benzaldehyde to the same reaction conditions did not afford the desired product. Dehydrating (±)-5,6- dihydro-6-phenylindolo[2,1-a]isoquinolin-5-ol using methanesulfonyl chloride in CH2Cl2 was unsuccessful. Further attempts at dehydrating (±)-5,6-dihydro-6- phenylindolo[2,1-a]isoquinolin-5-ol were prevented due to time constraints. In the last part of the project, a library of 3-substituted oxindoles (13 molecules) was synthesized successfully and the compounds were docked in silico in the active site of an X-ray crystal structure of PfPK5, a cyclin dependent kinase of the Plasmodium falciparum, the agent causing the most severe form of human malaria. Eleven of the thirteen compounds were synthesized by condensation of oxindole and a suitable aldehyde in the presence of piperidine. The other two, 3- (propan-2-ylidene)indolin-2-one and 5,6-dimethoxy-3-(methylthio)indolin-2-one, were synthesized differently. 3-(Propan-2-ylidene)indolin-2-one was synthesized by reacting the oxindole with acetone in the presence of HCl and 5,6-dimethoxy- 3-(methylthio)indolin-2-one was synthesized following Gassman’s methodology. Two molecules scored well in the molecular modelling studies using the X-ray crystal structure of PfPK5, namely, (E/Z)-3-(3,4-dimethoxybenzylidene)indolin-2- one and (Z)-3-(4-hydroxybenzylidene)indolin-2-one. 6 In conclusion, we managed to synthesize (±)-5,6-dihydro-6-phenylindolo[2,1- a]isoquinolin-5-ol using the Suzuki Miyaura cross-coupling reaction and reaction conditions that lead to aromatization (tBuOK in DMF at room temperature) as key steps and 2-(1-benzyl-1H-benzo[d]imidazol-2-yl)benzaldehyde using the Suzuki- Miyaura cross-coupling reaction. A library of 3-substituted oxindoles was made and using molecular modelling were docked in silico into the crystal structure of the active site of PfPK5 with 2 compounds showing promise, for further studies.

Thesis (Ph. D.)--University of Hong Kong, 1971. / Typewritten.

Thesis (M. Sc.)--University of Hong Kong, 1969. / Typewritten.

Herein describes our approaches to the Daphniphyllum alkaloids. Specifically targeted are the recently isolated daphnicyclidins. The first chapter describes the structural diversity and biological properties of this class of alkaloids. Chapter 2 discusses some exploratory chemistry towards the daphnicyclidin fused tricycle. Chapter 3 describes the use of cyclopropanes in synthesis and their use in our ring expansion strategy. Preliminary results on the key cyclopropane ring expansion and the stereoselective quaternary center formation are also discussed. The chemistry concerning the diasteroselective cyclopropanation of a key intermediate and further details concerning the cyclopropane ring expansion are delineated. Chapter 4 contains the experimental details and characterization data for all new reported compounds. / text

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.