Browsing by Author "Giles, Robin G F"

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    Some benzo- and naphtopyrans by novel cyclisations
    (1985) Pestana, José Alexandre Xavier; Giles, Robin G F
    It has recently been shown that the naphthalene dimethyl ethers E-2-Hydroxymethyl-1,4-dimethoxy-3-pent-1-enylnaphthalene and E-2-Hydroxyethyl-1, 4-dimethoxy-3-prop-1-enylnaphthalene cyclise to afford naphtho[2,3-c]pyrans when treated with two molar equivalents of cerium(IV) ammonium nitrate. It has also been shown that these naphthalenes cyclise readily and in high yield to give naphthopyrans when treated with potassium-t-butoxide in dimethylformamide under anaerobic conditions. In order to determine which structural features present in these compounds are required for each mode of cyclisation, a series of ortho-alkenylbenzyl and -naphthyl alcohols, unsubstituted or carrying methoxy or ethyl substituents at appropriate positions on the aromatic ring have been synthesized. The investigations which were carried out revealed that as far as the cerium(IV) ammonium nitrate reactions were concerned, a methoxy group ortho to the alkenyl side chain appeared to be imperative for the success of the reaction. A mechanism for the reaction is proposed. Although no conclusive general mechanism could be inferred from the results obtained from the base-promoted cyclisations, the explanation for this unusual reaction may involve steric effects, since it was those alcohols in which both the hydroxyalkyl and alkenyl side chains were flanked by bulky groups (forcing the reacting centres into close proximity) which cyclised in high yield.
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    The syntheses of some naturally derived naphthoquinones
    (1987) De Koning, Charles Bernard; Giles, Robin G F
    The synthesis of the naphthalene core of the ansamycin antibiotics, 8-acetyl-3-acetylamino-5,7-dihydroxy-1,4-naphthoquinone from benzoquinone by means of simple reactions including, Diels-Alder adduct formation, mild acetylation, oxime formation and Beckmann rearrangement in five steps with an overall yield of 22% is described in Chapter 1. The synthesis of the naturally occurring naphthoquinone derivative, possessing anti tumour and antiprotozoal properties, bikaverin is described in Chapter 2. Starting from vanillin the key intermediate 2-(2'-benzyloxy-6'-methyl-4'-methoxybenzoyl)-1,4,5,6,8-pentamethoxynaphthalene was prepared in six simple steps in an overall yield of 18%. This key intermediate was converted into bikaverin utilizing two independent routes. In the first route the benzyl group was removed from the key intermediate by hydrogenolysis followed by oxidative spiro ring formation , with 2,3-dichloro-5,6-dicyanobenzoquinone. After effecting xanthone ring formation and removal of two methyl groups with lithium iodide, bikaverin was produced in six steps in an overall yield of 32%. In the second route the key intermediate was first oxidised by silver (II) oxide this was followed by removal of the benzyl group and two methyl groups peri- to the quinone with boron trichloride, which led to spontaneous spiro ring formation, ultimately bikaverin was produced in three steps in an overall of 34%. The syntheses of the naturally occurring product ventiloquinone E and its trans-isomer as well as an isomer of the naturally occurring ventiloquinone J and its trans-isomer are described in Chapter 3. Starting from 1,2,4,5,8-pentamethoxynaphthalene, the synthesis of which has been described in Chapter 2, ventiloquinone E was prepared in nine steps in an overall yield of 7%. Similarly an isomer of ventiloquinone J was also prepared from 1,2,4,5,8-pentamethoxynaphthalene in ten steps in an overall yield of 6%. In both cases a mixture of cis-and trans-isomers was obtained, a successful resolution of both mixtures was accomplished by thin layer chromatography. By two other methods the trans-isomer of ventiloquinone E could be prepared in either nine steps in an overall yield of 23% or in six steps with an overall yield of 30% starting from the same pentamethoxynaphthalene.
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    The synthesis of derivatives of naturally occurring naphthalenes
    (1988) Knight, Lorraine Shirley; Giles, Robin G F
    The ansamycins are a large group of natural products which have attracted considerable attention, largely as a result of their range of biological activity. The laboratory synthesis of an ansamycin has been simplified into the independent construction of the aromatic nucleus and the ansa chain, followed by their combination to form the macrocyle. The project described in Chapter 1 was designed to devise a novel, convenient, and efficient synthesis of a substituted 1,4-naphthoquinone which would function as a model for the naphthoquinonoid nucleus of the rifamycin subclass of these antibiotics. In this synthesis, 1,4-benzoquinone was converted into 8- acetyl-5,7-dihydroxy-6-methyl-3-propionylamino-1,4-naphthoquinone in six steps in an overall yield of 20%. The key step in this reaction sequence was the introduction of the C-6 methyl group via a regioselective lithiation/methylation reaction. Compounds which can be structurally defined as bioreductive alkylating agents have considerable potential as antineoplastic agents, according to H.W. Moore (Science, 1977). The protoaphins possess certain structural features which suggest their capability to function as such alkylating agents. Reductive cleavage of the aphid pigment, protoaphin-fb has been shown to give quinone A together with glucoside B, while protoaphin-sl on similar treatment affords quinone A', epimeric with quinone A at C-4, together with the same glucoside B. Professor Giles and co-workers have synthesised the 7,9-dideoxyquinone derivatives of both quinone A and A', as well as quinone A and A' themselves. The second chapter in this thesis describes three different approaches to the synthesis of a 4,10-dihydroxy-7,9-dimethoxy- 1,3-dimethyl-1H-naphtho[2,3-c]pyran analogous to glucoside B. The first two routes describe the construction of a naphtho[ 2,3-c]pyran of the correct relative stereochemistry using the novel reactions pioneered in this Department during the synthesis of 7,9-dideoxyquinone A. In the first method, the pyran ring was constructed with a C-5 oxygen substituent which was subsequently removed. The second method however, differs substantially from this route in that the C-5 substituent was not present during ring closure, hence eliminating the need to remove it at a later stage. The key step in the third approach involved the isomerisation of a dioxolane substituted naphthalene by an intramolecular version of the Mukaiyama reaction. Treatment of a C-8 brominated dioxolanyl naphthalene with titanium tetrachloride resulted in the formation of two angular naphtho[l,2-c]pyrans with the same relative stereochemistry of the pyran ring. An interesting bromine migration occurred after isomerisation had taken place. However, it is suggested that decreasing the size of the C-4 protecting group on the naphthalene nucleus prior to isomerisation, may allow the formation of the linear naphthopyran.
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    The synthesis of some naphthol (2,3-c) pyrans
    (1981) Chorn, Trevor Anthony; Giles, Robin G F; Mitchell, P R K
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    The total synthesis of aristolindiquinone
    (1986) Botha, Marc Edgar; Giles, Robin G F
    Aristolindiquinone (1), a novel natural compound possibly: possessing anti-fertility activity, was synthesized via two independent routes. First, a Stobbe reaction unambiguously gave the naphthalene nucleus with the required substitution pattern (3,8-dioxygenated-2,5-dimethyl naphthalene), starting from 2-hydroxy-5-methylbenzaldehyde (31). Second, a general synthesis, of substituted C-5 oxygenated- 1,4-naphthoquinones is applied to the synthesis of (1). The critical step in the synthesis is the reaction of the novel Diels-Alder partners, dienophile (90), synthesized from 2,6-dihydroxytoluene (56), and diene (109).