The Electron microscopy of alkali halides

The various groups into which the triterpenes are divided are defined and emphasis is placed on the structural relationships which exist between these groups. A brief description is given of the methods used in the determination of the structure of triterpenes with particular reference to β-asyrin (I), a member of the oleanane (II) group. Recent progressin the problems of biogenesis and the total synthesis of triterpenes is reviewed.
All approaches, so far investigated, to the synthesis of pentacyclic triterpenes involve the fusion of two bicyclic moities representing rings A and B and rings D and E of the proposed structure. This thesis describes attempts to synthesise pentacyclic triterpenes of the oleanane (II) group, via the tetracyclic-cis-ketone (IIIa), the tetracyclic-trans-ketone (IIIc) or the tetracyclic-αβ-unsaturated-ketone (IVa).
The important bicylic intermediates in these syntheses are 5-(2'-bromoethyl)-6-exomethylene-1,1,10-trimethyl-trans-decaline(Va), 7,7,10-trimethyl-cis-decal-2-one (VI) and 7,7,10-trimethyl-Δ-octal-2-one (VII); the preparation of the last two compounds has been reported previously by Halsall and Thomas.
It was proposed originally to obtain the racemic modification of 5-(2'-bromoethyl)-6-exomethylene-1,1,10-tri- methyl-trans-decalin from Δ-podocarpen-7-one (VIII), the synthesis of which requires large amounts of 2,2,6-trimethyl- cyclohexanone. A rapid technique was developed for the preparation of this compound in high yield from 2-methylcyclo- hexanone.
The availability of sclareol (IX), which is a suitable relay in the synthesis of (+)-5-(2'-bromoethyl)-6- exomethylene-1,1,10-trimethyl-trans-decalin (Va) led to the abandonment of the route via Δ-podocarpen-7-one. Oxidation of sclareol with potassium permaganate gave the enol-ether (X). Ozonolysis of the enol-ether (X), followed by decomposition of the Oozonide (XI) with Raney nickel and reduction of the product with lithium aluminium hydride gave a mixture of 5-(2'-hydroxyethyl)-6-hydroxy-1,1,6,10- tetramethyl-trans-decalin (XII) and 5-(2'-hydroxyethyl)-6- exomethylene-1,1,10-trimethyl-trans-decalin (Vb). Treatment of either of these compounds with phosphorus oxybromide in pyridine gave (+)-5-(2'-bromoethyl)-6-exomethylene-1,1,10-trimethyl-trans- decalin (Va), from which ambreinolide (XXIII) was prepared.
The crude product, obtained after decomposing the ozonide (XI) with Raney nickel, was reduced with sodium borohydride but only small yields of compounds, which could be characterised were obtained. These were 5-(2'-hydroxyethyl- 6-acetoxy-1,1,6,10-tetramethyl-trans-decalin, 5-carboxymethyl- 6-acetoxy-1-1-6-10-tetramethyl-trans-decalin and the lactone derived from 5-carboxymethyl-6-hydroxy-1,1,6,,10-tetramethyl- trans-decaline. The first two of these compounds were obtained also by catalytic hydrogenation of the ozonide (XI); the lactone was the only compound isolated from the product obtained by oxidising the enol-ether (X) with sodium metaperiodate/ osmium tetroxide.
It has been predicted on theoretical grounds that that 7,7,10-trimethyl-cis-decal-2-one (VI) should enolise towards C - 3. Alkylation of this compound with ethyl iodide gave 3-ethyl-7,7,10-trimethyl-cis-decal-2-one, from which a mixture of 3-ethyl-7,7,10-trimethyl-Δ-cis-octal-2-one and 3-ethyl-7,7,10-trimethyl-Δ-octal-2-one was obtained by brominating and dehydrobrominating. 7,7,10-trimethyl— cis-decal-2-one (VI) was brominated in several ways and the crude product was dehydrobrominated to give, in all cases, a mixture of 7,7,10-trimethyl-Δ-cis-octal-2-one and 7,7,10-trimethyl- Δ-octal-2-one. The implications from the results of the alkylation and bromination/dehydrobromination experiments are discussed.
Alkynation of (±)-7,7,10-trimethyl-Δ-octal-2-one (VII) with (+)-5-(2-bromoethyl)—6-exomethylene-1,1,10-trimethyl- trans-decalin (Va) gave a mixture of the tetracyclic-αβ-unsaurated ketones (IVa and b). A second product was obtained from this alkylaqtion and may be a mixture of the isomeric tetracyclic-βδ-unsaturated- ketones (XIIIa and b). The tetracyclic-αβ-unstaurated- ketones ( IVa and b) were reduced with lithium in liquid ammonia to give the tetracyclic-trans-ketones (IIIc and d) this mixture was resolved.
The C,30-alcohols (XIVa and/or b) were prepared from the tetracylic-trans-ketones (IIIc and/or d) and lithium methyl, and they were treated with boron trifluoride etherate. A hydrocarbon (or mixture of hydrocarbons } was obtained and was stable to further treatment with acid. Possible products of this series of reactions are oleon-18-ene (IV) and 18βH-olean- 12—one (XVI); neither of these compounds was isolated.
The tetracyclic-hydrocarbons (XVIIa and b) were obtained by treating the tetracyclic-αβ-unsaturated-ketones (IVa and b) with methyl magnesium iodide. Spectroscopic analysis of the product obtained by treating the tetracyclic- hydrocarbons (XVIIa and b) with boron trifluoride etherate, fluoroboric acid or aluminium trichloride in nitromethane indicated that the yields of olean-11(12),13(18)-diene (XVIII) (one of the expected products of this series of reactions) was greater than that obtained from the tetracyclic-allylic-alcohols (XIXa and b) by Corey and co-workers, who used acetic acid saturated with hydrogen chloride as the cyclising agent. An investigation was made into the stability of the conjugated diene system in 3β-bezoyl-olean-11(12},13(18)-diene to treatment with acid.
An attempt was made to prepare (+)-7,7,10-trimethyl- Δ-octal-2-one (XX) for use in the alkynation with (+)-5-(2'-bromoethyl-6-exomethylene-1,1,10-trimethyl-trans- decalin (Va). Only partial resolution of (±)-7,7,10-tri- methyl-Δ-octal-2-one (VII) was achieved using standard procedures. 10-Carbethoxy-7,7,dimethyl-Δ-octal-2-one (XXIa) has been resolved and in the present work the racemic modification of this compound .was converted into 7,7,10-tri- methyl-Δ-octal-2-one by two routes. It is possible therefore, to obtoin the optical isomers of 7,7,10-trimethyl- Δ-octal-2-one (VII) by an indirect method.
The carbonyl group was protected by preparing the dioxolane-derivative (XXIIa), which was reduced with lithium aluminium hydride to give 10-hydroxymethyl-7,7-dimethyl-Δ-octal- 2-one-2-dioxolane (XXIIb). In naming dioxolane derivatives in this abstract it is assumed that the double bond is in the Δ position; no evidence was obtained to confirm this. 10-Methanesulphonyloxymethyl-7,7-dimethyl-Δ-octal-2-one-2- dioxolane (XXIIc) was prepared by treating 10-hydroxymethyl- 7,7,-dimethyl-Δ-octal-2-one-2-dioxolane (XXIIb) with methane sulphonyl chloride. the two routets to 7,7,10-trimethyl-Δ- octal-2-one diverge at this stage. In the first method 10-methanesulphonyloxymethyl-7,7-dimethyl-Δ-octal-2-one-2- dioxolane (XXIIc) was converted to the dioxolane-methanethiol (XXIId), which without purification, was desulphurised with hydrazine. The dioxolane protecting group was removed from the product and 7,7,10-trimethyl-Δ-octal-2-one was obtained.
In the second method 10-methanesulphonyloxymethyl-7,7-dimethyl- Δ-octal-2-one-2-dioxolane (XXIIc) was converted to 10-iodomethyl-7,7-dimethyl-Δ-octal-2-one-2-dioxolane (XXIIe), which was reduced with lithium aluminium hydride. The product was hydrolysed and 7,7,10-trimethly-Δ-octal-2-one was obtained.
10-(+)-Camphor-10-sulphonyloxymethyl-7,7,-dimethyl-Δ-octal-2- one-2-dioxolene (XXIIf) was prepared by treating 10-hydroxymethyl-7,7-dimethyl-Δ-octal-2-one-2-dioxolane (XXIIb) with (+)-camphor-10-sulphonyl chloride; the cli? ^tei^eoiaoi for;.^ of tlie ? f /4*dinltro_ ^•^.hydrfu.orue ve,-e resolved by euaiia' tion. Hydrolysis of the 2 f 2 oiie . ith .-ynivic ^cid and ace lie ncid pnve in-.^^ r or 1(9) yl- A -oct: a~?~orAe ( lc which ,-ee converted into 10~iodouethyl~7 f 7- t^thyl-A^ -. octf«l-?-one { D>. .hi;-, corapouiid v.eo obtniiicC from 8 10-ne thr,r,e s ul phonyl oxy rie thyl- 7»7-'. ; i o thyl- A - ,>c to l-?»oiio»2» dioxol^ne (''".He) by treptlng it v/ith aouiuia loJiac in nc^t