Robin B. Boar

Investigations on the biosynthesis of steroids and terpenoids. Part XII. Biosynthesis of 3β-hydroxy-triterpenoids and -steroids from (3S)-2,3-epoxy-2,3-dihydrosqualene

(3S)-2,3-Epoxy-2,3-dihydrosqualene has been shown to be the precursor of lanosterol in pig liver, of lanosterol and ergosterol in yeast, and of cycloartenol, β-amyrin, and lupeol in germinating pea seedlings.

X-Ray crystal and molecular structure of 3β-acetoxy-6,7-epidithio-19-norlanosta-5,7,9,11-tetraene, the stable dithiete tautomer of a dithio-o-quinone

The preparation and structure determination of the title compound, a representative of a novel structural class, is described.

β-Amyrin triterpenoids

Abstract The natural occurrence of β-amyrin triterpenoids is reviewed. The distribution of functiona groups within these compounds is tabulated and commented upon. The generation of artefacts is surveyed.

A new and convenient synthesis of the 17α,21-diacetoxy-20-oxopregnane side-chain

A convenient ‘one-pot’ synthesis of the corticosteroid side chain has been developed. 20-Oxopregnane oximes have been converted into 20-acetylamino-17(20)-ene derivatives, which with lead tetra-acetate in dry benzene afford 17α-acetoxy-20-acetylimines. The latter are rearranged by acid to 20-enamides [as (IV)]. Further reaction with lead tetra-acetate then introduces an acetoxy-group at C-21. The 20-acetylimines are hydrolysed to the corresponding ketones by aqueous acid. Overall yields are high. Some preliminary experiments with 16α- and 16β-methylpregnanes are outlined.

A simple synthesis of enamides from ketoximes

Ketoximes are converted into enimides [as (III)] in excellent yield by refluxing acetic anhydride in pyridine. Use of alumina chromatography during work-up affords the corresponding enamides [as (II)]. The latter are also prepared by reducing oxime acetates in the presence of acetic anhydride with reagents such as chromium(II). The generality of these reactions is established. Enamides show limited chemical reactivity in comparison with enamines. A particular exception is their efficient α-acetoxylation by reagents such as lead tetra-acetate. Attention is directed to the preparation and use of titanium(III) acetate.

On the reported transformation of β-amyrin into oleanolic acid

Reduction of 3β-acetoxy-12α,13α-epoxyoleanan-3β-yl acetate (β-amyrin acetate epoxide)(5) with lithium–ethylamine affords β-amyrin (17%), oleanane-3β,12α-diol (3; R1= R2= H)(50%) and 13α-oleanane-3β,12α-diol(6; R1= R2= H)(27%). On photolysis 3β-acetoxyoleanan-12α-yl nitrite (3; R1= Ac, R2= NO) affords the 27-oxime (10), which has been further transformed into the aldehyde (9; R1= H, R2= OH) and the corresponding lactone (11; R1R2= O). The latter had previously been identified erroneously as oleanolic lactone acetate (12; R1= Ac, R2R3= O).

Assimilation of the antipodal forms of squalene 2,3-oxide by mammalian, yeast, and plant systems

(S)-Squalene 2,3-epoxide was found to be the exclusive precursor of lanosterol in pig liver, lanosterol, and ergosterol in yeast (Saccharamyces cerevisiae), and β-amyrin, lupeol and cycloartenol in pea seedlings.

An improved synthesis of 13-epi-androstanes and of 13-epi-oestranes

Treatment of a 17-hydroxyimino-steroid with refluxing acetic anhydride and pyridine affords an equilibrium mixture of 13-epi-enimide and 13-epi-enamide. A free-radical mechanism is proposed. Acidic hydrolysis gives the 17-oxo-13-epi-steroid in high overall yield.

Triterpenoids of Aglaia odorata. Configuration of trisubstituted epoxides

Structures are established for three dammarane triterpenoids [(1c), (3a), and (3c)] isolated from Aglaia odorata. The stereochemistry at C-24 of these compounds and of aglaiol (1a) has been elucidated. The possibility that (3c)(a 24,25-dihydroxy-3-ketone) is identical with aglaiondiol, previously described as 3β,25-dihydroxy-5α-dammar-20-en-24-one, is discussed. It is shown that the configuration of trisubstituted epoxides can be conveniently determined by acid-catalysed methanolysis and application of Horeaus method to the resulting methoxy-alcohol.

On the relationship between intramolecular hydrogen abstraction by alkoxyl radicals and deshielding by the corresponding hydroxy-groups as indicated by nuclear magnetic resonance

The 1H n.m.r. spectra of various steroids and triterpenoids and their hydroxy-derivatives have been studied. It is shown that a consideration of deshielding by hydroxy-groups can provide valuable information on the likely course of intramolecular hydrogen abstraction reactions of alkoxyl radicals.