Arnold H. Ratcliffe

Structures of the cephalosporolides B–F, a group of C10 lactones from Cephalosporium aphidicola

The structures of the pentaketides lactones, the cephalosporolides B–F, were elucidated by a combination of spectroscopic, chemical, and X-ray analyses.

Aphidicolane metabolites of Cephalosporium aphidicola

Abstract 3α,6β,16β,17,18- and 3α,11β,16β,17,18-Pentahydroxyaphidicolane have been isolated from the fungus, Cephalosporium aphidicola and shown to be biosynthesized from aphidicolin. Two further minor aphidicolin derivatives are also reported.

Biotransformation of some aphidicolane derivatives by Cephalosporium aphidicola

Abstract Chlorocholine chloride (CCC) is shown to inhibit the formation of aphidicolin by Cephalosporium aphidicola . 3α,18-Dihydroxyaphidicolane is transformed into aphidicolin, whereas 3α,16α,18-trihydroxyaphidicolane is converted into 16-epi-aphidicolin.

Studies in terpenoid biosynthesis. Part 30. The acetate and mevalonate labelling patterns of the diterpenoid, aphidicolin

The 13C n.m.r. spectra of aphidicolin and its derivatives have been assigned. The enrichment and coupling patterns of aphidicolin biosynthesized from [1-13C]-, [2-13C]-, and [1,2-13C2]-acetate were determined and used to define the constituent isoprene units. The numbers of 2- and 5-mevalonoid hydrogen atoms incorporated into aphidicolin were determined by 3H labelling. The generation of2H–13C coupling which was observed in the 2H n.m.r. spectrum of aphidicolin biosynthesized from [4-2H2,3-13C] mevalonic acid, has established the migration of a 9β-hydrogen atom to C-8 during the biosynthesis.

Studies in terpenoid biosynthesis. Part 38. The role of an 16β,17-epoxyaphidicolane in the minor biosynthetic pathway leading to aphidicolin

The hydroxylation of [15-2H, 17-2H3]aphidicolane-3α,16β,18-triol at C-17 in the biosynthesis of aphidicolin is shown to involve an isotope effect whilst there is no effect in the incorporation of [15-2H, 17-2H2]aphidicol-16-ene-3α,18-diol suggesting that the transformation of the 16-ene involves epoxidation and hydrolysis rather than hydration and hydroxylation. Feeding experiments suggest that the 16β,17-epoxyaphidicolane-3α,18-diol is involved in this transformation.

Studies in terpenoid biosynthesis. Part 32. The incorporation of aphidicolan-16-ene and aphidicolon-16β-ol into the diterpenoid aphidicolin by the fungus Cephalosporium aphidicola

The preparation of [17-14C]aphidicol-16-ene and [17-14C]aphidicolan-16β-ol and their incorporation into aphidicolin by Cephalosporium aphidicola to the extent of 0.09 and 7.9% respectively, is described.

The structure of thiobiscephalosporolide A, A dimeric pentaketide macrolide from Cephalosporium aphidicola

The isolation, structure elucidation, and some chemical transformations of the dimeric macrolide, thiobiscephalosporolide A, are reported.

Oxidation of aphidicolin and its conversion into 19-noraphidicolan-16β-ol

The preparation of the 3α,18-monoacetonide of aphidicolin and its selective oxidation at C-17, is described. Catalytic oxidation of aphidicolin affords 16β-hydroxy-3-oxo-19-noraphidicolan-17-oic acid. The conversion of this into 19-noraphidicolan-16β-ol and its biotransformation by the fungus, Cephalosporium aphidicola, to a 19-noraphidicolin, is reported.

Studies in terpenoid biosynthesis. Part 39. The stereochemistry of the relationship between substrate and oxidant in the hydroxylation of aphidicolin at C-18 by Cephalosporium aphidicola

The preparation of some 3α, 18-oxetane analogues of intermediates in the biosynthesis of aphidicolin is described. Their stereoselective labelling at C-18 with deuterium is reported. Biotransformation studies using these substrates with Cephalosporium aphidicola have shown that the 18-pro-R-hydrogen is removed in hydroxylation at this centre suggesting a Re stereochemical relationship between the substrate and oxidant for the normal hydroxylation at C-18. The X-ray crystallographic structure of 3α,18-oxetane 6 is presented and compared with that of aphidicolin 17-nor-16-ketone 13.

Rearrangements of the C/D ring system of the tetracyclic diterpenoid, aphidicolin

The generation of a C-16 carbocation in the aphidicolane series by the hydrolysis of a 15β,16β- or a 16β,17-epoxide is shown to lead, inter alia, to skeletal rearrangement products arising from the migration of the C(12)–C(13) bond to C-16.