J.R. Knox

Tetracyclic diterpenoid hydrocarbons in some Australian coals, sediments and crude oils

Abstract Tetracyclic diterpenoid hydrocarbons (diterpanes) based on the ent -beyerane, phyllocladane and ent -kaurane skeletons have been identified in the hydrocarbon extracts of some Australian coals, sediments and crude oils. Structures were assigned to the geological diterpanes by comparison with synthetically prepared reference compounds. Studies of a sample suite consisting of low-rank coals and sediments indicate that the ratios of C-16 epimers of phyllocladane and ent -kaurane are maturity dependent, and that the relative proportion of the thermodynamically preferred 16β (H)-compounds increases with increasing thermal maturity. Thermodynamic equilibrium for the interconversion reactions is attained in sediments before the onset of crude oil generation. The most likely natural product precursors for the tetracyclic diterpanes are considered to be the tetracyclic diterpene hydrocarbons which occur widely in the leaf resins of conifers. Tetracyclic diterpanes have been identified in sediments and coals of Permian age or younger, suggesting that these compounds are markers for both modern and extinct families of conifers. In particular, phyllocladane is proposed as a marker for the Podocarpaceae family of conifers.

Chemical and microbiological syntheses of intermediates in gibberellin biosynthesis

A partial synthesis of kaurenoic acid 1 from the hydroxy acid 3 is described. The hydroxylation of the 2′-carboxyethyl ester of 1 by Gibberella fujikuroi has been utilized for the synthesis of 7β-hydroxykaurenoic acid 2. An alternative synthesis of 2 is provided by the microbiological conversion of 3 to the 7β-hydroxy derivative by Calonectria decora.

Metabolic transformations of some ent-kaurenes in Gibberella fujikuroi

Abstract The conversion of ent -kaur-16-enes to gibberellic acid in Gibberella fujikuroi is blocked by A-ring modifications. Thus ent -3β-hydroxykaur-16-en-19-yl succinate gives good conversion (46%) to the 7β-hydroxy derivative.* Under the same conditions the 3β-epimer gives 7β- or 6α-hydroxylation and the former occurs for the 3-oxo analogue. The succinoyloxy function acts as a less efficient block and ent -kaur-16-en-19-yl succinate is converted to 7β-hydroxy and 6β,7β-dihydroxy derivatives along with gibberellic acid. Hydrolysis of the succinate block of the metabolities provides the 7β, 19-diol and 6β,7β, 19-triol. Of this pair only the former was effectively metabolized to gibberellic acid in G. fujikuroi .

Gibberellin metabolites from ent-kaura-2,16-dien-19-ol and its succinate in Gibberella fujikuroi☆

Abstract Exposure of ent-kaura-2,16-dien-19-ol (1) or its succinate (2) to resuspended mycelia of G. fujikuroi has produced a complex mixture of acids which after methylation gave the esters of two C19 (24) and (30) and five C20 gibberellins (4, 11, 20, 32 and 33). The triester (32) and the lactone ester (24) have been prepared before from the esters of gibberellin A13 (8) and gibberellin A4 (26) respectively. The structures of the other metabolites were assigned on spectroscopic data and by chemical transformations. Thus the lactone diester (4) has been converted to the known keto triester (6). The epoxide (11) has been related to gibberellin A14 (14) and the aldehyde (33) has been related to gibberellin A13 trimethyl ester (8) by way of the triol (34). Selective de-epoxidation of the 16,17-epoxy function in diepoxides has provided a route from the dienes (20 and 24) to the epoxides (11 and 30) respectively, but not from the ester of gibberellin A5 (23) to that of gibberellin A6 (29). On the other hand the latter can be obtained by epoxidation of gibberellin A5 methyl ester trifluoroacetate. Backfeeding experiments carried out with the epoxy diacid (12), the diene diacid (21) and the derived diol (39) indicate pathways connecting the various metabolites. The natural gibberellins A5 and A6 were shown to be formed in some of the backfeeding experiments.

The synthesis of 13-hydroxylated ent-kaur-16-ene derivatives using an acyloin-like cyclization of keto esters

Abstract The synthesis of steviol ( 27 ) and two A-ring modified analogues ( 9 and 15 ) is described. The synthetic sequences involve the preparation of suitably constituted 17-nor-13,16-seco- ent -kauranoid keto esters ( 22, 7 and 13 ) which are then cyclized to 13,16-dooxygenated-17-nor- ent -kauranes ( 23, 8 and 14 ).

Cyclization and hydroxylation stereochemistry in the biosynthesis of gibberellic acid

Abstract In Gibberella fujikuroi cultures, ent -[3β- 3 H,17- 14 C]kaurene is converted to gibberellic acid with retention of the tritium label at the 3α-position. This evidence for the stereochemistry of 3-hydroxylation also permits the stereochemistry of the ‘proton-initiated’ cyclization step in gibberellic acid biosynthesis to be deduced.

The diterpenes of Goodenia Ramelii F. Muell

Abstract The ether extract of Goodenia ramelii has yielded 19-(β-carboxy-n-propionyloxy)(−)-kaur-16-en-3α-ol (I) and a new diterpene triol shown to be (14 R )-8β,13-epoxyeperuan-14,15,18-triol (III). The 14-epimer of III was obtained from stereoselective reaction of osmium tetroxide with 18-hydroxy-13-epi-(−)-manoyl oxide (VI) and the configuration of the 14-position firmly established. Unexpectedly the major product from reaction of osmium tetroxide with 13-epi-(−)-manoyl oxide requires approach of the reagent from the opposite side of the vinyl group to the side predominately attacked during epoxidation with perbenzoic acid.

Structural parallels between the cardiotonic steroids and the Erythrophleum alkaloids - I. Synthesis of phenanthrenone precursors to novel Erythrophleum alkaloid analogues

Abstract (4aR*,10aR*,10aR*)-10-Hydroxy-7-methoxy-3,4,4a,9,10,10a-hexahydrophenanthren-2(1H)-one (3) has been synthesised with the key step involving intramolecular electrophilic alkylation of the aromatic ring, via a Pummerer rearranged intermediate, to complete the B-ring of the phenanthrene nucleus. Phenanthrenones (4) and (5), bearing a 1-methyl or 1-ethyl group in an axial configuration, have also been prepared by a parallel route: during the cyclisation reaction the 1-alkyl group, lying α to a 1,3-dioxolane protecting group, underwent acid-catalysed epimerisation to give a preponderance of the desired axial epimer.

Bridged-ring products from the acyloin-like cyclization of diterpenoid keto-esters

Abstract Bridged-ring structures are readily formed from acyloin-like cyclization of suitably constituted keto esters. thus reaction of the keto ester ent -seco-kauranoid derivatives 1 and 2 with Na-liquid NH 3 affords mixtures of ent -kaurane, ent -beyerane and dimeric products.

Acidic ent-kauranoids from the metabolism of ent-kaura-2,16-dien-19-ol in gibberella fujikuroi

Abstract Three acidic ent -kauranoid metabolites have been obtained as the methyl esters ( 7, 8 , and 9 ) from incubation of the [17- 14 C]-labelled dienol ( 1 ) with Gibberella fujikuroi . Spectroscopic studies of the triol ester ( 7 ) and chemical degradation of B-ring cleaved products establish the assigned structure ( 7 ). The structures of the other two metabolite esters are indicated to be 8 and 9 from the spectroscopic data.