Ricardo Guillermo

Biotransformation of ent-kaur-16-ene and ent-trachylobane 7β-acetoxy derivatives by the fungus Gibberella fujikuroi (Fusarium fujikuroi).

Candol A (7β-hydroxy-ent-kaur-16-ene) (6) is efficiently transformed by Gibberella fujikuroi into the gibberellin plant hormones. In this work, the biotransformation of its acetate by this fungus has led to the formation of 7β-acetoxy-ent-kaur-16-en-19-oic acid (3), whose corresponding alcohol is a short-lived intermediate in the biosynthesis of gibberellins and seco-ring ent-kaurenoids in this fungus. Further biotransformation of this compound led to the hydroxylation of the 3β-positions to give 7β-acetoxy-3β-hydroxy-ent-kaur-16-en-19-oic acid (14), followed by a 2β- or 18-hydroxylation of this metabolite. The incubation of epicandicandiol 7β-monoacetate (7β-acetoxy-18-hydroxy-ent-kaur-16-ene) (10) produces also the 19-hydroxylation to form the 18,19 diol (20), which is oxidized to give the corresponding C-18 or C-19 acids. These results indicated that the presence of a 7β-acetoxy group does not inhibit the fungal oxidation of C-19 in 7β-acetoxy-ent-kaur-16-ene, but avoids the ring B contraction that leads to the gibberellins and the 6β-hydroxylation necessary for the formation of seco-ring B ent-kaurenoids. The biotransformation of 7β-acetoxy-ent-trachylobane (trachinol acetate) (27) only led to the formation of 7β-acetoxy-18-hydroxy-ent-trachylobane (33).

THE BIOTRANSFORMATION OF MANOYL OXIDE DERIVATIVES BY GIBBERELLA FUJIKUROI : THE FUNGAL EPIMERIZATION OF AN ALCOHOL GROUP

Abstract The microbiological transformations of jhanol (18-hydroxymanoyl oxide) and jhanidiol (1β,18-dihydroxymanoyl oxide) with the fungus Gibberella fujikuroi have been studied. In the biotransformation of the first compound there exists a preference for hydroxylation at C-1(α) and in lower yield at C-11(α or β), while in that of the second, which possesses a 1β-hydroxylation, the mainly reaction observed is the oxidation of this 1β-hydroxyl to an oxo group. This product is then mainly reduced to the 1α-alcohol or, in minor yield, hydroxylated at C-11(β), C-6(β) and C-2(α). The fungal epimerization of a hydroxyl group, as occurs in the biotransformation of the 1β-alcohol of jhanidiol to the 1α-alcohol, is a very rare process.

The chemical and microbiological preparation of 15-oxo-gibberellin derivatives

Abstract The biotransformalion of 15-oxo-cnt-kaur-16-cne (1) with the fungus Gibberella fujikuroi gave 16a. 17-dihydro-7β-hvdro15-oxo-kaurcnolidc (5). 16α, [7-dihydro-15-oxo-GA12 (7) 16α, 17-dihydro-15-oxo-GA25 (8) 16α.17-dihydro-15-oxo-GA24 (9), 7-aldchydc of 16α,17-dihydro-15-oxo-GA14 (10). ent−3α,7α−15-oxo-kauran-19-oic acid (11), and 16α,17-dihydro-15-oxo-GA7 (12). The hydrogenation of the 16,17-double bond observed in this incubation is directed by the presence of the 15-oxo group, and it docs not take place in the normal biosynthclic gibberellin pathway. The chemical preparation of some of these 15-oxo-gibbcrcllins has also been carried out.

Biotransformation of 7α-hydroxy- and 7-oxo-ent-atis-16-ene derivatives by the fungus Gibberella fujikuroi

The microbiological transformation of 7alpha,19-dihydroxy-ent-atis-16-ene by the fungus Gibberella fujikuroi gave 19-hydroxy-7-oxo-ent-atis-16-ene, 13(R),19-dihydroxy-7-oxo-ent-atis-16-ene, 7alpha,11beta,19-trihydroxy-ent-atis-16-ene and 7alpha,16beta,19-trihydroxy-ent-atis-16-ene, while the incubation of 19-hydroxy-7-oxo-ent-atis-16-ene afforded 13(R),19-dihydroxy-7-oxo-ent-atis-16-ene and 16beta,17-dihydroxy-7-oxo-ent-atisan-19-al. The biotransformation of 7-oxo-ent-atis-16-en-19-oic acid gave 6beta-hydroxy-7-oxo-ent-atis-16-en-19-oic acid, 6beta,16beta,17-trihydroxy-7-oxo-19-nor-ent-atis-4(18)-ene and 3beta,7alpha-dihydroxy-6-oxo-ent-atis-16-en-19-oic acid.

A study of the microbiological reduction of α,β-unsaturated carbonyl ent-kaurenes by Gibberella fujikuroi

Abstract The incubation of 18-hydroxy-15-oxo-ent-kaur-16-ene with the fungus Gibberella fujikuroi gave 16α,17-dihydro-15-oxo derivatives, whilst the feeding of 3-oxo-15α,16α-epoxy-ent-kaur-1-ene afforded a series of products, which conserve the 1,2-double bond. These results indicated that the hydrogenation of α,β-unsaturated carbonyl compounds with an ent-kaurene skeleton by this fungus is a stereospecific and regiospecific reduction, that does not depend on the biosynthetic route of gibberellins and kaurenolides.

Microbiological transformation of two 15α-hydroxy-ent-kaur-9(11),16-diene derivatives by the fungus Fusarium fujikuroi

The incubation of 15α-hydroxy-ent-kaur-9(11),16-dien-19-oic acid (15α-hydroxy-grandiflorenic acid) with the fungus Fusarium fujikuroi gave as main metabolite its 3β,6β-dihydroxy derivative, which by an oxidative decarboxylation afforded a 19-nor compound with a 4,18-double bond. Other substances obtained were a 3α-hydroxy-19,6α-lactone, 3β-hydroxy-6β,7β-epoxy-ent-kaur-9(11),16-dien-19-oic acid and 3β-hydroxy-6-oxo-ent-kaur-9(11),16-dien-19-oic acid. Moreover, the biotransformation of 15α,18-dihydroxy-ent-kaur-9(11),16-diene led to the isolation of the corresponding 3β-, 6β-, 7α- and 12β-hydroxy derivatives. Two metabolites formed by 16β,17-epoxidation of the last compound and of the substrate were also obtained. These results indicated that the presence of the 9,11-double bond in the substrate impedes its 7β-hydroxylation, which is necessary for the formation of gibberellins and seco-ring B ent-kaurenoids. However, this 9,11-unsaturation does not hinder a 6,7-dehydrogenation and further 6β,7β-epoxidation, characteristic steps of the kaurenolide biosynthetic pathway.

THE ACYLATION-DIMERIZATION OF PRECOCENE II

Abstract Ferric trichloride in acetic anhydride has been used in the acylation and dimerization-acylation of precocene II. The acylation of this antijuvenile hormone occurs in the chromene ring and not in the aromatic one, whilst in the dimers obtained one of the benzenic rings was acylated. In this reaction the first trimer of precocene II has also been obtained. The same reaction was studied using ZnBr2 as Lewis acid.

The formation of an ent-11a,16a-epoxykaurane of biosynthetic significance by Gibberella fujikuroi

We thank the DGICYT, Ministry of Education and Science, Spain for financial support (PB92-0118).