M. Esther Onorato

Biotransformation of 6β-Eudesmanolides Functionalized at C-3 with Curvularia lunata and Rhizopus nigricans Cultures

Abstract A series of biotransformations of 6β-santonin and its derivatives with functions at C-3, were carried out with Curvularia lunata and Rhizopus nigricans cultures. Rhizepus nigricans was more active in the biotransformation process against these substrates. The biotransformation of 6β-santonin yielded its 2α-hydroxy-1,2-dihydro derivative. The biotransformation of ketones at C-3 obtained by partial or total hydrogenation of double bonds in ring A led to 3S alcohols. Incubation of the 3S-hydroxyl-4S-13S- 6α-eudesmanolide with Rhizopus nigricans produced epimerization at C-4 and hydroxylation at C-8, C-1 or C-4, in decreasing order. This epimerization is probably produced with the participation of the hydraxyl goup at C-3. Microbial functionalization at C-8 can provide access to the synthesis of 8,12-eudesmanolides.

Terpenoids from Sideritis varoi subs oriensis

Abstract From the aerial parts of Sideritis varoi subs. oriensis the previously known 1 β-hydroxy-6β-acetoxyeudesm-4(15)-ene, 1β-hydroxy-6β-acetoxyeudesm-3-ene,1β-hydroxy-6β-acetoxyeudesm-4-ene, 1β,4β-dihydroxy-6β- acetoxyeudesmane and the new 1 β,4α-dihydroxy-6β-acetoxyeudesmane, as well as the ent -8α-hydroxylabda-13(16), 14-dienes 6-deoxyandalusoic acid, 6-deoxyandalusal, 6-deoxyandalusol, 18-deoxyandalusol, andalusol, the ent -13-epi- manoyl oxide varodiol and the ent -kaur- 15-ene sideridiol were isolated. The stereochemistry at C-4 of the isolated eudesmanes, which has been under discussion for other similar compounds, was elucidated by chemical and spectroscopic means.

Chemical-microbiological synthesis of 6β-eudesmanolides from 11-hydroxyl derivatives obtained by Rhizopus nigricans cultures : synthesis of 6β-dendroserins

Abstract The relationship between the structure of the substrates and the action of the fungus Rhizopus nigricans has been studied in order to obtain, in the highest possible yield, 11-hydroxyl derivatives which were dehydrated to the “exo” position, hydroborated with 9-BBN and oxidized with RuH2(Ph3P)4 to give 11-R and 11-S-6-epi-dendroserin. In the course of the biotransformation processes, 8α-hydroxyl and 7α-hydroxyl derivatives were also obtained, as well as the oxidation of the hydroxyl groups at C-1, an unusual process with Rhizopus nigricans. We have proved that the eudesmanones are more easily hydroxylated at C-11 than the hydroxyeudesmane compounds.

Diterpenoids from sideritis pusilla subsp. flavovirens

Abstract Several new 14-hydroxybeyerene acetates have been isolated from the aerial parts of Sideritis pusilla subsp. flavovirens . In addition, an ent -kaur-15-ene (siderol) and a new ent -7α, 18-dihydroxybeyer-15-ene (flavovirol) have been obtained from the same source. The structures of these new acetates have been established by chemical and spectroscopic means and the structure of flavovirol has been confirmed by 13 C NMR.

Microbial transformations of sesquiterpenoids: conversion of deoxyvulgarin by Rhizopus nigricans and Aspergillus ochraceous

Microbial transformation of the sesquiterpene lactone deoxyvulgarin (2) has been carried out with Aspergillus ochraceous and Rhizopus nigricans cultures. A. ochraceous converted deoxyvulgarin (2) into vulgarin (3) and 11,13-dihydrodouglanin (4). R. nigricans transformed deoxyvulgarin (2) into vulgarin (3), erivanin (6), and 1β-hydroxy-2-oxoeudesm-3-en-6,13-olide (7). Vulgarin (3) was obtained chemically by epoxidation of deoxyvulgarin (2) in a one-step process in virtually quantitative yield. A pathway proposed for the conversion of deoxyvulgarin (2) into the more functionalized metabolites is discussed.

Synthesis of enantio-manoyl oxides: Modifiers of the activity of adenylatecyclase enzyme

Cyclization of methyl ent-8 alpha-hydroxylabd-13(16),14-dien-18-oate with m-chloroperbenzoic acid gave methyl (13S)-ent-16-hydroxy-8 alpha,13-epoxylabd-14-en-18-oate and its epimer at C-13. Biotransformation of the former (which exhibits antileishmania activity) with Rhizopus nigricans cultures produced the methyl (13S)-ent-11 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate (carbomanoyl, which inhibits the activity of the adenylatecyclase enzyme), methyl (13S)-ent-3 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate, methyl (13S)-ent-3 beta,11 beta,16-trihydroxy-8 alpha,13-epoxilabd-14-en-18-oate and the (14S)-ent-3 beta-hydroxy-14,15-epoxy derivative that cyclized spontaneously to a spiran compound. Biotransformation of methyl (13S)-ent-16-hydroxy-3-oxo-8 alpha,13-epoxilabd-14-en-18-oate with R. nigricans produced ent-11 beta-hydroxylation, reduction of the keto group at C-3 (to give 3S-alcohol) and 14(S),15-epoxidation, which also rearranged to a spiro compound.

Chemical-microbiological synthesis of 6β-eudesmanolides from 11-hydroxyl derivatives: synthesis of 6β-dendroserins by Rhizopus nigricans

Abstract Microbial transformation of a 6β-acetoxyeudesmanone by Rhisopus nigricans cultures produced a high yield (72%) of an 11-hydroxyl derivative. The dehydration of this compound to the exo position, followed by hydroboration and then oxidation with RuH 2 (Ph 3 P) 4 yielded 11-R and 11-S-6-epi-dendroserin. An 8 α-hydroxyl derivative was also obtained in the bioconversion process.

Biotransformation of ent-13-epi- and ent-manoyl oxides by Rhizopus nigricans cultures

Microbial transformation of ent-6α,18-diacetoxy-16-hydroxy-13-epi-manoyl oxide (3) has been carried out with Rhizopus nigricans cultures, which converted the substrate (3) into its 20-hydroxy-, ent-3β-hydroxy-, and (14S)-spiro derivatives. R. nigricans transformed ent-6α,18-diacetoxy-16-hydroxymanoyl oxide (5) into its ent-11β-hydroxy and (14R)-spiro derivatives. The metabolite structures have been determined spectroscopically and sometimes by chemical correlation as well.