Biotransformation of clovane derivatives. Whole cell fungi mediated domino synthesis of rumphellclovane A

Abstract

Here we describe the biotransformation of clovane derivatives by filamentary fungi Pestalotiopsis palustris and Penicillium minioluteum, and the application of the latter to the synthesis and determination of the absolute configuration of rumphellclovane A (2). Methoxyclovanol (1), a growth inhibitor of the phytopathogen Botrytis cinerea, is metabolised by P. palustris to yield rumphellclovane A (2), a natural compound recently isolated from the gorgonian coral Rumphella antipathies, two new compounds, (1R,2S,5S,8R,9S,10R)-2-methoxyclovane-9,10-diol (5) and (1S,2S,5S,7R,8R,9R)-2-methoxyclovane-7,9-diol (6), hydroxylated in positions not easily accessed by classic synthetic chemistry, and clovanodiols 3 and 4. P. minioluteum is able to selectively transform methoxyclovanol (1) into clovanodiols 3 and 4 and, in turn, lactone 8, the putative intermediate in the above mentioned synthesis of rumphellclovane A (2), into compound 2 via a domino process. The ability of P. minioluteum to carry out the cleavage of ethers on clovane derivatives is also evaluated.

Marine natural products

“…825 As a consequence the authors have changed the name to trocheliol. 826 Syntheses of the modestly cytotoxic seco-caryophyllane rumphellaone A 827 and clovane rumphellclovane A 828 (Rumphella antipathies) have been reported; [829][830][831] the latter study used the lamentous fungi Pestalotiopsis palustris to biotransform synthetically prepared (1S,2S,5S,8R,9R)-2-methoxyclovan-9-ol into the so coral metabolite, simultaneously establishing the absolute conguration.…”

Drimane Sesquiterpene-Conjugated Amino Acids from a Marine Isolate of the Fungus Talaromyces minioluteus (Penicillium Minioluteum)

“…Fungi of the genus Penicillium are rich in bioactive compounds [ 4 , 5 , 6 , 7 , 8 ], and among them, Penicillium minioluteum produces bioactive metabolites, for example, polyketide-terpenoid hybrids [ 9 ], hydrazide derivative as a potentiator of nerve growth factor [ 10 ], and antifungal tetracyclic diterpenes [ 11 ]. The fungus P. minioluteum was recently found to produce isomeric furanones through epigenetic manipulation through the addition of azacitidine, a DNA methyltransferase inhibitor [ 12 ]; it was also used in the biotransformation of clovane derivatives for the synthesis of rumphellclovane A [ 13 ]. It should be noted that the name of the fungus P. minioluteum was recently revised to “ Talaromyces minioluteus ” [ 14 ].…”

(±)-Peniorthoesters A and B, Two Pairs of Novel Spiro-Orthoester en-antiomers With an Unusual 1,4,6-Trioxaspi-ro[4.5]decane-7-One Unit From Penicillium minioluteum

“…Previous studies on the secondary metabolites of Penicillium minioluteum have resulted in the identification of scores of bioactive metabolites, including isomeric furanones with cytotoxic activities against HeLa cell lines (Tang et al, 2015), sesquiterpene-conjugated amino acids with cytotoxic activities against HepG2 cells (Ngokpol et al, 2015), and hybrid polyketide-terpenoids (Iida et al, 2008). This fungus was also used to produce clovane derivatives, which are the raw materials for the synthesis of rumphellclovane A (Gontijo de Souza et al, 2012), and an enzyme from this fungus was used in the bioconversion (Kmiecik and Zymanczyk-Duda, 2017). During our ongoing search for structurally unique and biologically interesting constituents from fungi (Zhu et al, 2015; Chen et al, 2017; Zhou et al, 2017), P. minioluteum , obtained from China General Micro-biological Culture Collection Center (CGMCC), was phytochemically investigated, and two pairs of new orthoesters (Figure 1, compounds ± 1 and ± 2 ) were isolated along with their biosynthetic intermediate, sclerotinin A ( 3 ) (Xiao et al, 2009).…”