Lowdenic Acid:  A New Antifungal Polyketide-Derived Metabolite from a New Fungicolous Verticillium sp.

Abstract

Lowdenic acid (1), a new antifungal metabolite with an unusual structure and a mixed biogenetic origin, has been obtained from nonsporulating cultures of a previously undescribed Verticillium sp. (MYC-406 = NRRL 29280) that was isolated as a colonist of polypore basidiomata. The gross structure of 1 was proposed by analysis of NMR data and confirmed by X-ray diffraction analysis, which enabled assignment of relative stereochemistry. Compound 1 occurs as an equilibrium E/Z mixture. The known antifungal metabolite canescin A (2) was also isolated.

Cytotoxic and antiplasmodial substances from marine-derived fungi, Nodulisporium sp. and CRI247-01

“…The evidence from the similarity of 13 C NMR resonances (Table 1) of C-2 (d C 93.3) and C-1 0 (d C 180.1) of lowdenic acid (Angawi et al, 2003) and those [C-2 (d C 93.4) and C-1 0 (d C 179.4)] of nodulisporacid A (1) further confirmed the structure of nodulisporacid A (1). Assignment of 1 H and 13 C resonances for the E-isomer and Z-isomer of nodulisporacid A (1) was accomplished by correlation with E and Z isomers of lowdenic acid and carolic acid (Angawi et al, 2003;Jacobsen et al, 1978). Generally, d C of C-1 of the E-isomer was about 3 ppm lower field than that of the Z-isomer (Angawi et al, 2003;Jacobsen et al, 1978).…”

“…Unfortunately, there was no HMBC correlation to the sp 2 quaternary C-2 (d C 93.4). However, the information from the presence of an unsaturated ketone and the molecular formula implied the connection of C-2 to C-1 0 , establishing a gross structure of nodulisporacid A (1), which was a derivative of lowdenic acid (Angawi et al, 2003) (Fig. 1).…”

“…Assignment of 1 H and 13 C resonances for the E-isomer and Z-isomer of nodulisporacid A (1) was accomplished by correlation with E and Z isomers of lowdenic acid and carolic acid (Angawi et al, 2003;Jacobsen et al, 1978). Generally, d C of C-1 of the E-isomer was about 3 ppm lower field than that of the Z-isomer (Angawi et al, 2003;Jacobsen et al, 1978). Chemical transformations of nodulisporacid A (1) by methylation, benzylation, and hydrogenation yielded respective products 2, 3, and 4 ( Fig.…”

“…Spontaneous E/Z inter-conversion of compounds 1-4 may hinder uniform crystallization. The biosynthesis of nodulisporacid A (1) may be similar to that of lowdenic acid (Angawi et al, 2003), involving the condensation of a modified 12-carbon polyketide (decorating as a side chain, the furylidene ring, and C-1 and C-2 of the tetrahydrofurandione ring) with a four carbon dicarboxylic acid. Such tetronic acid biosynthesis had been experimentally proven, for examples, italicic acid (Arai et al, 1989), and carolic acid (Jacobsen et al, 1978;Simonsen et al, 1980).…”

Decrypting the Biochemical Function of an Essential Gene from Streptococcus pneumoniae Using ThermoFluor® Technology

“…Canescin A Binding-Another apparently tight-binding ligand detected in the ThermoFluor screen was canescin A, a natural product that inhibits fungal growth by an unknown mechanism (Table II) (20). This compound is one of the substances in the functional probe library, such as natural products and generic drugs, that have biological activity for which the target of interaction is not precisely known.…”