Viridin. Part 8. Structures of the analogues virone and wortmannolone

Abstract

The secondary metabolic products virone (from Gliocladium virens) and wortmannolone (from Penicillium wortmannii) are shown to be pregna-5,8-dieno[6,5,4-bc]furan-3,7,20-trione and 1 a,2aepoxy-3P-hydroxyandrosta-5,8-dieno[6,5,4-bc]furan-7,17-dione, respectively.Viridin (1; R ' = OH, R2 = OMe, R3R4 = 0),2 a steroidal secondary metabolite of the fungus Gliocludium uirens Miller,3 CMI 24039 (a fungus erroneously described in the early work 4*5' as Trichodermu uiride), has conventionally been produced in surface culture on Raulin Thom medium at 25 "C. When this fermentation is carried out at 32 "C, viridin is obtained in much reduced yield (5-10 mg/l as opposed to 25 mg/l) but is accompanied (2 mg/l) by a less polar metabolite of composition C22H2404 to which we have assigned the trivial name virone. Virone is not produced at all at 25 "C.The related steroidal metabolite wortmannin (2) ' *' is produced by some strains of Penicilfium wortmannii Klocker,* but not by all. With one strain (CMI 44277), wortmannin is accompanied by a metabolite (trivial name, wortmannolone) of composition CtOH2005. This paper is concerned with the chemistry and structural elucidation of virone (3) and wortmannolone ( 4 R'R2 = 0, R3 = OH, R4 = H).In common with viridin and its analogues,' wortmannolone and its derivatives tenaciously retained solvent of crystallisation and solvent-free material could not always be obtained for analysis. Wortmannolone (4; R'R2 = 0, R3 = OH, R4 = H) contained two carbonyl groups (vmx. 1 71 5 and 1 665 cm-') and a secondary hydroxy group (vmaX. 3 360 an-') which was readily acetylated to give acetylwortmannolone (4; R'R2 = 0, R3 = OAc, R4 = H) (vmaX. OH absent; 6,6.16), and readily oxidised by the chromic oxide-sulphuric acid reagent to a dehydro * Because of the biosynthetic implications of this work, triterpenoid rather than viridin numbering' is used. 21GOMe 0 -CH -CH-CHOR-

Secondary metabolites from species of the biocontrol agent Trichoderma

“…Chemical and biological properties have recently been reviewed for 38 (Wipf and Halter 2005). Wortmannolone (40) and virone (41) were obtained from a culture of Glioclaudium virens (Trichoderma virens), which had been grown at 32°C (Blight and Grove 1986).…”

Differential Effect of Wortmannolone Derivatives on MDA-MB-231 Breast Cancer Cells

“…The epoxide function is in the 1 and 2 α-position and in the 3β-position is the secondary hydroxyl (OH) group on ring A. All wortmannolone derivatives ( 1–6 ) obtained were synthesized according to the previously reported procedure by Blight and Grove, 1986(7). …”

“…Chemical reactions were performed following a previous published protocol for the preparation of the six known wortmannolone derivatives presented as part of this manuscript and the derivatives obtained were confirmed by nuclear magnetic resonance (NMR) and mass spectrometry (MS)(7). Wortmannolone (15 mg) was dissolved in dry DCM (5 mL) and 5 equivalents of NMO and 25 mg of powdered 3A molecular sieve added.…”

The synthesis and some chemical reactions of a 5a-methyl 2H-naphtho[1,8-bc]furan

“…IR (neat): 3093, 2893, 2106, 1727, 1638, 1481, 1460, 1373, 1232, 1137, 962, 745 cm-'; 'H NMR (250 MHz, CDC1,) 6: 2.61-2.83 (m, 2H, CHCH2COCHN2), 3.90-397 (m, lH, H-3), 4.21 (dd, J2, ,2p = 9.1, J3,2p = 6.0, IH, H-2P), 4.74 (t, J2p ,2, = J3,2, = 9.1, 1H, H-2a). 5.24 (br s, lH, COCHN2), 6.77-6.88 (m, 2H, H-5, H-7), 7.10-7.16 (m, 2H, H-4, H-6); LRMS (EI) d e : 202 (2,MC),192(4),174(19), 145 (7), 131 (51), 119(60), 103 (7),91 (100),77 (12), 65 (18), 55 (13). Anal.…”

“…Its 5a-methyl (angular methyl) derivative 1 is a particularly important target for synthetic chemists because the development of an efficient general method for the preparation of 1 and closely related tricycles will be a significant step towards the synthesis of many natural products such as the pentacyclic marine quinones 2 and 3 (I), the fungal metabolites of Gliocladium virens 4 and 5 (2), and Penicillium wortmanni 6 (3). Some synthetic activity in this area has already been recorded by Kanematsu et al (4) who applied their "furan transfer" protocol to prepare 7 in 6.3% yield from a-fury1 methanol.…”