374. Lactones. Part V. Experiments relating to mycophenolic acid

Abstract

The structure of mycophenolic acid has been confirmed as (I) by infrared spectroscopy and by the synthesis of the degradation product, 6-carboxymethyl-6 : 7-dimethoxy-4-methylphthalide (X ; R = CH2*C02H) .FROM degradative studies by Raistrick and his co-workers 1-4 the structure of mycophenolic acid, a metabolic product of strains of Penicillium brevi-compactum, is almost certainly structure (I). Birkinshaw, Raistrick, and ROSS,, however, admitted slight doubts as to which of the two nuclear hydroxyl groups in normycophenolic acid (11) was methylated in mycophenolic acid and as to whether the potential hydroxymethyl group in the phthalide ring was ortho or meta to the nuclear methyl group. Though the fact that mycophenolic acid gipes a ferric chloride colour f suggests the hydroxy-phthalide system given in structure (I) , the phthalide carbonyl stretching frequency region of the infrared spectra shows maxima at 1742 (CHCl,), 1748 (CCl,), and 1751 cm.-l (dioxan) while the dimethoxycompound (111) shows maxima at 1763, 1776, and 1770 cm.-l in the same solvents, respectively, clearly indicating intramolecular hydrogen bonding as expected from structure (I). 7

Bactericidal and fungicidal activity ofAspergillus ochraceusmetabolites and some derivatives

“…To compare the inhibitory e †ect of aspyrone (1) with the biological activity of aspyrone derivatives (3,4,5), asperlactone (2) and captan, a known fungicide, Ðve moulds were tested ( Table 2). The aspyrone derivatives with a modiÐcation only in the hydroxyl group (3,4) retained activity against Fusarium oxysporum and Colletotrichum coccodes, but this disappeared when the epoxy group was removed (5). Asperlactone (2) also showed no activity against the two fungi.…”

“…To compare the antibiotic e †ect of aspyrone (1) with the biological activity of aspyrone derivatives, asperlactone (2) and terramicin, a known antibiotic, four bacteria and one yeast were tested. Table 4 shows that, in general, aspyrone (1) showed better activity than asperlactone (2) or aspyrone derivatives (3,4,5), although terramicin always showed the best activity against all bacteria. Some of these results, mainly the activity against E. coli and S. aureus, could be explained in terms of product solubility or by supposing the bioactive compound was not directly the lactone group but a product resulting from opening the ring.…”

“…Growth Inhibition of Several Fungi by Aspyrone (1), Asperlactone (2), Some Aspyrone Derivatives (3,4,5) and Captan at a Concentration of 20 kg ml~1…”

“…This product was reinvestigated as an antibiotic in 1946, but its chemical structure was not Ðnally resolved until 1957. 3 At present, the number of known antibiotics is large and continues to increase.…”

GLC of mycophenolic Acid and Related Compounds

“…Recently, two groups of researchers (5, 6) reported on the antitumor activity of mycophenolic acid, while Williams et al (7) reported that the substance exhibited both antiviral and antitumor properties. Work has been done, both chemical and physical in nature, to elucidate the structure of mycophenolic acid (8,9 ) and some related compounds, which were isolated from the culture filtrates of a strain that produces mycophenolic acid (10). Birch and Wright (11) have devised a scheme for the total synthesis of mycophenolic acid.…”