Helvolic acid

P OH-ergosta-4,22-diene ergosterol 3P OH-5w,8a-c z-dioxyergosta-6,22-diene helvolic acid ... 

Steroid Antibiotics. The steroid antibiotics are a stmcturally diverse class of steroids that have a common biological function, ie, antibacterial, antifungal, antiviral, or antitumor activities. This group of compounds can overlap with other steroid classes listed above. Fusidic acid [6990-06-3] (67), helvolic acid [29400 2-8] (68), and cephalosporin [13258-72-5] (69) exemplify a set of antibacterial steroids that contain a prolanostane skeleton with an... 

Cephalosporium sp. are known producers of helvolic acid as well as fusidic acid (5). Helvolic acid has also been reported fi om the opportunistic human pathogen Aspergillus fumigatus (3) and the hypocrealean fungus Sarocladium oryzae (68). The extent to which these steroidal fusidanes are present in other entomopathogenic fungi is unknown at present. 

Helvolic acid (5.145) was the first of the steroidal fusidane antibiotics to be isolated. It was obtained from Aspergillus fumigatus var helvola in 1943 by Chain and Florey. Cephalosporin Pi (5.146) was deseribed by Abraham as a metabolite of the same Brotzu strain of Cephalosporium acremonium as that... 

Fusidic acid and helvolic acid were interrelated by an interesting microbiological strategy that has potentially wider applications. The fungus... 

The structure of helvolic acid has been revised to (13). The ring b acetoxy-group is at C-6 and not at C-7 as was previously suggested. As a result, a similar modification must be made to the structures of helvolinic acid, 7-deacetoxyhelvolic acid, and 7-oxofusidic acid. The two interesting double bond isomers (14) and... 

Fusidic acid (100) and helvolic acid (101) are interesting steroid-like triterpenoids derived from the carbonium ion (72) without rearrangement and subsequent loss of a 4-methyl group. As expected, [2- C,3R,4R- H]mevalonic acid only incorporated four tritium atoms [see (lOO)]. 2,3-Oxidosqualene (71)... 

Further details have been published relating to the structure of cephalosporin P, and the structure of the related helvolic acid has been revised to the 6j6-acetoxy-7-ketone (519). 

Helvolic acid (164) originally isolated from Aspergillus fumigatus has also been identified in Gliocladium species where it cooccurs with the 1, 2-dihydro analogue [59]. Helvolic acid shares the unusual tetracyclic triterpene skeleton of the fusidanes with fusidic acid and the cephalosporin Pi and all show antibacterial activity [230, 231]. 

Protostane and their 29-nor-derivatives denoted as fusidanes are fimgal metabolites. Cephalosporium caerulens, for instance, produces (-l-)-protosta-17(20)-( -24-diene-3p-ol. Fusidanes sueh as helvolic acid from the Helvola mutant of the mold Aspergillus fumigatus and related structures are widely used as antibacterials. Fusi-dic acid isolated from the fermentation broth of Fusidium coccineum and related tribes is an example. Its sodium salt has immunosuppressive and antibacterial properties, and is applied in ointments against multiresistant staphylococci during the therapy of wound infections... 

Aspergillus fumigatus Fumigaclavine C and helvolic acid B Alkaloid and acid coproducts. Conventional flavonoid compounds extraction, an acid aqueous solution partition followed by alkahzation with sodium carbonate (pHlO), may be an effective method of separating the two compounds simultaneously. 47,48... 

The structurally related cephalosporin and helvolic acid do not appear to have the same antibacterial potency as fusidic acid [271, 336, 337] and so would not seem destined for equivalent status in medicine. Similarly the antibacterial potency of the triterpenoid antibiotics polyporenic acid A [338] and polyporenic acid C [339], like that [340] of pristimerin (LXI) [341, 342], which is one of the most highly oxidised naturally occurring pentacyclic triterpenes... 

It remains to be seen, however, whether these latter compounds or structural modifications of them will find application chnically. Certainly any earher hopes for useful therapeutic application of the triterpenoid cucurbitacins as founded on the high order of their cytotoxicity in vitro [479-484] have been dashed on account of the very low margins between the active and the toxic doses as revealed in in vivo experiments. Since the earlier review was written the structures of the cucurbitacins have been elucidated in full and they have been found to represent an unusual structural type in which backbone rearrangement in the formal carbonium ion initially formed from the cychsation of squalene epoxide in chair-boat-chair-boat conformational sequence proceeds beyond the stages giving rise to lanosterol and cycloartenol. Thus they can be regarded as overshoots of the biosynthetic pathway giving rise to the steroids in the same way as fusidic acid (LX), cephalosporin and helvolic acid represent undershoots of the same pathway. The structure of cucurbitacin A is as depicted in LXIV [485, 486]. 

Isol. from Cephalosporium caerulens, also obt. by mild hydrol. of Helvolic acid. Needles. Mp 202.5-203°. -88.9° (c, 1 in CHCI3). 

Isol. from culture broth of C. caerulens. Needles. Mp 214.5-215°. [a] -51.7° (c, 0.5 in CHCI3). Originally descr. as 7-Deacetoxyhelvolic acid prior to the revision of struct, for Helvolic acid. 

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