Aspergillic acids

Both and H NMR data are also available for a range of 2(l//)-pyrazinones which are structurally related to the aspergillic acids (76T655). 

Following the discovery of penicillins, an extensive program for the screening of culture fluids and residual mycelial material commenced which resulted in the discovery of a large number of pyrazinones and related 1-hydroxy-2-pyrazinones with pronounced antibiotic character. Some examples are shown in Table 4. One of the earliest substances to be isolated, aspergillic acid (110 = OH, = Me, R = Et, R = R = H, R = Pr ), was found... 

Mikes and Turkova have given a classification of naturally occurring hydroxamic acids in terms of their biological function or activity. They have distinguished (a) growth factors, e.g., ferri-chromes, mycobactin, and ferrioxamines, ferrichrysins, ferrirubins, etc. (6) antibiotics, e.g, aspergillic acid, mycelianamide, albomycin, nocardamine and (c) microbial pigments such as pulcherrimin. 

The first natural products shown to be cyclic hydroxamic acids belong to the group of aspergillic acids, formed by cultures of Aspergillus flavus and related organisms. 

This type of synthesis has been used extensively in the preparation of hydroxamic acids resembling aspergillic acid. a-Aminohj droxamic acids react with a-dicarbonyl compounds to yield pyrazine hydroxamic acids (18). Glyoxal and diacetyl react readily, but poor... 

The aspergillic acids are an important group of naturally occurring pyrazine derivatives. They are formed by cultures of the Aspergillus species and were the first natural products shown to be cyclic hydrox-amic acids.9 Aspergillic acid itself was isolated10 in 1943 from A.flavus and subsequently shown to have structure 3. An isomer of deoxy-aspergillic acid, also isolated from A. flavus, was shown to be 3,6-diisobutyl-2-pyrazinone (4) and named flavacol.11... 

Other antibiotics structurally analogous to aspergillic acid are... 

A general synthesis of compounds with the aspergillic acid skeleton has been mentioned in Section III and this has been successfully applied to the synthesis of racemic aspergillic acid124 and to neo-... 

This substance is obviously related to pulcherriminic acid and the aspergillic acids (see below) and may be regarded as the anhydride formed from one mole of N-hydroxyalanine and one mole of an o-substituted a-p unsaturated analogue of N-hydroxytyrosine. There is no evidence connecting mycelianamide to metal ion metabolism save the statements... 

Mycelianamide nucleus Pulcherriminic acid nucleus Aspergillic acid nucleus Formula 2... 

A group of antibiotics formed by Aspergillus flavus and related organisms are described under the name aspergillic acids. Although grisein was discovered at about the same time, the aspergillic acids were the first natural products shown to contain the hydroxamic acid bond. 

Synthesis of a number of model diketopiperazines and their comparison with reduction products of aspergillic acid suggested the latter to contain... 

---