Of cyclic hydroxamic acids

The following discussion of hydroxamic acids includes saturated systems, e.g., 2, compounds such as 3, derived from aromatic systems, 7V-hydroxyimides such as 7V-hydroxyglutarimide (78), and certain of their derivatives including thiohydroxamic acids. Naturally occurring cyclic hydroxamic acids are discussed to show the range of structural types that has been found, hut macrocyclic polyhydroxamic acids are mentioned very briefly, because several comprehensive reviews of these compounds are already available. The main purpose of this review is to summarize the methods available for the synthesis of cyclic hydroxamic acids, to outline their characteristic reactions, and to present some useful physical data. Their synthesis and some biological properties have previously been reviewed by Coutts. ... 

Perhaps the most reliable method for the reductive cyclization of a nitro ester to a hydroxamic acid is that which involves treatment with sodium horohydride in the presence of palladium on charcoal. Although under these conditions aromatic nitro compounds are reduced to amines, o-nitro esters such as 53, in which the ester group is suitably oriented with respect to the nitro group, give good yields of cyclic hydroxamic acids (54). Coutts and his co-... 

Several reactions are particularly applicable to the synthesis of cyclic hydroxamic acids as they involve some kind of ring expansion. Some are quite general reactions which are of high preparative utility, whereas others exist as fairly isolated examples which have not as yet been generalized. 

Reduction of cyclic hydroxamic acids generally leads to lactams or the corresponding amines. Chemical methods have frequently been preferred to catalytic hydrogenation, probably because the choice of... 

Acyl derivatives of cyclic hydroxamic acids, like all 0-acyI derivatives of hydroxylamine, show infrared absorption because of the acjd carbonyl at characteristically high frequencies, generally near 1800 The range of frequencies is similar to that found for... 

There has as yet been no systematic work on the mass spectra of cyclic hydroxamic acids, but from the limited information available the direct loss of 0 or OH from the molecular ion is to be expected. The fragmentation behavior of the 0-alkyl derivatives is rather unpredictable, although again processes involving fission of the N—0 bond are generally important. Table II shows the prominent first-generation fragment ions from a few hydroxamic acids and their ethers. 

Hydroxamic acids constitute an important class of siderophores, which play a major role in iron solubilization and transport. Some of them are important as therapeutic agents. The Michael addition of nitroacetyl proline esters to allyl acrylate followed by Pd(0)-catalyzed intramolecular allyl transfer and subsequent reduction of the nitro group yields a novel class of cyclic hydroxamic acids related to pyroglutamic acid (Scheme 5.9).85... 

Hydroxy- and l,4-dihydroxypiperazine-2,5-diones belong to the class of cyclic hydroxamic acids. This moiety is known to occur in several natural products, such as mycelianamide. The chemistry of these fungal metabolites has been discussed by Sammes (75FOR51). A more recent review has also covered some synthetic aspects of 1-hydroxypiperazine-2,5-diones (88FOR203). 

The ring cleavage behavior of cyclopentyl nitrite has been used in an interesting synthesis of cyclic hydroxamic acids. Thus steroidal 17/8-nitrites (81) on photolysis yield the corresponding hydroxamic acids (82).29 This conversion can be rationalized in the following way (83 to... 

Scherlitz-Hofmann, I. Dubs, M. Krieg, R. Schoenecker, B. Kluge, M. Sicker, D. Hybrids of Natural Products. Synthesis of Cyclic Hydroxamic Acids of the Estra-l,3,5(10)-triene Series, Helv. Chim. Acta 1998,80, 2345. 

Heilmann, D. Sicker, D. Synthesis of Cyclic Hydroxamic Acids Derived From the Structure of l-Hydroxypyrido[2,3-b][l,4]oxazin-2(lH)-one, /. Prakt. Chem. 1990, 332, 265. 

Meyer, L. Role of Cyclic Hydroxamic Acids in Resistance of Maize to Microbial Diseases and Insects, Zentralbl. Mikrobiol. 1988, 143, 39. 

The electrosynthesis of hydroxylamines was also used for the production of cyclic hydroxamic acids 573) on the laboratory scale ... 

Desai, R. S., Kumar, P. and Chilton, W. S. 1996. Indole is an intermediate in the biosynthesis of cyclic hydroxamic acids in maize. Chem. Commun., 1321... 

Tays, K. and Atkinson, J. 1998. An improved synthesis of cyclic hydroxamic acids from Gramineae. Synth. Commun. 28, 903-912... 

Run in an one-pot procedure the whole sequence shown in Fig. (9) was the first a-hydroxylation of cyclic hydroxamic acids reported and independent from substituents in the aromatic ring. However, the overall yields of aglucones obtained have not been satisfactory. 

---