J. Philip Poyser

Experimental approaches to antifungal chemotherapy.

Publisher Summary This chapter discusses the experimental approaches to antifungal chemotherapy. Fungal diseases in general occur in all parts of the world and affect all ages, though a number of particular species are restricted geographically in their incidence. It goes without saying that a systemic fungal infection will require systemic treatment. When however the fungus is confined to the skin or mucosal membranes, then the possibility exists of applying a topical treatment to the affected area, or alternatively treating the infection systemically, getting the parasite from “behind.” With a topical treatment the patient may feel he is doing something positive by applying the medication to the lesion whereas an oral treatment may give the feeling of irrelevance. On the other hand there would seem little point in applying a messy treatment to an already messy lesion if an alternative oral treatment were available.

Metabolites of the higher fungi. Part 23. The punctaporonins. Novel bi-, tri-, and tetra-cyclic sesquiterpenes related to caryophyllene, from the fungus Poronia punctata(Linnaeus:Fries) Fries

Six new sesquiterpenes have been isolated from the culture medium of the fungus Poronia punctata. Punctaporonins A, D, E, and F are isomeric allylic alcohols possessing a tricyclic carbon skeleton not previously found in nature. Punctaporonin B is a related trihydroxycaryophyllene isomer, and punctaporonin C is a novel tetracyclic hemisuccinate. An additional major metabolite has been identified as (E)-methyl 3-(4-methoxyphenoxy)propenoate.

Punctatin A (antibiotic M95464): X-ray crystal structure of a sesquiterpene alcohol with a new carbon skeleton from the fungus, Paronia punctata

Physical methods and X-ray diffraction analysis have been used to establish the structure of a novel trihydroxysesquiterpene, punctatin A, produced, with a series of related compounds, by the dung fungus Poronia punctata(Linnaeus ex Fries).

Punctatins B and C (antibiotics M95154 and M95155): further sesquiterpene alcohols from the fungus Poronia punctata

Further studies on metabolites of the dung fungus Poronia punctata(Linnaeus ex Fries) have furnished the structure of punctatins B (2) and C (3) as a trihydroxycaryophyllene isomer of punctatin A (1) and a novel tetracyclic hemi-succinate ester of close biogenetic origin, respectively.

Stereospecific synthesis of (22R)-22-hydroxycholesterol and (22R)-cholesta-5,24-diene-3β,22-diol

A stereospecific method previously developed in the triterpene series for the synthesis of inotodiol (I) is shown to be equally valid in the steroid series. Addition of the appropriate Grignard reagent to (22ξ)-22,23-epoxy-6β-methoxy-3α,5α-cyclo-24-norcholane (VI) and (VII)[derived from the bromohydrins (Va–c)] furnished, after regeneration of the 5-en-3β-ol system, the title compounds in good yields, almost stereospecifically. It follows that electrophilic addition to the double bond occurs as previously defined for 24,25,26,27-tetranorlanosta-8,22-dien-3β-yl acetate, the (22S)-23-bromo-22-hydroxy- and (22R)-22-bromo-23-hydroxy-isomers being the major bromohydrins formed.

Metabolites of the higher fungi. Part 25. Punctaporonin G from the fungus Poronia punctata(linnaeus: Fries) Fries

Punctaporonin G is a new naturally occurring tricyclic sesquiterpene; it can also be produced from punctaporonin B by acid catalysed dehydration involving the 1- and 4-hydroxy substituents. The properties of punctaporonin G are compared with those of B and an additional major acid degradation product of B is identified.

Synthesis of a monocyclic β-lactam stereospecifically labelled at C-4

In connection with biosynthetic studies, the β-lactams (5; 4-HR=2H) and (5; 3-H = 4-HS=2H) have been synthesized. The 1H and 2H n.m.r. spectra of these compounds confirm the assignment of the stereochemistry to the two hydrogens at C-4 of monocyclic β-lactams such as nocardicin A. Samples of the amino-acid L-asparagine stereospecifically labelled at C-3 have been made in the course of this work.

Structure of cyclizidine (antibiotic M146791) : X-ray crystal structure of an indolizidinediol metabolite bearing a unique cyclopropyl side-chain

An unusual indolizidinediol with an α,β:γ,δ-unsaturated cyclopropyl side-chain has been isolated from a new Streptomyces species, and the structure established as (1) by X-ray crystallographic and spectroscopic methods.

Electrophilic addition to 24,25,26,27-tetranorlanosta-8,22-dien-3β-yl acetate

Addition of the elements of hypobromous acid to the Δ22-bond of the title compound(II) gives rise, after cyclisation, to the (22S)-epoxide (IIIa) in a highly selective manner. The two major bromohydrin intermediates have been shown to be the 23-bromo-22(S)-hydroxy- and 22(R)-bromo-23-hydroxy-isomers. A third, minor bromohydrin has the 23-bromo-22(R)-hydroxy-structure.

Antibiotics 13285 A1 and A2: novel cepham and penam metabolites from a Streptomyces species

The norpenicillin N (1b) and the isomeric cepham (2) have been isolated from a Streptomyces species and identified from 1H n.m.r. spectroscopy and detection of D-α-aminoadipic acid following acid hydrolysis.