Peter J. O'Hanlon

The chemistry of pseudomonic acid: Part 9. Reduction, inversion and replacement of the c-13 hydroxyl group

Abstract The preparations of methyl 13-deoxypseudomonate (2c) and methyl (13R)-monate (4f) via mesylate derivatives are described. Introduction of an amino function by nucleophilic displacement at the C-13 position was unsuccessful but the 13-amine (2f) was prepared via the o -methyloxime (7b) and lithium borohydrlde reduction.

The chemistry of pseudomonic acid. Part 6. Structure and preparation of pseudomonic acid D

Pseudomonic acid D (1c), a minor antibiotic produced by Pseudomonas fluorescens, has been isolated and identified. The preparation of pseudomonic acid D from monic acid A (1e) is described.

The preparation of 2-(heterocyclyl)thikno[3,2-b]pyridine derivatives

Abstract The preparation of a series of 2-(heterocyclyl)-4-ethyl-4,7-dihydro -7-oxothieno[3,2-b]pyridine-6-carboxylic acids (5j-1) by aminolysis of the corresponding 2-bromo derivative (5i) is described. None of the compounds (5j-1) showed any interesting antibacterial activity.

The chemistry of pseudomonic acid. Part 10. Preparation of heterocyclic derivatives

The preparation of a large variety of normonyl heterocycles is described. Methods involving cyclisation of monic acid derivatives gave access to only a limited number of types of heterocycles. Olefination methods proved to be of wider applicability with phosphonate stabilised anions providing the biologically active E-isomer in a 3–4 : 1 excess. The Peterson type olefination proved to be the most useful method with the largest range of heterocycles and stereoselectivity of E:Z 4 to >10 : 1.

The chemistry of pseudomonic acid, part II. Dehydrative cyclisation of α-acylamino ketones to oxazoles

A number of mild methods for the preparation of 2-substituted 5-normonyloxazoles (1) by dehydrative cyclisation of the corresponding monamides (2) have been developed and are described. The preferred conditions involve using trichloroacetyl chloride, pyridine, and 4-N,N-dimethylaminopyridine. The stabilities of the vinyloxazoles to both the reaction conditions and to light are also reported.

Synthesis of optically active α-phenylselenyl carbonyl derivatives

Abstract Homochiral silyl enol ethers derived from N -acyl oxazolidinones can be phenyselenylated in high diastereoselectivity and good yield with phenylselenyl chloride. Removal of the chiral auxiliary is accompanied by some epimerisation, leading to isolation of the corresponding α-phenylselenyl methyl esters in moderate enantiomeric excess. A slightly improved enantiomeric excess is achieved if 4( S )-benzyl-2-oxazolidinethione 17 is used as a chiral auxiliary.

The chemistry of pseudomonic acid. Part 5. Structure and chemistry of pseudomonic acid C. X-Ray crystal structure of ethyl monate C

A third and minor antibiotic component, designated pseudomonic acid C (1a),2 has been isolated from cultures of the strain Pseudomonas fluorescens NCIB 10586 which produced the structurally related pseudomonic acid A (2a) and B (3). The structure and stereochemistry of the acid (1a) have been confirmed by single-crystal X-ray analysis of the derived ethyl monate C (1f). Pseudomonic acid A has been converted stereospecifically into pseudomonic acid C in high yield. The epoxidation and the acid- and base-stability of pseudomonic acid C have been studied.

The chemistry of pseudomonic acid. Part 4. αβ-Unsaturated ketones derived from monic acid A and its derivatives

Routes to the preparation of αβ-unsaturated ketones (1k–m) have been investigated. n-Butylmanganese(II) chloride was particularly useful for preparing the ketones (1m) from the readily available monic acid A (1b), the nucleus of pseudomonic acid A (1a).

New methodology for the synthesis of unsaturated 8-, 9- and 10-membered lactams

Unsaturated 8-, 9- and 10-membered medium ring lactams 1 (n= 1,2,3) have been prepared in good yield by the Claisen rearrangement of the vinyl-substituted precursors 3 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

The chemistry of pseudomonic acid. Part 8. Electrophilic substitutions at C-2 and C-15 of the pseudomonic acid nucleus by means of lithium dienolates

The regiochemistry of substitution at C-2 (α) and C-15 (γ) of lithium dienolates (2) derived from esters of manic acid (1d) depends on the nature of the electrophile. Substitution at C-2 affords diastereoisomeric mixtures of the deconjugated esters (3). The stereochemistry of reconjugation can be controlled. The ester (3d) when heated with hindered bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) favours formation of methyl 2-methylisomonate (4f) whilst, in contrast, use of potassium t-butoxide favours the biologically active methyl 2-methylmonate (1 m).