Anthony C. O'Sullivan

The enantioselective synthesis of simplified southern-half fragments of soraphen A

Abstract The compound 2 comprises a southern-half subunit of the fungicidal macrolide soraphen A 1. It was prepared by a Meinwald reaction of the enolate of S-7 with the lactone S-8 . Its enantiomer and diastereomers were synthesized in a similar manner. The lactone S-8 and its enantiomer R-8 were prepared by three different routes, including the enantioselective catalytic reduction of the β-keto ester 17. These lactones are new and potentially useful as C-5 asymmetric building blocks.

A novel synthesis of sulfamoyl nucleosides

Abstract The sulfamoylated ribose derivative 8 was prepared on a kilogram scale, and used in conjunction with various heterocycles to prepare a series of natural and unnatural 5-O-sulfamoyl nucleosides ( 10 – 32 ). A modification of the Vorbruggen-Hilbert-Johnson reaction conditions for nucleoside formation was used.

The synthesis of imidazoline analogs of the kainoid family

Abstract In an effort to mimic the anthelmintic and insecticidal activties of kainic 1 and domoic 2 acids with compounds of simpler structure and much easier accessibility, the highly functionalised imidazolines 4, 27 and 28 were prepared. This involved a synthesis of suitably protected β-aminoglutamic acid derivatives as key intermediates, which were condensed with orthoesters and deprotected to yield the desired compounds.

The stereoselective derivatisation of the Re or Si faces of the Δ9,10-double bond of soraphen A

Abstract The Δ 9,10 double bond of soraphen A was found to react selectively on the Si face, whereas the same double bond in the hydroxy-ketone tautomer of soraphen A is attacked on the Re face. It became possible to prepare products of chosen stereochemistry by stabilising the requisite tautomer by use of the appropriate protecting groups. Attempts at S N 2 displacements on the soraphen molecule failed and electrophilic addition to the Δ 9,10 double bond in our experiences never took place in a 1,2 manner. Based on these results and results with other macrolides, it is suggested that S N 1 reactions are more likely to succeed than S N 2 reactions in macrolide derivatisation.

A new method for the synthesis of 2-carboxymethyl-2-hydroxy-tetrahydropyrans

Abstract A simple synthesis of the title compounds 5 from diketene, and the aldehyde 3 is described.

SYNTHESIS OF SUBSTRUCTURES OF SORAPHEN A: FORMATION OF THE ENOLATE OF BENZYL PROPIONATE

During the preparation of substructures of the fungicidal natural product soraphen A 1, it was observed that the β-keto ester 12 was formed as the major product upon deprotonation of benzyl propionate with LDA. Studies of the stability of the enolate 13 showed that two mechanisms previously described for the decomposition of ester enolates cannot be operating in this example. A competition between deprotonation and condensation is proposed, which is in accord with the results described here and in the literature. The use of a reactive base is shown to provide good yields of the enolate 13. In addition, temperature is shown to be another factor influencing the yield of 13.

The insecticidal activity of derivatives of the ionophore X-206

The naturally-occurring ionophore X206, originally isolated for its antibacterial activity, also exhibits broad insecticidal and acaricidal activity. This summary reports structure/activity studies with X206 and 34 derivatives as well as mode of action studies. Although many compounds showed promising insecticidal activity, it was only of a contact activity nature; furthermore, the acute LD50 of the compounds in rats precluded further development of these compounds. © 1999 Society of Chemical Industry