Philippa B. Cranwell

Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal–Knorr pyrrole formation and gas concentration measurement by inline flow titration

Using a simple and accessible Teflon AF-2400 based tube-in-tube reactor, a series of pyrroles were synthesised in flow using the Paal-Knorr reaction of 1,4-diketones with gaseous ammonia. An inline flow titration technique allowed measurement of the ammonia concentration and its relationship to residence time and temperature.

Tripodal molecules for the promotion of phosphoester hydrolysis

A series of low molecular weight tripodal amide/histidine-containing compounds (1-2) have been synthesised and shown to increase the rate of bis-(p-nitrophenyl) phosphate (BNPP) and soman (GD) breakdown in buffered aqueous solution.

N,O-Heterocycles as synthetic intermediates*

Hydroxylamines can be cyclized under various conditions according to the nature of the unsaturation in the N-substituent. Both isoxazolidines and tetrahydrooxazines can be formed with good synthetic control. The choice of the appropriate cyclization reaction leads to syntheses of the natural products sedamine and monomorine. The related N,O-acetals are shown to undergo efficient ring-opening under Sakurai conditions.

Synthesis of (±)-Mevashuntin

Significance: Mevashuntin was reported in 2005 by Shin-ya and co-workers (Tetrahedron Lett. 2005, 46, 1273). The relative and absolute configuration of the pyran substituents, as well as the relative positions of the sulfur and nitrogen atoms in the heteroaromatic ring were unknown. During characterization of the natural product, the NMR data was found to be concentration-dependent; therefore, comparison with reported data for the natural product was difficult. To circumvent this, the acid was converted into the methyl ester with TMS-diazomethane. The spectra of the ester matched very closely with the reported data for the natural product. Comment: Removal of the ketone present in G was achieved by conversion into the enol phosphate followed by displacement with MeLi. Formation of the γ-TMS enolate provided diene H. A late-stage Diels–Alder reaction provided access to the core, with the regioselectivity controlled by a bromine substituent. O