John H. Bateson

Olivanic acid analogues. Part 1. Total synthesis of the 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate system and some related β-lactams

4-Allylazetidin-2-one, prepared from penta-1,4-diene and chlorosulphonyl isocyanate, has been used to synthesise the parent 7-oxo-1-azabicyclo[3.2.0] hept-2-ene-2-carboxylate system of the naturally occurring olivanic acids, using an intramolecular Witting reaction to construct the 2,3-double bond. Cyclisation of ketones derived from the 4-allyl grouping produced 3-substituted derivatives, while use of the azetidin-2-one prepared from hexa-1,5-diene and chlorosulphonyl isocyanate has given the homologous 8-oxo-1-azabicyclo[4.2.0]oct-2-ene system.

Olivanic acid analogues. Part 2. Total synthesis of some C(6)-substituted 7-oxo-1 -azabicyclo[3.2.0] hept-2-ene-2-carboxylates

A number of 6-substituted 7-oxo-1 -azabicyclo[3.2.0] hept-2-ene-2-carboxylates related to the olivanic acids were prepared from the phosphorane (32). Generation of the anion α to the azetidin-2-one carbonyl group, followed by reaction with electrophiles and intramolecular cyclisation using the Wittig procedure gave the bicyclic products; in all cases the thermodynamically favoured trans-stereochemistry about the azetidinone ring predominated. In contrast, some less readily available cis-substituted analogues were obtained from the cyclohexa-1,4-diene derived phosphorane (61). The synthetic utility of a masked acetonyl ester group for preparing the free acids of these azabicycloheptene ring systems is described.

Reactions of 2-chloro-NN-diethyl-1,1,2-trifluoroethylamine with alcohols. Part I. Preparation of 2β- and 4β-fluorogibberellins

The allylic 2β-hydroxy-group in esters of gibberellic acid (9) reacts with 2-chloro-NN-diethyl-1,1,2-trifluoro-ethylamine to give the corresponding esters of 2β-fluoro-4aα,7-dihydroxy-1β-methyl-8-methylenegibb-3-ene-1α, 10β-dicarboxylic acid 1,4a-lactone (5) and its allylic isomer 4β-fluoro-4aα,7-dihydroxy-1β-methyl-8-methylenegibb-2-ene-1α,10β-dicarboxylic acid 1,4a-lactone (14). The fluoro-acids (5) and (14) themselves were obtained by de-esterification of the corresponding p-bromophenacyl esters (7) and (15).

Experiments on the synthesis of tetracycline. Part XIV. Closure of ring B by base-catalysed photocyclisation

The photocyclisation of 4-[2-(dioxolan-2-yl)benzyl]-2-phenylnaphtho[1,8-bc]furan-5-one (I) to the naphthacenofuran (II) is catalysed by strong base. The simpler 2-[2-(dioxolan-2-yl)benzyl]-1,4-naphthoquinone (V) was not efficiently photocyclised to the naphthacenequinone (VI). Extension of the base-catalysed photocyclisation procedure provided an efficient route to the fully substituted linear tetracyclic acetal (IX) from the naphthofuran (VIII). An alternative theory for the photocyclisation of acetals of the type (I) to the linear tetracycline-type acetals (II) is advanced.

The microbiological production of analogues of mould metabolites. Part I. Production of fluorogibberellic acid and fluorogibberellin A9 by Gibberella fujikuro

1β-Fluoromethyl-10β-formyl-4aα-methyl-8-methylenegibbane-1α-carboxylic acid (3) and 1β-fluoromethyl-4aα-methyl-8-methylenegibbane-1α,10β-dicarboxylic acid (fluorogibberellin A12)(4) have been prepared from 6α,7β,18-trihydroxykaur-16-en-19-oic acid 19,6-lactone (7). The aldehyde (3) was converted by G. fujikuroi into 1β-fluoromethyl-2β,4aα,7α-trihydroxy-8-methylenegibb-3-ene-1α,10β-dicarboxylic acid 1,4a-lactone (18) and 1β-fluoromethyl-4aα-hydroxy-8-methylenegibbane-1α,10β-dicarboxylic acid 1,4a-lactone (fluorogibberellin A9)(15).