Mark D. Andrews

Regioselective Dieckmann cyclisations leading to enantiopure highly functionalised tetramic acid derivatives

Regioselective Dieckmann cyclisations using an N-acyloxazolidine derived from L-serine give substituted tetramic acids in high yield and enantioselectivity. The products are easily deprotected under mild conditions to give hydroxymethyltetramic acids.

A concise approach to functionalised, homochiral tetramic acids

Abstract Dieckmann cyclisation of homochiral N-acyloxazolidines derived from serine gives good to excellent yields of α,α-disubstituted tetramic acid derivatives.

The azomethine ylide strategy for ??-lactam synthesis. Azapenams and 1-azacephamsThis paper is respectfully dedicated to the memory and many achievements of Professor Malcolm Campbell (1943???2001).

Reaction of the β-lactam-based oxazolidinone 5 with N-sulfonylimines provides the exo and endo azapenams 8 in 22–54% yield. The reactivity of 2H-azirines as 1,3-dipolarophiles towards β-lactam-based azomethine ylides derived from oxazolidinones 5 and 15 has also been evaluated. Azirines 11 and 12a provide cycloadducts 13a,b and 16 respectively, which incorporate the novel 2,6-diazatricyclo[4.2.0.02,4]octan-7-one ring system. These adducts were resistant towards C–N cleavage as the basis of an entry to 1-azacephams (1,5-diazabicyclo[4.2.0]octan-8-ones) 4. The use of the 3-(4-methoxyphenyl)-2H-azirine 19 provides a labile initial cycloadduct, which undergoes in situ ring-cleavage and further reaction to give the 2 ∶ 1 adduct 1-azacepham 22. The initial product is stable when 3-(4-nitrophenyl)-2H-azirine 23 is employed, and cycloadducts 24a and 24b are converted under mild reducing conditions to the 1-azacepham derivatives 25 and 26.

Convenient synthesis of enantiopure cyclic α-hydroxyalkyl α-amino esters

The preparation of cyclic α-hydroxyalkyl α-amino esters, the ring size of which varies varies from 4 to 7 members, in enantiopure form is readily achieved by intramolecular alkylative cyclisation of oxazolidine precursors.

Diastereocontrolled synthesis of hydroxylated lactams

Highly diastereoselective reductions and organometallic additions in bicyclic lactams have been observed, which appear to result either from a stereoelectronic interaction of the pyramidalised nitrogen lone pair or from steric interactions in the bicyclic system. These products can be readily deprotected to give hydroxylated lactams.