Nigel Hussain

A new synthesis of the GPIIb/IIIa receptor antagonist SB-214857-A

A new synthesis of lotrafiban SB-214857-A is reported. The key steps are the preparation of racemic (4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-yl)-acetic acid methyl ester from 2-nitrobenzyl alcohol, a resolution using an immobilised lipase enzyme and a palladium-catalysed aminocarbonylation reaction.

Alkoxy radicals in organic synthesis. A novel approach to a key intermediate in milbemycin chemistry

Abstract The fragmentation of nitrate ester ( 2 ) via an alkoxy radical to lactone ( 3 ) is described. This lactone is a key intermediate in the synthesis of semisynthetic milbemycins.

Spiroacetal synthesis from a key lactone intermediate leading to novel C24 and C25-substituted milbemycins

Abstract The lactone intermediates (3), (4) and (5) are converted via lithium acetylide chemistry to a range of novel C24 and C25-substituted milbemycins. The methdology has been extended to afford milbemycins containing 6,5-spiroacetal units.

A mild and efficient method for the formation of a key intermediate in penem chemistry

Abstract A mild, rapid and efficient method for the formation of phosphoranes 2 from oxalimides 1 is described. These phosphoranes can be cyclized to provide penems 3 .

Synthesis of an α-(aminooxy)arylacetic ester by the reaction of an α-diazo ester with n-hydroxyphthalimide

The α-diazo esters (6) and (7) react, in the absence of any catalyst, with a variety of HONR2 and HONCR2 compounds to give the 0-alkylated adducts (8) to (16). In particular, reaction of (7) with N-hydroxyphthalimide in refluxing benzene followed by deprotection gives the title compound (1)

Semi-synthetic C23-substituted milbemycins via spiroacetal cleavage and resynthesis

Abstract The lactone intermediates (2) and (3) are converted by lithium acetylide chemistry followed by mercury catalysed hydration to novel semi-synthetic 23-oxo C24 and C25 substituted milbemycins (7).

A practical synthesis of the milbemycin SB-201561

Abstract A 6-step synthesis of the potent anthelmintic SB-201561 is described. The key stage of the synthesis is a novel Beckmann type oxime fragmentation to give a lactone, followed by a 2-step reassembly of the spirolcetal moiety.

Fragmentations and rearrangements of 22-hydroxyl substituted milbemycins - synthesis of a key lactone intermediate

Abstract Beckmann fragmentation of 22-oximino milbemycins resulted in the cleavage of the C21–C22 bond to produce a key lactone intermediate which can be used to synthesise new spiroacetals. Cleavage of the C21–O25 bond and recyclisation to produce a furyl derivative is also described.

A convenient and concise synthesis of a key lactone intermediate in milbemycin chemistry

Abstract A short, convenient and inexpensive synthesis of lactone (3) from milbemycin (1) is described. This lactone is a key intermediate in the synthesis of milbemycins.