Ian C. Lennon

On the economic application of DuPHOS rhodium(I) catalysts: a comparison of COD versus NBD precatalysts

Abstract The effectiveness of cyclooctadiene and norbornadiene precatalysts of the type [Rh(DuPHOS)(diolefin)]BF 4 in catalytic asymmetric hydrogenation of various prochiral olefins has been examined. In some of the systems studied, the NBD complex gave rise to the catalytically active species more rapidly than the corresponding COD complex, as expected. However, as catalyst loadings were reduced to levels more conducive to economic manufacture, the difference between the use of COD and NBD precatalysts became increasingly insignificant. This was conveniently highlighted by the formation of low enantiomeric excess products upon using an equimolar mixture of ( S , S ) and ( R , R ) precatalysts, bearing COD and NBD respectively. With other substrates, the system displayed no induction time for either precatalyst and identical reaction profiles were observed.

A novel synthesis of 5-hydroxy-2,2-dimethyl-10-propyl-2H-pyrano[2,3-f]chromen-8-one

A concise synthesis of 5-hydroxy-2,2-dimethyl-10-propyl-2H-pyrano[2,3-f]chromen-8-one utilising a novel selective desulfonylation protocol is described. This method provides facile access to a key intermediate for the asymmetric synthesis of calanolide A.

Biosynthesis of tetronasin: Part 3 preparation of deuterium labelled tri- and tetraketides as putative biosynthetic precursors of tetronasin

Abstract The preparation of seven deuterium labelled N-acetyl cysteamine thioesters ( 2a ), ( 2b ), ( 3a ), ( 3b ), ( 4 ), ( 5 ) and ( 6 ) as putative biosynthesis precursors of the acyl tetronic acid ionophore tetronasin is described.

Biosynthesis of tetronasin: Part 2 identification of the tetraketide intermediate attached to the polyketide synthase

Abstract Incorporation experiments with deuterium labelled N-acetyl cysteamine analogues ( 4a ) and ( 4b ) of the proposed enzyme-bound tetraketide precursor ( 4 ) show that the acyl residue is incorporated intact into tetronasin ( 6 ). Equivalent experiments with the deuterium labelled N-acetyl cysteamine analogues ( 7 ), ( 8 ) and ( 9 ), all diastereoisomers of ( 4 ), result in no intact incorporation into ( 6 ).

Two new routes to the C19C26 tetrahydrofuran fragment of the acyl tetronic acid ionophore tetronasin (ICI M139603)

Abstract Two highly efficient and complementary synthetic routes to the C19C26 tetrahydrofuran fragment ( 2 ) of the novel acyltetronic acid ionophore antibiotic tetronasin (ICI 139603) ( 1 ) are described to provide multigramme quantities of the required product.

Novel polyene cyclisation routes to the acyl tetronic acid ionophore tetronasin (ICI M139603)

Abstract An approach to the total synthesis of the ionophore antibiotic tetronasin ( 1 ) is reported, in which the key step is a novel base catalysed cascade cyslisation of an activated polyene ( 2 ). This establishes two rings and four stereogenic centres in one step. A related polyene ( 16 ) has been cyclised in a similar fashion, illustrating the generality of the procedure.

Biosynthesis of tetronasin: Part 4, preparation of deuterium labelled C19-C26, C17-C26, C11-C26 and C3-C26 polyketide fragments as putative biosynthetic precursors of the ionophore antibiotic tetronasin (ICI 139603)☆

Abstract Six deuterium labelled N-acylcysteamine polyketide derivatives (3) – (8) have been prepared as putative precursors for incorporation in studies of the biosynthesis of the ionophore antibiotic tetronasin (1). The route to these compounds was designed to be flexible and to maximise the use of common synthetic fragments.

An Enantioconvergent Synthesis of (R)-4-Aryloxy-1-butyne-3-ols for Prostanoid Side Chains

The single enantiomer title alcohols, useful as ω-side chain precursors for pharmaceutically important prostaglandin analogues were synthesised from the corresponding racemic alcohols by a convenient 4-step sequence. After enzymatic acylation of the alcohol with a vinyl carboxylate, the residual (S)-alcohol in the mixture was converted to the mesylate. Subsequent displacement with the corresponding carboxylate anion, followed by enzymatic deacylation gave the desired (R)-alcohol. In this way, all of the starting alcohol was utilised without the need for separation of the starting material and product after the bioresolution.

A novel asymmetric route to 2-amino-1,2,3,4-tetrahydronaphthalenes

Abstract A novel asymmetric route to 2-amino-1,2,3,4-tetrahydronaphthalenes has been demonstrated starting from phthalimidovinylglycinol (PVG). Functionalisation of PVG via Heck reaction, olefin hydrogenation and cyclisation provides the title products.

A novel synthesis of tert-leucine via a Leuckart type reaction

An efficient synthesis of racemic tert-leucine from trimethylpyruvic acid using a Leuckart type reaction is described. A facile resolution of an intermediate with α-methylbenzylamine allows entry into either (R)-or (S)-tert-leucine.