Richard A. Ward

The total synthesis of swinholide A. Part 4: Synthesis of swinholide A and isoswinholide A from the protected monomeric seco acid, pre-swinholide A

Abstract Swinholide A and isoswinholide A were synthesised in 7 steps from the fully protected seco acid 4 . Key steps include: ( i) bimolecular acylation, 7 + 10 → 12 , ( ii ) selective hydrolysis of the methyl ester, 16 → 17 , and ( iii ) regioselective macrolactonisation. 17 → 18 . The monomeric lactone analogues 2 and 5 were prepared by regioselective macrolactonisation of the seco acid 6 , where the ring size was controlled by variation of the reaction conditions.

The total synthesis of swinholide A. Part 3: A stereocontrolled synthesis of (−)-pre-swinholide A.

Two coupling strategies for (−)-pre-swinholide A were devised based on the analysis in Scheme 1. In the first route, a boron-mediated aldol reaction between the ethyl ketone 19 and the aldehyde 3 was used to construct the C15-C16 bond with moderate diastereoselectivity. In the second route, a Mukaiyama aldol reaction between the methyl ketone 54 and the aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.

Studies in marine macrolide synthesis: Boron and silicon-mediated coupling strategies for Swinholide A

Abstract Reaction of aldehyde 6 with enol borinates 7 gives adduct 10 preferentially, whereas the allylsilane 18 provides the epimeric adduct 11 with 95% ds. Aldehyde 2 reacts mainly by si -face attack with simple Z enol borinates, which can be overturned by reagent control from (+)- 25 .

The total synthesis of scytophycin C. Part 1: stereocontrolled synthesis of the C1C32 protected seco acid

Abstract A stereocontrolled synthesis of the C1C32 seco acid derivative 9 for scytophycin C (1) was completed in 14 steps (18.2% yield, 85% ds) from aldehyde (S)-18. Key steps include: (i) the asymmetric crotylboration of (S)-18 to give homoallylic alcohol 15; (ii) the boron-mediated aldol construction of aldehyde 14 from (S)-17; (iii) the Ba(OH)2-promoted HWE reaction, 13 + 14 → 31; (iv) the highly stereocontrolled Mukaiyama aldol coupling between silyl enol ether 33 and aldehyde 11 to give adduct 10; (v) the chemoselective reduction at C17 of ketone 10 to produce 1,3-syn-diol 34.

Towards the synthesis of swinholide A and scytophycin C. A highly stereocontrolled synthesis of (−)-pre-swinholide A

Abstract The fully protected monomeric unit 19 of the marine macrodiolide, swinholide A ( 1 ), was obtained with > 97% ds by a Mukaiyama aldol reaction between 16 and 5 , followed by a boron-mediated reduction to give the syn 1,3-diol 18 . Deprotection gave (−)-pre-swinholide A ( 2 ), the putative biosynthetic precursor of 1 .

Stereoselective routes to substituted β-amino carbonyl compounds via heterodiene cycloadditions of an auxiliary-based C2-symmetric ketene acetal

Abstract Heterodiene cycloadditions of ( S , S )-4,5-bis( o -tolyl)-2-methylene-1,3-dioxolane 1 with a series of substituted β-amido-α,β-unsaturated carbonyl compounds are diastereoselective (dr ≥4:1). The cycloadducts from N -(2-(1-oxoethyl)-3-oxobut-1-enyl)ethanamide 2a can be purified by crystallisation and hydrolysed with acid to generate the corresponding β-amidoacetic esters, the sequence providing an auxiliary-based stereoselective route to such compounds.

Stereoselective routes to substituted β-amino carbonyl compounds via heterodiene [4π+2π] cycloadditions of auxiliary-based C2 symmetric ketene acetals

Heterodiene [4π+2π] cycloadditions of (S,S)-4,5-diaryl-2-methylene-1,3-dioxolanes 1 to a series of β-amido-α,β-unsaturated carbonyl compounds are diastereoselective (d.r.≥4:1). The products can be purified by trituration or crystallisation and hydrolysed with acid to generate the corresponding β-amido carbonyl compounds, the overall sequence effecting an auxiliary-based enantioselective conjugate addition of an acetate enolate, leading to β-aminoacid derivatives.