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A conceptually new total synthesis of oestrone, based on a novel cascade of radical cyclisations from the iodo aryl vinylcyclopropane 2 , via 10 , 15 , 16 and 17 , leading to the intermediate trans , anti , trans -oestradiol derivative 11 in one step, is described. Oxidation of 11 , followed by demethylation of the resulting aryl methyl ether 18 then gives (±)-oestrone 1 .

Full details of a total synthesis of the doubly prenylated cyclic peptide trunkamide A of marine origin, and also its C45 epimer, are described.

Full details of a total synthesis of the novel reverse prenyl substituted cyclic peptide mollamide, isolated from the ascidian Didemnum molle, are described.

A convergent total synthesis of phorboxazole A (1a), from the C(3–19), C(20–27) and C(33–46) fragments 5, 4 and 91, respectively, concentrating on stereocontrolled formation of the bonds at C(2–3), C(19–20) and C(27–28), is described. Although a coupling reaction between a macrolide ketone and the side chain substituted sulfone, at C(27–28) was not successful, a Wadsworth–Emmons olefination involving the oxane methyl ketone 4 and an oxazole produced the oxane 90 which was next coupled to 91 leading to the C(20–46) unit 100. A further coupling of 100 to 71c at C(19–20) then led to 105, ultimately, and the synthesis was completed by a macrocyclisation reaction from 105, at the C(2–3) alkene bond, followed by deprotection of 106.

A concise total synthesis of (+)-curacin A, a potent antimitotic agent isolated from the cyanobacterium Lyngbya majuscula, is described. The synthesis features a new strategy to the 2-cyclopropyl-4-alkenyl substituted thiazoline unit in the natural product involving facile and selective thioacylation of the amino-alcohol 10 with the benzotriazole derived thioamide 11, leading to 28, as a key step. Cyclodehydration of 28 using Burgess' reagent then completed the synthesis of curacin A 1.

A new and convergent synthesis of the antitumour macrolide rhizoxin D 2 is described. The synthesis features a Wadsworth–Emmons olefination and a facile intramolecular Stille reaction to elaborate the 16-membered macrocyclic core 5 from the vinyl iodide 3 and the vinyl stannane 4 as key steps.

A total synthesis of the doubly prenylated cyclic peptide trunkamide A of marine origin, and also its C45 epimer, is described.

A concise and convergent synthesis of the polyene thiazole-containing 19-membered bis-lactone ()-pateamine 1 is described. The synthesis features both the intra- and intermolecular Stille sp 2 – sp 2 coupling reactions to elaborate the E,Z -diene macrolide core and the side-chain all- E polyene portion of the natural product, and highlights the scope for enantiopure sulfinimine intermediates in the synthesis of chiral β - amino ester moieties in complex structures.

A range of methods for the synthesis of mono-, bis- and tris-2,4-disubstituted oxazoles were evaluated, which led ultimately to a concise synthesis of the three contiguous oxazole ring system 26 in the ulapualide family of 25-membered macrolides, e.g.1, found in marine organisms. The tris-oxazole macrolide core 30 in ulapualide A (1) was also synthesised based on a macrolactamisation strategy from the two functionalised mono-oxazole precursors 28 and 29, followed by oxazoline 45 and oxazole ring formation, exploiting the methodologies established in the synthesis of linear bis- and tris-oxazoles in the formation of 18 and 26. The tris-oxazole 26 was converted into the corresponding phosphonium salt 5 in readiness for elaboration to ulapualide A (1).

A total synthesis of ulapualide A (1), whose relative stereochemistry was assigned on the basis of an earlier molecular mechanics study of its hypothetical metal chelated complex 9, is described. The synthesis is based on: i, elaboration of the double functionalised tris-oxazole 11; ii, synthesis and installation of the top side chain 16 (C-26–C-41) via a stereoselective Wittig reaction, leading to 17; iii, conversion of 17 into 73a and attachment of the C-1–C-9 portion 18; iv, macrocyclisation of 19 by an intramolecular Wadsworth–Emmons olefination leading to the macrolide 20; v, incorporation of the C-9 methyl group (to 80) and, finally vi, manipulation of the side chain functionality in 80 and introduction of the terminal formyl enamine residue. The synthetic ulapualide A showed NMR spectroscopic data which were almost identical to those described for the natural product, and did not separate from the natural material in HPLC analysis. Small differences in the 13C NMR spectroscopic data however lead us to conclude that the stereochemistry of the synthetic ulapualide differs from that in the natural product at one or more of the stereogenic centres along the C-28–C-33 portion of the side chain.

A total synthesis of the proposed structure 1 for the oxazoline/thiazoline-based cyclopeptide cyclodidemnamide, isolated from the sea squirt Didemnum molle, is described. The synthesis features a novel double cyclodehydration, sequential formation of chiral thiazoline and oxazoline rings in a preformed cyclopeptide intermediate, as a key stratagem. The NMR spectroscopic data for synthetic 1 and natural cyclodidemnamide did not correlate. The configuration of the natural product was re-assigned as 15, the C-15-(R)-Val epimer, which was confirmed by total synthesis.

A total synthesis of the novel reverse prenyl substituted cyclic peptide mollamide, isolated from the ascidian Didemnum molle, is described.

A total synthesis of ulapualide A 1 , whose relative stereochemistry was assigned on the basis of an earlier molecular mechanics study of its hypothetical metal chelated complex 2 , is described.

A total synthesis establishes the structure and stereochemistry of the novel heterocycle-based cyclopeptide cyclodidemnamide isolated from the “sea squirt” Didemnum molle as 1b , not 1a .

Total synthesis demonstrates that the structures and stereochemistries of the cyclopeptides raocyclamide A and B isolated from a cyanobacterium should be altered to those shown in formulae 13 and 14 respectively.

A total synthesis of (+)-curacin A 1 which features a facile and selective thioacylation of the polyene amino-alcohol 2 with the benzotriazole-derived cyclopropyl thioamide 3, leading to 15, as a key step is described.

A cascade of three consecutive 6-endo-trig radical cyclisations from the polyene acyl radical intermediate 12 derived from the selenoate 11 is used to construct the trans,anti,trans,anti,cis-tetracyclic keto lactone 20 in one step. Manipulation of the ketone function in 20 to the corresponding gem-dimethyl substituted carbon then completed a concise synthesis of the marine metabolite spongian-16-one 1.

A total synthesis of the proposed structure 1 for cyclodidemnamide from the marine ascidian Didemnum molle is described, which features the novel double, sequential formation of chiral thiazoline and oxazoline rings as the key stratagem.

A concise total synthesis of the marine sponge metabolite spongian-16-one 1, which features a novel cascade of three consecutive 6-endo-trig radical cyclisations from a polyene acyl radical intermediate as a key step, viz 9 → 10 , is described.

In the first synthesis of a chiral thiazoline-containing macrocyclic peptide, a total synthesis of lissoclinamide 4 2c, produced by the marine tunicate Lissoclinum patella, is described.

The total synthesis of the cinnamyl-oxazole substituted tris-thiazoline containing metabolite (−)-thiangazole (1) is described. The synthesis is based on elaboration of the R-2-methylcysteine derived bis-thiazoline nitrile (5) and oxazole (6) intermediates, followed by a cyclocondensation reaction between (5) and (6), and treatment of the resulting tris-thiazoline oxazole ester (16) with methylamine.

A total synthesis of lissoclinamide 5, and some of its stereoisomers, shows that its stereostructure should be revised to 13.

A concise total synthesis of the cinnamyl-oxazole substituted tris-thiazoline containing metabolite thiangazole 1 is described.

A total synthesis of the novel antifungal substance myxothiazol 1 isolated from the myxobacterium Myxococcus fulvus is described. The synthesis is based on elaboration of the S-E,E -diene thioamide 1 5 and the 2 R S , 3 S R amide aldehyde 2 5 as key intermediates, followed by conversion of 1 5 into the bis -thiazole 1 9 and a final Wittig coupling reaction between 2 5 and the salt 2 0 c leading to 7 S ,18 S R , 19 R S myxothiazol.

A total synthesis of the new thiazoline-based siderophore desferrithiocin 1, isolated from Streptomyces antibioticus, is described. Thus, a concise synthesis of (S)-2-methylcysteine hydrochloride 11 is first developed based on a modification of Seebach's “self-reproduction of chirality” protocol using the thiazolidine intermediate 8 derived from (S)-cysteine and pivaldehyde as a key intermediate. When a solution of (S)-2-methylcysteine hydrochloride is heated with 2-cyano-3-hydroxypyridine in the presence of triethylamine, (S)-desferrithiocin is produced in 97% yield. In a similar manner, use of (R)-2-methylcysteine in a cyclocondensation with 2-cyano-3-hydroxypyridine led to (R)-desferrithiocin, in a similar yield.

A total synthesis of nannochelin A, a novel cinnamoyl-hydroxamate siderophore produced by Nannocystis exedens , is described.

A concise total synthesis of the thiazoline-thiazole containing metabolite didehydromirabazole A 1 is described. The synthesis uses the unusual amino acid (R)-2-methylcysteine 20 in sequential cyclocondensations with imino ethers as key steps, viz22→32 and 37→38.

A concise synthesis of optically active (−)-zearalenone (1) which uses a novel 14- endo trig macrocyclisation from an allylic radical intermediate (Scheme 1) as a key feature, is described.

The total synthesis of (±)-citreoviral, which co-occurs with citreoviridin, citreoviridinol, and citreodiol in Penicillium citreoviride, is described. The synthesis is based on a biogenetic model, and has as a key feature the elaboration of the dihydroxytetrahydrofuranyl ring portion 10 by an acidcatalysed cyclisation of the central epoxy alcohol intermediate 9 which is derived in ten steps from methyl tiglate.

A total synthesis of the all-cis cyclopentanetetraol moiety 2,3,4,5-tetrahydroxycyclopentane-1-acetonitrile, present in the antiviral substance funiculosin produced by Penicillium funiculosum, is described. Conversion of the known cyclopent-4-ene-1,2,3-triol into the 1-[1-(t-butyldimethylsiloxy)vinyl] 2,3-methylene trisether, followed by Claisen–lreland rearrangement in xylene at 190 °C, first provided the key intermediate all-cis-4,5-(methylenedioxy)cyclopent-2-ene-1-acetic acid. Iodolactonisation of this acid then led to the iodo lactone 4β-iodohexahydrofuro[2′,3′:4,3]cyclopenta [d][1,3]dioxolan-6-one, which on direct nucleophilic displacement using potassium superoxide in the presence of 18-crown-6 produced the corresponding 4β-hydroxy lactone by an SN1 mechanism probably via the C-4 radical intermediate. The structure and stereochemistry of the hydroxy lactone were determined by X-ray analysis of its t-butyldimethylsilyl ether.The above iodo lactone was converted into the iodohydrin-acetonitrile 2α-hydroxy-3β-iodo-4α,5α-(methylenedioxy)cyclopentane-1α-acetonitrile in three steps, which was then treated with methyl (chloroformyl)acetate to give the corresponding mixed malonate diester. Treatment of this diester with sodium hydride resulted in smooth, intramolecular oxygen nucleophile displacement leading to the all-cis ketene acetal methyl [7-(cyanomethyl)-3b,6a,7,7a-tetrahydro-3aH-cyclopenta [1,2-d;3,4-d′]-di [1,3]dioxol-2-ylidene]acetate in 92% yield, hydrolysis of which produced a mixture of positional isomers of all-cis-2-(cyanomethyl)-5-hydroxy-3,4-(methylenedioxy)cyclopentyl methyl malonate, which was then saponified to give the all-cis cyclopentane-substituted 2,3-dihydroxy-4,5-(methylenedioxy) cyclopentane-1-acetonitrile. The full structure and stereochemistry of this acetonitrile followed from X-ray analysis. The synthesis of (±)-all-cis-2,3,4,5-tetrahydroxycyclopentane-1-acetonitrile was then completed following treatment of the 4,5-methylenedioxy compound with ozone, leading to the 4-formate (and its 5-isomer), and saponification.

A number of complementary biomimetic approaches to the tetrahydrofuranyl portion of the dienal 13, which was used in a synthesis of preaurovertin, are described. Epoxidation of the trienoate 31 produces largely the β-epoxide 32, which on treatment with aqueous trifluoroacetic acid undergoes deacetalisation and concomitant cyclisation leading to compound 34. After conversion of 34 into dienal 13, a Wittig reaction with the ylide derived from the phosphonium salt 37 produces preaurovertin.Preaurovertin is a putative biogenetic precursor of aurovertin found in Calcarisporium arbuscula. Citreoviridin produced by Penicillium citreoviride relates to preaurovertin, and the citreoviridinols are related structurally to aurovertin. In addition, aurovertin is related biogenetically to asteltoxin found in Aspergillus stellatus. These structural and biosynthetic interrelationships are considered alongside the synthetic work.

A total synthesis of all-E-citreomontanin, produced by Pencillium pedemontanum and believed to be the putative precursor of citreoviridin and citreoviridinol, involving successive epoxidations of its terminal triene portion, is described. Elaboration of the pyrone 9a to the phosphonium salt 13b was smoothly accomplished via the key pyrone aldehyde intermediates 10 and 12. The all-E-trienal 7 required for Wittig coupling with compound 13b was readily produced from the aldehyde 14 by use of two successive stereoselective Wittig olefination reactions involving the stabilised phosphorane 15; i.e., 14+15→16, and 17+15→18. A Wittig coupling reaction between the ylide 8 derived from 13b and the trienal 7 then produced the all-E-polyene 1, as an orange solid, which was identical with citreomontanin isolated from P. pedemontanum.

A concise total synthesis of (±)-citreoviral which illustrates a new stereoselective approach to hydroxy-substituted tetrahydrofurans is described. Key features in the synthesis are: (i) elaboration of the Z-unsaturated epoxy ester 10, (ii) acid-catalysed cyclisation of ester 10 to the 4-hydroxyethyl-substituted but-2-enolide 14, (iii) stereoselective vicinal hydroxylation of the butenolide 14 to the diol15, (iv) cyclic ether formation from diol 15 to the bicyclic lactone 8via the benzylidene acetal 9, (v) transesterification of bicycle 8 to the tetrahydrofuran 21 containing three of the four centres in citreoviral in the correct relative configuration. Inversion of the secondary 3-OH group in compound 21, and elaboration of the C-2 side-chain, then completed the synthesis of (±)-citreoviral.

A total synthesis of the new thiazoline-based siderophore desferrithiocin 1, isolated from Streptomyces antibioticus, is described. Thus, a concise synthesis of (S)-2-methylcysteine hydrochloride 11 is first developed based on a modification of Seebach's “self-reproduction of chirality” protocol using the thiazolidine intermediate 8 derived from (S)-cysteine and pivaldehyde as a key intermediate. When a solution of (S)-2-methylcysteine hydrochloride is heated with 2-cyano-3-hydroxypyridine in the presence of triethylamine, (S)-desferrithiocin is produced in 97% yield. In a similar manner, use of (R)-2-methylcysteine in a cyclocondensation with 2-cyano-3-hydroxypyridine led to (R)-desferrithiocin, in a similar yield.

A total synthesis of the novel antifungal substance myxothiazol 1 isolated from the myxobacterium Myxococcus fulvus is described. The synthesis is based on elaboration of the S-E,E -diene thioamide 1 5 and the 2 R S , 3 S R amide aldehyde 2 5 as key intermediates, followed by conversion of 1 5 into the bis -thiazole 1 9 and a final Wittig coupling reaction between 2 5 and the salt 2 0 c leading to 7 S ,18 S R , 19 R S myxothiazol.

A concise total synthesis of the thiazoline-thiazole containing metabolite didehydromirabazole A 1 is described. The synthesis uses the unusual amino acid (R)-2-methylcysteine 20 in sequential cyclocondensations with imino ethers as key steps, viz22→32 and 37→38.

A total synthesis of pukeleimide A 5, a member of a rare family of naturally occurring 5-ylidenepyrrol-2(5H)-ones produced by the marine blue alga Lyngbya majuscula, is described. The synthesis is based on elaboration of the ylidenepyrrolone 11a from the maleimide 13a by a regioand stereo-selective Wittig reaction with ethoxycarbonylmethylene(triphenyl)phosphorane, followed by conversion of 11a into the amide 25, and oxidation of 25 with selenium dioxide.

A total synthesis of nannochelin A, a novel cinnamoyl-hydroxamate siderophore produced by Nannocystis exedens , is described.

A total synthesis of lissoclinamide 5, and some of its stereoisomers, shows that its stereostructure should be revised to 13.

The total synthesis of the cinnamyl-oxazole substituted tris-thiazoline containing metabolite (−)-thiangazole (1) is described. The synthesis is based on elaboration of the R-2-methylcysteine derived bis-thiazoline nitrile (5) and oxazole (6) intermediates, followed by a cyclocondensation reaction between (5) and (6), and treatment of the resulting tris-thiazoline oxazole ester (16) with methylamine.

The new total synthesis of the 4-methylthiazoline-based natural product didehydromirabazole A, produced by the blue green alga Scytonema mirabile, shows that its stereostructure is as shown in formula (12).

A concise total synthesis of the marine sponge metabolite spongian-16-one 1, which features a novel cascade of three consecutive 6-endo-trig radical cyclisations from a polyene acyl radical intermediate as a key step, viz 9 → 10 , is described.

A total synthesis of the proposed structure 1 for cyclodidemnamide from the marine ascidian Didemnum molle is described, which features the novel double, sequential formation of chiral thiazoline and oxazoline rings as the key stratagem.