Craig J. Forsyth

Highly chemoselective oxidation of 1,5-diols to δ-lactones with TEMPO/BAIB

Abstract The selective oxidative conversion of a variety of highly functionalized 1°,2°-1,5-diols into the corresponding δ-lactones has been effected simply and efficiently using a reagent system comprised of catalytic 2,2,6,6-tetrmethylpiperidinooxy (TEMPO) and excess bis-acetoxyiodobenzene (BAIB).

Convergent synthesis of the C31C46 domain of the phorboxazole natural products

Abstract A convergent synthesis of the C31C46 domain of the phorboxazole natural products has been developed. This involved the preparation of a C39C46 dienyl iodide and a C31C37 aldehyde, followed by their CrCl 2 -mediated coupling and final installation of the C46 ( E )-vinyl bromide via an alkyne hydrostannation-bromination sequence.

Synthesis of the central C18–C30 core of the phorboxazole natural products

Abstract A direct synthesis of the central C18C30 core of the phorboxazole natural products has been developed. This involves construction of an acyclic acrylate using Patersons ( E )-enol borinate aldol methodology followed by an intramolecular hetero-Michael addition to form the central pyran ring of the natural products.

Biomimetic studies towards the C28–C40 polycyclic domain of the azaspiracids

Abstract An acyclic intermediate representing a putative biomimetic precursor of the C28–C40 domain of the novel marine toxin azaspiracid was constructed convergently from C28–C34 and C35–C40 fragments. In studying the assembly of the C28–C34 dioxabicyclo[3.3.1]nonane system via an intramolecular hetero-conjugate addition upon a C34–C36 enone, a stereoselective C -Michael addition intervened to provide a highly substituted cyclohexane.

Remarkably chemoselective indium-mediated coupling en route to the C21–C40 acyclic portion of the azaspiracids

Abstract A densely functionalized acyclic intermediate representing the C21–C40 portion of the novel marine natural product azaspiracid was prepared via a chemoselective indium-mediated coupling between C21–C27 and C28–C40 intermediates. Although the coupling partners contained aldehyde, azide, ketone, enone, and lactone functionalities, the C21–C27 allylic species added selectively to the aldehyde of a C28–C40 intermediate under aqueous indium-mediated conditions. The C21–C27 and C35–C40 fragments were prepared in a divergent fashion from a common syn-1,3-dimethyl synthon 9 .

An in situ iminium formation-allylation approach towards the 1-aza-[4.5.0]-spirobicyclic core of halichlorine and pinnaic acid

Abstract A facile procedure for the formation and allylation α to the nitrogen of 1-azaspirobicyclic systems has been developed. In examining an approach towards the synthesis of the natural products halichlorine ( 1 ) and pinnaic acid ( 2 ), spontaneous condensation of an aldehyde-carbamate to form a spirobicyclic N -acylenamine was observed. Introduction of the C1–C5 moiety of the natural products was then initiated in a one pot procedure involving acid mediated enamine-imine conversion and treatment with allytrimethylsilane. This resulted in essentially a single diastereomeric product, which was determined to correspond to the C5 epimer of 1 and 2 .

Application of the double intramolecular hetero-Michael addition (DIHMA) approach in spiroketal synthesis: total synthesis of (±)-(4S*,6S*)-4-hydroxy-1,7-dioxaspiro[5.5]undecane, a Dacus oleae olive fly pheromone

Application of a novel double intramolecular hetero-Michael addition (DIHMA) strategy to spiroketal synthesis was illustrated by a concise synthesis of (±)-(4S*,6S*)-4-hydroxy-1,7-dioxaspiro[5.5]undecane, a Dacus oleae olive fly pheromone.

A stereoselective total synthesis of (±)-erythrodiene

Abstract Erythrodiene, a unique spirobicyclic sesquiterpene hydrocarbon from the Caribbean gorgonian coral Erythropodium caribaeorum, has been synthesized from 4-isopropylcyclohexanol in 8-steps and approximately 16% overall yield. The synthesis features a stereoselective intramolecular carbomercuration reaction as the key step.

Direct synthesis of substituted tetrahydrofurans via regioselective dehydrative polyol cyclization cascades

Abstract A one-pot procedure for the conversion of 1,2,4,5-tetraols into substituted tetrahydrofuran moieties has been developed. This involves the regioselective sulfonylation of the terminal hydroxyl of the polyol array followed by sequential oxirane and oxolane formation under basic conditions. A survey of reaction conditions has defined the use of N -(2,4,6-triisopropylbenzenesulfonyl)imidazole as sulfonylation reagent, potassium tert -butoxide as base, and tert -butanol as solvent to be optimal. Under these conditions, 8- O -benzyl-octan-1,2,4,5,8-pentaol was converted stereospecifically into tetrahydrofurans in 62% yield. Polyol substrates were derived from Sharpless asymmetric dihydroxylation of 1,4-dienes. Hence, substituted tetrahydrofurans could be obtained stereospecifically from diene substrates in two operations.

Importance of the C28-C38 hydrophobic domain of okadaic acid for potent inhibition of protein serine-threonine phosphatases 1 and 2A.

Okadaic acid is a potent inhibitor of select serine/threonine protein phosphatases. The importance of the C28-C38 hydrophobic domain of okadaic acid for inhibition of PP1 and PP2A was investigated. The hydrophobic domain is required but not sufficient for potent inhibition, and it also contributes to differential inhibition between PP1 and PP2A.