A double alkylation—ring closing metathesis approach to spiroimines

As part of a programme directed towards the synthesis of the marine toxins, the spirolides and gymnodimine, a convenient synthesis of the key bicyclic spiroimine ring systems has been developed. The method involves double alkylation of a simple lactam, Grubbs ring closing metathesis of the resultant dialkylated lactam then reduction of the lactam to an imine.     

Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies

Majucin‐type sesquiterpenes from Illicium sp., such as jiadifenolide ( 2 ), jiadifenin ( 3 ), and (1R,10S)‐2‐oxo‐3,4‐dehydroxyneomajucin ( 4 , ODNM), possess a complex caged chemical architecture and remarkable neurotrophic activities. As such, they represent attractive small‐molecule leads against various neurodegenerative diseases. We present an efficient, enantioselective, and unified synthesis of 2 , 3 , and 4 and designed analogues that diverge from tetracyclic key intermediate 7 . The synthesis of 7 is highlighted by the use of an enantioselective Robinson annulation reaction (construction of the AB rings), a Pd‐mediated carbomethoxylation reaction (construction of the C ring), and a one‐pot oxidative reaction cascade (construction of the D ring). Evaluation of the neurotrophic activity of these compounds led to the identification of several highly potent small molecules that significantly enhanced the activity of nerve growth factor (NGF) in PC‐12 cells. Moreover, efforts to define the common pharmacophoric motif suggest that substitution at the C‐10 center significantly affects bioactivity, while the hemiketal moiety of 2 and 3 and the C‐1 substitution might not be critical to the neurotrophic activity.     

Enantioselective synthesis of the ABC ring motif of norzoanthamine based on asymmetric Robinson annulation reactions

An enantioselective strategy for the synthesis of tetracyclic motif 5, representing the northern fragment of norzoanthamine, is presented. Key to the strategy is the use of two asymmetric Robinson annulation reactions that produce the tricyclic ABC ring system with excellent stereoselectivity. Further functionalization at the periphery of the C ring produces compound 5 containing six contiguous stereocenters of the natural product.     

Intramolecular Cyclization Strategies Toward the Synthesis of Zoanthamine Alkaloids

Stabilized 2-amino-1,3-dienes can participate in intramolecular Diels-Alder (IMDA) reactions with pendant dienophiles. We found that these dienes can be readily prepared via standard palladium-mediated coupling reactions and have comparable reactivity to 2-oxodienes. Application of these substrates to the synthesis of tetracyclic model systems representing the ABCE motif of the zoanthamines is presented.     

Singlet oxygen production by Peptide-coated quantum dot-photosensitizer conjugates

Peptide-coated quantum dot-photosensitizer conjugates were developed using novel covalent conjugation strategies on peptides which overcoat quantum dots (QDs). Rose bengal and chlorin e6, photosensitizers (PSs) that generate singlet oxygen in high yield, were covalently attached to phytochelatin-related peptides. The photosensitizer-peptide conjugates were subsequently used to overcoat green- and red-emitting CdSe/CdS/ZnS nanocrystals. Generation of singlet oxygen could be achieved via indirect excitation through F?rster (fluorescence) resonance energy transfer (FRET) from the nanocrystals to PSs, or by direct excitation of the PSs. In the latter case, by using two color excitations, the conjugate could be simultaneously used for fluorescence imaging and singlet oxygen generation. Singlet oxygen quantum yields as high as 0.31 were achieved using 532-nm excitation wavelengths.     

Nature-inspired total synthesis of (-)-fusarisetin A

A concise, protecting group-free total synthesis of (-)-fusarisetin A (1) was efficiently achieved in nine steps from commercially available (S)-(-)-citronellal. The synthetic approach was inspired by our proposed biosynthesis of 1. Key transformations of our strategy include a facile construction of the decalin moiety that is produced via a stereoselective IMDA reaction and a one-pot TEMPO-induced radical cyclization/aminolysis that forms the C ring of 1. Our route is amenable to analogue synthesis for biological evaluation.     

More than a protective group: synthesis and applications of a new chiral silane

Enantiomerically pure (-)-(R)- and (+)-(S)-(1-methoxy-2,2,2-triphenylethyl)dimethylsilanes (MOTES-H) were synthesized from triphenylacetaldehyde in five synthetic steps and with 60% overall yield. MOTES-protected alpha- and beta-hydroxycarbonyl compounds were used in Grignard and Diels-Alder reactions in the presence of MgBr2 to afford addition products with 87-98% yield and selectivities of up to >120:1 dr. With this method, the pine beetle pheromone (-)-frontalin (67%, 98.5% ee) and naturally occurring (-)-(R)-octane-1,3-diol (90%, >99% ee) were synthesized.     

A facile synthesis of fused aromatic spiroacetals based on the 3,4,3′,4′-tetrahydro-2,2′-spirobis(2H-1-benzopyran) skeleton

The facile synthesis of a series of aromatic 6,6-spiroacetals based on the parent 3,4,3′,4′-tetrahydro-2,2′-spirobis(2H-1-benzopyran) heterocyclic system is reported. Key steps included the use of a Sonogashira coupling for the synthesis of an aryl acetylene that was coupled to an aryl aldehyde to form a propargyl alcohol intermediate. Hydrogenation of the alkynol followed by oxidation produced a masked dihydroxy ketone that upon treatment with trimethylsilyl bromide underwent deprotection and cyclisation to the fused aromatic spiroacetal.