Ring-closing metathesis approaches for the solid-phase synthesis of cyclic peptoids

Cyclic peptoids were efficiently synthesized on a solid phase in high yields utilizing ring-closing metathesis (RCM). This method should be a valuable tool for easy access to cyclic peptoid libraries and various cyclic compounds.     

Synthesis of diverse macrocyclic peptidomimetics utilizing ring-closing metathesis and solid-phase synthesis

The synthesis of a range of highly functionalized peptidomimetic macrocycles has been accomplished using ring-closing metathesis and enyne tandem cross-metathesis-ring-closing metathesis reactions. This approach gives access to rigidified macrocycles modeled on the structures of cyclic peptides and designed to be biologically stable. The potential for peripheral functionalization of these templates has been demonstrated using Diels-Alder reactions, palladium(0) coupling reactions, and amide formation both in the solution phase and using polymer-supported syntheses.     

Cross metathesis functionalization of polyolefins

A cross metathesis strategy is reported for the post-polymerization functionalization of the pendant vinyl groups present in a range of polyolefin architectures. This represents a general strategy for the synthesis of tailored random and block copolymers as well as homopolymers.     

Ring-closing metathesis: development of a cyclisation-cleavage strategy for the solid-phase synthesis of cyclic sulfonamides

A series of novel 7-membered cyclic sulfonamides have been synthesised using a solid-phase cyclisation-cleavage RCM strategy. Model solution studies indicated the sulfonamides were suitable substrates for RCM using the Grubbs' catalyst 2. Starting from either 2-carboxyethyl polystyrene (21) or Merrifield resin, various seven-membered sulfonamides were prepared in good to excellent yields at low catalyst loadings (2.5-5 mol%) using a flexible spacer between the polymer and the substrate. In addition, a novel double-armed linker was shown to allow efficient RCM cleavage of sulfonamides with as little as 1 mol% of the ruthenium alkylidene complex 2.     

Cross metathesis as a general strategy for the synthesis of prostacyclin and prostaglandin analogues

[reaction: see text] A cross metathesis (CM) approach has been successfully applied to introduce fully functionalized omega-side chain appendages of various prostacyclin and prostaglandin analogues, resulting in high (E)-selectivities for the C13-C14 double bond and leading to the total syntheses of isocarbacyclin, 15R-TIC, carbacyclin, and PGF(2)(alpha) and the formal syntheses of 15-deoxy-TIC and PGJ(2).     

Cross enyne metathesis of para-substituted styrenes: a kinetic study of enyne metathesis

[Reaction: see text] The intermolecular enyne metathesis between alkynes and styrene derivatives was developed to study electronic effects in enyne metathesis. A Hammett plot for the overall reaction, catalyst initiation and vinyl carbene turnover was determined with the second generation Grubbs ruthenium carbene catalyst.     

Allosteric function facilitates template assisted olefin metathesis

Template assisted olefin metathesis of an allosteric host to give the corresponding bicyclic compound was achieved and can allosterically bind the template guest diamines, and with different affinity and cooperativity.     

Microwave assisted solid-phase synthesis of trisubstituted 2-(2,6-purin-9-yl)acetamides

In the course of developing a method for the parallel synthesis of purin-9-yl-acetamides, it was found that microwave irradiation was beneficial in accelerating the nucleophilic displacement of halogens by amines at the C-2 position of the purine nucleus.     

Cross metathesis with strained exocyclic enones: synthesis of 3-alkylideneoxetan-2-ones from 3-methyleneoxetan-2-ones

[reaction: see text] 3-Alkylideneoxetan-2-ones have been prepared in good to excellent yields with high Z-selectivity by olefin cross metathesis with 3-methyleneoxetan-2-ones in the presence of second generation metathesis catalysts 1 or 2.     

Cross metathesis of alpha-methylene lactones II: gamma- and delta-lactones

[reaction: see text] The cross metathesis reactivities of alpha-methylene-gamma-butyrolactone and an alpha-methylene-delta-lactone have been investigated. alpha-Methylene-gamma-butyrolactone undergoes rapid and efficient olefin isomerization in the presence of second-generation metathesis catalysts. However, cross metathesis can be achieved with the additive 2,6-dichlorobenzoquinone. In contrast, the alpha-methylene-delta-lactone neither isomerizes nor couples under similar conditions.     

Continuous-flow solid-phase peptide synthesis

We describe a simple manually operated synthesizer for solid-phase peptide synthesis (SPPS). The synthesis is performed on standard polystyrene-based resin in a flow reactor under low-pressure conditions. The usefulness of the present configuration of SPPS is exemplified on the synthesis of two octapeptide and one decapeptide amides.     

Formal synthesis of valienamine using ring-closing metathesis

(1R,2S,3S,4R)-2,3,4-Tri-O-benzyl-5-(benzyloxymethyl)-cyclohex-5-ene-1,2,3,4-tetrol, a precursor of the α-glucosidase inhibitor, valienamine, was synthesised in eight steps from tetrabenzyl glucose. The key steps were the selective protection of an open-chain diol, and the formation of the cyclohexene ring by ring-closing metathesis with the trisubstituted olefin of valienamine correctly in place.     

Stereoselective synthesis of bis-hydroxy-tetrahydrofurans using cross metathesis

A short asymmetric approach for the synthesis of bis-tetrahydrofuran units of various annonaceous acetogenins is described. The key steps of the synthesis are self-cross metathesis and Sharpless asymmetric dihydroxylation.     

Versatile solid-phase synthesis of s-arylisothioureas

Resin-bound amines 4a-m condense with di(benzotriazol-1-yl)methanimine 6 to give 1H-benzotriazole-1-carboximidamide resins 7a-m, which subsequently react with thiols 9a'-g' followed by cleavage affording nonprotected isothioureas 1aa'-mg' in high yields and with good purities. Analogous reactions with secondary amines activated with EtMgBr lead to guanidines 2a,b,e-g in moderate yields. Resin-bound isothioureas 1 are converted by acyl chlorides or carboxylic acids into acyl derivatives 12a-n in high yields and with good purities.     

Microwave-assisted solid-phase synthesis of peptoids

Microwave irradiation reduces the reaction time for the solid-phase synthesis of peptoids. Under these conditions, coupling of each residue requires only 1 min. The purity and yields of peptoids synthesized in this way are as good as or better than those achieved using standard methods. [reaction: see text]