Esteban Pombo-Villar

The aldol reaction of silyl enol ethers within a micro reactor

We have demonstrated the use of silyl enol ethers in the aldol reaction within a micro reactor. Quantitative conversion of the silyl enol ether to a beta-hydroxyketone was observed in a 20 min period compared to traditional batch systems, where quantitative yields were only obtained when extended reaction times of 24 h were employed.

Solution phase synthesis of β-peptides using micro reactors

Abstract The synthesis of β-peptides has been successfully performed using a borosilicate glass micro reactor, in which a network of channels has been produced using a photolithographic and wet etching method. The reagents were mobilised by electroosmotic flow (EOF). The micro reactor was initially evaluated using a carbodiimide coupling reaction to form a dipeptide. The methodology has been extended such that the peptides may also be produced via the pentafluorophenyl ester derivatives of amino acids. It was found that performing the pentafluorophenyl ester reactions in the micro reactor resulted in an increase in the reaction efficiency over the traditional batch method. We postulate that the enhancement in rate of reaction is an electrochemical phenomenon, due to the reaction being performed in an electric field, which is unique to micro reactor systems. It has also been demonstrated that selective deprotection of the resultant dipeptides can be achieved. This approach has been used in the synthesis of a tripeptide.

Enantiodivergent Synthesis of (R)- and (S)-Rolipram

Abstract : Both enantiomers of rolipram ( 1 ) have been prepared in large quantity from a commonintermediate rac- 3-(3’-cyclopentyloxy-4’-methoxy)phenyl-4-nitro butyric acid ( 6 ), which was resolved byway of the two readily separable diastereoisomeric amides obtained with ( S )-(−)-phenylethylamine. Reductionof the nitro group and intramolecular transamidation gave ( R )-(−)- 1 and ( S )-(+)- 1 , respectively. CD spectraof both enantiomers of rolipram are reported and discussed. Both enantiomers of rolipram presented the samepotency of inhibitory activity against recombinant cyclic-AMP-selective phosphodiesterase (PDE4) subtypes. Keywords: Rolipram, phosphodiesterase, circular dichroism (CD) spectra, enantiodivergent synthesis. Introduction Rolipram ( 1 ) is a compound with varied biologicalactivity. In particular, attention has been drawn to theemetic [1], antiinflammatory [2], immunosupressant [3],antidepressive [4,5], putative antiparkinsonian [6], andneuroprotective [7] effects. The best characterisedbiochemical activity of

1,4-Addition of enolates to α,β-unsaturated ketones within a micro reactor

We demonstrate the formation of a series of diketone enolates and their subsequent reaction with alpha,beta-unsaturated carbonyl compounds in order to prepare a variety of Michael adducts. In all cases, the conversions observed within a micro reactor were greater than those obtained in batch.

The regioselective preparation of 1,3-diketones

The regioselectivity of the acylation of Li enolates and silyl enol ethers is reported using acyl halides and acyl cyanides. We illustrate a simple method for the preparation of 1,3-diketones via the silyl enol ether in excellent yields, free from competing O-acylation and diacylation products.

Investigation of racemisation in peptide synthesis within a micro reactor

We demonstrate that peptides derived from alpha-amino acids may be prepared in a micro reactor. The peptides were prepared in 20 min with quantitative conversion, compared to batch reactions which require prolonged reaction times. We illustrate that by using dilute reagent concentrations and short reaction times, less racemisation is observed in micro reactions than in bulk reactions.

Synthesis of both D- and L-Fmoc-Abu[PO(OCH2CHCH2)2]-OH for solid phase phosphonopeptide synthesis

Abstract The Schollkopf bislactim ether asymmetric amino acid synthesis was coupled with a subsequent enzyme mediated ester hydrolysis to generate a practical synthesis of both D and L enantiomers of Fmoc-Abu[PO(OCH2CHCH2)2]-OH (6). With this building block phosphonopeptide isosteres of serine phosphopeptides are accessible by Fmoc-solid phase peptide synthesis.

The synthesis of peptides using micro reactors

We have demonstrated the first application of multi-step synthesis within a micro reactor and have shown that peptides may be prepared in quantitative yield in a period of 20 min, compared with batch reactions where only moderate yields (40–50%) were obtained in a 24 h period.

Asymmetric synthesis of a protected phosphonate isostere of phosphothreonine for solid-phase peptide synthesis

Abstract The first enantiospecific synthesis of 2 , a phosphonate isostere of phosphothreonine suitably protected for solid-phase peptide synthesis, has been achieved by coupling the highly face-selective conjugate addition of the lithium salt of Schollkopfs bislactim ether to E -prop-2-enyl-phosphonates with a selective enzymatic carboxylic ester hydrolysis. The absolute configuration of the products has been assigned from the X-ray structure of the adduct 9c .

Synthesis of (−)-δ-N-normethylskytanthine

Abstract (−)-δ-N-normethylskytanthine (1) has been synthesised from (1R,4R,1′S)-2-(phenylethyl)-2-azabicyclo[2.2.1]hept-5-ene (2) which undergoes a ketene-amino-Claisen rearrangement by reaction with dichloroketene to generate (1S,6R,1′S)-3-(phenylethyl)-5,5-dichloro-4-keto-3-azabicyclo[4.3.0]non-7-ene (3), which could be converted to 1 in eleven steps.