Enzymatic resolution of cyclic N-Boc protected β-aminoacids

Gram‐Scale Synthesis of the (−)‐Sparteine Surrogate and (−)‐Sparteine

“…We envisaged that the (−)‐sparteine surrogate would be derived from quinolizidine 3 through reduction and N‐methylation; the quinolizidine ring would be constructed from 2 by deprotection and conjugate addition of the amine to the α,β‐unsaturated nitrile, where we predicted that axial protonation of the intermediate nitrile anion would set the required cis relative stereochemistry for subsequent bispidine formation. Diastereoselective alkylation (for which there is precedent with other electrophiles) of piperidine ( R )‐ 1 obtained by enzymatic resolution would deliver nitrile 2 .…”

“…Using a known method,, racemic ester rac ‐ 1 was synthesised by pyridine hydrogenation and Boc protection in 90 % yield over 2 steps on a 30 g scale (no chromatography). Using conditions optimized from a related report, treatment of around 10 g batches of racemic 1 with lipase from Burkholderia cepacia , in a mixture of THF and phosphate buffer (pH 7.0) at 35 °C, resulted in the isolation (after simple filtration and aqueous work‐up, no chromatography) of acid ( S )‐ 6 (49 %, 98:2 er) and enantiopure ester ( R )‐ 1 (46 %, >99:1 er).…”

Gram‐Scale Synthesis of the (−)‐Sparteine Surrogate and (−)‐Sparteine

“…We envisaged that the (À)-sparteine surrogate would be derived from quinolizidine 3 through reduction and N-methylation;the quinolizidine ring would be constructed from 2 by deprotection and conjugate addition of the amine to the a,b-unsaturated nitrile,w here we predicted that axial protonation of the intermediate nitrile anion would set the required cis relative stereochemistry for subsequent bispidine formation. Diastereoselective alkylation (for which there is precedent with other electrophiles [19] )o fp iperidine (R)-1 obtained by enzymatic resolution [20] would deliver nitrile 2.…”

“…Using aknown method, [14b,c] racemic ester rac-1 was synthesised by pyridine hydrogenation and Boc protection in 90 %y ield over 2s teps on a3 0g scale (no chromatography). Using conditions optimized from arelated report, [20] treatment of around 10 gbatches of racemic 1 with lipase from Burkholderia cepacia,i namixture of THF and phosphate buffer (pH 7.0) at 35 8 8C, resulted in the isolation (after simple filtration and aqueous work-up,n oc hromatog-raphy) of acid (S)-6 (49 %, 98:2 er) and enantiopure ester (R)-1 (46 %, > 99:1 er).…”

A New Approach to the Synthesis of β-Amino Acids

“…[2][3][4] Therefore, the application of b-peptides as antibiotics or enzyme inhibitors has received considerable attention in recent years. [5][6][7] Most methods, described for the synthesis of b-amino acids, 1,8 have been successfully applied to the synthesis of bsubstituted or a,b-disubstituted 2 b-amino acid derivatives. a-Monosubstituted b-amino acids are less common because the monoalkylation of enolate derivatives is difficult to control and dialkylation is likely to occur under the strong reaction conditions required.…”