BOC-L-Aspartic acid

Y. Yamamoto and co-workers used L-aspartic acid 4-methyl ester (108) as their starting material for the synthesis of preussin [64]. The ester was transformed in nine steps to the TBDPS-protected aminoalcohol 109 (Scheme 28). Allylation of the iST-Boc-protected amine using allyl bromide... 

A comparative study of the (3-menthyl (Men) ester of aspartic acid with other cycloalkyl esters showed that this ester is less susceptible to base-catalyzed aspartimide formation than the cPe, Cy, cHp, or cOc derivatives. Boc-Asp(OMen)-OH is prepared by esterification of Boc-Asp-OBzl with menth-l-ol by the DCC/DMAP procedure (see Section 2.2.2.5), followed by hydrogenolysis. The menthyl ester is stable to TFA treatment and is cleaved by HF or 1M TfOH/thioanisole in TFA within 60 min in an ice bath. For some syntheses, dependent on the peptide sequence, an excess (1.4 equiv) of Boc-Asp(OMen)-OSu has to be used, presumably owing to the bulkiness of the protected side chain. For the cleavage of the Men group, in some cases diphenyl sulfide (20 equiv) has to be added as a scavenger to the 1M TfOH/thioanisole/TFA mixture to facilitate its removal. However, acid-catalyzed aspartimide formation cannot be fully prevented. 

Higher yields of L-[amide- N]asparagine have been obtained by a rapid, nonenzymatic method. The free -carboxyl group of L-a-N-f-Boc-a-t-Bu-aspartic acid is activated with N-hydroxysuccinimide to yield L-a-N-f-Boc-a-t-Bu- -N-hydroxysuccinimidyl aspartic ester, which is re-fiuxed for 10 min with [ N]anunonia. Hydrolysis for 1 min in IN HCl yields up to 30-40% of L-[ami fe- N]asparagine, which is then purified by cation-exchange column chromatography (31). 

Using chiral thiols for derivative formation, isoindoles are formed from amino acids and amino alcohols. BOC-L-cysteine, N-acetyl-L-cysteine, Af-acetyl-D-penicillamine [340] and l-thio-jS-D-glucose [341] have been shown to be suitable reagents which allow the separation of most amino acid enantiomers using reversed phase column chromatography. Thus, OPA/N-acetyl-L-cysteine has been used among others for the separation of enantiomers of aspartate [342], baclofen [343], norepinephrine, dopa [344] and lombricine [345]. 

Carboxyl group protection. The a -esters of aspartic and glutamic acids are formed readily using the DCC method, after the geminal functionalities are sequestered (by reaction with EtiB). The acid can be regenerated under conditions lO.l M BU4NF) that do not affect an N-Boc group. 

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