Mixed-anhydride couplings

Kinetic resolution of the racemic aziridine-2-carboxylate 82 (Scheme 3.26) was reported by Iqbal and co-workers [74], When 82 was allowed to react with N-cinna-moyl-L-proline (81) under mixed anhydride coupling conditions, the N-acyl azir-idine 83 was obtained in optically pure form along with aziridine 84. 

The rationale behind the synthesis of phosphohomoserine-containing peptides [Hse(P)] is that this phosphorylated residue is inert to base-mediated (3-elimination and thereby may provide an interesting surrogate for the study of Ser(P)-based processes. In initial work, Boc-Hse[PO(OPh)2]-OH[21l was prepared by a simple four-step procedure but was found to be unsuitable for use in Boc-based solution synthesis due to extensive amine-mediated intramolecular dephosphorylation of the Hse[PO(OPh)2] residue during mixed anhydride coupling of its N-terminus. This side reaction was subsequently minimized through the use of Fmoc-Hse[PO(OPh)2]-OH in a Fmoc-based solid-phase approach in which the use of a large... 

The synthesis of a dipeptide dihydrothiazole by way of an imidate is shown in Scheme 13.[521 The Boc-protected amino acid 37 (in this case Val) was converted into the primary amide 38 by the mixed anhydride coupling with ammonia. The amide was then directly converted into the imidate 39 using triethyloxonium hexafluorophosphate which was subsequently condensed with H-Cys-OEt to provide the dihydrothiazole 40. 

Enantiomerically pure tripeptide aldehydes are typically synthesized by azide or mixed anhydride coupling of dipeptides to a-amino aldehydes or their semicarbazone derivatives. For example, Ac-Leu-Leu-Phe-H was synthesized by the azide coupling of Ac-Leu-Leu-OH with Phe-H semicarbazone, prepared by catalytic hydrogenation of Z-Phe-H semicarbazone. The tripeptide semicarbazone was deprotected with 37% HCHO/HC1 solution (Table 2)J5 C-terminal argininal, ornithinal, and lysinal peptides such as Z-Leu-Leu-Orn(Boc)-H and Z-Leu-Leu-Lys(Boc)-H were prepared by mixed anhydride coupling of Z-Leu-Leu-OH with Orn(Boc)-H semicarbazone or Lys(Boc)-H semicarbazone. 3 Z-Leu-Leu-Arg(N02)-H was prepared by mixed anhydride coupling of Z-Leu-Leu-OH with Arg(N02)-H semicarbazone trifluoroacetate, prepared from the reaction of TFA and Boc-Arg(N02)-H semicarbazone (Table 2) J31... 

Table 2 Synthesis of Tripeptide Aldehydes R1-Xaa3-Xaa2-Xaa1-H by Mixed Anhydride Coupling of Semicarbazones to Peptide Acids Followed by Semicarbazone Deprotection 31 ...

Mixed Anhydride Coupling. This very popiilar method, involving the use of alkyl chloroformates as reagents to make anhydrides v/ith acylamino acids or acylpeptides, has been reinvestigated. Determann, Heuer, Pfaender and Reinartz o have shown that exposinre of the mixed anhydride... 

Deaza-ll-oxahomoAMT (IV.62) was synthesized by Nair / a/. [Ill] by a modification of their synthesis of lO-deaza-lO-oxaAMT (IV.52). 1-Bromo-4-[4-(carbomethoxy)phenoxy]-2-butanone (IV.63) was converted successively to the azide (IV.64), the ketal (IV.65), and the acid (IV.66). Mixed anhydride coupling of (IV.66) and diethyl L-glutamate, followed by catalytic hydrogenation of the azido group, yielded the amine (IV.67), which, on addition to 2,4-diamino-6-chloro-5-nitropyrimidine and hydrolysis of the ketal group with acid, gave the key intermediate, (IV.68). Dithionite reduction led... 

A representative of this class of analogues was synthesized in 1974 by Nair et al. [136] in the form of isoaminopterin (isoAMT, (IV. 152)). The key intermediate in the synthesis was 2,4-diamino-6-[A -(4-carboxybenzyl)ami-nojpteridine (IV. 153). Mixed anhydride coupling of (IV. 153) and a-benzyl L-glutamate linked at the y-position to Merrifield resin, followed by alkaline hydrolysis, afforded (IV. 152) along with 2-3% of the corresponding 2-amino-... 

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