Protected .beta.- and .gamma.-aspartic and -glutamic acid fluorides

Synthetic Routes to a Constrained Ring Analog of Didemnin B

“…Much time was spent investigating suitable conditions for the esterification of the HIP alcohol 4 with the cyclohexane amino acid 16d (diastereomeric mixturesdetermined by NMR analysis) . The best conditions were obtained using Carpino's acid fluoride activation. , Initially, the alkoxide of the HIP alcohol was added to the acid fluoride 20 of 2-methoxy-3-cyclohexenecarboxylic acid ( 10 ) to obtain the ester 18 in 75% yield (Scheme ). To convert the alcohol to its corrresponding alkoxide, several bases were used, but sodium hexamethyldisilazane proved to be the best.…”

Amino acid fluorides: viable tools for synthesis of peptides, peptidomimetics and enantiopure heterocycles

“…All the proteinogenic amino acids, except cysteine (Cys), Arg, and His were converted to their corresponding acid uorides. The acid sensitive tert-butyl ethers of serine (Ser), threonine (Thr), and tyrosine (Tyr), 3-Boc-Lysine (Lys), N-Trt derivatives of Asn, Gln 30 were also converted to their respective acid uorides with good yields. Fmoc-Trp-F (Trp ¼ tryptophan) could be obtained even without the side chain protection.…”

“…6). 30 Thus, all the four isomers of acid uorides from Boc/Cbz-Asp and Glu acid esters were made available.…”

“…Thus, the acid uorides of the Fmoc, Boc, Cbz-amino acids as well as mild acid sensitive t Bu, benzyl (Bn), and trityl (Trt) moiety based side chain protected amino acids could be easily accessed. 29,30 Despite all these advantages, the reactivity of the acid uorides was still very much retained at the level of acid chlorides. Within a short period of time, many more classes of acid uorides were prepared from non-proteinogenic amino acids such as a,a-disubstituted ones {a-aminoisobutyric acid (Aib), isovaline (Iva), a-ethylalanine, [31][32][33] a,a-diethylglycine (Deg), a,a-dibutylglycine and 1-aminocyclopentane-1-carboxylic acid (Ac 5 c), 1-aminocyclohexane-1-carboxylic acid (Ac 6 c), 1aminocycloheptane-1-carboxylic acid (Ac 7 c)}, 34 N-methylated (NMe) amino acids including NMe alanine (Ala), NMe leucine (Leu), NMe valine (Val), sarcosine (Sar or N-methylglycine) 34 and N-methylated C a,a -dimethylamino acids such as NMeAib}.…”

Synthesis of 1,1-Dioxobenzo[b]thiophene-2-ylmethyloxycarbonyl (Bsmoc) Protected N-Methyl Amino Acids by Reduction of Bsmoc-5-Oxazolidinones and Their Use in Peptide Synthesis

“…The synthesis of peptides employing acid fluorides is well known in peptide chemistry. In contrast to the corresponding acid chlorides, the acid fluorides have greater stability and are suitable for carrying out reactions bearing acid labile groups such as t Bu, Boc or trityl groups in the side chain [21]. Acid fluorides have been shown to accomplish difficult esterifications such as between a weakly nucleophilic secondary alcohol and a cyclohexyl amino acid, where other methods of activation such as DCC/DMAP, mixed anhydride, BOP-Cl or BOP have failed [22].…”