Pentafluorophenyl esters

Fig. 8. Rephcation. The amino adenosine X and the pentafluorophenyl ester Y form a hydrogen-bonded dimer XY, prior to reaction between the amine and the activated ester groups (shown in the circle). The reaction product is a <7 -amide conformer cis-Z that isomeri2es to the more stable trans- acnide Z. The rephcative process is cataly2ed by the reaction product Z (also referred to as the template). First, a termolecular complex XYZ is formed from X, Y, and Z.

NaBH/" or with HSCH2CH2CH2SH (DIPEA, CH2CI2, 94% yield). " The use of Zn (AcOH, AC2O, THE, 80-87% yield) cleaves the Dts group in the presence of the extremely sensitive pentafluorophenyl ester. ... 

A key step in the synthesis of 13-membered meta ansa and 14-membered para ansa peptide alkaloids involves catalytic hydrogenolysis of carbobenzyl-oxypeptide pentafluorophenyl esters. The most suitable solvent is dioxane with addition of a catalytic amount of pyrrolidinopyridine and 2% ethanol. Temperature should not exceed 90°C. The authors believe that after deblocking, the amino function remains on the surface until ring formation with the activated carboxylic function is accomplished (/5/). 

To find the most efficient selectors in the library, blue and red dye-labeled enantiomeric probe molecules 6 and 7 were prepared by linking pentafluorophenyl esters of L- and D-proline with Disperse Blue 3 and Disperse Red 1, respectively, through an isophthaloyl (shown in structures 6 and 7) or a succinyl moiety. Eor detection, a... 

S.P. solid-phase technique L.P. liquid-phase technique OPTcp pentachlorophenyl ester TEEP tetraethyl pyrophosphit OTCp trichlorophenyl ester ONp p-nitrophenyl ester ONSu N-hydroxysuccinimido ester OPFp pentafluorophenyl ester OQu 8-hydroxyquinyl ester OPy 3-hydroxy-pyridyl ester ODnp 2,4-dinitrophenyl ester DCC dicyclohexylcarbodiimide HOBn 3-hydroxy-4-oxo-3,4-dihydro-l,2,3-benzotriazin Opi JV-hy-droxypiperidine EEDQ 2-ethoxy-l-ethoxycarbonyl-l,2-dihydroquinoline Tos p-toluenesulfonyl PTC propanetricarboxylic acid OBu tm-butyl ester Nva norvaline Aha aminohexanoic acid Om ornithine... 

The pentacyclic core 15 of more complicated manzamines was built up by a final ring closure of the thirteen-membered ring lactam in 50% yield. The tetracyclic system and the alkyne unit of the reactant 13 supposed a pre-orientation, an intermediately formed activated pentafluorophenyl ester 14 led to the desired... 

P 13] The micro channels were primed with anhydrous DMF to remove air and moisture before carrying out the reaction [5, 88]. A 50 pi volume of a solution of the pentafluorophenyl ester of Fmoc-y9-alanine (0.1 M) in anhydrous DMF was placed in one reservoir of a micro chip, driven by electroosmotic flow (Figure 4.42). 

OS 25] [R 4] [P 17] For dipeptide formation from the pentafluorophenyl ester of (J )-2-phenylbutyric acid and (S)-a-methylbenzylamine an extent of racemization of 4.2% was found [86]. At higher concentration (0.5 instead of 0.1 M), a higher degree of racemization was found (7.8%). This experiment also served to demonstrate monitoring of the racemization of a simple carboxylic acid used in peptide synthesis. 

Otvos et al. (27) adopted the Fmoc-pentafluorophenyl ester methodology and have applied O-deacetylated glycopeptide intermediates (170 and 171) for solid-phase synthesis of glycopeptides. In this way, the A-glycopep-tide (26) H-Gly-L-Lys-L-Ala-L-Tyr-L-Thr-L-Ile-L-Phe-L-... 

L Kisfaludy, M Low, O Nyeki, T Szirtes, I Schon. Utilization of pentafluorophenyl esters in peptide synthesis (DCC-XPhOH 1 3 complex). Liebigs Ann Chem 1421, 1973. 

FIGURE 7.13 Preparation of an Fmoc-amino-acid pentafluorophenyl ester by reaction of the acid with pentafluorophenyl trifluoroacetate in the presence of pyridine.32... 

M Green, J Berman. Preparation of pentafluorophenyl esters of Fmoc protected amino acids with pentafluorophenyl trifluoroacetate. Tetrahedron Lett 31, 5851, 1990. 

M Meldal, B Klaus. Pentafluorophenyl esters for temporary carboxyl group protection in solid phase synthesis of A-linked glycopeptides. Tetrahedron Lett 48, 6987, 1990. 

M Meldal, KJ Jense. Pentafluorophenyl esters for temporary protection of the a-carboxy group in solid phase glycopeptide synthesis. J Chem Soc Chem Commun 483, 1990. 

YH Wang, JC Xu. One-pot liquid-phase synthesis of DSIP and 5-DSIP using fluoren-9-ylmethoxycarbonyl-protected amino acid pentafluorophenyl esters. (3-diethylami-nopropane-2-ol) Synthesis 845, 1990. 

Because of the strong nucleophilicity of the amino group, weak activation of the carboxylic acid is often sufficient to effect macrocyclization. For example, the pentacyclic core of the manzamines was constructed by connection of a secondary amine and a pentafluorophenyl ester [36]. 

If the terminal Hmb-substituted amino acid is glycine then the subsequent residue, even if p-branched, may be coupled through its pentafluorophenyl ester or similar. 151 For any other Hmb amino acid the subsequent residue must be coupled as its symmetric anhydride in dichloromethane. The only limitation to the inclusion of Hmb into a sequence is that 3-branched amino acids will not quantitatively N-acylate a terminal Hmb residue, except glycine, on a practical timescale. 

The Se-(4-methoxybenzyl)selenocysteine is obtained by reduction of selenocystine with NaBH4 and in situ reaction with 4-methoxybenzyl chloride. 7 The optimized procedure of Tanaka and Soda 32 is preferentially used for the synthesis of the starting selenocystine, which involves reaction of (1-chloroalanine with a 2.3-fold excess of disodium diselenide in aqueous solution at pH 9. Alternatively, the significantly less selenium demanding synthesis of Stocking et al. 33 is used for the preparation of expensive 77Se-selenocystine, this consists of the reaction of methyl (2R)-2-[(/ert-butoxycarbonyl)amino]-3-iodopropanoate with equivalent amounts of dilithium diselenide. Subsequent conversion of SeC(Mob) into the M -Fmoc derivative 7 and finally into the pentafluorophenyl ester 10 is performed following standard procedures. 

V -(Fluoren-9-ylmethoxycarbonyl)-0-[0-(3,4,6-tri-0-acetyl-2-azido-2-deoxy-a-D-galactopyranosyl)-(1 3)-(4,6-di-0-acetyl-2-azido-2-deoxy-a-D-galactopyranosyl)]-L-threonine Pentafluorophenyl Ester... 

V -(Fluoren-9-yhnethoxycarbonyl)-0-[4,6-di-0-acetyl-2-0-benzoyl-3-0-(2,3,4,6-tetra-0-acetyl-a-man-nopyranosyl)-a-D-mannopyranosyl]-/ra s-L-hydroxyproline Pentafluorophenyl Ester (99) [347 ... 

Due to the low reactivity of the nitrogen, incorporation of the pyroglutamic acid into endo-positions by stepwise chain elongation is difficult (see reft49 and refs cited therein). It may be achieved using suitably protected aminoacyl-pyroglutamic acid derivatives as dipeptide synthons. These are accessible in satisfactory yields, e.g. by acylation of pGlu-OBzl with N-protected amino acid pentafluorophenyl esters in the presence of NaH or LiHMDS. 49 ... 

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