SPPS acid-labile resins

To overcome the chain fragmentation of sensitive peptides that contain /V-alkyl amino acids caused by acids as described vide supra, the following measures are recommended (1) in solution synthesis the exploitation of protecting groups removed by acids should be minimized (e.g., apply Fmoc chemistry, use acid-labile side-chain protection as little as possible) (2) if the peptides must be subjected to acid use low temperatures (—20 °C) for the shortest time possible (monitor the reaction by HPLC ) (3) in SPPS if the peptide does not contain functionalized side chains, prepare the peptide by Fmoc chemistry on Trt resin and remove the peptide from the resin with HFIP (see Section 10.1.1.2.2). If the peptides have functionalized side chains see point (1). 

Observations - Compatible with Boc/Bnz SPPS strategy. - More acid-labile than BHA resin. Chemical reaction Reductive methylation [142], N-alkylation, reduction with BHVTHF, cyclization with thiophosgene and triphosgene [143], ... 

The two major chemistries for SPPS involve the use of either base labile a-amino protecting group (Fmoc) or acid labile a-amino protecting group (Boc). Each method involves different side chain protecting group, and consequent cleavage/deprotection methods and resins (Table 1). 

The preparation of the decapeptide H-Val-Gln-Ala-Ile-Asp-Tyr-lle-Asn-Gly-OH (4) will be used as an example of pentafluorophenyl esters in SPPS. This is a good example to use since it contains normal, sterically hindered, and functionalized amino acids. All Fmoc-pentafluorophenyl esters were prepared by the method of Kisfaludy and Schon already described. Beaded polymethylacrylamide gel resin was used as the solid phase with fivefold excesses of the pentafluorophenyl esters dissolved in a minimum of DMF. The resin was first functionalized with a reference norleucine residue and then with an acid-labile linkage agent (5). 

Our group has initiated a project to search for milder methods for the preparation of organometallic peptide conjugates by SPPS. By using a base-labile linker to the resin and suitable side-chain protecting groups, we were able to prepare acid-sensitive organometallics amendable to SPPS techniques. As an example, enkephalin derivatives with the covalently bound Mo(allyl)(GO)2 moiety such as 17 were successfully prepared (Scheme 19). An attractive... 

Sorbus and Crataegus spp. Used for manuf. of sorbose, propylene glycol, ascorbic acid, resins, plasticisers and as antifreeze mixts. with glycerol or glycol. Tablet excipient, sweetening agent and humectant. Used in photometric detn. of Ru(K/) and Ru(F//7) in acid-base titration of borate. Needles -f- 5 or IHjO (EtOH) with sweet taste (60% of sucrose). Freely sol. H2O fairly sol. hot EtOH spar. sol. cold EtOH. Mp 97° (stable form), Mp 92° (labile form), Mp 110-112° (anhyd.). [a] +7° (borax), [a]j 4-31° (molybdate). pA 13.00 (60°). 

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