Resin Marshall

A recent study concerned the microwave-assisted parallel synthesis of di- and tri-substituted ureas utilizing dedicated 96-well plates in the CombiCHEM system [60], In a typical procedure, modification of the Marshall resin utilized was achieved by treatment with p-nitrophenyl chloroformate and N-methylmorpholine (NMM) in dichloromethane at low temperatures. The resulting resin was further modified by attaching various amines to obtain a set of polymer-bound carbamates (Scheme 7.48). 

An important reagent in fluorous chemistry is the fluorous version of the Marshall resin, dubbed FluoMar (4). This separation tag is reported to dissolve readily in dichloromethane, tetrahydrofuran, and ethyl acetate and can, as many other fluorous reagents, be monitored by traditional chromatographic and spectroscopic methods. The usefulness of (4) was demonstrated in a multistep parallel synthesis of a 3 X 3 array of diamides, where the final products were efficiently purified by F-SPE and cleaved from the FluoMar tag. Tentative results indicated that the homogeneous kinetics of the soluble (4) resulted in reactions that proceeded approximately three times faster than polymer-support bound reactions using standard Marshall resin. 

Sdieme 3.L Carbxoylic acid coupling to Marshall resin. 

Figure 3.2. Single-bead FTIR spectra of Marshall resin 1 (bottom) and resin 3 (top). Disappearance of the phenol—OH group (broad stretch at 3278cnr ) and the appearance of the carbonyl group (strong stretch at 1710 cm" ) indicate the coupling of the carboxylic acid 2 to the Marshall resin.

Irving, M.M. et al.. Repeated use of solid supports in combinatorial synthesis the case of Marshall resin recycling, J. Comb. Chem., 3, 407, 2001. 

State College of Franklin and Marshall College (1939-44) and published the first book for use in colleges (Synthetic Resins and Rubbers, John Wiley, 1943). 

The Marshall Unker [23] has been widely used to synthesize compounds that can be cleaved by primary and secondary amines to afford the corresponding amides. Marshall linker was used in the synthesis of three or more diversity-site hbraries because it allowed the addition of one more diversity element at the cleavage step. While the original reported linker [23] involved the oxidation of the Unker before cleavage, the efficient release of the resin-bound compounds using nucleophiles from the unoxidized linker has been reported [16, 24]. Similarly to the acid-labile linkers, the kinetics of the cleavage reaction and time required for this reaction directly affect the synthesis efficiency, purity and yield of the final products. A cleavage study was carried out on seven resin-bound thiophenol esters (34—40) on Marshall Unker with 3 amines (41-43) (Scheme 12.11 and Tab. 12.4). 

According to Marshall [23] and Beech [26], the oxidation of the thiophenol linker would increase the reaction rate. To study this effect, the linker in resin (35) was oxidized to sulfone/sulfoxide using mCPBA. Cleavage reaction of resin (35) -OX with n-butylamine went to completion in less than 4 min (Fig. 12.20), compared with 24 h needed for this resin under the same conditions without oxidation. The rate constant was determined to be 0.0179, which was a 580-fold increase compared with the unoxidized form. This result indicated that a linker oxidation was preferred for high yield when the products will not be affected by oxidation conditions. 

In the Liber Ignium of Marcus Graecus, which was probably translated into Latin from an Arabic source ca 1300, were several references to incendiaries used by Arabs. One of them ignis volatilis (flying fire) consisted of resin 1, sulfur 1 and saltpeter 2 parts, dissolved into a hollow reed or wood. This was in the opinion of Marshall 1 (Ref 11, p 17) an incendiary ( wild fire )... 

On the basis of all these experiments Kast [17] expressed the opinion that different colours are produced by differences in the size and shape of the crystals and not by impurities. This however appears to be incorrect. There seems every reason to believe that the grey and particularly the brown colour of mercury fulminate are produced by the presence of organic impurities, i.e. resinous product of the polymerization of fulminic acid (Marshall [18]). The white product, in Marshall s opinion, contains the same impurities, but in disguised form. 

Chiaratzit. A Get expl contg K chlorate petchlorate together with aromatic nitrocompds, resins and carbohydrates. Cooling agents were incorporated for mixts intended for use in coal mines, and die name was changed to Kohlen- or Wetter- Chloratzit Ref Marshall, Dict(1920), 21... 

Several syntheses of the peptide have been reported by solution methods (74-76). After the introduction of solid-phase peptide synthesis, Marshall and Merrifield conducted the first study of the synthesis of the peptide by using the new technique (77). A -Boc chemistry was used, and Merrifield resin was selected as the solid support. The side chain protections were as follows His, Arg, and Asp were protected by Bn groups Arg by a NO2 group. The Phe was esterified onto the resin in ethanol with the presence of 1 equivalent of triethylamine. The symmetric anhydride method was used for the coupling of the amino acids, and DCC was the coupling reagent. The following cycle of reactions was used to introduce each new residue (Table 7) ... 

Phenol-type resins 13-15 have also been used to prepare LH-RH, enkephalin and bradykinin peptide analogs. Peptides were successfully cleaved by ammonoly-sis (NH3 in MeOH-DMF or DMF, 5-18h) or aminolysis with protected amino acid or peptide esters bearing the free a-amino group [24, 25, 35]. Marshall s mercaptophenol resin (16) has been used to prepare libraries of piperazine-2-carboxamides (consisting of 22 different amines) and 6-carboxybenzopyran-4-ones. Cleavage was performed using an excess of appropriate amines in pyridine for 24 to 48 h [36, 37]. Tetrahydro-P-carboline-3-carboxamides have also been similarly synthesized and released [38]. 

The first reported solid-phase synthesis of head-to-tail cyclic peptides was based on the intramolecular aminolysis of resin-bound o-nitrophenyl esters. The cyclization proceeds concurrently to cleave the peptide from the resin, after deprotection and neutralization of the AT-terminal residue (Scheme 2A). Accordingly, Fridkin et al. [3] reported the preparation of several simple, unhindered cyclopeptides, such as cyc/o(Ala-Gly-Ala-Ala). Similarly, Flanigan and Marshall [4] obtained activation of the resin-bound peptide ester, after elongation of the peptide chain, by oxidation of the 4-(methyl-thio)phenyl (MTP) linker to a sulfonyl ester. Subsquent deblocking of the A-terminal residue and intramolecular condensation yielded the desired cyclic peptide. However, this method was found not to be suitable for the synthesis of longer and more hindered cyclic peptides [5]. 

The use of ion-exchange resins (Figure 4.41) offers an effective method for the preparation of high-quality whey protein products, referred to as whey protein isolates (WPI), containing 90-95% protein (see Marshall, 1982 Mulvihill, 1992). Although the functional properties of WPI are superior to those of WPCs on an equiprotein basis (due to lower levels of lipids, lactose and salts), their production is rather limited, due to higher production costs. 

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