Sarcosine amide

Experimental support for the above mechanistic interpretation comes from the work of Bizzozero and Zweifel (9) who have studied the behavior of N-acetyl-j -phenyl al anyl- -prol i ne amide ( ) and N-acetyl-L-phenylalanyl-sarcosine amide (32) toward enzymic hydrolysis with o-chymotrypsin. These two dipeptides were found to be good competitive inhibitors with a specific substrate (Ac-Phe-0CH3 (33)) but no hydrolysis was observed. These two peptides thus form an enzyme-substrate complex and the reason for their nonreactivity has to be sought in the nature of the enzyme-substrate interactions occurring during the subsequent bond-change steps. 

Two additional routes gave low yields12 of l,2-benzothiazine-3-carbox-amide 20 (sudoxicam). Thus, (V-carbobenzyloxysarcosine was converted to the sarcosine amide 18. Formation of sulfonamide 19 using the sulfonyl chloride 17 followed by cyclization produced the 3-carboxamide 20 (Scheme 1). 

Amides, coconut oil. See Cocamide Amides, coconut oil, with sarcosine, ammonium salts. See Ammonium cocoyl sarcosinate Amides, coconut oil, with sarcosine, sodium salts. See Sodium cocoyl sarcosinate Amides, corn-oil, N-[2-[N-(2-hydroxyethyl)-N-(2-carboxyethyl) amino] ethyl]-, sodium salts. 

One of the closest approaches so far developed is by Bizzozero and Zweifel (118) who tried to explain in 1975 why a proline residue involved in a peptide bond is resistant to a-chymotrypsin cleavage. The objective was to find if the unreactivity of the peptide bond results from an unfavorable interaction of the methylene groups of the proline ring with the enzyme active site or whether the steric hindrance occurs upon formation of the enzyme-substrate complex or during the subsequent bond-change steps, and whether this steric hindrance is related to the ring structure of proline or simply to substitution of the amido nitrogen. In order to answer these questions, the dipeptides N-acetyl-L-phenylalanyl-L-proline amide and iV-acetyl-L-phenyl-alanyl-sarcosine amide were synthesized and their behavior as model substrates of a-chymotrypsin studied. 

Almost all actinomycins have the same chromophore, a planar phenoxa2inone dicarboxyUc acid called actinocin. In dactinomycin, the stmcture of which is shown in Figure 12, the two pendent pentapeptide lactones are identical, but in other actinomycins these lactones may be different. In other actinomycins the first amino acid, amide linked with actinocin, is usually L-threonine, as in dactinomycin the second position is sometimes D-aHo-isoleucine instead of D-valine the third position may be sarcosine or oxoproline the fourth position is sarcosine and the fifth position is sometimes /V-methyl isoleucine instead of /V-methylvaline. The lactone ring is always present. 

Amino-4,6-dimethyl-3-oxo-3//-phenoxazine-l,9-dicarboxylic acid also named actinocin is the chromophor of the red antineoplastic chromopeptide aetinomyein D (formula A). Two cyclopenta-peptide lactone rings (amino acids L-threonine, D-valine, L-proline, sarcosine, and 7V-methyl-L-valine) are attached to the carboxy carbons of actinocin by two amide bonds involving the amino groups of threonine. 

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

Not surprisingly, the diacid 13 and its diamide are waterlogged with 2-4 molecules of HzO from which they are difficult to liberate. Binding experiments in CHC13, a non-competing solvent, revealed that stoichiometric complexes, e.g. 48 were formed with diketopiperazines 40) (Kh 104) and amides such as malonamide. With structures of inadequate hydrogen bonding capacity, such as sarcosine anhydride, com-plexation does not occur. 

The earliest report on such lactim ether formation was from Sammes [72JCS(P1)2494], who converted piperazine-2,5-dione to 2,5-diethoxy-3,6-dihydropyrazine (173) with an excess of triethyloxonium fluoroborate. Subsequently, Rajappa and Advani (73T1299) converted proline-based piperazine-2,5-diones into the corresponding monolactim ethers. The starting material was a piperazinedione in which one of the amino acid units was the secondary amino acid proline, and the other a primary amino acid. This naturally led to the regiospecific formation of a monolactim ether (169) (on O-alkylation) from the secondary amide, whereas the tertiary amide remained intact. This was later extended to piperazine-2,5-diones in which the secondary amino acid was sarcosine [74JCS(P 1)2122], leading to the monolactim ethers (170). 

As shown in Table 9 acetylation of polysarcosine destroys the effect and the addition of such a polymer to phenylalanine dimethyl amide only slightly accelerates the process. (5) No effect is observed when sarcosine NCA is block-polymerised in poly-D.L-phenylalanine. 

Salt is a by-product. Due to the stability of the amide group, the free acid can be formed and separated from the reaction mixture to give a salt-free product. The stability of the amide group also allows sarcosinates to be used in a wider range of chemical environments than isethionates (see below). Sarcosinates are stable under moderately acidic conditions but will degrade at low pH or with elevated temperature. The surfactants are moderately soluble at high pH and the sodium salts are supplied as a 30% solution. 

Peptoid helices are detected in structure-supporting solvents even in relatively short oligomers. Because intramolecular C=0- H-N H-bond formation cannot be the driving force for peptoid secondary structure, the steric influence of the bulky and chiral side chain is likely to provide the required constraint. Interactions between side-chain groups, and between side chains and the carbonyls of the main-chain amides, may add stability to the ordered secondary structure. However, for very short oligomers (34) or peptoids based on N-substituted a-amino acids with a small side chain (35), such as Nala (also termed sarcosine, Sar, 9), complex mixtures of conformers associated with either cis or trans tertiary amide groups have been detected. In addition to the classic CD technique, the contribution of other spectroscopies, such as pulsed ESR (36), may be of value for the 3-D structural validation of peptoid molecules. 

Copolymers of L-proline and sarcosine have been prepared by Fasman and Blout (1961). These were found to exist in two forms, analogous to poly-L-proline. Form I, which is obtained directly from the copolymerization mixture showed anomalous optical rotatory dispersion and relatively low viscosity. On dissolving form I in 2-chloroethanol, form II is obtained which exhibits normal optical rotatory dispersion and relatively high viscosity. Fasman and Blout have suggested that the transition, form I —> form II, involves a conversion of the structure from ds- amide bonds to fmns-amide bonds. 

The C33-C37-unit of (-F)-calyculin A (a marine natural product) is an amide derived from 5-0-methyl-4-deoxy-4-dimethylamino-D-ribonic acid that has been prepared by Evans and co-workers [250]. A-Protection of sarcosine as benzyl carbamate affords acid 118 which is activated and used to iV-acylate the (5)-phenylalanine-derived oxazolidinone. This gives 119 that is methoxymethylated diastereoselectively (98 2) to give 120. Reductive removal of the chiral auxiliary, followed by Swem oxidation forms aldehyde 121 with little racemization if... 

Sarcosinate specialty surfactants are currently made by acylation of naturally occurring amino acids with an acyl chloride. The use of a secondary amide for amidocarbonylation has been reported to give poor yields of amido acid since the corresponding oxazolone intermediate cannot be formed. Lin has demonstrated, however, that the amidocarbonylation of A-methylamine gives excellent yields of A-acyl sarcosinates (eq. (11)) when conducted in the presence of dicobalt octacarbonyl at 120°C with CO/H2 = 3 1. Sarcosinate selectivity is typically 95 %, at 92 % A-methylamine conversion. 

Substitutions for Gly" are well tolerated, particularly in the tetrapeptide derivatives. Sarcosine (NMeGly, Sar) at position 4 in tetrapeptide derivatives enhances opioid activity in antinociceptive assays (879). Substitution of Phe in position 4 of the tetrapeptide amide yields the dermorphin/enkephalin hybrid TAPP (T -D-Ala-Phe-PheNHa) (831), which is a potent p-selective agonist (see Table 7.18). This peptide can also be considered an analog of en-domorphin-2, although TAPP was synthesized several years before the discovery of the endo-... 

As shown above (Scheme 4), this strategy has been employed for the synthesis of thiohydantoins 18, as well as for the synthesis of amides and ureas 45 (Scheme 15) [10, 44]. Glycine and potassium sarcosinate were chosen as the quenching agents for their bifunctional nature. The amine end of the amino acid quenches the excess electrophile and the carboxylic acid functionality renders the amino acid bound impurity soluble in aqueous media. 

Preparation of 45 [44] The amides and sulfonamides were synthesized by treating N-benzyhnethylamine 44 (0.302 g, 2.5 mmol) with an acid chloride or sulfonyl chloride (3.5 mmol) in DMF (2 mL) containing triethylamine (5 mmol). The reaction mixture was stirred for 4 h and then quenched with potassium sarcosinate (0.127 g, 1 mmol) and water (6 mL). The product 45 was isolated by filtration in the case of sohds, and extracted into ethyl acetate (10 mL) in the case of oils. In the latter case, evaporation of the solvent from the organic extract gave fhe product. 

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