1 - propyl-3-ethylcarbodiimide hydrochloride

The only example to date of direct addition of a carbohydrate residue to a peptide chain was the coupling72 of 2-acetamido-4-0-(2-acetamido-2-deoxy-/ -D-glucopyranosyl)-2-deoxy-/ -D-glucopyranosylamine (37) with sodium poly(L-aspartate) in the presence of 3-(3-dimethylamino-propyl)-l-ethylcarbodiimide hydrochloride.73 The proportion of sugar residues introduced into the peptide chain was limited. 

The following procedure describes the preparation and analysis of the (R)-a-methylbenzylamide of (R)-a-methylbenzenepropanoic add. A flame-dried, 10-mL, round-bottomed flask equipped with a Teflon-coated magnetic stirring bar and a rubber septum is charged with 25 mg (0.15 mmol) of (R)-a-methylbenzenepropanoic acid, 31 mg (0.23 mmol) of 1-hydroxybenzotriazole hydrate, 44 mg (0.23 mmol) of 1-(3-dimethylamino)propyl-3-ethylcarbodiimide hydrochloride, and 0.50 mL of anhydrous N,N-dimethylformamide. This mixture is stirred at 23°C for 10 min, then cooled to 0°C in an ice-water bath. To the cooled solution, 24 pL (0.19 mmol) of R-(+)-a-methylbenzylamine and 86 pL (0.62 mmol) of triethylamine are added. Within 1 min, a fine white precipitate appears. The mixture is stirred for 1 hr at 0°C, then warmed to 23°C. After stirring for 20 hr at 23°C, the mixture is transferred to a 30-mL separatory funnel with 10 mL of dichloromethane. The product solution is extracted, sequentially, with four 10-mL portions of 1 N aqueous hydrochloric acid solution, 10 mL of saturated... 

Dimethylamino)propyl-3-ethylcarbodiimide hydrochloride Carbodiimide, [3-(dimethylamino)propyl]ethyl-, monohydrochloride (8) 1,3-Propanediamine, N -(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride (9) (25952-53-8) N.N-Dimethylformamide cancer suspect agent Formamide, N,N-dimethyl- (8,9) (68-12-2)... 

A,- 3-(Diiiietliylaiiiiiio)propyll-Ar-ethylcarbodiimide Hydrochloride/ 7-Aza-l,2,3-benzotriazol-l-ol Activation... 

Fig. 8. Nicolaou s total synthesis ketalization and homologation of the carboxylic acid side chain. TFA = trifluoroacetic acid, EDC = l-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride, DMAP = 4-(/V,/ /-dimethylamino)pyridine.

Threading such an oriented ring onto a dumbbell end capped with two different stoppers will give rise to two diastereoisomers, as shown schematically in Figure 2.12c. Such rotaxanes were actually described by Isnin and Kaifer, and were characterized as CDX-positional isomers (Figure 2.17).41 Thus reaction of ferrocenyl derivative 40 (1 equiv) with 2 equiv of a-CDX, and potassium 5-amino-2-naphthalene sulfonate 41 in water, in the presence of EDC (EDC = l-(3-[dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride) as a catalyst, afforded a mixture of diastereoisomeric [2]-rotaxanes 42a and 42b in 15% yield and 6 4 ratio. 

A solution of the Step 10 product (1.018mmol) in 10.0ml DMF was treated with T/.A-diisopropylethylamine (5.167 mmol), /V-hydroxybcnzolriazole (1.241 mmol), and l-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride (1.232 mmol). After stirring 30 minutes at ambient temperature, the mixture became homogeneous and was then treated with 4-(Cbz-amidino)-benzylamine (1.126 mmol) and stirred an additional 18 hours. The solution was then diluted with 50 ml EtOAc, washed once with 25 ml apiece 5% citric acid, saturated NaHC03 solution and brine, dried, and concentrated. The residue was purified by trituration with diethyl ether and the product isolated as a white solid. 

Subsequent coupling of the tripeptide 23 in the presence of EDC/FIOAt ([(l-(3-dimethylamino-propyl)-3-ethylcarbodiimide-hydrochloride]/[7-aza-1-hydroxy-17/-benzotriazole]) yielded the corre-... 

To 18 ml DMSO was added l-(3-aminopropyl)-2-pyrrolidinone (6.7 mmol), the product from Step 3 (4.79 mmol), l-[3-dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride (5.99 mmol) and 1-hydroxyIbenzotriazole hydrate (7.2 mmol), and the reaction stirred overnight at ambient temperature. The crude products were diluted with EtOAc, rinsed with saturated NH4CI solution, and washed twice with water. The organic layer was dried, concentrated, purified by chromatography on silica gel using CH2Cl2/methyl alcohol, 9 1, and the product isolated in 95% yield. 

The levulinoyl esters are prepared from the free hydroxyl group by treatment of levulinic acid with DCC [255,256] or l-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) [257] in the presence of DMAP (O Scheme 38). Additionally, 3 - and 5 -0-levulinyl protected derivatives of 2 -deoxy nucleosides have been prepared by regioselective enzymatic acylation using a variety of lipases and acetonoxime levulinate as acylating agent [258]. In contrast to other ester substituents, the 0-levulinoyl group is far less prone to migration [259]. 

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