Benzyloxy-carbonyl

A much more elaborate synthesis of 4-aryl-2-(benzyloxy)carbonyl-3-hydroxy tetrahydrofurans 88 from aryl epoxides requires the use of benzyl diazoacetate. This methodology can now be extended to a highly stereoselective synthesis of chiral tetrahydrofurans starting from optically active epoxides. The mechanism is believed to involve a Williamson-type cyclization as illustrated below <00TL8059>. 

A protected serine hydrazide was condensed by the azide method to an S-protected tripeptide H-Asn-Cys-Tyr-NHNH-Cbz to form a protected tetrapeptide Boc-Ser-Asn-Cys-Tyr-NHNH-Cbz 1.02 g of N-rerr-butoxycarbonylserine hydrazide (Boc-Ser-NH-NHj) >n DMF containing HCI in dioxane was mixed at -20 °C with reri-butyl nitrite. This mixture containing the azide Boc-Ser-Nj was neutralized with triethylamine, and a solution of 3.4 g asparaginyl-S-(ethylcarbamoyl)cysteinyl-tyrosinyl 2-(benzyloxy-carbonyl)hydrazide trifluoroacetate was added. After 72 hours at 4 °C a simple work-up procedure and precipitation from methanol-petroleum ether yielded 3 g of impure protected retrapeptide hydrazide. It... 

Fig. 6.15 P reparative separation of the enantiomers of (a) a chiral c/s-diamino-cyclohexane derivative on Chiralpak AD (column 50 x 500 mm, injection 500 mg, flow rate 150 mL min ), and of (b) 0,0-dimethyl-2-benzyloxy-carbonyl-N-ethylamino-phosphate on Chiralcel OJ (column 100 x 500 mm, mobile phase heptane/ethanol 40/60, injection 4 g, flow rate 140 mL min ).

NH-NH-CO-0-CHz-C6H5 ch3 H Cl Ethanol Riickfl. 2- (2-Benzyloxy carbonyl-hydra- 95 196 402... 

Spedfic monomers incorporating functional groups in a protected form, for example, protected functional cydic carbonates or l-GIu-OCA or (3S)-3- 2-[(benzyloxy)carbonyl]ethyl -... 

A similar series of reactions was performed by Paulsen and Hdlck141 for the preparation of the T-antigenic, unprotected, amino acid-disaccha-rides 200 and 201, starting from the 4,6-0-benzylidene-N-(benzyloxy-carbonyl) benzyl esters 198 and 199, respectively, by condensation with 110 in the presence of mercury dicyanide-mercury dichloride and molecular sieves 4A, and deprotection of the product. Sinay and co-workers148 also reported the synthesis of hexa-O-acetyl derivatives of 200 and 201 by application of the sequence of azido-nitration-bromination. 

N-(benzyloxycarbonyl)-, benzyl ester 2,3,4,6-tetra-O-benzy 1-N- (benzyloxy carbonyl) - + 75 MeOH 141... 

L-alanylglycyl-L-cysteinyl-L-lysyl-L-asparaginyl-L-phenylalanyl-L-phenylalanyl-L-tryptophanyl-L-lysyl-L-threonyl-L-threonyl-L-cysteine 6-0-benzoyl-N-(benzyloxycarbonyl) methylamide 4,6-0-benzylidene-N-benzylidene-N-(benzyloxycarbonyl) methylamide N- (benzyloxy carbonyl) -N-(benzyloxycarbonyl)-, amide N-(benzyloxycarbonyl)-, hydrazide N-(benzyloxycarbonyl)-, methylamide N-(benzyloxycarbonyl)-, methyl ester N-(benzyloxycarbonyl)-L-alanyl-L-alanine methyl ester N-(benzyloxycarbonyl)-L-alanylglycine ethyl ester N-(benzyloxycarbonyl)glycyl-L-alanine methyl ester 3,4,6-tri-0-acetyl-2-amino-2-deoxy-N-(benzyloxycarbonyl)-, benzyl ester, hydrochloride... 

The syntheses of these three compounds share a common route as described by Brickner et al. [53] and Barbachyn et al. [54]. Namely, the coupling reaction of 3,4-difluoronitrobenzene (82) with piperazine, morpholine, or thiomorpholine to yield the corresponding 4-substituted 3-fluoro-nitrobenzene (83), which upon reduction gives rise to the aniline derivative (84). Carbobenzoxy protection of the active nitrogen of 84 using benzyloxy-carbonyl chloride (CbzCl) results in the formation of carbamates 85a and 85b. Treatment of 85a,b with n-BuLi and (i -glycidyl butyrate yields a 5-(R)-... 

LA Carpino, EME Mansour, D Sadat-Aalaee. lerl-WutoxycarbonyI and benzyloxy-carbonyl amino acid fluorides. New, stable rapid-acting acylating agents for peptide synthesis. J Org Chem 56, 2611, 1991. 

A- [(Acy loxy )methyl] derivatization was also examined for its potential to improve the biological stability of peptides. For example, the peptide-like model A-[(benzyloxy )carbonyl]glycine benzylamide (8.171, R = H) was de-rivatized to a few N-/Yacyloxy)methyl] derivatives whose chemical and enzymatic hydrolysis was investigated [225], The results compiled in Table 8.13 indicate a fast chemical hydrolysis, the mechanism of which is depicted as Reaction b in Fig. 8.21. Enzymatic hydrolysis also occurs in human plasma, resulting in short half-lives, with the exception of the pivaloyl analogue. 

The initial medicinal chemistry route to the azabicyclo[3.3.0]octane-3-carboxylic acid produced the azabicyclo system in a diastereoselective but racemic manner, and required a classical resolution to achieve enantioenriched material (Teetz et al., 1984a, b 1988). Reaction of (R)-methyl 2-acetamido-3-chloropropanoate (43) and 1-cyclopentenylpyrrolidine (44) in DMF followed by an aqueous acidic work-up provided racemic keto ester 45 in 84% yield (Scheme 10.11). Cyclization of 45 in refluxing aqueous hydrochloric acid provided the bicyclic imine, which was immediately reduced under acidic hydrogenation conditions. The desired cis-endo product 46 was obtained upon recrystaUization. The acid was protected as the benzyl ester using thionyl chloride and benzyl alcohol, providing subunit 47 as the racemate. Resolution of 47 was accomplished by crystallization with benzyloxy-carbonyl-L-phenylalanine or L-dibenzoyl-tartaric acid. 

N-Acylation and 3-alkoxycarbonylation reactions may be achieved by conventional acylation procedures. A variety of 3-acyl derivatives 157 can be prepared most conveniently by the treatment of DPPOx 266 with carboxylic acids in the presence of a tertiary amine. tert-Butoxycarbonyl (Boc-Ox, 236) and benzyloxy carbonyl (Cbz-Ox, 267) (Cbz = benzyloxycarbonyl) compounds are of practical use for introduction of nitrogen protecting groups. ... 

Q-siiCH])3 xyc cHj HaCO ZnCl2/H3C-CN/ 25s 0CH3 4- Benzyloxy carbonyl-5, 6-diphe-nyl-3-[2-( 4-me-thoxy-phenyl)-2-oxo-ethyl -2-oxo-... 2,9 1 anti 30b 178-181 1... 

The pyrimidine ring of the title compounds (701) were formed upon condensative cyclization of anthranilic acids with the 1-benzyloxy-carbonyl-5-ethoxy-l,4-diazocine (700), followed by removal of the N-benzyloxycarbonyl group (66USP3280117). 

To a stirred suspension of NaH (4.8 g, 200 mmol) in DMF (100 mL) under N2, a soln of l-(benzyloxy-carbonyl)-2-(ferf-butoxycarbonyl)hydrazine 161 (26.6 g, 100 mmol) in DMF (250 mL) was added slowly. The mixture was further stirred under N2 for 30 min. Then a soln of 1,3-dibromopropane (20.2 g, 100 mmol) was added and the reaction was allowed to proceed overnight. The solvent was removed, the residue dissolved in EtOAc, and washed with H20, aq citric acid, sat. aq NaHC03, and H20. After removal of the solvent, Z-[2N]Pro-OtBu (formally identical to Boc-[2N]Pro-OBzl) was obtained as an oil yield 25.5 g (83%). 

S, 5.S )-2-(2-Aminopropyl)-5-[(benzyloxycarbonyl)amino]-6-(indol-3-yl)-4-oxohexanoic Add Hydrochloride Salt (22, R1 = 3-methylindolyl R2=2-NH2Pr) and (2R/S,5S)-5-[(Benzyloxy-carbonyl)amino]-2-(2-guanidylpropyl)-6-(indol-3-yl)-4-oxohexanoic Add Hydrochloride Salt (22,... 

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