L-Alanine, N-[(phenylmethoxy)carbonyl]-, 2,5-dioxo-1-pyrrolidinyl ester

White to off-white powder

N-benzyloxycarbonyl-alanine N-hydroxy-succinimide ester (1) was synthesised according to the procedure described by G. W. Anderson et al., J Am Chem Soc (1964) 86:1839. Briefly, equal moles of N-Cbz-ala, N-hydroxy-succinimide, and dicyclohexylcarbodiimide were added in THF in an ice-water bath with stirring. The mixture was kept in a cool room (0 C.) overnight. The dicyclohexylurea precipitate was removed by filtration, and the solvent evaporated in vacuo. The residue was crystallized from isopropanol to yield 1.Saturated aqueous NaHCO3 solution (200 1iL) was added to a solution of(1 S, 2S, 3 aR, 5 S, 6aR)-2, 5 -diamino- 1 -(3 -boronopropyl)octahydropentalene-2-carboxyl ate (1:1:3 salt with t-butylamine and HC1, 61 mg, 0.14 mmol) in water (880 1iL) and acetonitrile (1.0 mL) at 23 C, until pH = 9 was achieved. A solution of 2, 5-dioxopyrrolidin-1-yl ((benzyloxy)carbonyl)-L10 alaninate (Cbz-Ala-OSu, 65 mg, 0.20 mmol) in acetonitrile (2.5 mL) was added next. Additionalsaturated aqueous NaHCO3 solution was added as required in order to maintain pH = 9. The mixture was stirred at 23 C for 16 h before it was concentrated under reduced pressure. The crude residue was purified by RP-HPLC (C 18 column, water [0.1% TFA] -acetonitrile) to give(1S, 2S, 3 aR, 5 S, 6aR)-2-amino-5-((S)-2-(((benzyloxy)carbonyl)amino)propanamido)- 1 -(3-boronopropyl)octahydropentalene-2-carboxylic acid as a TFA salt. LCMS (C23H33BN3O6) (ES, m/z): 458 [M-H20+H]tTo a solution of N02-GOx-Ala-Tyr(Bn)-Leu-OBn (47) (1.26 g, (0345) 1.90 mmol, 1.0 equiv) in TH F (20 mL) was added Cbz-Ala-OSu (1.22 g, 3.80 mmol, 2.0 equiv), NaHC03 (638 mg, 7.60 mmol, 4.0 equiv) and Raney Ni (slurry in H20, 4.0 mL). The solution was placed under an atmosphere of nitrogen, evacuated and filled with hydrogen (balloon). The mixture was stirred for 2.5 h at room temperature, filtered through a plug of Celite eluting with EtOAc, and the filtrate was concentrated in vacuo. Penta peptide 48 was afforded after purification by column chromatography (Si02, EtOAc->CH2Cl /MeOH 9:1) as an off-white foam (989 mg, 1.18 mmol, 83%).

Molecular Weight:320.30
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:7
Exact Mass:320.10083623
Monoisotopic Mass:320.10083623
Topological Polar Surface Area:102
Heavy Atom Count:23
Complexity:470
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes