27167-53-9

Basic information

• Product Name: Z-D-ALA-OSU
• Synonyms: 1-[(R)-1-Oxo-2-[[(benzyloxy)carbonyl]amino]propoxy]-2,5-pyrrolidinedione;N-[(Phenylmethoxy)carbonyl]-D-alanine 2,5-dioxo-1-pyrrolidinyl ester;Z-D-alanine-N-hydroxysuccinimide ester≥ 98% (HPLC);CBZ-D-ALANINE HYDROXYSUCCINIMIDE ESTER;CBZ-D-ALANINE-OSU;BENZYLOXYCARBONYL-D-ALANINE N-HYDROXYSUCCINIMIDE ESTER;N-ALPHA-CBZ-D-ALANINE N-HYDROXYSUCCINIMIDE ESTER;Z-D-ALA-OSU
• CAS NO: 27167-53-9
• Molecular Formula: C₁₅H₁₆N₂O₆
• Molecular Weight: 320.3
• Product Categories: Amino Acid Derivatives
• Mol File: 27167-53-9.mol
• Article Data: 4

Chemical Properties

• Appearance: /
• Density: 1.36
• Storage Temp.: -15°C
• CAS DataBase Reference: Z-D-ALA-OSU(CAS DataBase Reference)
• NIST Chemistry Reference: Z-D-ALA-OSU(27167-53-9)
• EPA Substance Registry System: Z-D-ALA-OSU(27167-53-9)

Safety Data

• Hazardous Substances Data: 27167-53-9(Hazardous Substances Data)

Usage

Chemical Properties

White powder

Uses

Z-D-Ala-OSu is an intermediate used in the preparation of N-α-aminoacyl derivatives of melphalan for potential use in drug targeting.

Synthetic route

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + N-benzyloxycarbonyl-D-alanine (26607-51-2) → N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9)

Conditions	Yield
With dicyclohexyl-carbodiimide In acetonitrile at 0 - 20℃; for 12.5h;	85%
With dicyclohexyl-carbodiimide In acetonitrile at -20℃;	57%
With dicyclohexyl-carbodiimide In 1,4-dioxane for 12h; Ambient temperature;

di(succinimido) carbonate (74124-79-1) + N-benzyloxycarbonyl-D-alanine (26607-51-2) → N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 0℃; for 1h;

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + diethyl aminomalonate hydrochloride (13433-00-6) → Z-D-Ala-Ama(OEt)-OEt (130548-14-0)

Conditions	Yield
With triethylamine In chloroform Ambient temperature;	88.9%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (S)-2-amino-4-methylpentan-1-ol (7533-40-6) → (2S)-2-[N-(Benzyloxycarbonyl-(R)-alanyl)amino]-4-methylpentan-1-ol (177657-04-4)

Conditions	Yield
In 1,4-dioxane for 12h; Ambient temperature;	88%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (S)-4-Amino-4-(ethoxycarbonylmethyl-carbamoyl)-butyric acid tert-butyl ester (73995-22-9) → Z-D-Ala-Glu(OBut)-Gly-OEt (126027-24-5)

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide for 8h; Ambient temperature;	76%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (S)-2-Amino-3-{4-[bis-(2-hydroxy-ethyl)-amino]-phenyl}-propionic acid benzyl ester (184684-98-8) → N-(N-benzyloxycarbonyl-D-alanyl)-p-bis(2-hydroxyethyl)amino-L-phenylalanine benzyl ester (184685-00-5)

Conditions	Yield
In 1,4-dioxane at 25℃; for 1.5h;	73%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + D-arginine (157-06-2) → Z-D-Ala-D-Arg-OH hydrochloride

Conditions	Yield
Stage #1: N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester; D-arginine In water; acetonitrile at 20℃; Stage #2: With hydrogenchloride In water; acetonitrile pH=2.5;	73%

tryptamine (61-54-1) + N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) → N-(benzyloxycarbonyl)-D-alanine tryptamide (940290-20-0)

Conditions	Yield
In tetrahydrofuran at 20℃;	71%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (S)-(2-amino-4-(tert-butoxy)-4-oxobutanoyl)glycine (58651-64-2) → Z-D-Ala-Asp(OBut)-Gly-OH (126027-23-4)

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide for 8h; Ambient temperature;	68%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (S)-1-aminoethylphosphonic acid (66068-76-6) → [(S)-1-((R)-2-Benzyloxycarbonylamino-propionylamino)-ethyl]-phosphonic acid (98820-76-9)

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water	56%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (R)-(1-aminoethyl)phosphonic acid (60687-36-7) → [(R)-1-((R)-2-Benzyloxycarbonylamino-propionylamino)-ethyl]-phosphonic acid (98820-75-8)

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water	41%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + L-Glu-L-Phe-O-Me (22839-63-0) → Z-D-Ala-L-Glu(OH)-L-Phe-O-Me

Conditions	Yield
	28%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + 1-aminoethanephosphonic acid (6323-97-3) → [(R)-1-((R)-2-Benzyloxycarbonylamino-propionylamino)-ethyl]-phosphonic acid (98820-75-8) + [(S)-1-((R)-2-Benzyloxycarbonylamino-propionylamino)-ethyl]-phosphonic acid (98820-76-9)

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water	A 18% B 2%

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + methyl (L)-leucinate hydrochloride (7517-19-3) → Z-D-Ala-L-Leu-OMe (27167-66-4)

Conditions	Yield
With triethylamine In chloroform

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + Aminomethylphosphonic acid (1066-51-9) → [((R)-2-Benzyloxycarbonylamino-propionylamino)-methyl]-phosphonic acid

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (S)-3-Amino-N-((R)-1-methoxycarbonyl-ethyl)-succinamic acid benzyl ester → Z-D-Ala-L-Asp(OBzl)-D-Ala-O-Me

Conditions	Yield
With triethylamine In chloroform 1) ice bath, 1 h, 2) RT, 3 h + overnight; Yield given;

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + Z-Trp-Nle-Asp(OBzl)-Phe-NH2 (65864-26-8) → Z-D-Ala-Trp-Nle-Asp-Phe-NH2

Conditions	Yield
With hydrogen; N-ethyl-N,N-diisopropylamine; palladium on activated charcoal 1.) DMF, AcOH, H2O, RT, 2.) DMF, 3 h, RT; Yield given. Multistep reaction;

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + 1-aminopropanephosphonic acid (14047-23-5) → [1-((R)-2-Benzyloxycarbonylamino-propionylamino)-propyl]-phosphonic acid

Conditions	Yield
With triethylamine In ethanol

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (1R,S)-1-(D-alanylamino)propanephosphonic acid → {1-[(R)-2-((R)-2-Benzyloxycarbonylamino-propionylamino)-propionylamino]-propyl}-phosphonic acid

Conditions	Yield
With triethylamine In ethanol

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + Z-D-Ala-NHNH-Boc (27454-32-6) → Z-D-Ala-D-Ala-NHNH-Boc (27454-33-7)

Conditions	Yield
(i) H2, PdO, (ii) /BRN= 1553989/; Multistep reaction;

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + 7-<(2R,3S)-3-amino-2-methyl-1-azetidinyl>-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo=1,8-naphthyridine-3-carboxylic acid (132832-29-2) → 7-<(2R,3S)-3-N-CBZ-D-Ala-amino-2-methyl-1-azetidinyl>-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid (148496-72-4)

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide for 8h; Ambient temperature;

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + 7-<(2S,3R)-3-amino-2-methyl-1-azetidinyl>-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid (132832-30-5) → 7-<(2S,3R)-3-N-CBZ-D-Ala-amino-2-methyl-1-azetidinyl>-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid (148496-71-3)

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide for 8h; Ambient temperature;

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + cetefloxacin (141725-88-4) → 7-[(2S,3R)-3-((R)-2-Benzyloxycarbonylamino-propionylamino)-2-methyl-azetidin-1-yl]-1-(2,4-difluoro-phenyl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid

Conditions	Yield
With 4-methyl-morpholine In N,N-dimethyl-formamide for 8h; Ambient temperature;

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + 1,5-diamino-3-azapentane (111-40-0) → ((R)-1-{2-[2-((R)-2-Benzyloxycarbonylamino-propionylamino)-ethylamino]-ethylcarbamoyl}-ethyl)-carbamic acid benzyl ester

Conditions	Yield
With triethylamine In dichloromethane

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (S)-2-Amino-3-{4-[bis-(2-hydroxy-ethyl)-amino]-phenyl}-propionic acid benzyl ester; hydrochloride → N-(N-benzyloxycarbonyl-D-alanyl)-p-bis(2-hydroxyethyl)amino-L-phenylalanine benzyl ester (184685-00-5)

Conditions	Yield
In 1,4-dioxane	2.2 g

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + 2-Aminoisobutyric acid (62-57-7) → N-phenylmethoxycarbonyl-D-alanyl-2-methylalanine (105590-88-3)

Conditions	Yield
In N,N-dimethyl-formamide

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) + (R)-2-amino-3-(4-(benzyloxy)phenyl)propanoic acid (65733-15-5) → C27H28N2O6

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃;

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) → N-(N-benzyloxycarbonyl-D-alanyl)-p-bis(2-chloroethyl)amino-L-phenylalanine benzyl ester (184685-04-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2.2 g / dioxane 2: 71 percent / SOCl2 / CHCl3 / 1) room temperature, 1 h, 2) 40-45 deg C, 2 h View Scheme

N-(benzyloxycarbonyl)-D-alanine N-hydroxysuccinimide ester (27167-53-9) → (2S,3S)-3--5-methylhexan-2-ol (144408-38-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 88 percent / dioxane / 12 h / Ambient temperature 2: 1.) (COCl)2, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) -78 deg C, 15 min 3: 1.) CuBr*S(CH3)2 / 1.) THF, ether, -78 deg C to -30 deg C, 2.) THF, -35 deg C, overnight View Scheme

Upstream product

• 6066-82-6 1-hydroxy-pyrrolidine-2,5-dione 
• 26607-51-2 N-benzyloxycarbonyl-D-alanine 
• 74124-79-1 di(succinimido) carbonate 

Downstream Products

• 27454-33-7 Z-D-Ala-D-Ala-NHNH-Boc 
• 104055-35-8 N-benzyloxycarbonyl-D-alanyl-α-L-aspartyl-D-alanine isopropyl ester 
• 104055-08-5 N-benzyloxycarbonyl-D-alanyl-α-L-aspartyl-L-phenylalanine methyl ester 
• 130385-18-1 Z-D-Ala-DL-Ama(OBzl)-OH 
• 144345-62-0 (2S)-2--4-methylpentan-1-al 
• 144408-38-8 (2S,3S)-3--5-methylhexan-2-ol 
• 940290-20-0 N-(benzyloxycarbonyl)-D-alanine tryptamide 
• 105590-88-3 N-phenylmethoxycarbonyl-D-alanyl-2-methylalanine 
• 184685-00-5 N-(N-benzyloxycarbonyl-D-alanyl)-p-bis(2-hydroxyethyl)amino-L-phenylalanine benzyl ester 
• 177657-04-4 (2S)-2-[N-(Benzyloxycarbonyl-(R)-alanyl)amino]-4-methylpentan-1-ol 
• 148496-71-3 7-<(2S,3R)-3-N-CBZ-D-Ala-amino-2-methyl-1-azetidinyl>-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid 
• 148496-72-4 7-<(2R,3S)-3-N-CBZ-D-Ala-amino-2-methyl-1-azetidinyl>-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid 
• 126027-23-4 Z-D-Ala-Asp(OBu^t)-Gly-OH 
• 126027-24-5 Z-D-Ala-Glu(OBu^t)-Gly-OEt 

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