112661-85-5

Usage

Uses

Used in Photodynamic Therapy for Cancer Treatment:
N-CBZ-5-AMINOLEVULINIC ACID is used as a photosensitizer for the treatment of cancer. It is applied due to its ability to selectively accumulate in cancerous cells and tissues, which, upon exposure to light, triggers a photochemical reaction that leads to the destruction of these cells.
Used in Photodynamic Diagnosis of Tumors:
N-CBZ-5-AMINOLEVULINIC ACID is used as a diagnostic agent in photodynamic diagnosis to identify and visualize tumors. Its selective accumulation in tumor tissues allows for the detection and differentiation of cancerous cells from healthy ones, facilitating more accurate diagnosis and treatment planning.
Used in the Synthesis of Bioactive Compounds:
N-CBZ-5-AMINOLEVULINIC ACID is used as a key intermediate in the synthesis of various bioactive compounds. Its unique chemical properties make it a valuable component in the development of new pharmaceuticals and therapeutic agents.
Used in Medicinal and Biochemical Research:
N-CBZ-5-AMINOLEVULINIC ACID is used as a research tool in medicinal and biochemical studies. Its involvement in the biosynthesis of tetrapyrroles and its potential applications in photodynamic therapy and diagnosis make it an important subject of investigation for understanding disease mechanisms and developing novel treatment strategies.

Synthetic route

ALA (106-60-5) + benzyl chloroformate (501-53-1) → 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5)

Conditions	Yield
With sodium carbonate In 1,4-dioxane; water at 20℃; for 18h; pH=8 - 10;	52%
In methanol at 0 - 20℃;

5-aminolevulinic acid hydrochloride (5451-09-2) + benzyl chloroformate (501-53-1) → 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water	46%
With sodium hydroxide In 1,4-dioxane; water	46%
With sodium hydrogencarbonate In water at 20℃; Cooling with ice;

5-amino-4-oxo-valeric acid-hydrochloride → 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5)

Conditions	Yield
With water; magnesium oxide; benzyl chloroformate

benzyl chloroformate (501-53-1) → 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / dichloromethane / 0.5 h / 0 °C 2: sodium hypochlorite; sodium dihydrogenphosphate / water; tert-butyl alcohol / 3 h / 0 °C 3: hydrogenchloride; iron / water / 1 h / 100 °C View Scheme

C13H13NO5 → 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5)

Conditions	Yield
With hydrogenchloride; iron In water at 100℃; for 1h;

furan-2-ylmethanamine (617-89-0) → 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / dichloromethane / 0.5 h / 0 °C 2: sodium hypochlorite; sodium dihydrogenphosphate / water; tert-butyl alcohol / 3 h / 0 °C 3: hydrogenchloride; iron / water / 1 h / 100 °C View Scheme

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → caesium 5-(Cbz-amino)-4-oxopentanoate (1552321-93-3)

Conditions	Yield
With caesium carbonate In water	100%

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) + trichloroacetic acid (76-03-9) → 5-aminolevulinic acid 2,2,2-trichloroacetate

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol under 760.051 Torr; for 24h;	92%

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) + 1-[2'-(hydroxy)ethyl]-2-ethyl-3-benzyloxy-4(1H)-pyridinone (210244-51-2) → 2-(3-(benzyloxy)-2-ethyl-4-oxopyridin-1(4H)-yl)ethyl 5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate (1574379-22-8)

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 24h;	87%
With dmap; dicyclohexyl-carbodiimide In dichloromethane for 24h;	87%
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 1-[2'-(hydroxy)ethyl]-2-ethyl-3-benzyloxy-4(1H)-pyridinone In dichloromethane at 20℃; Inert atmosphere;	77%
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 1-[2'-(hydroxy)ethyl]-2-ethyl-3-benzyloxy-4(1H)-pyridinone In dichloromethane; N,N-dimethyl-formamide at 20℃;	77%

3-(benzyloxy)-2-ethyl-1-(6-hydroxyhexyl)pyridin-4(1H)-one + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 6-(3-(benzyloxy)-2-ethyl-4-oxopyridin-1(4H)-yl)hexyl 5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate

Conditions	Yield
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 3-(benzyloxy)-2-ethyl-1-(6-hydroxyhexyl)pyridin-4(1H)-one In dichloromethane at 20℃; Inert atmosphere;	80%

3-(benzyloxy)-1-(6-hydroxyhexyl)-N-methyl-4-oxo-1,4-dihydropyridine-2-carboxamide + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 6-(3-(benzyloxy)-2-(methylcarbamoyl)-4-oxopyridin-1(4H)-yl)hexyl-5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate

Conditions	Yield
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 3-(benzyloxy)-1-(6-hydroxyhexyl)-N-methyl-4-oxo-1,4-dihydropyridine-2-carboxamide In dichloromethane at 20℃; Inert atmosphere;	80%
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 3-(benzyloxy)-1-(6-hydroxyhexyl)-N-methyl-4-oxo-1,4-dihydropyridine-2-carboxamide In dichloromethane; N,N-dimethyl-formamide at 20℃;	80%

C20H27NO5 + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 2-(2-(2-(3-(benzyloxy)-2-ethyl-4-oxopyridin-1(4H)-yl)ethoxy)ethoxy)ethyl 5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate

Conditions	Yield
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Stage #2: C20H27NO5 In dichloromethane at 20℃; Inert atmosphere;	80%
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.833333h; Inert atmosphere; Stage #2: C20H27NO5 In dichloromethane; N,N-dimethyl-formamide at 20℃;	70%

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) + 3-(benzyloxy)-2-ethyl-1-(4-hydroxybutyl)pyridin-4(1H)-one (739342-23-5) → 4-(3-(benzyloxy)-2-ethyl-4-oxopyridin-1(4H)-yl)butyl 5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate

Conditions	Yield
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 3-(benzyloxy)-2-ethyl-1-(4-hydroxybutyl)pyridin-4(1H)-one In dichloromethane at 20℃; Inert atmosphere;	79%

benzyl 2-bromopropionate (3017-53-6) + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 1-(benzyloxycarbonyl)ethyl 5-(Cbz-amino)-4-oxopentanoate (1552321-78-4)

Conditions	Yield
With triethylamine In ethyl acetate for 48h; Inert atmosphere; Reflux;	77%

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) + Benzyl 9-hydroxynonanoate → 8-(benzyloxycarbonyl)octyl 5-(Cbz-amino)-4-oxopentanoate (1552322-00-5)

Conditions	Yield
With 4-pyrrolidin-1-ylpyridine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 72h; Inert atmosphere;	77%

3-(benzyloxy)-2-ethyl-1-(8-hydroxyoctyl)pyridin-4(1H)-one + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 8-(3-(benzyloxy)-2-ethyl-4-oxopyridin-1(4H)-yl)octyl 5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate

Conditions	Yield
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 3-(benzyloxy)-2-ethyl-1-(8-hydroxyoctyl)pyridin-4(1H)-one In dichloromethane at 20℃; Inert atmosphere;	75%

3-(benzyloxy)-2-ethyl-1-(12-hydroxydodecyl)pyridin-4(1H)-one + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 12-(3-(benzyloxy)-2-ethyl-4-oxopyridin-1(4H)-yl)dodecyl 5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate

Conditions	Yield
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 3-(benzyloxy)-2-ethyl-1-(12-hydroxydodecyl)pyridin-4(1H)-one In dichloromethane at 20℃; Inert atmosphere;	73%

3-(benzyloxy)-2-ethyl-1-(10-hydroxydecyl)pyridin-4(1H)-one + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 10-(3-(benzyloxy)-2-ethyl-4-oxopyridin-1(4H)-yl)decyl 5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate

Conditions	Yield
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.833333h; Inert atmosphere; Stage #2: 3-(benzyloxy)-2-ethyl-1-(10-hydroxydecyl)pyridin-4(1H)-one In dichloromethane at 20℃; Inert atmosphere;	72%

tert-butyl (3-((1,7-dihydroxy-4-(3-hydroxypropyl)heptan-4-yl)amino)-3-oxopropyl)carbamate + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 4-(3-((5-(((benzyloxy)carbonyl)amino)-4-oxopentanoyl)oxy)propyl)-4-(3-((tert-butoxycarbonyl)amino)propanamido)heptane-1,7-diyl is[5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate]

Conditions	Yield
Stage #1: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.833333h; Inert atmosphere; Stage #2: tert-butyl (3-((1,7-dihydroxy-4-(3-hydroxypropyl)heptan-4-yl)amino)-3-oxopropyl)carbamate With dmap In dichloromethane; N,N-dimethyl-formamide at 20℃; for 25h; Inert atmosphere;	36.5%

16-hydroxyhexadecanoic acid (506-13-8) + 5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) + benzyl alcohol (100-51-6) → 15-(benzyloxycarbonyl)pentadecyl 5-(Cbz-amino)-4-oxopentanoate (1552322-11-8)

Conditions	Yield
Stage #1: 16-hydroxyhexadecanoic acid; benzyl alcohol With toluene-4-sulfonic acid In toluene Reflux; Dean-Stark; Stage #2: benzyl alcohol With sodium hydride at 100℃; for 3h; Inert atmosphere; Stage #3: 5-(benzyloxycarbonylamino)-4-oxopentanoic acid With 4-pyrrolidin-1-ylpyridine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 72h; Inert atmosphere;	0.57 g

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 4-(benzyloxycarbonyl)butyl 5-(Cbz-amino)-4-oxopentanoate (1552321-94-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate / water 2: sodium iodide / dimethyl sulfoxide / 100 °C / Inert atmosphere View Scheme

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 5-(benzyloxycarbonyl)pentyl 5-(Cbz-amino)-4-oxopentanoate (1552321-96-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate / water 2: sodium iodide / dimethyl sulfoxide / 48 h / 100 °C / Inert atmosphere View Scheme

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) → 7-(benzyloxycarbonyl)heptyl 5-(Cbz-amino)-4-oxopentanoate (1552321-98-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: caesium carbonate / water 2: sodium iodide / dimethyl sulfoxide / 48 h / 100 °C / Inert atmosphere View Scheme

5-(benzyloxycarbonylamino)-4-oxopentanoic acid (112661-85-5) + benzyl 2-bromo-2,2-difluoroacetate (155820-63-6) → (benzyloxycarbonyl)difluoromethyl 5-(Cbz-amino)-4-oxopentanoate (1552321-80-8)

Conditions	Yield
With triethylamine In acetonitrile for 18h; Reflux;	6.7 g

Upstream product

• 106-60-5 ALA 
• 501-53-1 benzyl chloroformate 
• 123391-60-6 furan-2-ylmethyl-carbamic acid benzyl ester 
• 617-89-0 furan-2-ylmethanamine 
• 5451-09-2 5-aminolevulinic acid hydrochloride 

Downstream Products

• 1574379-22-8 2-(3-(benzyloxy)-2-ethyl-4-oxopyridin-1(4H)-yl)ethyl 5-(((benzyloxy)carbonyl)amino)-4-oxopentanoate 
• 5451-09-2 5-aminolevulinic acid hydrochloride 
• 1552322-00-5 8-(benzyloxycarbonyl)octyl 5-(Cbz-amino)-4-oxopentanoate 
• 1552321-80-8 (benzyloxycarbonyl)difluoromethyl 5-(Cbz-amino)-4-oxopentanoate 
• 1552321-98-8 7-(benzyloxycarbonyl)heptyl 5-(Cbz-amino)-4-oxopentanoate 

Relevant academic research and scientific papers

PDT (photodynamics therapy) prodrug based on carbonylated polycaprolactone as well as preparation method and application of PDT prodrug

The invention discloses a PDT (photodynamics therapy) prodrug based on carbonylated polycaprolactone. The structure of the PDT prodrug is represented in the description, wherein x is equal to 10-40, and y is equal to 10-40. The PDT prodrug based on carbonylated polycaprolactone is an amphiphilic polymer and can be prepared into micelles. A cell experiment proves that compared with pure 5-aminolevulinic acid, the content of the prodrug micelles converted into protoporphyrin is higher, and the prodrug has better destruction property on tumor cells. 5-aminolevulinic acid is introduced into functionalized polycaprolactone with a chemical grafting method, esterification of the 5-aminolevulinic acid is realized, lipid solubility and stability of 5-aminolevulinic acid are improved, and the prodrug has better targeting performance, higher conversion rate and better photodynamic effect.

Synthesis method of 5-aminolevulinic acid hydrochloride

The invention relates to a synthesis method of 5-aminolevulinic acid hydrochloride (5-ALA), furfuryl amine (2-furylamine) is used as an initial raw material, and the target product is synthesized through four steps of amino protection, oxidation reaction, reduction reaction and hydrolysis decarboxylation. Reagents used in the synthesis method are low in price, easy to obtain, and environment-friendly and the operation is simple.

Hydroxypyridinone and 5-Aminolaevulinic Acid Conjugates for Photodynamic Therapy

Photodynamic therapy (PDT) is a promising treatment strategy for malignant and nonmalignant lesions. 5-Aminolaevulinic acid (ALA) is used as a precursor of the photosensitizer, protoporphyrin IX (PpIX), in dermatology and urology. However, the effectiveness of ALA-PDT is limited by the relatively poor bioavailability of ALA and rapid conversion of PpIX to haem. The main goal of this study was to prepare and investigate a library of single conjugates designed to coadminister the bioactive agents ALA and hydroxypyridinone (HPO) iron chelators. A significant increase in intracellular PpIX levels was observed in all cell lines tested when compared to the administration of ALA alone. The higher PpIX levels observed using the conjugates correlated well with the observed phototoxicity following exposure of cells to light. Passive diffusion appears to be the main mechanism for the majority of ALA-HPOs investigated. This study demonstrates that ALA-HPOs significantly enhance phototherapeutic metabolite formation and phototoxicity.

Synthesis of chemically diverse esters of 5-aminolevulinic acid for photodynamic therapy via the multicomponent Passerini reaction

5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) is gaining increasing acceptance in medicine as an effective technique for the treatment of a variety of neoplastic lesions. Unfortunately, the efficacy of ALA-PDT is limited by the hydrophilic nature of the molecule, leading to poor penetration through malignant tissues. This fact prompted the development of more lipophilic ALA derivatives, such as alkyl esters, although this strategy has potential drawbacks, mainly associated with the instability of ALA in solution. In this paper we describe a more versatile methodology for obtaining ALA esters based on the three-component Passerini reaction, which involves mild conditions and a straightforward procedure, allowing efficient generation of chemically diverse libraries of ALA conjugates. The preliminary in vitro evaluation of the new designed compounds allowed us to find a new promising conjugate with enhanced photodynamic properties compared to ALA.

PYRIDINONE COMPOUNDS FOR USE IN PHOTODYNAMIC THERAPY

A compound which is a compound of formula (I) or any salt thereof: wherein R1 is a Ci-C6 alkyl group, R2 is H or a Ci-C6 alkyl group, R3 is H or a Ci-C6 alkyl group, and n is an integer from 0 to 5.

PYRIDINONE COMPOUNDS FOR USE IN PHOTODYNAMIC THERAPY

A compound which is a compound of formula (I) or any salt thereof: wherein R1 is a Ci-C6 alkyl group, R2 is H or a Ci-C6 alkyl group, R3 is H or a Ci-C6 alkyl group, and n is an integer from 0 to 5.