Afegostat

Base Information

• Chemical Name: Afegostat
• CAS No.: 169105-89-9
• Molecular Formula: C6H13NO3^.HCl
• Molecular Weight: 147.174
• UNII: G23AP190YS
• DSSTox Substance ID: DTXSID20168651
• Nikkaji Number: J716.157C
• Wikipedia: Afegostat
• Wikidata: Q21396373
• NCI Thesaurus Code: C83520
• Pharos Ligand ID: ZM4Z6CGUGJXQ
• Metabolomics Workbench ID: 148987
• ChEMBL ID: CHEMBL206468
• Mol file: 169105-89-9.mol

Synonyms:4-epi-isofagomine;5-hydroxymethyl-3,4-piperidinediol;iso-fagomine;isofagomine

Chemical Property of Afegostat

Chemical Property:

• Appearance/Colour: yellow low-melting solid
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.535
• Boiling Point: 317.2 °C at 760 mmHg
• PKA: 14.19±0.60(Predicted)
• Flash Point: 171.8 °C
• PSA: 72.72000
• Density: 1.279g/cm³
• LogP: -0.94930
• Storage Temp.: 2-8°C(protect from light)
• XLogP3: -1.5
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 1
• Exact Mass: 147.08954328
• Heavy Atom Count: 10
• Complexity: 109

Purity/Quality:

97% ^*data from raw suppliers

Isofagomine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1C(C(C(CN1)O)O)CO
• Isomeric SMILES: C1[C@@H]([C@H]([C@@H](CN1)O)O)CO
• General Description: Isofagomine hydrochloride, also known as 3,4-Piperidinediol,5-(hydroxymethyl)-, [3R-(3a,4b,5a)]-, Afegostat, or D-Isofagomine, is a polyhydroxylated piperidine derivative synthesized via ring-closing double reductive amination. ISOFAGOMINE, HYDROCHLORIDE is obtained through an asymmetric synthetic route starting from cyclopentadiene, involving oxidative cleavage and reductive amination with O-substituted hydroxylamines, followed by deprotection. Isofagomine and its analogues are of interest due to their potential as glycosidase inhibitors, offering a concise and flexible approach for producing optically pure derivatives with therapeutic applications.

Technology Process of Afegostat

There total 109 articles about Afegostat which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.0%

(3R,4R,5S)-N-tert-butoxycarbonyl-3-(tert-butyldiphenylsilyloxy)-4-hydroxy-5-(hydroxymethyl)piperidine (858614-82-1) → isofagomine (169105-89-9,275363-98-9,275363-86-5,346408-06-8,275363-99-0)

Guidance literature:

With hydrogenchloride; In 1,4-dioxane; for 1h; Heating;

DOI:10.1021/jo050519j

Reference yield: 98.0%

(3R,4R,5R)-N-tert-butoxycarbonyl-3-benzoyloxy-5-(tert-butyldiphenylsilyloxymethyl)-4-hydroxypiperidine → isofagomine (169105-89-9,275363-98-9,275363-86-5,346408-06-8,275363-99-0)

Guidance literature:

With hydrogenchloride; at 120 ℃; for 12h;

DOI:10.3987/com-07-s(k)58

Reference yield: 95.0%

N-benzyl (+)-isofagomine (215724-77-9) → isofagomine (169105-89-9,275363-98-9,275363-86-5,346408-06-8,275363-99-0)

Guidance literature:

With hydrogen; palladium hydroxide - carbon; In ethanol; for 10h; under 3878.61 Torr;

DOI:10.1016/S0040-4039(00)01553-7

upstream raw materials:

(3R,4R,5R)-5-(tert-Butyl-diphenyl-silanyloxymethyl)-piperidine-3,4-diol

N-benzyl (+)-isofagomine

(3R,4R,5R)-3,4-Dihydroxy-5-hydroxymethyl-piperidine-1-carboxylic acid phenyl ester

tert-butyl 3-hydroxymethyl-4,5-epoxypiperidine-1-carboxylate

Downstream raw materials:

(3R,4R,5R)-5-Hydroxymethyl-1-[2-((2R,3R,4S,5R,6S)-3,4,5-tris-benzyloxy-6-methoxy-tetrahydro-pyran-2-yl)-ethyl]-piperidine-3,4-diol

10-chloro-9-anthracenemethanol

(3R,4R,5R)-5-(hydroxymethyl)-3,4-piperidinediol L-(+)-tartrate salt

(3R,4R,5R)-5-(hydroxymethyl)-3,4-piperidinediol D-(-)-tartrate salt

Refernces

Asymmetric synthesis of polyhydroxylated N -alkoxypiperidines by ring-closing double reductive amination: Facile preparation of isofagomine and analogues

10.1021/ol203213f

The study presents a de novo asymmetric synthesis of polyhydroxylated N-alkoxypiperidines and their analogues, including isofagomine, using ring-closing double reductive amination. The synthesis begins with the desymmetrization of cyclopentadiene to produce an optically enriched cyclopentene derivative, which is then oxidatively cleaved to yield the necessary dialdehyde. The key ring-closing double reductive amination involves reacting the dialdehyde with O-substituted hydroxylamines, such as O-benzylhydroxylamine, to form N-alkoxypiperidines. Various functionalized dialdehydes are synthesized to produce a range of N-alkoxypiperidines with different substituents. The final products, including isofagomine, are obtained by deprotecting the synthesized compounds using reagents like BCl3 or BBr3. This method provides a flexible and concise route to produce optically pure polyhydroxylated piperidines and their derivatives, which have potential applications in the development of glycosidase inhibitors.