176199-48-7

Basic information

• Product Name: Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)- (9CI)
• Synonyms: Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)- (9CI);Eglumegad;Eglumetad;LY 354740;(1S,2S,5R,6S)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid;Bicyclo[3.1.0]hexane-2,6-dicarboxylicacid, 2-aMino-, [1S-(1a,2b,5a,6a)]-;Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid,2-amino-,(1S,2S,5R,6S)-
• CAS NO: 176199-48-7
• Molecular Formula: C₈H₁₁NO₄
• Molecular Weight: 185.17724
• Product Categories: CYCLOPENTANE;Glutamate
• Mol File: 176199-48-7.mol
• Article Data: 4

Chemical Properties

• Melting Point: 270-271 °C
• Boiling Point: 376.4 °C at 760 mmHg
• Flash Point: 181.4 °C
• Appearance: /
• Density: 1.569
• Vapor Pressure: 1.06E-06mmHg at 25°C
• Refractive Index: 1.619
• Storage Temp.: Store at +4°C
• PKA: 2.06±0.40(Predicted)
• CAS DataBase Reference: Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)- (9CI)(CAS DataBase Reference)
• NIST Chemistry Reference: Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)- (9CI)(176199-48-7)
• EPA Substance Registry System: Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)- (9CI)(176199-48-7)

Safety Data

• Hazardous Substances Data: 176199-48-7(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 176199-48-7 differently. You can refer to the following data:
1. Treatment ofgeneral anxiety disorders and smoking cessation (metabotropic glutamate agonist).
2. LY 354740 is a highly selective and potent agonist of group II mGluR.

Biological Activity

Highly selective and potent agonist of group II mGlu receptors (EC 50 values are 5.1 and 24.3 nM at mGlu 2 and mGlu 3 receptors respectively and > 100000 nM at mGlu 4 , mGlu 7 , mGlu 1a and mGlu 5a receptors). Displays antianxiety and antiaddictive activity in vivo . Orally and systemically active.

InChI:InChI=1/C8H11NO4/c9-8(7(12)13)2-1-3-4(5(3)8)6(10)11/h3-5H,1-2,9H2,(H,10,11)(H,12,13)/t3-,4-,5-,8-/m0/s1

Upstream product

• 188885-79-2 C₁₁H₁₄O₄ 
• 219762-25-1 (1S,2R,3S,4R,5R,6R)-2-Acetylamino-3,4-dihydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 219762-27-3 (1S,2S,5R,6S)-2-Acetylamino-bicyclo[3.1.0]hex-3-ene-2,6-dicarboxylic acid dimethyl ester 
• 188885-69-0 C₁₅H₂₀O₅ 
• 597540-63-1 (1S,2S,5R,6R)-2-tert-Butoxycarbonylamino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 597540-95-9 (2aR,2bR,4aS,4bS)-2-Oxo-hexahydro-1-aza-cyclopropa[cd]pentalene-1,4a-dicarboxylic acid 1-tert-butyl ester 4a-methyl ester 
• 597540-62-0 (2aR,2bR,4aS,4bS)-2-Oxo-hexahydro-1-aza-cyclopropa[cd]pentalene-4a-carboxylic acid methyl ester 
• 695814-88-1 (1S,2S,5R,6S)-2-Amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-methyl ester 
• 219762-29-5 (1S,2S,5R,6S)-2-Acetylamino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 188885-88-3 (1S,2S,5R,6S)-ethyl 2-spirohydantoin-bicyclo[3.1.0]hexane-6-carboxylate 
• 188885-85-0 (1S,5R,6S)-2-oxo-bicyclo[3.1.0]hexane-6-carboxylic acid ethyl ester 
• 188885-82-7 ethyl (1SR,5RS,6SR)-2-oxobicyclo[3.1.0]hex-3-ene-6-carboxylate 
• 219762-26-2 (1R,1aR,1bR,4aS,5R,5aS)-5-Acetylamino-3-ethoxy-hexahydro-2,4-dioxa-cyclopropa[a]pentalene-1,5-dicarboxylic acid dimethyl ester 
• 597540-60-8 (2aR,2bR,4aS,4bS)-1-(4-Methoxy-benzyl)-2-oxo-hexahydro-1-aza-cyclopropa[cd]pentalene-4a-carboxylic acid methyl ester 

Downstream Products

• 869290-30-2 C₁₄H₂₇NO₄Si₂ 
• 488859-03-6 (1S,2S,5R,6S)-2-Allyloxycarbonylamino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 
• 441765-96-4 (1S,2S,5R,6S)-2-[(2'S)-(2'-tert-butoxycarbonylamino)-propionyl]amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 
• 488859-10-5 (1S,2S,5R,6S)-2-tert-butoxycarbonylaminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-methyl ester 
• 441775-51-5 (1S,2S,5R,6S)-2-[(2'S)-(2',6'-bis(tert-butoxycarbonyl)amino)hexanoyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 488859-30-9 (1S,2S,5R,6S)-2-allyloxycarbonylamino-2-[(1'S)-allyloxycarbonyl-2'-phenylethyl]carbamoylbicyclo[3.1.0]hexane-6-carboxylic acid allyl ester 
• 488859-13-8 (1S,2S,5R,6S)-2-allyloxycarbonylamino-2-[(1'S)-allyloxycarbonyl-3'-methylbutyl]carbamoylbicyclo[3.1.0]hexane-6-carboxylic acid allyl ester 
• 441775-61-7 (1S,2S,5R,6S)-2-[(2'S)-2'-tert-butoxycarbonylamino-3'-(tert-butyldimethylsilanyloxy)propionylamino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 863323-37-9 (1S,2S,5R,6S)-2-[(2S)-(tert-butoxycarbonylamino)propionyl]amino-2-[(1S)-3-methyl-1-methoxycarbonylbutyl]carbamoylbicyclo[3.1.0]hexane-6-carboxylic acid methyl ester 
• 488859-28-5 (1S,2S,5R,6S)-methyl 2-[(2'S)-tert-butoxycarbonylamino-3-(tert-butyldimethylsilanyloxy)propionylamino]bicyclo[3.1.0]hexane-2,6-dicarboxylate 
• 488859-32-1 (1S,2S,5R,6S)-2-allyloxycarbonylamino-2-[(1'S)-allyloxycarbonyl-2'-methylpropyl]carbamoylbicyclo[3.1.0]hexane-6-carboxylic acid allyl ester 
• 488859-21-8 (1S,2S,5R,6S)-2-tert-butoxycarbonylamino-2-[2-(4-hydroxyphenyl)-(1'S)-methoxycarbonylethyl]carbamoylbicyclo[3.1.0]hexane-6-carboxylic acid methyl ester 
• 441775-57-1 (1S,2S,5R,6S)-2-[(2'S)-(2'-tert-butoxycarbonylamino)-3'-(p-hydroxyphenyl)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 488859-19-4 (1S,2S,5R,6S)-2-allyloxycarbonylamino-2-[(1'S)-methoxycarbonyl-3'-methylthiopropyl]carbamoylbicyclo[3.1.0]hexane-6-carboxylic acid allyl ester 

Relevant articles and documents

Constrained cycloalkyl analogues of glutamic acid: Stereocontrolled synthesis of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) and its 6-phosphonic acid analogue

A new stereocontrolled synthesis of (+)-2-aminobicyclo[3.1.0]hexane-2.6- dicarboxylic acid (LY354740) 1, a potent and selective 2mGluR agonist, has been accomplished in four steps with an overall yield of 27% starting from the enantiopure (+)-(R)-2-(p-tolylsulfinyl)cyclopent-2-enone 3. The key steps include asymmetric cyclopropanation of 3 with (dimethylsulfuranylidene)acetate (EDSA) and removal of the chiral p-tolylsulfinyl auxiliary from the cycloadduct ent-4c upon treatment with iso-propylmagnesium chloride. The stereoselective hydantoin formation from the bicyclic ketone 6 formed (Bucherer-Bergs reaction) and subsequent hydrolysis completed the synthesis of 1. The same reaction sequence has been applied in the first synthesis of enantiopure (+)-2-amino-6-phosphonobicyclo[3.0.1]hexane-2-carboxylic acid 2, a structural 6-phosphono analogue of 1. The starting bicyclic ketophosphonates 9-11 have been obtained by asymmetric cyclopropanation of (-)-(S)-3 with phosphoryl sulfonium ylides, producing only two endo-isomers. The major endo-isomer (+)-11a containing the 6-diisopropoxyphosphoryl group has been converted in three steps into (+)-endo-2 in 46% overall yield.

Enantiospecific synthesis of (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane- 2,6-dicarboxylic acid by a modified Corey-Link reaction

(1S,2S,5R,6S)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) was synthesised enantiospecifically from a sugar derived enantiomerically pure cyclopentenone. The α-amino acid stereogenic centre was formed by reacting the ketone with chloroform anion and then the alcohol so formed was reacted with sodium azide/DBU in methanol to give an azido ester. Critically, this modified Corey-Link reaction gives the opposite stereochemical outcome to the traditional Bucherer-Bergs and Strecker reactions. The azide was reduced and acylated, the 1,2 diol deoxygenated and the protecting groups removed to give LY354740 with an e.e.>98%.