176199-48-7

Usage

Uses

1. Used in Pharmaceutical Industry:
Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)(9CI) is used as a metabotropic glutamate receptor (mGluR) agonist for the treatment of general anxiety disorders and smoking cessation. Its agonist activity at group II mGluRs, such as LY 354740, may help modulate neuronal excitability and neurotransmission, providing therapeutic benefits in these conditions.
2. Used in Chemical Synthesis:
Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)(9CI) can be used as a building block or intermediate in the synthesis of various complex organic molecules, including pharmaceuticals, agrochemicals, and specialty chemicals. Its unique bicyclic structure and functional groups may offer specific advantages in the development of novel compounds with desired properties.
3. Used in Research and Development:
Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)(9CI) may serve as a valuable research tool for studying the structure-activity relationships of mGluR agonists and other biologically active molecules. Its unique stereochemistry and functional groups can provide insights into the design and optimization of new compounds with improved pharmacological profiles.
4. Used in Material Science:
The compound's unique structure and functional groups may also find applications in the development of novel materials with specific properties, such as chiral catalysts, enantioselective sensors, or functional polymers. Further research and development in this area could lead to new applications and technologies based on the properties of Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-, (1S,2S,5R,6S)(9CI).

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

• 219762-29-5 (1S,2S,5R,6S)-2-Acetylamino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 188885-69-0 C₁₅H₂₀O₅ 
• 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 
• 188885-79-2 C₁₁H₁₄O₄ 
• 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 
• 219762-25-1 (1S,2R,3S,4R,5R,6R)-2-Acetylamino-3,4-dihydroxy-bicyclo[3.1.0]hexane-2,6-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 
• 488859-10-5 (1S,2S,5R,6S)-2-tert-butoxycarbonylaminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-methyl ester 
• 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 
• 188885-88-3 (1S,2S,5R,6S)-ethyl 2-spirohydantoin-bicyclo[3.1.0]hexane-6-carboxylate 
• 219762-23-9 C₁₈H₂₅NO₇ 

Downstream Products

• 743414-22-4 (1S,2S,5R,6S)-2-Amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 869290-30-2 C₁₄H₂₇NO₄Si₂ 
• 695814-88-1 (1S,2S,5R,6S)-2-Amino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-methyl ester 
• 488859-03-6 (1S,2S,5R,6S)-2-Allyloxycarbonylamino-bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 
• 441765-93-1 (1S,2S,5R,6S)-2-[(2'S)-(2'-tert-butoxycarbonylamino)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid dimethyl ester 
• 488859-05-8 (1S,2S,5R,6S)-2-allyloxycarbonylaminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid 6-allyl ester 

Relevant academic research and scientific papers

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.

Stereocontrolled synthesis of a potent agonist of group II metabotropic glutamate receptors, (+)-LY354740, and its related derivatives

Efficient synthesis of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740: 1) and its structurally related analogs (-)-2 and (-)-3 has been accomplished starting with (1S,2R)-1-amino-2-hydroxycyclopentane- or cyclohexanecarboxylic acid (4 or 17 ) via an intramolecular cyclopropanation of α-diazo acetamide.

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%.

Asymmetric synthesis of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740)

The assymetric synthesis of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740) 1, a potent and selective group 2 mGluR agonist, has been accomplished starting from the readily available enantiomerically pure cyclopentenone 4. Thus, cyclopropanation with ethyl(dimethylsulfuranylidene)acetate generated in situ with DBU, followed by deketalization gave rise to the dihydroxy bicyclic ketone 9. After protecting the ketone as 1,3-dioxolane and its transformation to the orthoformate 11, this was pyrolytically deoxygenated in a sealed tube to the bicyclic enone 13. The synthesis was completed after hydrogenation, stereoselective Bucherer-Bergs reaction and hydantoin hydrolysis, yielding LY354740 (+)-1 with an e.e. ≤98%. reserved.