Cypenamine

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Cypenamine
Trans-(±)-Cypenamine Enantiomers Structural Formulae.png
Systematic (IUPAC) name
(±)-trans-2-phenylcyclopentan-1-amine
Clinical data
Legal status
?
Identifiers
CAS number 15301-54-9 YesY
ATC code None
PubChem CID 21786
ChemSpider 20476 YesY
UNII VP9115827H YesY
ChEMBL CHEMBL2110918
Chemical data
Formula C11H15N 
Mol. mass 161.2435 g/mol
 YesY (what is this?)  (verify)

Cypenamine, or phenylcyclopentamine, is a stimulant drug developed by a team at the William S. Merrill company in the 1940s.[1] It is currently known only in scientific research and has never been developed for market use. Cypenamine is currently legal throughout the entire world, and though its chemical structure has a vague similarity to certain controlled stimulants like fencamfamine (Glucoenergan, Reactivan), it is likely that it is too distant for it to be considered an illicit analogue under the United States (U.S.) Federal Analogue Act (FAA) of the Controlled Substances Act (CSA).

Stereochemistry[edit]

2-Phenylcyclopentan-1-amine is a compound with two stereocenters. Thus, the following two enantiomeric pairs may exist:

  • (1RS,2SR)-trans-2-phenylcyclopentan-1-amine
  • (1RS,2RS)-cis-2-phenylcyclopentan-1-amine

The racemate (±)-trans-2-phenylcyclopentan-1-amine [1:1 mixture of (1R,2S)-trans-2-phenylcyclopentan-1-amine (box, left) and (1S,2R)-trans-2-phenylcyclopentan-1-amine (box, right)] is the active ingredient of cypenamine.[2] Furthermore, the kinetic resolution of (±)-trans-2-phenylcyclopentan-1-amine by lipase B from Candida antarctica may effectivily performed by an aminolysis reaction.[2]

Racemic cis-2-phenylcyclopentan-1-amine [1:1 mixture of (1R,2R)-cis-2-phenylcyclopentan-1-amine and (1S,2S)-cis-2-phenylcyclopentan-1-amine] has found no pharmacological application.[citation needed]

Homology[edit]

Cypenamine is a homolog of tranylcypromine, containing an expanded alicyclic ring that is two methylene units larger than the highly strained/reactive cyclopropane. The cyclohexane homologue has been reported, although the LD50s were all less than for plain amphetamine, it was still a functional stimulant.[citation needed]

Synthesis[edit]

Clinical success with the monoamine oxidase inhibitor and amphetamine analogue tranylcypromine led to an exploration of the effect of ring size on activity.[3]

Convenient syntheses makes use of the finding that hydroxylamine-O-sulfonic acid is soluble in diglyme and therefore is suitable for conversion of organoboranes from hindered and unhindered olefins into the corresponding amines, 1-Phenylcyclopentene is hydroborated in the usual way with borohydride and BF3. Addition of H2NOSO3H followed by acid hydrolysis completes the synthesis of cypenamine with excellent regio and stereospecificity.[4] I.e. anti-Markovnikov

See also[edit]

References[edit]

  1. ^ US patent 2520516, van Zoeren, G. J., "Cyclic Amines and Method of Making Them", issued 1950-08-29 
  2. ^ a b González-Sabín, J.; Gotor, V.; Rebolledo, F. (2004). "Kinetic resolution of (±)-trans- und (±)-cis-phenylcyclopentanamine by CALB-catalyzed aminolysis of esters: The key role of the leaving group". Tetrahedron:Asymmetry 15 (3): 481–488. doi:10.1016/j.tetasy.2003.11.013. 
  3. ^ W. R. McGrath and W. L. Kuhn, Arch. Int. Pharmacodyn. Ther. , 172, 405 (1968).
  4. ^ Rathke, Michael W. (1966). "A Stereospecific Synthesis of Alicyclic and Bicyclic Amines via Hydroboration". Journal of the American Chemical Society 88 (12): 2870–2871. doi:10.1021/ja00964a057.  edit