Lomevactone

Lomevactone (INN; developmental code name DR-250) is a drug described as a psychostimulant and antidepressant which was synthesized and assayed in the 1980s, but was never marketed.^[1][2]

Lomevactone

Clinical data
ATC code	None
Identifiers
IUPAC name 4-(4-Chlorophenyl)-6-methyl-3-phenyltetrahydro-2H-pyran-2-one
CAS Number	81478-25-3 (3R,4R,6R): 82510-81-4 rel-(3R,4R,6R): 75115-73-0
PubChem CID	100079
ChemSpider	90435
UNII	TP71SPS85C
CompTox Dashboard (EPA)	DTXSID601024659
Chemical and physical data
Formula	C18H17ClO2
Molar mass	300.78 g·mol−1
3D model (JSmol)	Interactive image
SMILES Clc1ccc(cc1)C2C(C(=O)OC(C)C2)c3ccccc3

Stereoisomers

There are eight possible stereoisomers of lomevactone. It is the (3R,4R,6R)-form that has the psychotherapeutic properties.^[3][4]

(3R,4R,6R)-Lomevactone

Synthesis

The conjugate 1,4-alkylation reaction between 4-chlorobenzylideneacetone (1) and phenylacetonitrile (2) gives 3-(4-chlorophenyl)-5-oxo-2-phenylhexanenitrile (3). The selective reduction of the keto group to the alcohol with sodium borohydride gives 3-(4-chlorophenyl)-5-hydroxy-2-phenylhexanenitrile (4). Hydrolysis of the nitrile to an acid gives 3-(4-chlorophenyl)-5-hydroxy-2-phenylhexanoic acid. This is followed by lactone formation completing the synthesis of lomevactone (5).

Synthesis:^[5] Patents:^[6][7]