合成路线1

The reduction of 1-indanone (I) with NaBH4 in methanol gives 1-indanol (II), which is brominated with Tms-Br in chloroform to yield 1-bromoindane (III) (1). The condensation of (III) with triethyl phosphonoacetate (IV) and NaH in DMF affords 2-(diethoxyphosphoryl)-2-(1-indanyl)acetic acid ethyl ester (V), which is treated with paraformaldehyde and K2CO3 in refluxing THF to provide 2-(1-indanyl)acrylic acid ethyl ester (VI). The hydrolysis of (VI) with NaOH in acetone/water gives the corresponding acrylic acid (VII), which is condensed with thioacetic acid (VIII) in refluxing chloroform to yield 3-(acetylsulfanyl)-2-(1-indanyl)propionic acid ethyl ester (IX) as a mixture of the two (R,R)+(S,S) and (R,S)+(S,R) racemates. These two racemates are easily separated by HPLC affording the desired (R,R)+(S,S)-(X) racemate. The condensation of (X) with L-tryptophan methyl ester (XI) by means of EDC and HOBT in THF/chloroform to provide a diastereomeric mixture (R,R,S)+(S,S,S) of compounds that is separated by HPLC to provide the desired (R,R,S) diastereomer (XII). Finally, this compound is hydrolyzed with NaOH in methanol/water to furnish the target tryptophan derivative.