合成路线1

The title compound was prepared by solid phase peptide synthesis. The dioxoborolane-linked resin (XI) was obtained as shown in Scheme 1. 3,7-Dimethyl-6-octenoic acid (I) was protected as the tert-butyl ester (II) by treatment with isobutylene and sulfuric acid, and subsequently oxidized with KMnO4 to afford the hydroxy ketone (III). Addition of methylmagnesium bromide to the keto group of (III) provided diol (IV), which upon reaction with dichloromethyl diisopropoxyborane furnished dioxaborolane (V). Displacement of one chlorine group of (V) with ethylmagnesium bromide at -78 C gave rise to the chloropropyl dioxaborolane (VI). The remaining chlorine atom of (VI) was displaced with lithium bis(trimethylsilyl)amide to yield, after acid desilylation, amine (VII). This was coupled with N-Fmoc-L-leucine (VIII) via the mixed anhydride with isobutyl chloroformate to give amide (IX). After cleavage of the tert-butyl ester of (IX) with trifluoroacetic acid, the resulting carboxylic acid (X) was coupled to the 4-methylbenzhydrylamine resin by means of 2-benzotriazolyl-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), yielding resin (XI).