合成路线1

The esterification of N-(tert-butoxycarbonyl)-L-tert-butylglycine (I) with DBU and methyl iodide gives the corresponding methyl ester (II), which is condensed with dimethyl methylphosphonate by means of butyllithium in THF yielding N-(tert-butoxycarbonyl)-L-tert-butylglycylmethylphosphonic acid dimethyl ester (III). The reaction of benzyl glyoxylate (IV) (obtained by IO4H oxidation of dibenzyl L-tartrate (V)) with phosphonic ester (III) by means of triethylamine in acetonitrile affords 5(S)-(tert-butoxycarbonylamino)-6,6-dimethyl-4-oxo-2-heptenoic acid benzyl ester (VI). The condensation of (VI) with allyl 2-pivaloylacetate (VII)(obtained by reaction of pivaloyl chloride (VIII) with allyl acetate (A) by means of LHDMS in THF) by means of NaH in THF provides the intermediate (IX). Selective elimination of the allyloxycarbonyl group of (IX) by means of Pd(PPh3)4 and pyrrolidine in dichloromethane/acetonitrile gives 5(S)-(tert-butoxycarbonylamino)-6,6-dimethyl-4-oxo-2(R)-(pivaloylmethyl)heptanoic acid benzyl ester (X). Hydrogenolysis of the benzyl ester group of (X) with H2 over Pd/C in ethanol gives the heptanoic acid (XI), which is condensed with the amino group of the cyclopentanecarboxylic ester (XII) by means of TBTU and NMM in dichloromethane to afford the corresponding amide (XIII).