Tetralone (I) was reduced with NaBH4 and the resulting alcohol (II) was dehydrated with p-TsOH in refluxing toluene to yield the dihydronaphthalene (III). Oxidation of (III) with N-methylmorpholine N-oxide and OsO4 produced diol (IV), which was converted to the 2-tetralone (V) by acid-catalyzed rearrangement. The unstable tetralone (V) was condensed with the sodium salt of tert-butyl diethyl phosphonoacetate (VI) providing a mixture of olefin isomers (VII). Catalytic hydrogenation of the olefin (VIIa-c) with simultaneous removal of the carbobenzoxy group furnished the aminotetralin (VIII). This was coupled with 4-cyanobenzoic acid (IX) using EDC to give amide (X). Addition of H2S to the nitrile group of (X), followed by S-methylation provided (XI). Then, displacement of the methylthio group of (XI) by ammonium acetate and further treatment with di-tert-butyl dicarbonate yielded the Boc-protected benzamidine (XII). Deprotection with trifluoroacetic acid produced the amidino acid (XIII), which was finally esterified with EtOH and HCl.

Tetralone (I) was reduced with NaBH4 and the resulting alcohol (II) was dehydrated with p-TsOH in refluxing toluene to yield the dihydronaphthalene (III). Oxidation of (III) with N-methylmorpholine N-oxide and OsO4 produced diol (IV), which was converted to the 2-tetralone (V) by acid-catalyzed rearrangement. The unstable tetralone (V) was condensed with the sodium salt of tert-butyl diethyl phosphonoacetate (VI) providing a mixture of olefin isomers (VII). Catalytic hydrogenation of the olefin (VIIa-c) with simultaneous removal of the carbobenzoxy group furnished the aminotetralin (VIII). This was coupled with 4-cyanobenzoic acid (IX) using EDC to give amide (X). Addition of H2S to the nitrile group of (X), followed by S-methylation provided (XI). Then, displacement of the methylthio group of (XI) by ammonium acetate and further treatment with di-tert-butyl dicarbonate yielded the Boc-protected benzamidine (XII). Deprotection with trifluoroacetic acid produced the amidino acid (XIII), which was finally esterified with EtOH and HCl.

Tetralone (I) was reduced with NaBH4 and the resulting alcohol (II) was dehydrated with p-TsOH in refluxing toluene to yield the dihydronaphthalene (III). Oxidation of (III) with N-methylmorpholine N-oxide and OsO4 produced diol (IV), which was converted to the 2-tetralone (V) by acid-catalyzed rearrangement. The unstable tetralone (V) was condensed with the sodium salt of tert-butyl diethyl phosphonoacetate (VI) providing a mixture of olefin isomers (VII). Catalytic hydrogenation of the olefin (VIIa-c) with simultaneous removal of the carbobenzoxy group furnished the aminotetralin (VIII). This was coupled with 4-cyanobenzoic acid (IX) using EDC to give amide (X). Addition of H2S to the nitrile group of (X), followed by S-methylation provided (XI). Then, displacement of the methylthio group of (XI) by ammonium acetate and further treatment with di-tert-butyl dicarbonate yielded the Boc-protected benzamidine (XII). Deprotection with trifluoroacetic acid produced the amidino acid (XIII), which was finally esterified with EtOH and HCl.

Hydrogenation of 6-nitrocoumarin (I) in the presence of Pd/C and di-tert-butyl dicarbonate provided (II). Partial reduction of the lactone function of (II) with DIBAL at low temperature gave rise to lactol (III), which was submitted to a Wittig condensation with (ethoxycarbonyl)triphenylphosphorane (IV) yielding chromaneacetic acid ethyl ester (V). The Boc protecting group of (V) was then removed with trifluoroacetic acid to afford aniline (VI), which was acylated with 4-cyanobenzoic acid (VII) in the presence of EDC to give amide (VIII). Addition of H2S to the nitrile group of (VIII), followed by S-methylation provided (IX). Then, displacement of the methylthio group of (IX) by ammonium acetate and further treatment with di-tert-butyl dicarbonate yielded the Boc-protected benzamidine (X). Finally, Boc-deprotection with trifluoroacetic acid furnished the title amidino ester.