Catalytic hydrogenation of methyl isobutyrylacetate (I) in the presence of chiral ruthenium catalyst afforded the (S)-hydroxy ester (II). Subsequent alkylation of the lithium enolate of (II) with 3-bromo-2-methyl-1-propene (III) proceeded with diastereoselectivity, yielding (IV). The olefin double bond of (IV) was then hydrogenated over Pd/C to provide the saturated compound (V). After basic hydrolysis of the methyl ester group of (V), the resultant carboxylic acid (VI) was coupled to O-tetrahydropyranylhydroxylamine (VII) to furnish the tetrahydropyranyl-protected hydroxamate (VIII). Conversion of (VIII) into the corresponding mesylate, followed by cyclization under basic conditions, gave rise to the azetidinone (IX). Further azetidinone ring opening under conditions of basic hydrolysis generated the N-hydroxyaminoacid derivative (X). This was converted to the formamide (XI) upon treatment with formic acetic anhydride in pyridine.

N-Boc-L-isoleucine (XII) was coupled to 2-aminopyridine (XIII) via activation with carbonyldiimidazole to give the corresponding amide (XIV). Subsequent acidic cleavage of the Boc protecting group of (XIV) afforded the amino amide (XV), which was further coupled with the intermediate acid (XI), yielding the dipeptide derivative (XVI). The tetrahydropyranyl group of (XVI) was finally removed by hydrolysis with 80% acetic acid.