合成路线1

Esterification of (S)-2-bromo-4-methylpentanoic acid (I) with isobutylene in the presence of H2SO4 affords the corresponding tert-butyl ester (II). Subsequent alkylation of dibenzyl malonate with bromoester (II) gives triester (III). After acidic tert-butyl group cleavage in (III), the resultant acid (IV) is coupled with L-phenylglycine-N-methylamide (V), yielding diamide (VI). Transfer hydrogenolysis of the dibenzyl ester (VI) with ammonium formate and Pd/C produces diacid (VII). Mannich reaction of malonic acid (VII) with formaldehyde and piperidine, with concomitant decarboxylation, leads to the alpha-methylene carboxylic acid (VIII), which is further coupled to O-benzyl hydroxylamine giving hydroxamate (IX). Simultaneous double bond hydrogenation and O-debenzylation of (IX) then produces a diastereomeric mixture of alpha-methyl hydroxamic acids, from which the desired diastereoisomer is isolated by preparative HPLC.