合成路线1

Alternatively, intermediate omuralide (XI) can also be obtained by following this synthetic sequence: Methylsulfanyl derivative (LVII) is transformed into chiral mono ester (LVIII) by enantioselective hydrolysis with porcine liver esterase (PLE) followed by recrystallization of the quinine salt. Treatment of (LVIII) with oxalyl chloride in DMF, followed by coupling in dichloromethane with N-p-methoxybenzylglycinate (PMB-NHCH2COOMe) (B) and Et3N and subsequent Dieckmann cyclization with LDA in THF, affords keto lactam (LIX). Stereoselective alpha-hydroxymethylation of (LIX) by means of formalin and DBU in THF, followed by stereospecific reduction with NaBH(OAc)3 in AcOH, gives dihydroxy lactam (LX), which is then converted into TBDMS ether (LXI) by the following sequence: i) esterification of primary hydroxyl group by pivaloyl chloride (PivCl) in pyridine; ii) silylation of the secondary hydroxyl group by means of TBSOTf and 2,6-lutidine; and iii) cleavage of the pivalate ester by treatment with NaOMe in MeOH. Desulfurization of (LXI) with Ni Raney followed by Dess-Martin periodinane oxidation furnishes aldehyde (LXII), which then reacts with Grignard reagent (LXIII) and TMSCl to yield the addition product (LXIV). Hydrogenation of (LXIV) over Pd/C followed by desilylation with TFA/H2O produces (LXV), which is hydrolyzed by means of LiOH in THF/H2O and treated with BOP-Cl and Et3N, affording beta-lactone (LXVI). Finally, cleavage of the N-p-methoxybenzyl protecting group of (LXVI) with Ceric ammonium nitrate in acetonitrile/H2O yields omuralide (XI).