合成路线1

Preparation of the 15-methylerythromycin A precursor (XI) is accomplished by a chemobiosynthetic approach, utilizing the diketide surrogate (IX). Synthesis of (IX) is carried out as follows. Acylation of (S)-4-benzyl-2-oxazolidinone (I) with propionyl chloride (II) affords the N-propionyl oxazolidinone (III). Diastereoselective aldol condensation of (III) with butyraldehyde (IV) employing dibutylboron triflate leads to adduct (V). Deacetylation of cysteamine hydrochloride (VI) with Ac2O provides (VII). Then, selective hydrolysis of the thioester function of (VII) under alkaline conditions provides thiol (VIII). Condensation of the acyl oxazolidinone (V) with thiol (VIII) in the presence of AlMe3 gives rise to the thioester substrate (IX) (1). Incubation of a recombinant Streptomyces coelicolor strain with the diketide surrogate (IX) leads to the production of 6-deoxy-15-methylerythronolide B (X). Subsequent bioconversion of the aglycone (X) in a Saccharopolyspora erythraea strain affords the desired 15-methylerythromycin A (XI).