Chiral Synthesis of Bicyclomycin and Diastereomeric Stereoselectivity of the Key Aldol Condensation

Article abstract of DOI:10.1021/jo00261a009

Optically pure bicyclomycin (1) was synthesized via aldol condensation of racemic 7,9-bis(p-methoxybenzyl)-5-methylene-6-<(tert-butyldimethylsilyl)oxy>-7,9-diaza-2-oxabicyclo<4.2.2>decane-8,10-dione (2) with 2,3-di-O-isopropylidene-2-C-methyl-L-glyceraldehyde (3).The major condensation product 4 was then N-de(p-methoxybenzyl)ated and O-deisopropylidenated simultaneously with CAN and O-de(tert-butyldimethylsilyl)ated with Bu4NF under finely optimized conditions, respectively, to give 1.The structures of three other diastereomers of 4 were elucidated through comparisonwith the products of the aldol condensation of optically pure 2 and 3.The compounds (+)-2 and (-)-2 were prepared by diastereomeric separation of the synthetic precursor of 2, i.e., 5,6-dihydroxy-7,9-bis(p-methoxybenzyl)-7,9-diaza-2-oxabicyclo<4.2.2>decane-8,10-dione as its (-)-MTPA ester, followed by the previously established four-step conversion.The stereoselectivity of the aldol condensation was explained by the chair conformation-like transition states.