Facile entry to substituted decahydroquinoline alkaloids. Total synthesis of lepadins A-E and H

Article abstract of DOI:10.1021/jo061070c

Condensation of a L-alanine derived δ-bromo-β-silyloxy- propylamine with 1,3-cyclohexadione followed by alkylative cyclization produces a bicyclic enone. Diastereoselective Pt/C-catalyzed hydrogenation of this enone in HOAc provides a 5-oxo-cis-fused decahydroquinoline. Wittig olefination of this decahydroquinoline and subsequent epimerization of the resulting 5-formyl intermediate gives rise to a 5-β-formyl decahydroquinoline exclusively. In a parallel procedure, Peterson reaction of this decahydroquinoline and subsequent hydrogenation of the generated 5-exo-olefin provides a decahydroquinoline with a 5-α-substituent predominantly. For these two diastereoselective processes, using the intermediates without N-protection as the substrates is essential because the corresponding N-Boc intermediates give poor diastereoselectivity. The intermediate with β-form side chain is further converted into lepadins A-C via carbon chain elongation, while the intermediate with α-form side chain is transformed into lepadins D, E, and H and corresponding 5′-epimers via connection with two sulfones generated from two Sharpless epoxidation products. By comparison of the rotations and NMR data, the stereochemistry of lepadins D, E, and H is assigned as 2S,3R,4aS,5S,8aR,5′R.