Synthesis of (3aS-cis)-(−)- and (3aR-cis)-(+)-debromoflustramine B

A synthesis of the (3aS-cis)-(−)- and (3aR-cis)-(+)-enantiomers of debromoflustramine B 1 is reported. The synthesis involves the chromatographic separation of the corresponding (−)- and (+)-N-phenylethyl lactams 10 and 11, obtained by the reaction of racemic lactone 6 with (S)-(−)-1-phenylethylamine, followed by hydrolysis to give both enantiomers of 6 with very high enantiomeric excesses. The lactamization of (−)-6 gives (−)-7, which was converted to (−)-1 by reduction with LiAlH4 without racemization. Optically active (+)-1 was similarly prepared from (+)-6. The absolute configurations were established by comparison with the known negative Cotton effect of (3aS-cis)-(−)-physostigmine.

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(3aS,8aR)-(−)-3a,8-Bis(3-methyl-2-buten-1-yl)-2-oxo-2,3,3a,8a-tetrahydro-8H-furo[2,3-b]indoleC20H25NO2Ee = >98%[α]D25=-98.6 (c 0.5, CHCl3)Source of chirality: (S)-(−)-1-phenylethylamineAbsolute configuration: (3aS,8aR)

(3aS,8aR)-(−)-1-Methyl-3a,8-bis(3-methyl-2-buten-1-yl)-2-oxo-2,3,3a,8a-tetrahydro-8H-pyrrolo[2,3-b]indoleC21H28N2OEe = >98%[α]D25=-138.6 (c 1.3, CHCl3)Source of chirality: (S)-(−)-1-phenylethylamineAbsolute configuration: (3aS,8aR)

(3aR,8aS,1′S)-(−)-Bis(3-methyl-2-buten-1-yl)-2-oxo-1-(1′-phenylethyl)-2,3,3a,8a-tetrahydro-8H-pyrrolo[2,3-b]indoleC28H34N2OEe = >98%[α]D25=+79.3 (c 1.4, CHCl3)Source of chirality: (S)-(−)-1-phenylethylamineAbsolute configuration: (3aR,8aS,l′S)

(3aS,8aR,1′S)-(−)-Bis(3-methyl-2-buten-1-yl)-2-oxo-1-(1′-phenylethyl)-2,3,3a,8a-tetrahydro-8H-pyrrolo[2,3-b]indoleC28H34N2OEe = >98%[α]D25=-126.5 (c 2.3, CHCl3)Source of chirality: (S)-(−)-1-phenylethylamineAbsolute configuration: (3aS,8aR,1′S)