Stereoselective synthesis of (−)-centrolobine

The stereoselective synthesis of (−)-centrolobine has been accomplished starting from d-glyceraldehyde acetonide by a combination of chelation-controlled diastereoselective alkylation and ring-closing metathesis. A high degree of 1,3-asymmetric induction has been realized in an ether system.

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2-((R)-((R)-2,2-Dimethyl-1,3-dioxolan-4-yl)(4-methoxyphenyl)methoxy)-N,N-diethylacetamideC19H29NO5[α]D28=-67.5 (c 0.2, CHCl3)Ee >98%Configuration: (R,R)Source of chiarlity: d-Mannitol

(S)-4-(4-(Benzyloxy)phenyl)-2-((R)-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)(4-methoxyphenyl)methoxy)-N,N-diethylbutanamideC34H43NO6[α]D28=-47.9 (c 1.0, CHCl3)Ee >98%Configuration: (S,R,R)Source of chiarlity: d-Mannitol

(S)-4-(4-(Benzyloxy)phenyl)-2-((1R,2R)-2,3-dihydroxy-1-(4-methoxyphenyl)propoxy)-N,N-diethylbutanamideC31H39NO6[α]D25=-110.4 (c 0.43, CHCl3)Ee >98%Configuration: (S,R,R)Source of chiarlity: d-Mannitol

(S)-4-(4-(Benzyloxy)phenyl)-N,N-diethyl-2-((R)-(4-methoxyphenyl)((R)2-thioxo-1,3-dioxolan-4-yl)methoxy)butanamideC32H37NO6S[α]D25=-140.8 (c 0.4, CHCl3)Ee >98%Configuration: (S,R,R)Source of chiarlity: d-Mannitol

(S)-4-(4-(Benzyloxy)phenyl)-N,N-diethyl-2-((S)-1-(4-methoxyphenyl)allyloxy)butanamideC31H37NO4[α]D25=-31.2 (c 0.3, CHCl3)Ee >98%Configuration: (S,S)Source of chiarlity: d-Mannitol

(S)-6-(4-(Benzyloxy)phenyl)-4-((S)-1-(4-methoxyphenyl)allyloxy)hex-1-en-3-oneC29H30O4[α]D25=-38.7 (c 0.37, CHCl3)Ee >98%Configuration: (S,S)Source of chiarlity: d-Mannitol

(2S,6S)-2-(4-(Benzyloxy)phenethyl)-6-(4-methoxyphenyl)-2H-pyran-3(6H)-oneC27H26O4[α]D25=-183.9 (c 0.58, CHCl3)Ee >98%Configuration: (S,S)Source of chiarlity: d-Mannitol

4-(2-((2R,6S)-6-(4-Methoxyphenyl)tetrahydro-2H-pyran-2-yl)ethyl)phenolC20H24O3[α]D27=-89.3 (c 1, CHCl3)Ee >98%Configuration: (R,S)Source of chiarlity: d-Mannitol