e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Tetrahedron

Total synthesis of optically active monocrotaline, a carcinogenic pyrrolizidine alkaloid possessing an eleven-membered retronecine dilactone

H Niwa, T Ogawa, O Okamoto, K Yamada

Index: Niwa, Haruki; Ogawa, Takeshi; Okamoto, Osamu; Yamada, Kiyoyuki Tetrahedron, 1992 , vol. 48, # 48 p. 10531 - 10548

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Citation Number: 33

Abstract

A total synthesis of the natural enantiomer of monocrotaline (1), a representative of carcinogenic pyrrolizidine alkaloids having an 11-membered retronecine dilactone was achieved through regioselective coupling of (+)-retronecine (3) and the optically active protected necic acid 8, the latter being prepared enantioselectively from the meso-diester 11.

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentene Structure

(2'R,3R,4S)-5-[...

~%

(2R,3R,4R)-2,3,4-trimethyl-2,3-methylenedioxypentanedioic anhydride Structure

(2R,3R,4R)-2,3,...

(2'R,2S,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxypentanoic acid Structure

(2'R,2S,3R,4S)-...

~%

(2R,3R,4R)-2,3,4-trimethyl-2,3-methylenedioxypentanedioic anhydride Structure

(2R,3R,4R)-2,3,...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentanol Structure

(2'R,3R,4S)-5-[...

~%

(2R,3R,4R)-2,3,4-trimethyl-2,3-methylenedioxypentanedioic anhydride Structure

(2R,3R,4R)-2,3,...

(2'R,2S,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxypentanoic acid Structure

(2'R,2S,3R,4S)-...

~88%

(2R,3R,4R)-2,3,4-Trimethyl-2,3-(methylenedioxy)pentanedioic acid Structure

(2R,3R,4R)-2,3,...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentene Structure

(2'R,3R,4S)-5-[...

~%

(2R,3R,4R)-2,3,4-Trimethyl-2,3-(methylenedioxy)pentanedioic acid Structure

(2R,3R,4R)-2,3,...

(2R,3R,4R)-2,3,4-Trimethyl-2,3-(methylenedioxy)pentanedioic acid Structure

(2R,3R,4R)-2,3,...

~%

(R)-2-((4R,5R)-5-((((1R,7aR)-1-hydroxy-2,3,5,7a-tetrahydro-1H-pyrrolizin-7-yl)methoxy)carbonyl)-4,5-dimethyl-1,3-dioxolan-4-yl)propanoic acid Structure

(R)-2-((4R,5R)-...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentene Structure

(2'R,3R,4S)-5-[...

~%

(R)-2-((4R,5R)-5-((((1R,7aR)-1-hydroxy-2,3,5,7a-tetrahydro-1H-pyrrolizin-7-yl)methoxy)carbonyl)-4,5-dimethyl-1,3-dioxolan-4-yl)propanoic acid Structure

(R)-2-((4R,5R)-...

(2'R,2S,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxypentanoic acid Structure

(2'R,2S,3R,4S)-...

~%

(R)-2-((4R,5R)-5-((((1R,7aR)-1-hydroxy-2,3,5,7a-tetrahydro-1H-pyrrolizin-7-yl)methoxy)carbonyl)-4,5-dimethyl-1,3-dioxolan-4-yl)propanoic acid Structure

(R)-2-((4R,5R)-...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentanol Structure

(2'R,3R,4S)-5-[...

~%

(R)-2-((4R,5R)-5-((((1R,7aR)-1-hydroxy-2,3,5,7a-tetrahydro-1H-pyrrolizin-7-yl)methoxy)carbonyl)-4,5-dimethyl-1,3-dioxolan-4-yl)propanoic acid Structure

(R)-2-((4R,5R)-...

(2R,3R,4R)-2,3,4-Trimethyl-2,3-(methylenedioxy)pentanedioic acid Structure

(2R,3R,4R)-2,3,...

~%

monocrotaline methylene acetal Structure

monocrotaline m...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentene Structure

(2'R,3R,4S)-5-[...

~%

monocrotaline methylene acetal Structure

monocrotaline m...

(2'R,2S,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxypentanoic acid Structure

(2'R,2S,3R,4S)-...

~%

monocrotaline methylene acetal Structure

monocrotaline m...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentanol Structure

(2'R,3R,4S)-5-[...

~%

monocrotaline methylene acetal Structure

monocrotaline m...

(2R,3R,4R)-2,3,4-trimethyl-2,3-methylenedioxypentanedioic anhydride Structure

(2R,3R,4R)-2,3,...

~%

monocrotaline methylene acetal Structure

monocrotaline m...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentene Structure

(2'R,3R,4S)-5-[...

~%

(2'R,2S,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxypentanoic acid Structure

(2'R,2S,3R,4S)-...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentanol Structure

(2'R,3R,4S)-5-[...

~%

(2'R,2S,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxypentanoic acid Structure

(2'R,2S,3R,4S)-...

(2'R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-2-pentanol Structure

(2'R,3R,4S)-5-[...

~%

(2'R,2R,3R,4S)-5-[2'-methoxy-2'-(trifluoromethyl)phenylacetoxy]-2,3,4-trimethyl-3,4-methylenedioxy-1-pentanol Structure

(2'R,2R,3R,4S)-...

Total synthesis of optically active monocrotaline, a carcino...

[Niwa, Haruki; Okamoto, Osamu; Yamada, Kiyoyuki Tetrahedron Letters, 1988 , vol. 29, # 40 p. 5139 - 5142]