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

Stereoselective synthesis of the pyrrolizidine alkaloids (-)-integerrimine and (+)-usaramine

JD White, JC Amedio Jr, S Gut, S Ohira…

Index: White, James D.; Amedio, John C.; Gut, Samuel; Ohira, Susumu; Jayasinghe, Lalith R. Journal of Organic Chemistry, 1992 , vol. 57, # 8 p. 2270 - 2284

Full Text: HTML

Citation Number: 39

Abstract

Two routes to the pyrrolizidine alkaloid (-)-integerrimhe (1) are described. The first, starting from methyl (R)-(-)-3-hydroxy-2-methylpropionate, proceeded in 19 steps to integerrinecic acid lactone (5) which was transformed to the necic acid derivative 30. The latter was coupled to protected retronecine 31, and the synthesis of 1 was completed by lactonization employing Vedejs' protocol. A second, shorter synthesis of (-)-1 was accomplished via 5, ...

(4R)-4-[(4S)-2,2-Dimethyl-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,2-dioxolanyl]pentanoic Acid Structure

(4R)-4-[(4S)-2,...

~%

(2S,3R)-2-(trimethylsilyl)ethyl 2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R)-2-(trim...

(3R)-α-methylene-3,7-dimethyl-6-octen-1-al Structure

(3R)-α-methylen...

~%

(2S,3R)-2-(trimethylsilyl)ethyl 2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R)-2-(trim...

(4R)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-(hydroxymethyl)-1,3-dioxolane Structure

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

~%

(2S,3R)-2-(trimethylsilyl)ethyl 2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R)-2-(trim...

(2S,3R)-3,7-Dimethyl-2-hydroxy-2-(hydroxymethyl)-6-octenyl Pivalate Structure

(2S,3R)-3,7-Dim...

~%

(2S,3R)-2-(trimethylsilyl)ethyl 2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R)-2-(trim...

(4R)-4-[(4S)-2,2-Dimethyl-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,2-dioxolanyl]pentanoic Acid Structure

(4R)-4-[(4S)-2,...

~%

(4R,5S)-5-[[2-(Trimethylsilyl)ethoxy]carbonyl]-5-(hydroxymethyl)-4-methyl-5-pentanolide Structure

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

(3R)-α-methylene-3,7-dimethyl-6-octen-1-al Structure

(3R)-α-methylen...

~%

(4R,5S)-5-[[2-(Trimethylsilyl)ethoxy]carbonyl]-5-(hydroxymethyl)-4-methyl-5-pentanolide Structure

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

(4R)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-(hydroxymethyl)-1,3-dioxolane Structure

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

~%

(4R,5S)-5-[[2-(Trimethylsilyl)ethoxy]carbonyl]-5-(hydroxymethyl)-4-methyl-5-pentanolide Structure

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

(2S,3R)-3,7-Dimethyl-2-hydroxy-2-(hydroxymethyl)-6-octenyl Pivalate Structure

(2S,3R)-3,7-Dim...

~%

(4R,5S)-5-[[2-(Trimethylsilyl)ethoxy]carbonyl]-5-(hydroxymethyl)-4-methyl-5-pentanolide Structure

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

(3R)-α-methylene-3,7-dimethyl-6-octen-1-al Structure

(3R)-α-methylen...

~%

((S)-2-((R)-6-methylhept-5-en-2-yl)oxiran-2-yl)methanol Structure

((S)-2-((R)-6-m...

(3R)-α-methylene-3,7-dimethyl-6-octen-1-al Structure

(3R)-α-methylen...

~%

(4R)-4-[(4S)-2,2-Dimethyl-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,2-dioxolanyl]pentanoic Acid Structure

(4R)-4-[(4S)-2,...

(4R)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-(hydroxymethyl)-1,3-dioxolane Structure

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

~%

(4R)-4-[(4S)-2,2-Dimethyl-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,2-dioxolanyl]pentanoic Acid Structure

(4R)-4-[(4S)-2,...

(2S,3R)-3,7-Dimethyl-2-hydroxy-2-(hydroxymethyl)-6-octenyl Pivalate Structure

(2S,3R)-3,7-Dim...

~%

(4R)-4-[(4S)-2,2-Dimethyl-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,2-dioxolanyl]pentanoic Acid Structure

(4R)-4-[(4S)-2,...

(4R)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-(hydroxymethyl)-1,3-dioxolane Structure

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

~%

(4S)-2,2-Dimethyl-4-[(1R)-1,5-dimethyl-4-hexenyl]-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,3-dioxolane Structure

(4S)-2,2-Dimeth...

(2S,3R)-3,7-Dimethyl-2-hydroxy-2-(hydroxymethyl)-6-octenyl Pivalate Structure

(2S,3R)-3,7-Dim...

~%

(4S)-2,2-Dimethyl-4-[(1R)-1,5-dimethyl-4-hexenyl]-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,3-dioxolane Structure

(4S)-2,2-Dimeth...

(4S)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-[(pivalyloxy)methyl]-1,3-dioxolane Structure

(4S)-2,2-Dimeth...

~%

(4S)-2,2-Dimethyl-4-[(1R)-1,5-dimethyl-4-hexenyl]-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,3-dioxolane Structure

(4S)-2,2-Dimeth...

((S)-2-((R)-6-methylhept-5-en-2-yl)oxiran-2-yl)methanol Structure

((S)-2-((R)-6-m...

~%

(4S)-2,2-Dimethyl-4-[(1R)-1,5-dimethyl-4-hexenyl]-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,3-dioxolane Structure

(4S)-2,2-Dimeth...

(2S,3R)-3,7-Dimethyl-2-hydroxy-2-(hydroxymethyl)-6-octenyl Pivalate Structure

(2S,3R)-3,7-Dim...

~%

(4R)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-(hydroxymethyl)-1,3-dioxolane Structure

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

((S)-2-((R)-6-methylhept-5-en-2-yl)oxiran-2-yl)methanol Structure

((S)-2-((R)-6-m...

~%

(4R)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-(hydroxymethyl)-1,3-dioxolane Structure

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

(3R)-α-methylene-3,7-dimethyl-6-octen-1-al Structure

(3R)-α-methylen...

~%

(4R)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-(hydroxymethyl)-1,3-dioxolane Structure

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

((S)-2-((R)-6-methylhept-5-en-2-yl)oxiran-2-yl)methanol Structure

((S)-2-((R)-6-m...

~%

(4S)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-[(pivalyloxy)methyl]-1,3-dioxolane Structure

(4S)-2,2-Dimeth...

(3R)-α-methylene-3,7-dimethyl-6-octen-1-al Structure

(3R)-α-methylen...

~%

(4S)-2,2-Dimethyl-4-[1(1R)-1,5-dimethyl-4-hexenyl]-4-[(pivalyloxy)methyl]-1,3-dioxolane Structure

(4S)-2,2-Dimeth...

(3R)-α-methylene-3,7-dimethyl-6-octen-1-al Structure

(3R)-α-methylen...

~%

(2S,3R)-3,7-Dimethyl-2-hydroxy-2-(hydroxymethyl)-6-octenyl Pivalate Structure

(2S,3R)-3,7-Dim...

(4R,5S)-5-[[2-(Trimethylsilyl)ethoxy]carbonyl]-5-(hydroxymethyl)-4-methyl-5-pentanolide Structure

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

~%

(R,E)-4-((S)-2,2-dimethyl-4-((2-(trimethylsilyl)ethoxy)carbonyl)-1,3-dioxolan-4-yl)-2-ethylidenepentanoic acid Structure

(R,E)-4-((S)-2,...

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-(hydroxymethyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

~%

(R,E)-4-((S)-2,2-dimethyl-4-((2-(trimethylsilyl)ethoxy)carbonyl)-1,3-dioxolan-4-yl)-2-ethylidenepentanoic acid Structure

(R,E)-4-((S)-2,...

(2S,3R)-2-(trimethylsilyl)ethyl 2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R)-2-(trim...

~%

(R,E)-4-((S)-2,2-dimethyl-4-((2-(trimethylsilyl)ethoxy)carbonyl)-1,3-dioxolan-4-yl)-2-ethylidenepentanoic acid Structure

(R,E)-4-((S)-2,...

(4R)-4-[(4S)-2,2-Dimethyl-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,2-dioxolanyl]pentanoic Acid Structure

(4R)-4-[(4S)-2,...

~%

(R,E)-4-((S)-2,2-dimethyl-4-((2-(trimethylsilyl)ethoxy)carbonyl)-1,3-dioxolan-4-yl)-2-ethylidenepentanoic acid Structure

(R,E)-4-((S)-2,...

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

~%

(R,E)-4-((S)-2,2-dimethyl-4-((2-(trimethylsilyl)ethoxy)carbonyl)-1,3-dioxolan-4-yl)-2-ethylidenepentanoic acid Structure

(R,E)-4-((S)-2,...

(4R,5S)-5-[[2-(Trimethylsilyl)ethoxy]carbonyl]-5-(hydroxymethyl)-4-methyl-5-pentanolide Structure

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

~%

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

(2S,3R)-2-(trimethylsilyl)ethyl 2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R)-2-(trim...

~%

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

(4R)-4-[(4S)-2,2-Dimethyl-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,2-dioxolanyl]pentanoic Acid Structure

(4R)-4-[(4S)-2,...

~%

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

~92%

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-(hydroxymethyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

(4R,5S)-5-[[2-(Trimethylsilyl)ethoxy]carbonyl]-5-(hydroxymethyl)-4-methyl-5-pentanolide Structure

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

~%

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-(hydroxymethyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

(2S,3R)-2-(trimethylsilyl)ethyl 2-((methoxymethoxy)methyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R)-2-(trim...

~%

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-(hydroxymethyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...

(4R)-4-[(4S)-2,2-Dimethyl-4-[[2-(trimethylsilyl)ethoxy]carbonyl]-1,2-dioxolanyl]pentanoic Acid Structure

(4R)-4-[(4S)-2,...

~%

(2S,3R,E)-2-(trimethylsilyl)ethyl 5-ethylidene-2-(hydroxymethyl)-3-methyl-6-oxotetrahydro-2H-pyran-2-carboxylate Structure

(2S,3R,E)-2-(tr...