Total Synthesis of (−)-Lycorine and (−)-2-epi-Lycorine by Asymmetric Conjugate Addition Cascade

Abstract

Total syntheses of (-)-lycorine and (-)-2-epi-lycorine were accomplished using chiral ligand-controlled asymmetric cascade conjugate addition methodology, which enables the formation of two C-C bonds and three stereogenic centers in one pot to give synthetically useful chiral cyclohexane derivatives.

Synthesis of Amaryllidaceae Constituents and Unnatural Derivatives

“…[110] Scheme 27. Thenitro functionality was then reduced to an amine and subsequent treatment with sodium methoxide in methanol gave access to cyclized product 141 (Scheme 29).…”

“…Thenitro functionality was then reduced to an amine and subsequent treatment with sodium methoxide in methanol gave access to cyclized product 141 (Scheme 29). [110] Angewandte Chemie Reviews 142 was then subjected to aB ischler-Napieralski reaction to provide 143,c ompleting the construction of ring B. Deprotection of the thioketal, and reduction of the resulting ketone afforded the corresponding alcohol 144.M esylation of the alcohol with methanesulfonyl chloride (MsCl)/Et 3 Na nd subsequent elimination produced amide 145,w ith complete regioselectivity.Compound 145 is aknown intermediate (also known as Torssells intermediate) in the racemic synthesis of lycorine reported by Torssell. Synthesis of isoquinolinone 128 by Tomioka.…”

“…Chos synthesis of racemic lycorine [112] is very different from those reported by others,n amely Tomioka [110] and Shao. [111] Cho employed the Diels-Alder strategy,that he also used in the synthesis of (AE)-1-epi-pancratistatin, for the construction of ring C. [23] Alkyne 58,u sed previously in Hudlickys synthesis of 7-deoxypancratistatin (2), [52] was subjected to ah ydroboration reaction with 146 to obtain organoborane 147.D iels-Alder cycloaddition of 147 with diene 18 proceeded exclusively to provide the endo product 148 (Scheme 30).…”

“…Tomioka, [110] employed ac onsecutive Michael addition strategy in the synthesis of (À)-lycorine (5). Tomioka, [110] employed ac onsecutive Michael addition strategy in the synthesis of (À)-lycorine (5).…”

Amaryllidaceae and Sceletium alkaloids

“…72 In the presence of the chiral ligand 89, a cascade asymmetric conjugate addition reaction of aryllithium 87 to a symmetric Michael acceptor 88 led to the formation of two C-C bonds and three stereogenic centers in one pot to give the functionalized cyclohexane 90, which bore the requisite three adjacent stereogenic centers in lycorine (Scheme 1). 72 In the presence of the chiral ligand 89, a cascade asymmetric conjugate addition reaction of aryllithium 87 to a symmetric Michael acceptor 88 led to the formation of two C-C bonds and three stereogenic centers in one pot to give the functionalized cyclohexane 90, which bore the requisite three adjacent stereogenic centers in lycorine (Scheme 1).…”