Protecting Group-Free Total Synthesis of (−)-Lannotinidine B

Abstract

The first total synthesis of (-)-lannotinidine B, a unique tetracyclic constitutent of Lycopodium annotinum, has been accomplished in 10 steps with 23% overall yield. The completed short and efficient synthesis is characterized with three highly chemo- and/or stereoselective reductive-amination steps to furnish the desired trans-fused 6/6 bicycle and the aza seven-membered ring system, and a direct intramolecular acyloin condensation to deliver the cyclopentanone moiety, as well as successful application of a protecting group-free strategy and an optimal redox order.

Total Synthesis of (−)‐Rotundone and (−)‐epi‐Rotundone from Monoterpene Precursors

“…We nevertheless continued the sequence with decarboxylation of β‐keto ester 9 to ketone 10 , hoping for detection of compounds with desired configuration further downstream of the sequence. Because electrocyclization of mixture 10 to hydroxy‐rotundone mixture 5 gave only poor yields in our hands we went through a detour comprising hydrolysis of nitrile 10 and methylation of the acid followed by acylanion cyclization of methyl ester 11 with Li‐naphthalenide ( Scheme 4), as described for similar transformations [28] . This detour gave hydroxy‐ketone mixture 5a – 5c with much better overall yield and purity.…”

“…Because electrocyclization of mixture 10 to hydroxy-rotundone mixture 5 gave only poor yields in our hands we went through a detour comprising hydrolysis of nitrile 10 and methylation of the acid followed by acylanion cyclization of methyl ester 11 with Li-naphthalenide (Scheme 4), as described for similar transformations. [28] This detour gave hydroxy-ketone mixture 5a-5c with much better overall yield and purity. The three (3aSR,5RS,8RS)-configurated main diastereomers of 5a-5c were chromatographically separated and their structures assigned by NMR-analysis.…”

The Glycol Cleavage in Natural Product Synthesis: Reagent Classics and Recent Advances

“…Yao and co-workers reported the first total synthesis of (-)lannotinidine B, a member of the Lycopodium alkaloid family. 35 For the construction of the third of four rings of the natural product, a reductive amination was planned. The prerequisite aldehyde was generated by treatment of olefin 45 with potassium osmate(VI) dihydrate and Nmethylmorpholine N-oxide followed by oxidative cleavage with sodium periodate in aqueous tetrahydrofuran, affording aldehyde 46 in 87% yield over two steps (Scheme 26).…”

Enantioselective Total Synthesis of Lycoposerramine-Z Using Chiral Phosphoric Acid Catalyzed Intramolecular Michael Addition

“…As part of our natural-product synthesis program, we recently examined several new approaches to the biologically interesting phlegmarine-type Lycopodium alkaloids (Figure ). The first phlegmarine was discovered by Braekman and co-workers in 1978, and this type of alkaloid commonly contains a variable C 16 N 2 skeleton, in which a piperidine ring and a 5,7-disubstituted decahydroquinoline ring were connected through a methylene unit. , They were also proposed as the biogenetic precursor of main classes of Lycopodium alkaloids, such as lycopodine, lycodine, and fawcettimine .…”