Cascade cyclization triggered by imine formation. Formal synthesis of the alkaloid (±)-stemoamide and its 9a-epimer

Unified Total Synthesis of Stemoamide-Type Alkaloids by Chemoselective Assembly of Five-Membered Building Blocks

“…While saxorumamide ( 2 ) and isosaxorumamide ( 3 ) have an additional γ-lactone on the γ-lactone carbonyl group of stemoamide ( 1 ), stemonine ( 4 ) possesses an additional γ-lactone on the γ-lactam carbonyl group of stemoamide ( 1 ) . More than 20 syntheses of stemoamide ( 1 ) have been reported to date due to its relatively simple structure. , In contrast, the tetracyclic derivatives of stemoamide ( 1 ) drastically increase the structural complexity. Indeed, only the Williams’ group achieved a landmark total synthesis of stemonine ( 4 ) through sequential, late-stage ring closure reactions of an acyclic intermediate .…”

Synthesis of the Proposed Structures of Parvistemoamide and Their Transformations to Stemoamide Derivatives

“…The 10-membered lactam ring in parvistemoamide is proposed to be constructed via the macrolactamization of the amphoteric compound 5 , which can be further traced back to ketone 6 via the protection of the keto-carbonyl group and the deprotection of the ester and amine. Ketone 6 is a known compound and could be easily obtained . On the other hand, parvistemoamide may be derived from stemoamide via the C9a–N oxidative cleavage proposed by Xu, or stemoamide could come from parvistemoamide via the C–N bond formation proposed by Pilli or transannular cyclization.…”

“…With the above retrosynthetic analysis in mind, we commenced the synthesis of stereoisomers 3a – 3d , which encompass the two structures proposed for parvistemoamide ( 3 ) by Xu and co-workers , (Scheme ). Starting from ketone 6 , the protection of the ketone carbonyl group with 1,3-dimercaptopropane and the hydrolysis of the methyl ester with LiOH generated carboxylic acid 7 . Under the promotion of TMSI, the carboxybenzyl group (Cbz) in 7 was deprotected to render the unprotected amine, which was then subjected to the Corey–Nicolaou macrolactamization reaction to construct the 10-membered lactam 8 in a 50% yield in a rather high-dilution solvent ( c = 1.0 × 10 –3 M).…”

Tailored Synthesis of Skeletally Diverse Stemona Alkaloids through Chemoselective Dyotropic Rearrangements of β‐Lactones

“…Subsequently, hydrogenation of the C1=C2 double bond followed by the replacement of bromide with sodium azide led to the key precursor 19 . With all requisite functionalities set up, the A/B rings were constructed through a one‐pot reaction involving Staudinger/aza‐Wittig reaction, Borch reductive amination [26] and lactam formation, which gave (−)‐stemoamide ( 1 ) and (−)‐9a‐ epi ‐stemoamide [27] ( 22 ) in excellent combined yield (90 %) and good diastereoselectivity (dr 5:1). To get deep insight into the stereochemical outcome of the transformation, we carried out a computational study to search for the optimal transition‐state conformation for the Borch reduction.…”