Total Syntheses of Vellosimine, N‐Methylvellosimine, and 10‐Methoxyvellosimine and Formal Synthesis of 16‐Epinormacusine B through a [5+2] Cycloaddition

Abstract

To date, more than 100 members of the sarpagine alkaloid family have been isolated. Their structural variations originate from oxidative transformations of the carboskeleton and the presence of both absolute configurations at the C‐16 atom, which is established in the course of their biosynthesis. More than 40 sarpagine alkaloids belong to the either the 16‐regular or 16‐epi subgroups, depending on the stereochemistry at C‐16. Herein, we report the formal synthesis of 16‐epinormacusine B, a member of the 16‐epi group, by using our well‐established generalized strategy for the total synthesis of these alkaloids. Furthermore, we provide the synthetic details and pitfalls of the asymmetric total syntheses of vellosimine, N‐methylvellosimine, and 10‐methoxyvellosimine, all members of the 16‐regular group.

Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloids

“…The third category comprises Martin's approach via Pauson-Khand reaction 45 , olefin metathesis 46 , Kuethe's intramolecular Heck cyclization approach 47 , and most recently, Zhang's Copper-catalyzed oxidative cyclization 48,49 . The fourth category includes Ohba's intramolecular oxazole-olefin Diels-Alder cycloaddition 50 , and Gaich's [5 + 2] cycloaddition followed by ring enlargement and Fischer indole annulation [51][52][53] . The last category is Kwon's intramolecular Friedel-Crafts acylation approach 54 .…”

Enantioselective Total Syntheses of Methanoquinolizidine-Containing Akuammiline Alkaloids and Related Studies

“…Overall, the conversion of ketolactone 9 to indoline 6 proceeds with installation of two new rings, three new bonds, and two new stereocenters, all with complete diastereoselectivity. This transformation represents one of the most complex Fischer indolization reactions reported in the literature . Interestingly, hydride approach from the more congested face of the [3.3.1]-azabicycle appears to be favorable (see transition structure 7 ).…”

Merging Chemo- and Biocatalysis to Facilitate the Syntheses of Complex Natural Products: Enantioselective Construction of an N-Bridged [3.3.1] Ring System in Indole Terpenoids

“…42 The 1,4reduction of 18 with Stryker's reagent set the stage for the Fischer indole synthesis. 43 Treatment of 19 with phenylhydrazine in acetic acid provided the indole-fused azabicyclo[3.3.1]nonane architecture and the following hydrolysis/oxidation led to the desired product 5, a known intermediate of (−)-panarine, 16b (+)-vellosimine, 44 and (−)-alkaloid Q 3 16b (Scheme 6). 16c−i 5-Methoxy indole variant 6, which is a synthetic intermediate of (+)-spegatrine 16i and (+)-lochnerine, 45 was also obtained in 69% yield by a similar reaction protocol.…”