Asymmetric syntheses of (8R,8aS)- and (8R,8aR)-8-hydroxy-5-indolizidinones: Two promising oxygenated indolizidine building blocks

Abstract

Starting from the oxygenated piperidine building block 20, two synthetic approaches to new building blocks (8R,8aS)- and (8R,8aR)-8-hydroxy-5-indolizidinones 19a/19b and 15a/15b have been developed, respectively. The first one is based on the trans-diastereoselective reductive alkylation (dr = 93:7), followed by a four-step procedure; and the second one called for the RCM reaction on the N,O-acetal derived from a vinylation, which was followed by a pyrrole formation, and a stereocontrolled cis-selective (dr = 91:9) catalytic hydrogenation. Reduction of the diastereomer 15a produced (8R,8aR)-8-indolizidinol (18).NSF of China[20672089, 20832005]; NFFTBS[J1030415]; National Basic Research Program of China[2010CB833200

Concise Asymmetric Total Synthesis of 9-epi-Sessilifoliamide J

“…To date, no synthetic study toward sessilifoliamide J ( 6 ) has been reported. In continuation with our efforts in developing 3-hydroxyglutarimide-based synthetic methodology, , we were engaged in the development of a novel strategy for the total synthesis of sessilifoliamide J. Preliminary results of this study are reported herein, which include the synthesis of 9- epi -sessilifoliamide J ( 20 ) and the establishment of the absolute configuration of the natural product by characterization of minor diastereomer (−)-sessilifoliamide J ( 6 ).…”

A Formal Enantioselective Total Synthesis of FR901483

“…Formation of α,β-unsaturated lactams by the RCM reaction of acrylamides has been well documented using either Grubbs' first or second generation catalyst . The reaction generally proceeded in CH 2 Cl 2 . , However in our case all attempts to perform the RCM reaction of 12 by the use of the Grubbs first or second generation catalyst in CH 2 Cl 2 were unsuccessful. Considering the steric hindrance of the substrate, it was envisioned that a higher reaction temperature would favor the reaction.…”

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

“…In recent years, we have been engaged in the development of efficient methodologies for the synthesis of nitrogen-containing bioactive heterocycles [ 33 – 37 ], and recently reported an approach for the synthesis of (8 R ,8a S )-8-hydroxy-5-indolizidinone ( 6 ) [ 38 ]. As a continuation of that study, the synthesis of (8 S ,8a S )- 5 starting from compound 6 was envisioned.…”

“…On the basis of the abovementioned analysis, a retrosynthetic analysis of (8 S ,8a S )- 5 is displayed in Scheme 5 , which features the formation of the fused pyrrolidine ring from the but-3-ene-1-yl group, the expected trans -diastereoselective methylation as the key step, and protected ( R )-3-hydroxyglutarimide-based regio- and trans -diastereoselective reductive alkylation, a synthetic methodology developed from our laboratory [ 32 , 38 , 45 – 46 ], as the starting point.…”