Diastereoselective Total Synthesis of (±)‐Schindilactone A, Part 1: Construction of the ABC and FGH Ring Systems and Initial Attempts to Construct the CDEF Ring System

Abstract

First-generation synthetic strategies for the diastereoselective total synthesis of schindilactone A (1) are presented and methods for the synthesis of the ABC, FGH, and CDEF moieties are explored. We have established a method for the synthesis of the ABC moiety, which included both a Diels-Alder reaction and a ring-closing metathesis as the key steps. We have also developed a method for the synthesis of the FGH moiety, which involved the use of a Pauson-Khand reaction and a carbonylative annulation reaction as the key steps. Furthermore, we have achieved the construction of the central 7-8 bicyclic ring system by using a [3,3]-rearrangement as the key step. However, unfortunately, when this rearrangement reaction was applied to the construction of the more advanced CDEF moiety, the anticipated annulation reaction did not occur and the development of an alternative synthetic strategy would be required for the construction of this central core.

Application of Pauson–Khand reaction in the total synthesis of terpenes

“…142 (AE)-Schindilactone A 210 is a member of family of Schisandraceae which is valuable from both economic and medicinal points of view. 145 More than 20 species of Schisandraceae were found in China which have extensively been used as traditional medicines 146 over 2000 years in 2008 Han-Dong Sun research group isolated over 70 nortriterpenoids from Schisandraceae. 147,148 Among them, schindilactone A 210 (ref.…”

Bamford‐Stevens and Shapiro Reactions in Organic Synthesis

“…In many cases, Shapiro reaction is not employed merely to install olefin; it also functions as a means to generate vinylic anion, which can be trapped with various electrophiles. In a pursuit of total synthesis of schindilactone A, Yang reported initial attempts to construct a core ring system of the natural product [38] . The authors carried out [4+2] cycloaddition of 104 and 105 to provide 106 (scheme 21).…”

Schinortriterpenoids: A Case Study in Synthetic Design

“…In 2011, the first synthesis of a schinortriterpenoid, namely (±)‐schindilactone A ( 7 ), was accomplished after an eight‐year effort by Yang and co‐workers . Their approach started with the intermolecular Diels–Alder reaction of dienophile 59 and diene 60 to provide methyl ketone 61 in good yield and exclusive regioselectivity (Scheme ).…”

“…(2) and (3)]. They specifically attributed this failure to the reactions being entropically disfavored as well as to “bond‐angle deformations and transannular interactions” . Paquette and Lai employed a related [3,3]‐sigmatropic approach in their synthetic efforts towards this natural product with only modest (48 % yield) success; however, this example lacks the fully functionalized surrounding ring systems and no further applications towards the total synthesis of lancifodilactone G have appeared from this laboratory.…”