skip to main content


Title: Recent Syntheses and Strategies toward Polycyclic Gelsemium Alkaloids
Abstract

This Minireview is focused on an in‐depth discussion of comparative strategies to construct the gelsemine and gelsedine classes of the gelsemium alkaloids. This document highlights the diversity of strategies used to access specific motifs found within these targets: a) the fused “[3.2.1]bicycle” (in gelsemine) and “oxabicycle” (in gelsedine class); b) the “piroxindole” moiety with C7 quaternary center; c) the “N‐heterocycles” and d) the “THP” moiety with C20 quaternary center (in gelsemine).

 
more » « less
NSF-PAR ID:
10078556
Author(s) / Creator(s):
 ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Angewandte Chemie
Volume:
131
Issue:
3
ISSN:
0044-8249
Page Range / eLocation ID:
p. 692-705
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    The enantioselective total synthesis of the rearranged spongian diterpenoid (−)‐macfarlandin C is reported. This is the first synthesis of a rearranged spongian diterpenoid in which the bulky hydrocarbon fragment is joined via a quaternary carbon to the highly hindered concave face of thecis‐2,8‐dioxabicyclo[3.3.0]octan‐3‐one moiety. The strategy involves a late‐stage fragment coupling between a tertiary carbon radical and an electrophilic butenolide resulting in the stereoselective formation of vicinal quaternary and tertiary stereocenters. A stereoselective Mukaiyama hydration that orients a pendant carboxymethyl side chaincisto the bulky octahydronapthalene substituent was pivotal in fashioning the challenging concave‐substitutedcis‐dioxabicyclo[3.3.0]octanone fragment.

     
    more » « less
  2. Abstract

    The enantioselective total synthesis of the rearranged spongian diterpenoid (−)‐macfarlandin C is reported. This is the first synthesis of a rearranged spongian diterpenoid in which the bulky hydrocarbon fragment is joined via a quaternary carbon to the highly hindered concave face of thecis‐2,8‐dioxabicyclo[3.3.0]octan‐3‐one moiety. The strategy involves a late‐stage fragment coupling between a tertiary carbon radical and an electrophilic butenolide resulting in the stereoselective formation of vicinal quaternary and tertiary stereocenters. A stereoselective Mukaiyama hydration that orients a pendant carboxymethyl side chaincisto the bulky octahydronapthalene substituent was pivotal in fashioning the challenging concave‐substitutedcis‐dioxabicyclo[3.3.0]octanone fragment.

     
    more » « less
  3. Abstract Importance

    Thiamine is an essential vitamin for the vast majority of organisms. There are multiple strategies to synthesize and salvage this vitamin. The predominant pathway for synthesis of the pyrimidine moiety of thiamine involves the Fe‐S cluster protein ThiC. An alternative pathway utilizes Thi5, a novel enzyme that uses PLP as a substrate. The Thi5‐dependent pathway is poorly characterized in yeast and has not been characterized in Bacteria. Here we demonstrate that a Thi5‐dependent pathway is necessary for thiamine biosynthesis inLegionella pneumophilaand provide biochemical data to extend knowledge of the Thi5 enzyme, the corresponding biosynthetic pathway, and the role of metabolic network architecture in optimizing its function.

     
    more » « less
  4. Abstract

    The reactivity of phosphaalkynes, the isolobal and isoelectronic congeners to alkynes, with metal alkylidyne complexes is explored in this work. Treating the tungsten alkylidyne [tBuOCO]W≡CtBu(THF)2(1) with phosphaalkyne (10) results in the formation of [O2C(tBuC=)W{η2‐(P,C)−P≡C−Ad}(THF)] (13‐tBuTHF) and [O2C(AdC=)W{η2‐(P,C)−P≡C−tBu}(THF)] (13‐AdTHF); derived from the formal reductive migratory insertion of the alkylidyne moiety into a W−Carenebond. Analogous to alkyne metathesis, a stable phosphametallacyclobutadiene complex [tBuOCO]W[κ2‐C(tBu)PC(Ad)] (14) forms upon loss of THF from the coordination sphere of either13‐tBuTHFor13‐AdTHF. Remarkably, the C−C bonds reversibly form/cleave with the addition or removal of THF from the coordination sphere of the formal tungsten(VI) metal center, permitting unprecedented control over the transformation of a tetraanionic pincer to a trianionic pincer and back. Computational analysis offers thermodynamic and electronic reasoning for the reversible equilibrium between13‐tBu/AdTHFand14.

     
    more » « less
  5. Abstract

    The reactivity of phosphaalkynes, the isolobal and isoelectronic congeners to alkynes, with metal alkylidyne complexes is explored in this work. Treating the tungsten alkylidyne [tBuOCO]W≡CtBu(THF)2(1) with phosphaalkyne (10) results in the formation of [O2C(tBuC=)W{η2‐(P,C)−P≡C−Ad}(THF)] (13‐tBuTHF) and [O2C(AdC=)W{η2‐(P,C)−P≡C−tBu}(THF)] (13‐AdTHF); derived from the formal reductive migratory insertion of the alkylidyne moiety into a W−Carenebond. Analogous to alkyne metathesis, a stable phosphametallacyclobutadiene complex [tBuOCO]W[κ2‐C(tBu)PC(Ad)] (14) forms upon loss of THF from the coordination sphere of either13‐tBuTHFor13‐AdTHF. Remarkably, the C−C bonds reversibly form/cleave with the addition or removal of THF from the coordination sphere of the formal tungsten(VI) metal center, permitting unprecedented control over the transformation of a tetraanionic pincer to a trianionic pincer and back. Computational analysis offers thermodynamic and electronic reasoning for the reversible equilibrium between13‐tBu/AdTHFand14.

     
    more » « less