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 the
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 “
- NSF-PAR ID:
- 10078556
- 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
-
Abstract cis ‐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 chaincis to the bulky octahydronapthalene substituent was pivotal in fashioning the challenging concave‐substitutedcis ‐dioxabicyclo[3.3.0]octanone fragment. -
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 the
cis ‐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 chaincis to the bulky octahydronapthalene substituent was pivotal in fashioning the challenging concave‐substitutedcis ‐dioxabicyclo[3.3.0]octanone fragment. -
Abstract The production of the pyrimidine moiety in thiamine synthesis, 2‐methyl‐4‐amino‐5‐hydroxymethylpyrimidine phosphate (HMP‐P), has been described to proceed through the Thi5‐dependent pathway in
Saccharomyces cerevisiae and other yeast. Previous work found thatSc Thi5 functioned poorly in a heterologous context. Here we report a bacterial ortholog to the yeast HMP‐P synthase (Thi5) was necessary for HMP synthesis inLegionella pneumophila . UnlikeSc Thi5,Lp Thi5 functioned in vivo inSalmonella enterica under multiple growth conditions. The proteinLp Thi5 is a dimer that binds pyridoxal‐5′‐phosphate (PLP), apparently without a solvent‐exposed Schiff base. A small percentage ofLp Thi5 protein co‐purifies with a bound molecule that can be converted to HMP. Analysis of variant proteins both in vivo and in vitro confirmed that residues in sequence motifs conserved across bacterial and eukaryotic orthologs modulate the function ofLp Thi5.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 in
Legionella pneumophila and 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. -
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 [
t BuOCO]W≡Ct Bu(THF)2(1 ) with phosphaalkyne (10 ) results in the formation of [O2C(t BuC=)W{η 2‐(P ,C )−P≡C−Ad}(THF)] (13‐ t BuTHF ) and [O2C(AdC=)W{η 2‐(P ,C )−P≡C−t Bu}(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 [t BuOCO]W[κ 2‐C(t Bu)PC(Ad)] (14 ) forms upon loss of THF from the coordination sphere of either13‐ t BuTHF or13‐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‐ t Bu/AdTHF and14 . -
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 [
t BuOCO]W≡Ct Bu(THF)2(1 ) with phosphaalkyne (10 ) results in the formation of [O2C(t BuC=)W{η 2‐(P ,C )−P≡C−Ad}(THF)] (13‐ t BuTHF ) and [O2C(AdC=)W{η 2‐(P ,C )−P≡C−t Bu}(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 [t BuOCO]W[κ 2‐C(t Bu)PC(Ad)] (14 ) forms upon loss of THF from the coordination sphere of either13‐ t BuTHF or13‐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‐ t Bu/AdTHF and14 .