26 research outputs found
A Strategy for the Convergent and Stereoselective Assembly of Polycyclic Molecules
The stereoselective
oxidative coupling of cyclic ketones via silyl
bis-enol ethers followed by ring-closing metathesis is shown to be
a general and powerful reaction sequence for the preparation of diverse
polycyclic scaffolds from simple precursors. The modular strategy
successfully constructs substructures prevalent in numerous bioactive
natural product families, varying in substitution and carbocyclic
composition. Several of the prepared compounds were shown to possess
potent cytotoxic activity against a panel of tumor cell lines. The
utility of this strategy was further demonstrated by a concise and
highly convergent 17-step formal synthesis of the complex antimalarial
marine diterpene, (+)-7,20-diisocyanoadociane
Correction to āA Strategy for the Convergent and Stereoselective Assembly of Polycyclic Moleculesā
Correction
to āA Strategy for the Convergent
and Stereoselective Assembly of Polycyclic Molecules
A Strategy for the Convergent and Stereoselective Assembly of Polycyclic Molecules
The stereoselective
oxidative coupling of cyclic ketones via silyl
bis-enol ethers followed by ring-closing metathesis is shown to be
a general and powerful reaction sequence for the preparation of diverse
polycyclic scaffolds from simple precursors. The modular strategy
successfully constructs substructures prevalent in numerous bioactive
natural product families, varying in substitution and carbocyclic
composition. Several of the prepared compounds were shown to possess
potent cytotoxic activity against a panel of tumor cell lines. The
utility of this strategy was further demonstrated by a concise and
highly convergent 17-step formal synthesis of the complex antimalarial
marine diterpene, (+)-7,20-diisocyanoadociane
A Strategy for the Convergent and Stereoselective Assembly of Polycyclic Molecules
The stereoselective
oxidative coupling of cyclic ketones via silyl
bis-enol ethers followed by ring-closing metathesis is shown to be
a general and powerful reaction sequence for the preparation of diverse
polycyclic scaffolds from simple precursors. The modular strategy
successfully constructs substructures prevalent in numerous bioactive
natural product families, varying in substitution and carbocyclic
composition. Several of the prepared compounds were shown to possess
potent cytotoxic activity against a panel of tumor cell lines. The
utility of this strategy was further demonstrated by a concise and
highly convergent 17-step formal synthesis of the complex antimalarial
marine diterpene, (+)-7,20-diisocyanoadociane
A Direct Synthesis of Allenes by a Traceless Petasis Reaction
A one-pot synthesis of allenes by the 2-nitrobenzenesulfonylhydrazide-mediated
coupling of hydroxyaldehydes or ketones with alkynyl trifluoroborate
salts is reported. This mild process involves in situ formation of
a sulfonylhydrazone that reacts with alkynyl trifluoroborates to generate
a transient propargylic hydrazide species. Decomposition of this unstable
hydrazide via an intermediate monoalkyldiazine produces the allene
products through an alkene walk mechanism
Enantioselective Total Synthesis of (ā)-Maoecrystal V
The enantioselective
synthesis of maoecrystal V, a cytotoxic polycyclic
diterpene, is described. Key reactions in the synthesis include an
intramolecular Heck reaction, an oxidative cycloetherification, and
an intermolecular DielsāAlder reaction to forge the carbocyclic
core in a concise and stereoselective manner. Late-stage amine and
CāH oxidation is used to install the final functional groups
required to complete the synthesis
Enantioselective Synthesis of Allenes by Catalytic Traceless Petasis Reactions
Allenes
are useful functional groups in synthesis as a result of
their inherent chemical properties and established reactivity patterns.
One property of chemical bonding renders 1,3-substituted allenes chiral,
making them attractive targets for asymmetric synthesis. While there
are many enantioselective methods to synthesize chiral allenes from
chiral starting materials, fewer methods exist to directly synthesize
enantioenriched chiral allenes from achiral precursors. We report
here an asymmetric boronate addition to sulfonyl hydrazones catalyzed
by chiral biphenols to access enantioenriched allenes in a traceless
Petasis reaction. The resulting Mannich product from nucleophilic
addition eliminates sulfinic acid, yielding a propargylic diazene
that performs an alkyne walk to afford the allene. Two enantioselective
approaches have been developed; alkynyl boronates add to glycolaldehyde
imine to afford allylic hydroxyl allenes, and allyl boronates add
to alkynyl imines to form 1,3-alkenyl allenes. In both cases, the
products are obtained in high yields and enantioselectivities
Investigations into Apopinene as a Biorenewable Monomer for Ring-Opening Metathesis Polymerization
The ring-opening metathesis polymerization
(ROMP) of apopinene
is reported. We find that apopinene reacts with Ru-based metathesis
catalysts to provide an all <i>trans</i>-polymer with a
polydispersity index (PDI) as low as 1.6 and molecular weights in
the 1100 to 15āÆ600 gĀ·mol<sup>ā1</sup> range (9ā127
monomer units). Because apopinene is readily prepared in one-step
from myrtenal or two-steps from Ī±-pinene, both of which are
commercially available and naturally abundant, these studies indicate
that apopinene might find future use as a new biorenewable precursor
for the sustainable production of ROMP-based materials
Elimination of Butylcycloheptylprodigiosin as a Known Natural Product Inspired by an Evolutionary Hypothesis for Cyclic Prodigiosin Biosynthesis
The cyclic prodigiosins are an important
family of bioactive natural
products that continue to be the subject of numerous structural, synthetic,
and biosynthetic studies. In particular, the structural assignments
of the isomeric cyclic prodigiosins butylcycloheptylprodigiosin (BCHP)
and streptorubin B have been the cause of significant confusion. Herein,
we report detailed studies regarding the electron impact (EI) mass
spectra of synthetic BCHP and streptorubin B that have allowed us
to distinguish the two compounds in the absence of quality historical
isolation NMR data. On the basis of these fragmentation differences,
the status of BCHP as a natural product is challenged. The proposed
mechanism of fragmentation is supported by the EI mass spectra of
synthetic pentyl-chain analogues of BCHP and streptorubin B, X-ray
crystallography, and DFT calculations. Elimination of BCHP from the
prodigiosin family supports a proposed evolutionary hypothesis for
the surprising biosynthesis of cyclic prodigiosins
Elimination of Butylcycloheptylprodigiosin as a Known Natural Product Inspired by an Evolutionary Hypothesis for Cyclic Prodigiosin Biosynthesis
The cyclic prodigiosins are an important
family of bioactive natural
products that continue to be the subject of numerous structural, synthetic,
and biosynthetic studies. In particular, the structural assignments
of the isomeric cyclic prodigiosins butylcycloheptylprodigiosin (BCHP)
and streptorubin B have been the cause of significant confusion. Herein,
we report detailed studies regarding the electron impact (EI) mass
spectra of synthetic BCHP and streptorubin B that have allowed us
to distinguish the two compounds in the absence of quality historical
isolation NMR data. On the basis of these fragmentation differences,
the status of BCHP as a natural product is challenged. The proposed
mechanism of fragmentation is supported by the EI mass spectra of
synthetic pentyl-chain analogues of BCHP and streptorubin B, X-ray
crystallography, and DFT calculations. Elimination of BCHP from the
prodigiosin family supports a proposed evolutionary hypothesis for
the surprising biosynthesis of cyclic prodigiosins