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Collective Asymmetric Synthesis of Thiosilvatins

Liu, Jian LU ; Ekberg, Robin LU ; Koning, Nicolas R. LU and Strand, Daniel LU (2024) In Angewandte Chemie (International edition) 63(51).
Abstract
Thiosilvatins are a family of biologically active sulfenylated
diketopiperazine natural products. The first members were reported over
40 years ago, but total synthesis of a thiosilvatin has remained
elusive. Here, we describe the first, collective, synthesis of the
parent epidithiodiketopiperazine (−)-dithiosilvatin and ten related
thiosilvatins. Several of the targets are structurally revised. A
catalytic asymmetric sulfenylation of triketopiperazines efficiently
controls absolute configuration at the thioaminal units. Further
synthetic highlights include a diastereoconvergent installation of the
requisite cis-orientation of the sulfur atoms and a tandem epidisulfide... (More)
Thiosilvatins are a family of biologically active sulfenylated
diketopiperazine natural products. The first members were reported over
40 years ago, but total synthesis of a thiosilvatin has remained
elusive. Here, we describe the first, collective, synthesis of the
parent epidithiodiketopiperazine (−)-dithiosilvatin and ten related
thiosilvatins. Several of the targets are structurally revised. A
catalytic asymmetric sulfenylation of triketopiperazines efficiently
controls absolute configuration at the thioaminal units. Further
synthetic highlights include a diastereoconvergent installation of the
requisite cis-orientation of the sulfur atoms and a tandem epidisulfide formation/O-prenylation
under mild Mitsunobu conditions. The described methods for late-stage
diversification of sensitive bis(methylthio)diketopiperazines offer a
blueprint for systematically exploring this interesting 3D-pharmacophore
in stereochemically pure form. (Less)
Abstract (Swedish)
Abstract Thiosilvatins are a family of biologically active sulfenylated diketopiperazine natural products. The first members were reported over 40?years ago, but total synthesis of a thiosilvatin has remained elusive. Here, we describe the first, collective, synthesis of the parent epidithiodiketopiperazine (?)-dithiosilvatin and ten related thiosilvatins. Several of the targets are structurally revised. A catalytic asymmetric sulfenylation of triketopiperazines efficiently controls absolute configuration at the thioaminal units. Further synthetic highlights include a diastereoconvergent installation of the requisite cis-orientation of the sulfur atoms and a tandem epidisulfide formation/O-prenylation under mild Mitsunobu conditions. The... (More)
Abstract Thiosilvatins are a family of biologically active sulfenylated diketopiperazine natural products. The first members were reported over 40?years ago, but total synthesis of a thiosilvatin has remained elusive. Here, we describe the first, collective, synthesis of the parent epidithiodiketopiperazine (?)-dithiosilvatin and ten related thiosilvatins. Several of the targets are structurally revised. A catalytic asymmetric sulfenylation of triketopiperazines efficiently controls absolute configuration at the thioaminal units. Further synthetic highlights include a diastereoconvergent installation of the requisite cis-orientation of the sulfur atoms and a tandem epidisulfide formation/O-prenylation under mild Mitsunobu conditions. The described methods for late-stage diversification of sensitive bis(methylthio)diketopiperazines offer a blueprint for systematically exploring this interesting 3D-pharmacophore in stereochemically pure form. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
natural products, epidithiodiketopiperazines, total synthesis, organocatalysis, diastereoconvergent synthesis
in
Angewandte Chemie (International edition)
volume
63
issue
51
pages
6 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:39157913
  • scopus:85206578588
ISSN
1433-7851
DOI
10.1002/anie.202412397
language
English
LU publication?
yes
id
787ca156-a996-41d8-8480-4c6ae834f03b
date added to LUP
2024-11-28 18:29:23
date last changed
2025-04-04 15:02:03
@article{787ca156-a996-41d8-8480-4c6ae834f03b,
  abstract     = {{Thiosilvatins are a family of biologically active sulfenylated <br>
diketopiperazine natural products. The first members were reported over <br>
40 years ago, but total synthesis of a thiosilvatin has remained <br>
elusive. Here, we describe the first, collective, synthesis of the <br>
parent epidithiodiketopiperazine (−)-dithiosilvatin and ten related <br>
thiosilvatins. Several of the targets are structurally revised. A <br>
catalytic asymmetric sulfenylation of triketopiperazines efficiently <br>
controls absolute configuration at the thioaminal units. Further <br>
synthetic highlights include a diastereoconvergent installation of the <br>
requisite <i>cis</i>-orientation of the sulfur atoms and a tandem epidisulfide formation/<i>O</i>-prenylation<br>
 under mild Mitsunobu conditions. The described methods for late-stage <br>
diversification of sensitive bis(methylthio)diketopiperazines offer a <br>
blueprint for systematically exploring this interesting 3D-pharmacophore<br>
 in stereochemically pure form.}},
  author       = {{Liu, Jian and Ekberg, Robin and Koning, Nicolas R. and Strand, Daniel}},
  issn         = {{1433-7851}},
  keywords     = {{natural products; epidithiodiketopiperazines; total synthesis; organocatalysis; diastereoconvergent synthesis}},
  language     = {{eng}},
  number       = {{51}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Angewandte Chemie (International edition)}},
  title        = {{Collective Asymmetric Synthesis of Thiosilvatins}},
  url          = {{http://dx.doi.org/10.1002/anie.202412397}},
  doi          = {{10.1002/anie.202412397}},
  volume       = {{63}},
  year         = {{2024}},
}