Total Synthesis of Chloptosin: A Dimeric Cyclohexapeptide

Alexander J. Oelke; Francesca Antonietti; Leonardo Bertone; Philippa B. Cranwell; David J. France; Rebecca J. M. Goss; Tatjana Hofmann; Stephan Knauer; Steven J. Moss; Paul C. Skelton; Richard M. Turner; Georg Wuitschik; Steven V. Ley

doi:10.1002/chem.201003216

Total Synthesis of Chloptosin: A Dimeric Cyclohexapeptide

Alexander J. Oelke, Francesca Antonietti, Leonardo Bertone, Philippa B. Cranwell, David J. France, Rebecca J. M. Goss, Tatjana Hofmann, Stephan Knauer, Steven J. Moss, Paul C. Skelton, Richard M. Turner, Georg Wuitschik, Steven V. Ley^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Here we describe in full our investigations into the synthesis of the dimeric cyclohexapeptide chloptosin in 17 linear steps. Particularly, this work features an organocatalytic tandem process for the synthesis of the embedded piperazic acids, in which a differentially protected azodicarboxylate is used together with pyrrolidinyl tetrazole as the catalyst. The central biaryl bond is being formed by Stille coupling of two sterically demanding ortho-chloropyrroloindole fragments. The inherent flexibility of the synthetic strategy proved beneficial as the route could be adjusted smoothly during the progression of the synthesis programme.

Original language	English
Pages (from-to)	4183-4194
Number of pages	12
Journal	Chemistry - A European Journal
Volume	17
Issue number	15
DOIs	https://doi.org/10.1002/chem.201003216
Publication status	Published - Apr 2011

Keywords

CYCLODEPSIPEPTIDE ANTIBIOTICS
(3S)-PIPERAZIC ACIDS
cyclopeptide
ASYMMETRIC-SYNTHESIS
natural products
piperazic acid
ORGANOCATALYTIC ROUTE
ENANTIOSELECTIVE SYNTHESIS
total synthesis
organocatalysis
(3S)-2,3,4,5-TETRAHYDROPYRIDAZINE-3-CARBOXYLIC ACID
PHOSPHORUS COMPOUNDS
QUINOXAPEPTIN A-C
ALPHA-AMINO-ACIDS
VINYLTRIPHENYLPHOSPHONIUM BROMIDE

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@article{989bb073c2054177b8af23b9874375cb,

title = "Total Synthesis of Chloptosin: A Dimeric Cyclohexapeptide",

abstract = "Here we describe in full our investigations into the synthesis of the dimeric cyclohexapeptide chloptosin in 17 linear steps. Particularly, this work features an organocatalytic tandem process for the synthesis of the embedded piperazic acids, in which a differentially protected azodicarboxylate is used together with pyrrolidinyl tetrazole as the catalyst. The central biaryl bond is being formed by Stille coupling of two sterically demanding ortho-chloropyrroloindole fragments. The inherent flexibility of the synthetic strategy proved beneficial as the route could be adjusted smoothly during the progression of the synthesis programme.",

keywords = "CYCLODEPSIPEPTIDE ANTIBIOTICS, (3S)-PIPERAZIC ACIDS, cyclopeptide, ASYMMETRIC-SYNTHESIS, natural products, piperazic acid, ORGANOCATALYTIC ROUTE, ENANTIOSELECTIVE SYNTHESIS, total synthesis, organocatalysis, (3S)-2,3,4,5-TETRAHYDROPYRIDAZINE-3-CARBOXYLIC ACID, PHOSPHORUS COMPOUNDS, QUINOXAPEPTIN A-C, ALPHA-AMINO-ACIDS, VINYLTRIPHENYLPHOSPHONIUM BROMIDE",

author = "Oelke, {Alexander J.} and Francesca Antonietti and Leonardo Bertone and Cranwell, {Philippa B.} and France, {David J.} and Goss, {Rebecca J. M.} and Tatjana Hofmann and Stephan Knauer and Moss, {Steven J.} and Skelton, {Paul C.} and Turner, {Richard M.} and Georg Wuitschik and Ley, {Steven V.}",

year = "2011",

month = apr,

doi = "10.1002/chem.201003216",

language = "English",

volume = "17",

pages = "4183--4194",

journal = "Chemistry - A European Journal",

issn = "0947-6539",

publisher = "John Wiley & Sons, Ltd",

number = "15",

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T1 - Total Synthesis of Chloptosin: A Dimeric Cyclohexapeptide

AU - Oelke, Alexander J.

AU - Antonietti, Francesca

AU - Bertone, Leonardo

AU - Cranwell, Philippa B.

AU - France, David J.

AU - Goss, Rebecca J. M.

AU - Hofmann, Tatjana

AU - Knauer, Stephan

AU - Moss, Steven J.

AU - Skelton, Paul C.

AU - Turner, Richard M.

AU - Wuitschik, Georg

AU - Ley, Steven V.

PY - 2011/4

Y1 - 2011/4

N2 - Here we describe in full our investigations into the synthesis of the dimeric cyclohexapeptide chloptosin in 17 linear steps. Particularly, this work features an organocatalytic tandem process for the synthesis of the embedded piperazic acids, in which a differentially protected azodicarboxylate is used together with pyrrolidinyl tetrazole as the catalyst. The central biaryl bond is being formed by Stille coupling of two sterically demanding ortho-chloropyrroloindole fragments. The inherent flexibility of the synthetic strategy proved beneficial as the route could be adjusted smoothly during the progression of the synthesis programme.

AB - Here we describe in full our investigations into the synthesis of the dimeric cyclohexapeptide chloptosin in 17 linear steps. Particularly, this work features an organocatalytic tandem process for the synthesis of the embedded piperazic acids, in which a differentially protected azodicarboxylate is used together with pyrrolidinyl tetrazole as the catalyst. The central biaryl bond is being formed by Stille coupling of two sterically demanding ortho-chloropyrroloindole fragments. The inherent flexibility of the synthetic strategy proved beneficial as the route could be adjusted smoothly during the progression of the synthesis programme.

KW - CYCLODEPSIPEPTIDE ANTIBIOTICS

KW - (3S)-PIPERAZIC ACIDS

KW - cyclopeptide

KW - ASYMMETRIC-SYNTHESIS

KW - natural products

KW - piperazic acid

KW - ORGANOCATALYTIC ROUTE

KW - ENANTIOSELECTIVE SYNTHESIS

KW - total synthesis

KW - organocatalysis

KW - (3S)-2,3,4,5-TETRAHYDROPYRIDAZINE-3-CARBOXYLIC ACID

KW - PHOSPHORUS COMPOUNDS

KW - QUINOXAPEPTIN A-C

KW - ALPHA-AMINO-ACIDS

KW - VINYLTRIPHENYLPHOSPHONIUM BROMIDE

U2 - 10.1002/chem.201003216

DO - 10.1002/chem.201003216

M3 - Article

SN - 0947-6539

VL - 17

SP - 4183

EP - 4194

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 15

ER -

Total Synthesis of Chloptosin: A Dimeric Cyclohexapeptide

Abstract

Keywords

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