Asymmetric synthesis of substituted 1-aminocyclopropane1-carboxylic acids via diketopiperazine methodology

Elena Buñuel; Steven D. Bull; Stephen G. Davies; A. Christopher Garner; Edward D. Savory; Andrew D. Smith; Richard J. Vickers; David J. Watkin

doi:10.1039/b303348a

Asymmetric synthesis of substituted 1-aminocyclopropane1-carboxylic acids via diketopiperazine methodology

Elena Buñuel, Steven D. Bull, Stephen G. Davies^*, A. Christopher Garner, Edward D. Savory, Andrew D. Smith, Richard J. Vickers, David J. Watkin

^*Corresponding author for this work

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

Abstract

Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N, N′-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-²H ₂]-1-aminocyclopropane-l-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.

Original language	English
Pages (from-to)	2531-2542
Number of pages	12
Journal	Organic and Biomolecular Chemistry
Volume	1
Issue number	14
DOIs	https://doi.org/10.1039/b303348a
Publication status	Published - 13 Oct 2003

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title = "Asymmetric synthesis of substituted 1-aminocyclopropane1-carboxylic acids via diketopiperazine methodology",

abstract = "Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N, N′-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-2H 2]-1-aminocyclopropane-l-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.",

author = "Elena Bu{\~n}uel and Bull, {Steven D.} and Davies, {Stephen G.} and Garner, {A. Christopher} and Savory, {Edward D.} and Smith, {Andrew D.} and Vickers, {Richard J.} and Watkin, {David J.}",

year = "2003",

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doi = "10.1039/b303348a",

language = "English",

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journal = "Organic and Biomolecular Chemistry",

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publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - Asymmetric synthesis of substituted 1-aminocyclopropane1-carboxylic acids via diketopiperazine methodology

AU - Buñuel, Elena

AU - Bull, Steven D.

AU - Davies, Stephen G.

AU - Garner, A. Christopher

AU - Savory, Edward D.

AU - Smith, Andrew D.

AU - Vickers, Richard J.

AU - Watkin, David J.

PY - 2003/10/13

Y1 - 2003/10/13

N2 - Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N, N′-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-2H 2]-1-aminocyclopropane-l-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.

AB - Diketopiperazinespirocyclopropane 12 is prepared in > 98% d.e. via the conjugate addition of a phosphorus ylide to (6S)-N, N′-bis(p-methoxybenzyl)-3-methylenepiperazine-2,5-dione 2. Deprotection and hydrolysis of adduct 12 and subsequent peptide coupling demonstrate the applicability of this methodology to the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acids for incorporation into novel peptides. A model for the high level of diastereofacial selectivity observed in the cyclopropanation reaction is presented. A highly selective asymmetric approach (> 98% d.e.) to (S)-[2,2-2H 2]-1-aminocyclopropane-l-carboxylic acid 29 is also reported via a deuterated sulfur ylide addition to acceptor 2.

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U2 - 10.1039/b303348a

DO - 10.1039/b303348a

M3 - Article

AN - SCOPUS:18244426598

SN - 1477-0520

VL - 1

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EP - 2542

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 14

ER -

Asymmetric synthesis of substituted 1-aminocyclopropane1-carboxylic acids via diketopiperazine methodology

Abstract

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