Studies towards a Novel Synthesis of Tubulysins: Highly Asymmetric Aza-Michael Reactions of 2-Enoylthiazoles with Metalated Chiral Oxazolidinones

Sreejith P. Shankar, Monica Sani, Giancarlo Terraneo, Matteo Zanda

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Herein we report the highly asymmetric aza-Michael reactions of alpha,beta-enones (2-enoylthiazoles) with metalated chiral oxazolidinones under different reaction conditions and for different substituents at the beta-position of the Michael acceptor. The reaction proceeds with complete diastereoselectivity to give exclusively one of the two diastereomers. The significance of the reaction is that no catalyst has been used; the steric requirements of the chiral Michael nucleophile drive the stereospecificity of the reaction and the reaction time is much less compared to the reported procedures. This methodology might be useful for an improved total synthesis of the highly cytotoxic peptides known as the tubulysins.

Original languageEnglish
Pages (from-to)1341-1345
Number of pages5
JournalSynlett
Issue number8
DOIs
Publication statusPublished - 15 May 2009

Keywords

  • asymmetric
  • aza-Michael Reaction
  • diastereoselectivity
  • noncatalytic
  • oxazolidinone
  • beta-amino acids
  • conjugate addition
  • enantioselective synthesis
  • alpha,beta-unsaturated compounds
  • stereoselective-synthesis
  • cyclohexyl sulfonates
  • derivatives
  • enones
  • water

Cite this

Studies towards a Novel Synthesis of Tubulysins: Highly Asymmetric Aza-Michael Reactions of 2-Enoylthiazoles with Metalated Chiral Oxazolidinones. / Shankar, Sreejith P.; Sani, Monica; Terraneo, Giancarlo; Zanda, Matteo.

In: Synlett, No. 8, 15.05.2009, p. 1341-1345.

Research output: Contribution to journalArticle

Shankar, Sreejith P. ; Sani, Monica ; Terraneo, Giancarlo ; Zanda, Matteo. / Studies towards a Novel Synthesis of Tubulysins: Highly Asymmetric Aza-Michael Reactions of 2-Enoylthiazoles with Metalated Chiral Oxazolidinones. In: Synlett. 2009 ; No. 8. pp. 1341-1345.
@article{c0e82f03f5554ff58b266df7027ad576,
title = "Studies towards a Novel Synthesis of Tubulysins: Highly Asymmetric Aza-Michael Reactions of 2-Enoylthiazoles with Metalated Chiral Oxazolidinones",
abstract = "Herein we report the highly asymmetric aza-Michael reactions of alpha,beta-enones (2-enoylthiazoles) with metalated chiral oxazolidinones under different reaction conditions and for different substituents at the beta-position of the Michael acceptor. The reaction proceeds with complete diastereoselectivity to give exclusively one of the two diastereomers. The significance of the reaction is that no catalyst has been used; the steric requirements of the chiral Michael nucleophile drive the stereospecificity of the reaction and the reaction time is much less compared to the reported procedures. This methodology might be useful for an improved total synthesis of the highly cytotoxic peptides known as the tubulysins.",
keywords = "asymmetric, aza-Michael Reaction, diastereoselectivity, noncatalytic, oxazolidinone, beta-amino acids, conjugate addition, enantioselective synthesis, alpha,beta-unsaturated compounds, stereoselective-synthesis, cyclohexyl sulfonates, derivatives, enones, water",
author = "Shankar, {Sreejith P.} and Monica Sani and Giancarlo Terraneo and Matteo Zanda",
year = "2009",
month = "5",
day = "15",
doi = "10.1055/s-0029-1216729",
language = "English",
pages = "1341--1345",
journal = "Synlett",
issn = "0936-5214",
publisher = "Georg Thieme Verlag",
number = "8",

}

TY - JOUR

T1 - Studies towards a Novel Synthesis of Tubulysins: Highly Asymmetric Aza-Michael Reactions of 2-Enoylthiazoles with Metalated Chiral Oxazolidinones

AU - Shankar, Sreejith P.

AU - Sani, Monica

AU - Terraneo, Giancarlo

AU - Zanda, Matteo

PY - 2009/5/15

Y1 - 2009/5/15

N2 - Herein we report the highly asymmetric aza-Michael reactions of alpha,beta-enones (2-enoylthiazoles) with metalated chiral oxazolidinones under different reaction conditions and for different substituents at the beta-position of the Michael acceptor. The reaction proceeds with complete diastereoselectivity to give exclusively one of the two diastereomers. The significance of the reaction is that no catalyst has been used; the steric requirements of the chiral Michael nucleophile drive the stereospecificity of the reaction and the reaction time is much less compared to the reported procedures. This methodology might be useful for an improved total synthesis of the highly cytotoxic peptides known as the tubulysins.

AB - Herein we report the highly asymmetric aza-Michael reactions of alpha,beta-enones (2-enoylthiazoles) with metalated chiral oxazolidinones under different reaction conditions and for different substituents at the beta-position of the Michael acceptor. The reaction proceeds with complete diastereoselectivity to give exclusively one of the two diastereomers. The significance of the reaction is that no catalyst has been used; the steric requirements of the chiral Michael nucleophile drive the stereospecificity of the reaction and the reaction time is much less compared to the reported procedures. This methodology might be useful for an improved total synthesis of the highly cytotoxic peptides known as the tubulysins.

KW - asymmetric

KW - aza-Michael Reaction

KW - diastereoselectivity

KW - noncatalytic

KW - oxazolidinone

KW - beta-amino acids

KW - conjugate addition

KW - enantioselective synthesis

KW - alpha,beta-unsaturated compounds

KW - stereoselective-synthesis

KW - cyclohexyl sulfonates

KW - derivatives

KW - enones

KW - water

U2 - 10.1055/s-0029-1216729

DO - 10.1055/s-0029-1216729

M3 - Article

SP - 1341

EP - 1345

JO - Synlett

JF - Synlett

SN - 0936-5214

IS - 8

ER -