Total synthesis of (±)-aspidospermidine, (±)-aspidofractinine, (±)-limaspermidine, and (±)-vincadifformine via a cascade and common intermediate strategy

David Cain; Niall Anderson; David B. Cordes; Alexandra M. Z. Slawin; Allan J. B. Watson

doi:10.1021/acs.joc.2c02099

Total synthesis of (±)-aspidospermidine, (±)-aspidofractinine, (±)-limaspermidine, and (±)-vincadifformine via a cascade and common intermediate strategy

David Cain, Niall Anderson, David B. Cordes, Alexandra M. Z. Slawin, Allan J. B. Watson^*

^*Corresponding author for this work

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

Abstract

A concise strategy for the total synthesis of several Aspidosperma alkaloids is reported. A Suzuki–Miyaura cross-coupling provides access to a 2-vinyl indole that undergoes a Diels–Alder cascade reaction with butyn-2-one to deliver a pyrroloindoline intermediate. This undergoes cascade amidation, reduction, skeletal rearrangement, and intramolecular Michael addition to provide a common intermediate containing the full framework of the Aspidosperma alkaloids. The utility of this intermediate is shown in the synthesis of four different natural products.

Original language	English
Pages (from-to)	15559–15563
Number of pages	5
Journal	The Journal of Organic Chemistry
Volume	87
Issue number	22
Early online date	19 Oct 2022
DOIs	https://doi.org/10.1021/acs.joc.2c02099
Publication status	Published - 18 Nov 2022

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Copyright © 2022 The Authors. Published by American Chemical Society. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is correctly attributed.
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Dataset underpinning "Total synthesis of (±)-aspidospermidine, (±)-aspidofractinine, (±)-limaspermidine, and (±)-vincadifformine via a cascade and common intermediate strategy"
Cain, D. (Creator), Anderson, N. (Creator), Cordes, D. B. (Creator), Slawin, A. M. Z. (Creator) & Watson, A. J. B. (Creator), University of St Andrews, 28 Oct 2022
DOI: 10.17630/b4202d38-1f7c-4344-9816-efdb070d7d37
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title = "Total synthesis of (±)-aspidospermidine, (±)-aspidofractinine, (±)-limaspermidine, and (±)-vincadifformine via a cascade and common intermediate strategy",

abstract = "A concise strategy for the total synthesis of several Aspidosperma alkaloids is reported. A Suzuki–Miyaura cross-coupling provides access to a 2-vinyl indole that undergoes a Diels–Alder cascade reaction with butyn-2-one to deliver a pyrroloindoline intermediate. This undergoes cascade amidation, reduction, skeletal rearrangement, and intramolecular Michael addition to provide a common intermediate containing the full framework of the Aspidosperma alkaloids. The utility of this intermediate is shown in the synthesis of four different natural products.",

author = "David Cain and Niall Anderson and Cordes, {David B.} and Slawin, {Alexandra M. Z.} and Watson, {Allan J. B.}",

note = "Funding: D.L.C. thanks EPSRC and GSK for a Ph.D. studentship.",

year = "2022",

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doi = "10.1021/acs.joc.2c02099",

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TY - JOUR

T1 - Total synthesis of (±)-aspidospermidine, (±)-aspidofractinine, (±)-limaspermidine, and (±)-vincadifformine via a cascade and common intermediate strategy

AU - Cain, David

AU - Anderson, Niall

AU - Cordes, David B.

AU - Slawin, Alexandra M. Z.

AU - Watson, Allan J. B.

N1 - Funding: D.L.C. thanks EPSRC and GSK for a Ph.D. studentship.

PY - 2022/11/18

Y1 - 2022/11/18

N2 - A concise strategy for the total synthesis of several Aspidosperma alkaloids is reported. A Suzuki–Miyaura cross-coupling provides access to a 2-vinyl indole that undergoes a Diels–Alder cascade reaction with butyn-2-one to deliver a pyrroloindoline intermediate. This undergoes cascade amidation, reduction, skeletal rearrangement, and intramolecular Michael addition to provide a common intermediate containing the full framework of the Aspidosperma alkaloids. The utility of this intermediate is shown in the synthesis of four different natural products.

AB - A concise strategy for the total synthesis of several Aspidosperma alkaloids is reported. A Suzuki–Miyaura cross-coupling provides access to a 2-vinyl indole that undergoes a Diels–Alder cascade reaction with butyn-2-one to deliver a pyrroloindoline intermediate. This undergoes cascade amidation, reduction, skeletal rearrangement, and intramolecular Michael addition to provide a common intermediate containing the full framework of the Aspidosperma alkaloids. The utility of this intermediate is shown in the synthesis of four different natural products.

U2 - 10.1021/acs.joc.2c02099

DO - 10.1021/acs.joc.2c02099

M3 - Article

SN - 0022-3263

VL - 87

SP - 15559

EP - 15563

JO - The Journal of Organic Chemistry

JF - The Journal of Organic Chemistry

IS - 22

ER -

Total synthesis of (±)-aspidospermidine, (±)-aspidofractinine, (±)-limaspermidine, and (±)-vincadifformine via a cascade and common intermediate strategy

Abstract

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