Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid

Dimitri Perusse, Michael J Smanski

Research output: Contribution to journalArticle

Abstract

We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces ent-atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configuration of the C15 hydroxyl group and C16 methylene is a critical step that occurs late in each published total or formal synthesis. Here we explore the use of alternative reducing reagents, stereochemical directing agents, reaction order, and product recycling to improve the diastereoselectivity of this step. We find that installing and oxidizing the C17 methylsulfide prior to reducing the C15 ketone provides the greatest yield of the desired C15,C16 diastereomer. This represents an improved total synthesis of serofendic acid.

Original languageEnglish (US)
Pages (from-to)951-960
Number of pages10
JournalMedChemComm
Volume10
Issue number6
DOIs
StatePublished - Jan 1 2019

Fingerprint

Biological Products
Equipment Reuse
Synthetic Biology
Ketones
Hydroxyl Radical
Stereochemistry
Carbon
Bacteria
Acids
Recycling
serofendic acid

PubMed: MeSH publication types

  • Journal Article

Cite this

Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid. / Perusse, Dimitri; Smanski, Michael J.

In: MedChemComm, Vol. 10, No. 6, 01.01.2019, p. 951-960.

Research output: Contribution to journalArticle

@article{672973497fc542b293a9efe2e1240542,
title = "Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid",
abstract = "We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces ent-atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configuration of the C15 hydroxyl group and C16 methylene is a critical step that occurs late in each published total or formal synthesis. Here we explore the use of alternative reducing reagents, stereochemical directing agents, reaction order, and product recycling to improve the diastereoselectivity of this step. We find that installing and oxidizing the C17 methylsulfide prior to reducing the C15 ketone provides the greatest yield of the desired C15,C16 diastereomer. This represents an improved total synthesis of serofendic acid.",
author = "Dimitri Perusse and Smanski, {Michael J}",
year = "2019",
month = "1",
day = "1",
doi = "10.1039/c9md00145j",
language = "English (US)",
volume = "10",
pages = "951--960",
journal = "MedChemComm",
issn = "2040-2503",
publisher = "Royal Society of Chemistry",
number = "6",

}

TY - JOUR

T1 - Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid

AU - Perusse, Dimitri

AU - Smanski, Michael J

PY - 2019/1/1

Y1 - 2019/1/1

N2 - We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces ent-atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configuration of the C15 hydroxyl group and C16 methylene is a critical step that occurs late in each published total or formal synthesis. Here we explore the use of alternative reducing reagents, stereochemical directing agents, reaction order, and product recycling to improve the diastereoselectivity of this step. We find that installing and oxidizing the C17 methylsulfide prior to reducing the C15 ketone provides the greatest yield of the desired C15,C16 diastereomer. This represents an improved total synthesis of serofendic acid.

AB - We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces ent-atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configuration of the C15 hydroxyl group and C16 methylene is a critical step that occurs late in each published total or formal synthesis. Here we explore the use of alternative reducing reagents, stereochemical directing agents, reaction order, and product recycling to improve the diastereoselectivity of this step. We find that installing and oxidizing the C17 methylsulfide prior to reducing the C15 ketone provides the greatest yield of the desired C15,C16 diastereomer. This represents an improved total synthesis of serofendic acid.

UR - http://www.scopus.com/inward/record.url?scp=85067606199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067606199&partnerID=8YFLogxK

U2 - 10.1039/c9md00145j

DO - 10.1039/c9md00145j

M3 - Article

VL - 10

SP - 951

EP - 960

JO - MedChemComm

JF - MedChemComm

SN - 2040-2503

IS - 6

ER -