THERESA Synthesis Examples

Overview [hide]
  1. Introduction
  2. Drugs
  3. Non drugs

Introduction

This page shows some retrosynthetic routes obtained with the help of THERESA.

Please note that the proposed synthesis routes neither have been checked in the laboratory nor a careful literature and patent search has been performed to check for the novelty of the routes.

The results obtained with THERESA depend on the organic chemist's expertise and the reaction database that is used for a study.

Most of the examples were chosen from the following three books.

  • Contemporary Drug Synthesis ("CDS") by Douglas S. Li, Jie Jack Sliskovic, Drago R. Roth, Bruce Johnson
  • Workbook for Organic Synthesis: The Disconnection Approach ("TDA"), 1st edition by Stuart Warren
  • Designing Organic Syntheses: a Programmed introduction to the Synthon Approach ("DOS"), by Stuart Warren
  • Two different reaction databases were used for the retrosynthesis engine in THERESA.
  • Current Chemical Reactions by Thomson Reuters, year 2005 with about 32 thousand reactions (THERESA-CCR2005). THERESA-CCR2005 is also available for evaluation purposes.
  • CrossFire Beilstein by Elsevier Information Systems, subset with about 1.3 million reactions (THERESA-CrossFire Beilstein)

Drugs

  • Synthesis of Diketo-coriolin
    Diketo-coriolin is an anti-tumor compound (immuno-modulator). The original synthesis required eight steps (example taken from TDA, page 399).
    With THERESA-CCR2005, a two steps synthesis was obtained.
  • Synthesis of Quetiapine fumarate
    Quetiapine fumarate is an antipsychotic drug developed in 1987 by AstraZeneca. The original synthesis required six steps (excluding the formation of the fumarate salt)(example taken from CDS, page 99).
    With THERESA-CrossFire Beilstein, a two steps synthesis was obtained.
  • Synthesis of Taladafil
    Taladafil is a PDE 5 inhibitor discovered at ICOS. The original synthesis required three reactions and one isomer separation (example taken from CDS, page 197).
    With THERESA-CCR2005, a two steps synthesis was obtained. The first step of this route is identical to the original route. The second step might require an excess of the commercially available chemical methylaminoacetic acid. The isomer separation is necessary but not shown in the report.
    With THERESA-CrossFire Beilstein, the original three steps synthesis route was reproduced.
  • Synthesis of Ciprofloxacin
    Ciprofloxacin is an antibacterial agent. The synthesis was patented by Bayer in 1981 and required nine steps (example taken from CDS, page 79).
    With THERESA-CCR2005, a three steps synthesis was obtained.
  • Synthesis of Naratriptan
    Naratriptan was patented by GSK for the treatment of migraine headaches. The first published synthesis required four steps (example taken from CDS, page 171).
    With THERESA-CCR2005, a three steps synthesis was obtained. This route requires the chemical N-methyvinylsulfonamide at step one. This reagent was not found in the catalog of commercially available compounds. The same reagent is used in the second step of the published synthesis of GSK.
  • Synthesis of Zatosetron
    Zatosetron is a potent, selective, orally effective 5HT3 receptor antagonist which has been successfully tested on rats. The first published synthesis required six steps (Robertson, David W. et al., Journal of Medicinal Chemistry, 1992, 35(2), 310-319)
    With THERESA-CCR2005, a two steps synthesis was obtained.

Non drugs

  • Synthesis of 4M-I3G
    4-methoxyindol-3-ylmethylglucosinolate(4M-I3G) is a natural product involved in the defense of plants against fungal pathogens. Its discovery may lead to the developement of new fungicides (example taken from C&EN December 22, 2008, page 8). Due to the knowledge of the authors, no synthesis of 4M-I3G has been published as of February 2009.
    With THERESA-CrossFire Beilstein, a four steps synthesis was obtained. The stereochemistry was not taken into account during the retrosynthesis computation.
  • Synthesis of twistane
    Twistane (C10H16) is an isomer of the diamondoid adamantane with its cyclohexane rings permanently forced into the "twisted" conformation.
    With THERESA-CCR2005, a four steps synthesis was obtained. The saturated ketone at step 2 needs to be protected. If the protection/deprotection is added to the route, then the route found is identical to the one described in DOS p.244