Subtopic Deep Dive

Total Synthesis of Ecteinascidin
Research Guide

What is Total Synthesis of Ecteinascidin?

Total synthesis of ecteinascidin refers to the complete chemical construction of ecteinascidin 743 (ET-743), a tetrahydroisoquinoline marine antitumor antibiotic, from simple precursors via multi-step enantioselective routes.

Ecteinascidin 743, isolated from marine tunicates, exhibits potent antiproliferative activity against tumor cells. Key syntheses include the enantioselective total synthesis by Corey et al. (1996, 338 citations) using stereoselective coupling strategies. Semisynthetic processes by Cuevas and Francesch (2009, 309 citations) address supply limitations for clinical development like Yondelis®.

Curated Papers

Key Challenges

Why It Matters

Total synthesis enables production of ecteinascidin 743 for clinical trials as Yondelis®, overcoming scarce natural supply from marine sources (Cuevas and Francesch, 2009). These routes inspire methodologies for other tetrahydroisoquinoline alkaloids in cancer research. Synthetic access supports structure-activity studies and analog development for improved antitumor agents.

Key Research Challenges

Enantioselective Tetrahydroisoquinoline Construction

Achieving stereocontrol over multiple chiral centers in the bis-tetrahydroisoquinoline core remains difficult. Corey et al. (1996) employed chiral auxiliaries and asymmetric couplings, yet overall yields stay low. Optimization of these steps limits scalability for pharmaceutical production.

Scalable Semisynthetic Processes

Transitioning from total to semisynthesis requires efficient precursor sourcing and late-stage modifications. Cuevas and Francesch (2009) developed a process solving supply issues for Yondelis®, but fermentation variability poses ongoing hurdles. High-throughput reaction screening is needed for industrial yields.

Carbinolamine Functional Group Stability

The active carbinolamine moiety degrades during synthesis, complicating isolation. Early syntheses like Corey et al. (1996) protected this group strategically. Improved stabilization methods are essential for analog synthesis and biological evaluation.

Essential Papers

Marine natural products

John W. Blunt, Anthony R. Carroll, Brent R. Copp et al. · 2018 · Natural Product Reports · 718 citations

This review of 2016 literature describes the structures and biological activities of 1277 new marine natural products and the structure revision and absolute configuration of previously reported MN...

Marine natural products and their potential applications as anti-infective agents

Marwa S. Donia, Mark T. Hamann · 2003 · The Lancet Infectious Diseases · 422 citations

Marine Natural Products: A New Wave of Drugs?

Rana Montaser, Hendrik Luesch · 2011 · Future Medicinal Chemistry · 419 citations

The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel 'validated' structures with novel modes of action that cover biologic...

Marine Sponges as Pharmacy

Detmer Sipkema, Maurice C. R. Franssen, Ronald Osinga et al. · 2005 · Marine Biotechnology · 408 citations

Marine Sponge Derived Natural Products between 2001 and 2010: Trends and Opportunities for Discovery of Bioactives

Mohammad F. Mehbub, Jie Lei, Christopher M. M. Franco et al. · 2014 · Marine Drugs · 404 citations

Marine sponges belonging to the phylum Porifera (Metazoa), evolutionarily the oldest animals are the single best source of marine natural products. The present review presents a comprehensive overv...

Bioactive Compounds from Marine Bacteria and Fungi

Abdessamad Debbab, Amal H. Aly, Wen Han Lin et al. · 2010 · Microbial Biotechnology · 358 citations

Summary Marine bacteria and fungi are of considerable importance as new promising sources of a huge number of biologically active products. Some of these marine species live in a stressful habitat,...

Enantioselective Total Synthesis of Ecteinascidin 743

E. J. Corey, David Y. Gin, Robert S. Kania · 1996 · Journal of the American Chemical Society · 338 citations

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEnantioselective Total Synthesis of Ecteinascidin 743E. J. Corey, David Y. Gin, and Robert S. KaniaView Author Information Department of Chemistry,...

Reading Guide

Foundational Papers

Read Corey et al. (1996) first for the enantioselective total synthesis blueprint (338 citations), then Cuevas and Francesch (2009) for semisynthetic scaling to clinical supply.

Recent Advances

Study Blunt et al. (2018, 718 citations) for ecteinascidin context in marine natural products and Montaser and Luesch (2011, 419 citations) for drug development challenges.

Core Methods

Enantioselective couplings with chiral auxiliaries (Corey 1996); late-stage semisynthetic modifications from precursors (Cuevas 2009); stereocontrolled tetrahydroisoquinoline assembly.

How PapersFlow Helps You Research Total Synthesis of Ecteinascidin

Discover & Search

Research Agent uses searchPapers and citationGraph to map syntheses citing Corey et al. (1996), revealing 338 downstream works, then findSimilarPapers uncovers related alkaloid routes. exaSearch queries 'ecteinascidin total synthesis yield optimization' for overlooked marine natural product reviews like Blunt et al. (2018).

Analyze & Verify

Analysis Agent applies readPaperContent to extract reaction schemes from Corey et al. (1996), verifies stereochemistry claims with verifyResponse (CoVe), and runs PythonAnalysis to compute overall yields from step data using pandas. GRADE grading scores synthetic efficiency evidence as high-confidence based on citation metrics.

Synthesize & Write

Synthesis Agent detects gaps in scalable ecteinascidin routes via contradiction flagging across Corey (1996) and Cuevas (2009), generates exportMermaid diagrams of reaction networks. Writing Agent uses latexEditText for scheme revisions, latexSyncCitations to integrate references, and latexCompile for publication-ready reviews.

Use Cases

"Calculate overall yield of Corey 1996 ecteinascidin synthesis from step efficiencies"

Research Agent → searchPapers 'Corey ecteinascidin' → Analysis Agent → readPaperContent → runPythonAnalysis (pandas chain multiplication of yields) → output: 0.8% overall yield plot.

"Draft LaTeX review of ecteinascidin synthetic routes with schemes"

Research Agent → citationGraph → Synthesis Agent → gap detection → Writing Agent → latexEditText + latexSyncCitations (Corey 1996, Cuevas 2009) + latexCompile → output: Compiled PDF with embedded reaction diagrams.

"Find code for modeling ecteinascidin stereoselectivity"

Research Agent → paperExtractUrls (Corey 1996) → Code Discovery → paperFindGithubRepo → githubRepoInspect → output: Python scripts for asymmetric induction simulations.

Automated Workflows

Deep Research workflow scans 50+ marine natural product papers via searchPapers, structures ecteinascidin synthesis timeline in a report citing Blunt et al. (2018). DeepScan applies 7-step CoVe analysis to Cuevas (2009) semisynthesis, verifying yield claims with statistical checkpoints. Theorizer generates hypotheses for new carbinolamine protections from synthesis gaps.

Try Doxa for Total Synthesis of Ecteinascidin Research

Frequently Asked Questions

What is total synthesis of ecteinascidin?

It is the chemical construction of ecteinascidin 743 from simple starting materials, exemplified by Corey et al. (1996) enantioselective route achieving the full tetrahydroisoquinoline structure.

What are key methods in ecteinascidin synthesis?

Corey et al. (1996) used chiral auxiliary-based couplings for enantioselectivity; Cuevas and Francesch (2009) developed semisynthesis from fermentation precursors for Yondelis® production.

What are the most cited papers?

Corey et al. (1996, JACS, 338 citations) for total synthesis; Cuevas and Francesch (2009, Natural Product Reports, 309 citations) for semisynthetic process.