Natural Product Identification
AI-Guided Dereplication 
Prep-HPLC/SFC Isolation 
600/800 MHz NMR + XRD 
Metabolomics-Guided Prioritization Natural product extracts contain hundreds of chemically diverse metabolites. Traditional bioassay-guided fractionation consumes months of effort—often rediscovering already-reported compounds while missing low-abundance novel scaffolds. The Creative Biostructure platform integrates AI-driven dereplication, automated chromatographic separation, and high-resolution structural biology to transform crude matrices into structurally authenticated, drug-ready compounds under predictable timelines. Whether you are a seed-stage biotech extending your chemistry capabilities or a pharma team seeking novel chemical matter against difficult targets, we deliver pure, characterized leads without building a natural product isolation infrastructure.
Why Natural Product Identification Is the Critical Gate Between Raw Matrix and Drug Discovery?
Bioactive extracts are data-rich but hypothesis-poor. Seed-stage biotechs lack prep-HPLC farms, high-field NMR suites, and the cheminformatics pipelines required to navigate complex metabolomes—forcing them to outsource crude extracts to academic collaborators with incompatible timelines. Pharma teams pursuing PPI modulators or allosteric inhibitors watch promising botanical leads stall at the isolation phase because dereplication bottlenecks and structural ambiguity consume quarters of development time.
The Creative Biostructure platform eliminates that friction. We integrate AI-powered LC-MS dereplication, automated prep-chromatography, and AI-assisted NMR/XRD structural elucidation into a single execution system. Computational metabolomics predicts bioactive fractions before isolation begins; high-field NMR and X-ray crystallography resolve absolute configuration with atomic precision—creating a closed loop that transforms raw plant tissue or fermentation broth into patentable, synthesis-ready scaffolds.
AI-First Dereplication
Deep learning algorithms cross-reference LC-HRMS/MS² and NMR spectra against global natural product databases in real time, eliminating known compounds before costly preparative isolation begins. This typically reduces dereplication cycles by 60% and prevents wasted FTE hours on redundant scaffolds.
Structure-Grade Analytical Depth
600/800 MHz high-field NMR and X-ray diffraction hardware, combined with AI-assisted spectral deconvolution software, deliver structural determination packages that withstand the most rigorous patent scrutiny and regulatory audits.
Single-Vendor Accountability
From crude extract receipt to purified compound with full CoA, one project team manages extraction, chromatography, spectroscopy, and data interpretation. No handoff delays between a botanical supplier, an analytical CRO, and a structural biology facility.
Natural Product Identification Technology Suite
Compound Isolation & Purification
From Complex Matrix to Pure Compound
Key Features:
- Multi-modal chromatographic platform: Flash chromatography, prep-HPLC (Waters AutoPurification / Shimadzu LC-20AP), SFC, and countercurrent chromatography for full-polarity-range fractionation.
- LC-MS-guided fraction collection: Real-time mass spectrometry feedback during prep-HPLC ensures collection decisions target high-value molecular ions, not just UV-active peaks.
- AI retention time modeling: Predictive algorithms estimate compound polarity and optimal solvent gradients before the first column is packed, reducing method development time.
Ideal For: Isolation of trace bioactives from plant, microbial, fungal, and marine matrices; separation of closely related isomers and glycosides; recovery of thermally labile compounds via room-temperature countercurrent methods.
What We Offer:
For seed-stage biotechs, this means receiving milligram-scale pure compounds without investing in prep-chromatography infrastructure or natural product isolation FTEs. For pharma teams, our integrated platform eliminates the classic vendor triangle—botanical supplier → analytical CRO → structural facility—replacing it with a single accountability chain and unified data package.
Structural Elucidation
Atomic-Resolution Characterization for Patent and Regulatory Certainty
Key Features:
- High-field NMR: Bruker AVANCE NEO 600/800 MHz with AI-assisted spectral deconvolution; multi-dimensional experiments (COSY, HSQC, HMBC, NOESY) for unambiguous connectivity and stereochemistry.
- High-resolution MS: Waters Xevo G2-XS QTof and Thermo Q Exactive HF-X for exact mass determination, MS/MS fragmentation mapping, and molecular formula assignment (sub-ppm accuracy).
- X-ray crystallography: Rigaku XtaLAB Synergy for absolute configuration determination of novel scaffolds; single-crystal and micro-crystal capabilities for compounds that resist traditional NMR stereochemical assignment.
Ideal For: Novel natural product structure determination; stereochemical confirmation of chiral centers; solid-form and polymorph characterization for downstream formulation.
What We Offer:
Every compound exiting our platform ships with a structural identity report including HRMS, multi-dimensional NMR assignments, and—where applicable—XRD-validated absolute configuration. These packages are formatted for immediate patent filing and IND-enabling documentation, eliminating the gap between isolation and intellectual property prosecution.
Dereplication & Identity Confirmation
Eliminate Redundancy Before You Isolate
Key Features:
- AI-powered spectral matching: LC-HRMS/MS² and NMR data are auto-cross-referenced against curated global repositories (Dictionary of Natural Products, MarinLit, NPAtlas, PubChem) using deep learning similarity scoring.
- Combinatorial HRMS formula search: Sub-ppm mass accuracy filtering assigns molecular formulas and flags known compounds with >95% confidence, typically within 48 hours of extract receipt.
- Reference standard confirmation: Identity verification against authenticated standards for quality control and batch-to-batch consistency.
Ideal For: Preventing costly re-isolation of known compounds; rapid novelty assessment for patent positioning; QC confirmation of sourced botanical or microbial materials.
What We Offer:
For virtual biotechs managing burn rate, AI dereplication ensures your synthesis budget targets only patentable scaffolds—conserving cash for lead optimization. For pharma outsourcing teams, real-time dereplication reports provide immediate go/no-go decisions on extract investment, protecting procurement budgets from botanical commodity risk.
Metabolomics & Biosynthetic Profiling
Map the Metabolome to Prioritize the Right Fraction
Key Features:
- Untargeted and targeted LC-MS metabolomics: Comprehensive chemical profiling of crude extracts, fermentation time-courses, or comparative mutant strains.
- Multivariate statistical analysis: PCA and OPLS-DA identify chemical markers correlated with bioactivity, guiding fraction prioritization before isolation.
- Pathway enrichment: KEGG/GO mapping and in-silico metabolite annotation reveal biosynthetic gene cluster (BGC) products and guide genome mining strategies.
Ideal For: Bioassay-guided fractionation optimization; comparative metabolomics across species or growth conditions; biosynthetic pathway elucidation for engineered production strains.
What We Offer:
When your bioactive fraction contains 50+ co-eluting metabolites, metabolomics tells you which 5 to prioritize. This transforms fractionation from a blind, iterative process into a data-driven, hypothesis-led operation—compressing timeline and reducing compound consumption by 40–50%.
Platform Instrumentation
| Instrument | Throughput / Sensitivity |
|---|---|
| Waters AutoPurification System | Prep-HPLC; mg-to-g scale purification with mass-triggered fractionation |
| Shimadzu LC-20AP Prep-HPLC | Preparative scale isolation; automated fraction collection |
| Bruker AVANCE NEO 600/800 MHz | Multi-dimensional NMR; AI-assisted spectral deconvolution for trace-component characterization |
| Waters Xevo G2-XS QTof | LC-MS/MS; exact mass confirmation and molecular formula assignment |
| Thermo Q Exactive HF-X | HRMS; sub-ppm mass accuracy for dereplication and metabolomics |
| Rigaku XtaLAB Synergy | X-ray diffractometer; absolute configuration determination |
Standardized Workflow
Project Workflow
A standardized, milestone-driven execution system. From crude extract receipt to structurally authenticated compound delivery—managed by a single project team, tracked in real time.
01 Sample Preparation & Fractionation
- Extraction protocol optimization and solubility assessment
- Multi-step chromatographic fractionation (flash, prep-HPLC, SFC, CCC)
- Real-time LC-MS profiling of all fractions to guide collection
Deliverable: Fractionation scheme + LC-MS chromatographic profiles
02 Analytical Profiling & Dereplication
- LC-HRMS/MS² profiling and combinatorial molecular formula assignment
- AI dereplication against curated natural product databases
- Novelty assessment and priority ranking for downstream isolation
Deliverable: Dereplication report + prioritized fraction hit list
03 Spectroscopic Characterization
- Multi-dimensional NMR (COSY, HSQC, HMBC, NOESY) for connectivity and stereochemistry
- HRMS fragmentation mapping and isotope pattern confirmation
- X-ray crystallography for absolute configuration (when required)
Deliverable: Structural identity report with atomic-level characterization
04 AI-Assisted Structure Validation
- AI spectral deconvolution and database cross-validation
- Biosynthetic pathway classification and BGC correlation
- Purity assessment (HPLC-UV/LC-MS area %) and Certificate of Analysis
Deliverable: Validated structural report + CoA + biosynthetic annotation
05 Regulatory Reporting & Transition
- Patent-ready structural data package (NMR, HRMS, XRD coordinates)
- Hit-to-Lead / Lead Optimization transition plan with SAR rationale
- Regulatory-formatted documentation for IND-enabling studies
Deliverable: Final technical report + electronic data package
Note: Standard identification projects complete in 10–12 weeks. Dereplication-only projects for known extracts can be delivered in 4–6 weeks. Complex novel structures requiring XRD may extend to 14–16 weeks.
Sample Requirements
| Requirement | Specification |
|---|---|
| Sample Type | Dry powder, lyophilized extract, fermentation broth, or plant/marine tissue (source organism documentation required) |
| Minimum Quantity | 10–50 mg crude extract for initial profiling; ≥1 mg purified isolate for full NMR characterization |
| Purity Preference | ≥90% estimated purity preferred for NMR analysis |
| Solubility Data | DMSO, MeOH, or water compatibility recommended prior to submission |
| Data Input | Prior literature, reference standards, or preliminary bioassay data welcome for targeted AI modeling |
Standard Deliverables
- Fractionation scheme with LC-MS chromatographic profiles and UV/ELSD traces
- Dereplication report: database matches, molecular formula predictions, and novelty assessment
- Full NMR spectral dataset (1D/2D as applicable) with AI-assisted assignments
- HRMS data with molecular formula assignment and isotope pattern confirmation
- Certificate of Analysis (HPLC or LC-MS area % purity)
- Interpretive structural elucidation report with proposed biosynthetic classification
- Patent-ready structural data package formatted for regulatory submission
Frequently Asked Questions
Case Study
Case Study: Identification of a Novel Pseudo-Natural Product IDO1 Inhibitor: Structural Biology Validates a Heme-Displacing Chemotype
Goal: Identify and structurally characterize a novel pseudo-natural product (PNP) chemotype—apoxidoles—as first-in-class indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors, demonstrating the power of fragment-based natural product design combined with high-resolution structural validation.
Key Data:
- Design strategy: Fragment-based merging of indole and tetrahydropyridine scaffolds via enantioselective [4+2] annulation to access biologically relevant chemical space beyond traditional natural products.
- Structural validation: X-ray crystallography at 1.8 Å resolution (PDB 8ABX) revealed apoxidole-1 as a unique Type IV inhibitor binding apo-IDO1, displacing the essential heme cofactor across sub-pockets A and D.
- Potency: Nanomolar-level IDO1 inhibition confirmed via biochemical assays.
- Novelty: Previously unreported chemotype with a non-traditional binding mechanism preventing heme reconstitution
Why it matters:
For drug developers, this peer-reviewed case demonstrates that natural product-inspired scaffolds—when paired with rigorous structural biology—can yield first-in-class mechanisms inaccessible to synthetic libraries. The ability to resolve a heme-displacing binding mode at atomic resolution transforms a synthetic curiosity into a patentable, development-ready lead with clear mechanistic differentiation.
Figure 1. Crystal structure of apoxidole-1 bound to apo-IDO1 (PDB 8ABX). (Davies C, et al., 2022)
Reference:
- Davies C, Dötsch L, Ciulla MG, et al. Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype. Angew Chem Int Ed Engl. 2022 Oct 4;61(40):e202209374.
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